Heavy flavor puzzle at LHC: a serendipitous interplay of jet suppression and fragmentation.
Djordjevic, Magdalena
2014-01-31
Both charged hadrons and D mesons are considered to be excellent probes of QCD matter created in ultrarelativistic heavy ion collisions. Surprisingly, recent experimental observations at LHC show the same jet suppression for these two probes, which--contrary to pQCD expectations--may suggest similar energy losses for light quarks and gluons in the QCD medium. We here use our recently developed energy loss formalism in a finite-size dynamical QCD medium to analyze this phenomenon that we denote as the "heavy flavor puzzle at LHC." We show that this puzzle is a consequence of an unusual combination of the suppression and fragmentation patterns and, in fact, does not require invoking the same energy loss for light partons. Furthermore, we show that this combination leads to a simple relationship between the suppressions of charged hadrons and D mesons and the corresponding bare quark suppressions. Consequently, a coincidental matching of jet suppression and fragmentation allows considerably simplifying the interpretation of the corresponding experimental data.
Wagner, Nicholas; Mroczka, Andrew; Roberts, Peter D; Schreckengost, William; Voelker, Toni
2011-09-01
Suppression of the microsomal ω6 oleate desaturase during the seed development of soybean (Glycine max) with the 420-bp soybean FAD2-1A intron as RNAi trigger shifts the conventional fatty acid composition of soybean oil from 20% oleic and 60% polyunsaturates to one containing greater than 80% oleic acid and less than 10% polyunsaturates. To determine whether RNAi could be attenuated by reducing the trigger fragment length, transgenic plants were generated to express successively shorter 5' or 3' deletion derivatives of the FAD2-1A intron. We observed a gradual reduction in transcript suppression with shorter trigger fragments. Fatty acid composition was less affected with shorter triggers, and triggers less than 60 bp had no phenotypic effect. No trigger sequences conferring significantly higher or lower suppression efficiencies were found, and the primary determinant of suppression effect was sequence length. The observed relationship of transcript suppression with the induced fatty acid phenotype indicates that RNAi is a saturation process and not a step change between suppressed and nonsuppressed states and intermediate suppression states can be achieved. © 2010 Monsanto. Plant Biotechnology Journal © 2010 Society for Experimental Biology and Blackwell Publishing Ltd.
Robust Object Tracking Using Valid Fragments Selection.
Zheng, Jin; Li, Bo; Tian, Peng; Luo, Gang
Local features are widely used in visual tracking to improve robustness in cases of partial occlusion, deformation and rotation. This paper proposes a local fragment-based object tracking algorithm. Unlike many existing fragment-based algorithms that allocate the weights to each fragment, this method firstly defines discrimination and uniqueness for local fragment, and builds an automatic pre-selection of useful fragments for tracking. Then, a Harris-SIFT filter is used to choose the current valid fragments, excluding occluded or highly deformed fragments. Based on those valid fragments, fragment-based color histogram provides a structured and effective description for the object. Finally, the object is tracked using a valid fragment template combining the displacement constraint and similarity of each valid fragment. The object template is updated by fusing feature similarity and valid fragments, which is scale-adaptive and robust to partial occlusion. The experimental results show that the proposed algorithm is accurate and robust in challenging scenarios.
Fragmentation and reactivity of energy-selected ferrocenium ions
International Nuclear Information System (INIS)
Mestdagh, H.; Dutuit, O.; Heninger, M.; Thissen, R.; Alcaraz, C.
2002-01-01
In this study, results concerning the discussion of state-selected ferrocenium ions (c-C 5 H 5 ) 2 Fe + commonly called Cp 2 Fe + , as well as their reactions with methanol and ethanol are presented. Parent ions Cp 2 Fe + were produced by vacuumultraviolett (VUV) photoionization of neutral ferrocene using synchrotron radiation, and selected in internal energy by threshold photoelectron-photoion coincidences. The apparatus is divided into three differentially pumped regions: the source, the reaction and the detection zones. In source, state-selected parent ions are formed and can be selected in mass by a first quadrupole filter. State-selected ions are then injected in the second zone which is a RF octopole ion guide where reaction product ions are mass analyzed by a second quadrupole filter and detected by microchannelplates. In addition, the long flight time in the octopoles (several hundreds of microseconds) allows studying long-lived metastable ions. Total mass spectra were recorded at different photon energies, in addition to the main CpFe + and Fe + fragments, several minor fragments were detected such as C 10 H 10 + which reflects the formation of a C-C bond between the two Cp ligands. Losses of CH 3 , C 2 H 2 and C-4H 4 also indicate that important structure rearrangements take place before cleavage. The appearance energies of each mass-selected fragment ion were measured by recording fragment ion yields as a function of photon energy. Surprisingly, all fragments were found to have the same energy onset, i.e. 13.2 eV photon energy, except for C 3 H 3 Fe + (m/z 95). For Fe + ions, a sharp increase was observed at 17 eV, above the thermochemical onset of Fe + + 2 Cp. The 13.2 eV appearance energy of Fe + is thus assigned to the formation of Fe - + C 10 H 10 . The reactivity of ferrocenium ion with methanol and ethanol was investigated as a function of photon energy. While no reaction occurs at lower photon energies, several reaction products appear at 13.0 e
Chen, J J; Du, Q Y; Yue, Y Y; Dang, B J; Chang, Z J
2010-08-01
In this study, a sex subtractive genomic DNA library was constructed using suppression subtractive hybridization (SSH) between male and female Cyprinus carpio. Twenty-two clones with distinguishable hybridization signals were selected and sequenced. The specific primers were designed based on the sequence data. Those primers were then used to amplify the sex-specific fragments from the genomic DNA of male and female carp. The amplified fragments from two clones showed specificity to males but not to females, which were named as Ccmf2 [387 base pairs (bp)] and Ccmf3 (183 bp), respectively. The sex-specific pattern was analysed in a total of 40 individuals from three other different C. carpio. stocks and grass carp Ctenopharyngodon idella using Ccmf2 and Ccmf3 as dot-blotting probes. The results revealed that the molecular diversity exists on the Y chromosome of C. carpio. No hybridization signals, however, were detected from individuals of C. idella, suggesting that the two sequences are specific to C. carpio. No significant homologous sequences of Ccmf2 and Ccmf3 were found in GenBank. Therefore, it was interpreted that the results as that Ccmf2 and Ccmf3 are two novel male-specific sequences; and both fragments could be used as markers to rapidly and accurately identify the genetic sex of part of C. carpio. This may provide a very efficient selective tool for practically breeding monosex female populations in aquacultural production.
Laser-assisted shape selective fragmentation of nanoparticles
Energy Technology Data Exchange (ETDEWEB)
Kazakevich, P.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38, Vavilov street, 117942 Moscow (Russian Federation); Simakin, A.V. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38, Vavilov street, 117942 Moscow (Russian Federation); Shafeev, G.A. [Wave Research Center, General Physics Institute of the Russian Academy of Sciences, 38, Vavilov street, 117942 Moscow (Russian Federation)]. E-mail: shafeev@kapella.gpi.ru; Viau, G. [ITODYS, UMR 7086, Universite Paris 7-Denis Diderot, case 7090, 2 place Jussieu, 75251 Paris Cedex 05 (France); Soumare, Y. [ITODYS, UMR 7086, Universite Paris 7-Denis Diderot, case 7090, 2 place Jussieu, 75251 Paris Cedex 05 (France); Bozon-Verduraz, F. [ITODYS, UMR 7086, Universite Paris 7-Denis Diderot, case 7090, 2 place Jussieu, 75251 Paris Cedex 05 (France)
2007-07-31
Experimental results are presented on laser-assisted fragmentation of gold-containing nanoparticles suspended in liquids (either ethanol or water). Two kinds of nanoparticles are considered: (i) elongated Au nanorods synthesized by laser ablation of a gold target immersed in liquid phase; (ii) gold-covered NiCo nanorods with high aspect ratio ({theta} {approx} 10) synthesized by wet chemistry processes. The shape selectivity induced by laser fragmentation of these nanorods is gained via tuning the wavelength of laser radiation into different parts of the spectrum of their plasmon resonance corresponding to different aspect ratios {theta}. Fragmentation is performed using three laser wavelengths, involving a Cu vapour laser (510 and 578 nm) and a Nd:YAG (1064 nm). Nanoparticles are characterized by UV-vis spectrometry, Transmission Electron Microscopy (TEM). The effect of laser pulse duration (nanosecond against picosecond range) is also studied in the case of fragmentation with an IR laser radiation.
Selective disulfide reduction for labeling and enhancement of Fab antibody fragments.
Kirley, Terence L; Greis, Kenneth D; Norman, Andrew B
2016-11-25
Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab') 2 fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab') 2 fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neither homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. Copyright © 2016 Elsevier Inc. All rights reserved.
Selective disulfide reduction for labeling and enhancement of Fab antibody fragments
International Nuclear Information System (INIS)
Kirley, Terence L.; Greis, Kenneth D.; Norman, Andrew B.
2016-01-01
Many methods have been developed for chemical labeling and enhancement of the properties of antibodies and their common fragments, including the Fab and F(ab’) 2 fragments. Somewhat selective reduction of some antibody disulfide bonds has been previously achieved, yielding antibodies and antibody fragments that can be labeled at defined sites, enhancing their utility and properties. Selective reduction of the two hinge disulfide bonds present in F(ab’) 2 fragments using mild reduction has been useful. However, such reduction is often not quantitative and results in the reduction of multiple disulfide bonds, and therefore subsequent multiple labeling or conjugation sites are neither homogenous nor stoichiometric. Here, a simple and efficient selective reduction of the single disulfide bond linking the partial heavy chain and the intact light chain which compose the Fab fragment is accomplished utilizing tris(2-carboxyethyl)phosphine (TCEP) immobilized on agarose beads. The resultant reduced cysteine residues were labeled with several cysteine-selective fluorescent reagents, as well as by cysteine-directed PEGylation. These two cysteine residues can also be re-ligated by means of a bifunctional cysteine cross-linking agent, dibromobimane, thereby both restoring a covalent linkage between the heavy and light chains at this site, far removed from the antigen binding site, and also introducing a fluorescent probe. There are many other research and clinical uses for these selectively partially reduced Fab fragments, including biotinylation, toxin and drug conjugation, and incorporation of radioisotopes, and this technique enables simple generation of very useful Fab fragment derivatives with many potential applications. - Highlights: • TCEP agarose is effective for selective reduction of a single Fab disulfide bond. • This disulfide is solvent accessible and distant from the antigen binding site. • A variety of buffers of varying pHs can be used, simplifying
ALIS-FLP: Amplified ligation selected fragment-length polymorphism method for microbial genotyping
DEFF Research Database (Denmark)
Brillowska-Dabrowska, A.; Wianecka, M.; Dabrowski, Slawomir
2008-01-01
A DNA fingerprinting method known as ALIS-FLP (amplified ligation selected fragment-length polymorphism) has been developed for selective and specific amplification of restriction fragments from TspRI restriction endonuclease digested genomic DNA. The method is similar to AFLP, but differs...
Modelling the negative effects of landscape fragmentation on habitat selection
Langevelde, van F.
2015-01-01
Landscape fragmentation constrains movement of animals between habitat patches. Fragmentation may, therefore, limit the possibilities to explore and select the best habitat patches, and some animals may have to cope with low-quality patches due to these movement constraints. If so, these individuals
Attosecond-recollision-controlled selective fragmentation of polyatomic molecules.
Xie, Xinhua; Doblhoff-Dier, Katharina; Roither, Stefan; Schöffler, Markus S; Kartashov, Daniil; Xu, Huailiang; Rathje, Tim; Paulus, Gerhard G; Baltuška, Andrius; Gräfe, Stefanie; Kitzler, Markus
2012-12-14
Control over various fragmentation reactions of a series of polyatomic molecules (acetylene, ethylene, 1,3-butadiene) by the optical waveform of intense few-cycle laser pulses is demonstrated experimentally. We show both experimentally and theoretically that the responsible mechanism is inelastic ionization from inner-valence molecular orbitals by recolliding electron wave packets, whose recollision energy in few-cycle ionizing laser pulses strongly depends on the optical waveform. Our work demonstrates an efficient and selective way of predetermining fragmentation and isomerization reactions in polyatomic molecules on subfemtosecond time scales.
Cationization increases brain distribution of an amyloid-beta protofibril selective F(ab')2 fragment
Syvänen, Stina; Edén, Desireé; Sehlin, Dag
2017-01-01
Antibodies and fragments thereof are, because of high selectivity for their targets, considered as potential therapeutics and biomarkers for several neurological disorders. However, due to their large molecular size, antibodies/fragments do not easily penetrate into the brain. The aim of the present study was to improve the brain distribution via adsorptive-mediated transcytosis of an amyloid-beta (A beta) protofibril selective F(ab')2 fragment (F(ab')2-h158). F(ab')2-h158 was cationized to d...
Attentional selection and suppression in children and adults.
Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan
2018-05-15
The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.
Santos, Alexandre Rosa Dos; Antonio Alvares Soares Ribeiro, Carlos; de Oliveira Peluzio, Telma Machado; Esteves Peluzio, João Batista; de Queiroz, Vagner Tebaldi; Figueira Branco, Elvis Ricardo; Lorenzon, Alexandre Simões; Domingues, Getulio Fonseca; Marcatti, Gustavo Eduardo; de Castro, Nero Lemos Martins; Teixeira, Thaisa Ribeiro; Dos Santos, Gleissy Mary Amaral Dino Alves; Santos Mota, Pedro Henrique; Ferreira da Silva, Samuel; Vargas, Rozimelia; de Carvalho, José Romário; Macedo, Leandro Levate; da Silva Araújo, Cintia; de Almeida, Samira Luns Hatum
2016-12-01
The Atlantic Forest biome is recognized for its biodiversity and is one of the most threatened biomes on the planet, with forest fragmentation increasing due to uncontrolled land use, land occupation, and population growth. The most serious aspect of the forest fragmentation process is the edge effect and the loss of biodiversity. In this context, the aim of this study was to evaluate the dynamics of forest fragmentation and select potential forest fragments with a higher degree of conservation for seed harvesting in the Itapemirim river basin, Espírito Santo State, Brazil. Image classification techniques, forest landscape ecology, and multi-criteria analysis were used to evaluate the evolution of forest fragmentation to develop the landscape metric indexes, and to select potential forest fragments for seed harvesting for the years 1985 and 2013. According to the results, there was a reduction of 2.55% of the occupancy of the fragments in the basin between the years 1985 and 2013. For the years 1985 and 2013, forest fragment units 2 and 3 were spatialized with a high potential for seed harvesting, representing 6.99% and 16.01% of the total fragments, respectively. The methodology used in this study has the potential to be used to support decisions for the selection of potential fragments for seed harvesting because selecting fragments in different environments by their spatial attributes provides a greater degree of conservation, contributing to the protection and conscious management of the forests. The proposed methodology can be adapted to other areas and different biomes of the world. Copyright © 2016 Elsevier Ltd. All rights reserved.
Multitarget Tracking with Spatial Nonmaximum Suppressed Sensor Selection
Directory of Open Access Journals (Sweden)
Liang Ma
2015-01-01
Full Text Available Multitarget tracking is one of the most important applications of sensor networks, yet it is an extremely challenging problem since multisensor multitarget tracking itself is nontrivial and the difficulty is further compounded by sensor management. Recently, random finite set based Bayesian framework has opened doors for multitarget tracking with sensor management, which is modelled in the framework of partially observed Markov decision process (POMDP. However, sensor management posed as a POMDP is in essence a combinatorial optimization problem which is NP-hard and computationally unacceptable. In this paper, we propose a novel sensor selection method for multitarget tracking. We first present the sequential multi-Bernoulli filter as a centralized multisensor fusion scheme for multitarget tracking. In order to perform sensor selection, we define the hypothesis information gain (HIG of a sensor to measure its information quantity when the sensor is selected alone. Then, we propose spatial nonmaximum suppression approach to select sensors with respect to their locations and HIGs. Two distinguished implementations have been provided using the greedy spatial nonmaximum suppression. Simulation results verify the effectiveness of proposed sensor selection approach for multitarget tracking.
Bobrovnikov, S. M.; Gorlov, E. V.; Zharkov, V. I.
2018-05-01
A technique for increasing the selectivity of the method of detecting high-energy materials (HEMs) based on laser fragmentation of HEM molecules with subsequent laser excitation of fluorescence of the characteristic NO fragments from the first vibrational level of the ground state is suggested.
Schleuning, Matthias; Farwig, Nina; Peters, Marcell K.; Bergsdorf, Thomas; Bleher, Bärbel; Brandl, Roland; Dalitz, Helmut; Fischer, Georg; Freund, Wolfram; Gikungu, Mary W.; Hagen, Melanie; Garcia, Francisco Hita; Kagezi, Godfrey H.; Kaib, Manfred; Kraemer, Manfred; Lung, Tobias; Schaab, Gertrud; Templin, Mathias; Uster, Dana; Wägele, J. Wolfgang; Böhning-Gaese, Katrin
2011-01-01
Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the
Selection of monoclonal anti-CEA antibody fragments for tumor detection by immunoscintigraphy
International Nuclear Information System (INIS)
Mach, J.P.; Buchegger, F.
1986-01-01
It is described how individual MAb directed against carcinoembryotic antigen (CEA) is selected which does not crossreact with granulocytes and gives the best tumor localization in the model of nude mice grafted with human colon carcinoma. Using this model, the superiority of F(ab')/sub 2/ and particularly Fab fragments from high affinity MAb for the localization of relatively small tumor nodules is demonstrated. These MAb fragments are also successfully used in an ongoing clinical trial for the detection of primary and metastatic colorectal carcinomas
Site-specific fragmentation of polystyrene molecule using size-selected Ar gas cluster ion beam
International Nuclear Information System (INIS)
Moritani, Kousuke; Mukai, Gen; Hashinokuchi, Michihiro; Mochiji, Kozo
2009-01-01
The secondary ion mass spectrum (SIMS) of a polystyrene thin film was investigated using a size-selected Ar gas cluster ion beam (GCIB). The fragmentation in the SIM spectrum varied by kinetic energy per atom (E atom ); the E atom dependence of the secondary ion intensity of the fragment species of polystyrene can be essentially classified into three types based on the relationship between E atom and the dissociation energy of a specific bonding site in the molecule. These results indicate that adjusting E atom of size-selected GCIB may realize site-specific bond breaking within a molecule. (author)
Overcoming fixation with repeated memory suppression.
Angello, Genna; Storm, Benjamin C; Smith, Steven M
2015-01-01
Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.
Virtual fragment preparation for computational fragment-based drug design.
Ludington, Jennifer L
2015-01-01
Fragment-based drug design (FBDD) has become an important component of the drug discovery process. The use of fragments can accelerate both the search for a hit molecule and the development of that hit into a lead molecule for clinical testing. In addition to experimental methodologies for FBDD such as NMR and X-ray Crystallography screens, computational techniques are playing an increasingly important role. The success of the computational simulations is due in large part to how the database of virtual fragments is prepared. In order to prepare the fragments appropriately it is necessary to understand how FBDD differs from other approaches and the issues inherent in building up molecules from smaller fragment pieces. The ultimate goal of these calculations is to link two or more simulated fragments into a molecule that has an experimental binding affinity consistent with the additive predicted binding affinities of the virtual fragments. Computationally predicting binding affinities is a complex process, with many opportunities for introducing error. Therefore, care should be taken with the fragment preparation procedure to avoid introducing additional inaccuracies.This chapter is focused on the preparation process used to create a virtual fragment database. Several key issues of fragment preparation which affect the accuracy of binding affinity predictions are discussed. The first issue is the selection of the two-dimensional atomic structure of the virtual fragment. Although the particular usage of the fragment can affect this choice (i.e., whether the fragment will be used for calibration, binding site characterization, hit identification, or lead optimization), general factors such as synthetic accessibility, size, and flexibility are major considerations in selecting the 2D structure. Other aspects of preparing the virtual fragments for simulation are the generation of three-dimensional conformations and the assignment of the associated atomic point charges.
Directory of Open Access Journals (Sweden)
K. Anne-Isola Nekaris
2015-01-01
Full Text Available Flagship species are traditionally large, charismatic animals used to rally conservation efforts. Accepted flagship definitions suggest they need only fulfil a strategic role, unlike umbrella species that are used to shelter cohabitant taxa. The criteria used to select both flagship and umbrella species may not stand up in the face of dramatic forest loss, where remaining fragments may only contain species that do not suit either set of criteria. The Cinderella species concept covers aesthetically pleasing and overlooked species that fulfil the criteria of flagships or umbrellas. Such species are also more likely to occur in fragmented habitats. We tested Cinderella criteria on mammals in the fragmented forests of the Sri Lankan Wet Zone. We selected taxa that fulfilled both strategic and ecological roles. We created a shortlist of ten species, and from a survey of local perceptions highlighted two finalists. We tested these for umbrella characteristics against the original shortlist, utilizing Maximum Entropy (MaxEnt modelling, and analysed distribution overlap using ArcGIS. The criteria highlighted Loris tardigradus tardigradus and Prionailurus viverrinus as finalists, with the former having highest flagship potential. We suggest Cinderella species can be effective conservation surrogates especially in habitats where traditional flagship species have been extirpated.
The N-end rule pathway counteracts cell death by destroying proapoptotic protein fragments.
Piatkov, Konstantin I; Brower, Christopher S; Varshavsky, Alexander
2012-07-03
In the course of apoptosis, activated caspases cleave ∼500 to ∼1,000 different proteins in a mammalian cell. The dynamics of apoptosis involve a number of previously identified, caspase-generated proapoptotic protein fragments, defined as those that increase the probability of apoptosis. In contrast to activated caspases, which can be counteracted by inhibitor of apoptosis proteins, there is little understanding of antiapoptotic responses to proapoptotic protein fragments. One possibility is the regulation of proapoptotic fragments through their selective degradation. The previously identified proapoptotic fragments Cys-RIPK1, Cys-TRAF1, Asp-BRCA1, Leu-LIMK1, Tyr-NEDD9, Arg-BID, Asp-BCL(XL), Arg-BIM(EL), Asp-EPHA4, and Tyr-MET bear destabilizing N-terminal residues. Tellingly, the destabilizing nature (but not necessarily the actual identity) of N-terminal residues of proapoptotic fragments was invariably conserved in evolution. Here, we show that these proapoptotic fragments are short-lived substrates of the Arg/N-end rule pathway. Metabolic stabilization of at least one such fragment, Cys-RIPK1, greatly augmented the activation of the apoptosis-inducing effector caspase-3. In agreement with this understanding, even a partial ablation of the Arg/N-end rule pathway in two specific N-end rule mutants is shown to sensitize cells to apoptosis. We also found that caspases can inactivate components of the Arg/N-end rule pathway, suggesting a mutual suppression between this pathway and proapoptotic signaling. Together, these results identify a mechanistically specific and functionally broad antiapoptotic role of the Arg/N-end rule pathway. In conjunction with other apoptosis-suppressing circuits, the Arg/N-end rule pathway contributes to thresholds that prevent a transient or otherwise weak proapoptotic signal from reaching the point of commitment to apoptosis.
Directory of Open Access Journals (Sweden)
Sondergaard Bodil-Cecilie
2009-12-01
Full Text Available Abstract Background Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. Findings Bovine cartilage explants were cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM and tumor necrosis factor alpha (TNFα. In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo-epitope specific immunoassays; (1 sandwich 342FFGVG-G2 ELISA, (2 competition NITEGE373ELISA (3 sandwich G1-NITEGE373 ELISA (4 competition 374ARGSV ELISA, and (5 sandwich 374ARGSV-G2 ELISA all detecting aggrecan fragments, and (6 sandwich CTX-II ELISA, detecting C-telopeptides of type II collagen. We found that (1 aggrecanase-derived aggrecan fragments are released in the early (day 2-7 and mid phase (day 9-14 into the supernatant from bovine explants cultures stimulated with catabolic cytokines, (2 the release of NITEGE373 neo-epitopes are delayed compared to the corresponding 374ARGSV fragments, (3 the MMP inhibitor GM6001 did not reduce the release of aggrecanase-derived fragment, but induced a further delay in the release of these fragments, and finally (4 the MMP-derived aggrecan and type II collagen fragments were released in the late phase (day 16-21 only. Conclusion Our data support the model, that aggrecanases and MMPs act independently in the processing of the aggrecan molecules, and furthermore that suppression of MMP-activity had little if
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.
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
International Nuclear Information System (INIS)
Band, Y.B.; Freed, K.F.
1977-01-01
The full quantum theory of dissociation processes in polyatomic molecules is converted to a form enabling the isolation of a selected fragment vibration. This form enables the easy evaluation of the probability distribution for energy partitioning between this vibration and all other degrees of freedom that results from the sudden Franck--Condon rearrangement process. The resultant Franck--Condon factors involve the square of the one-dimensional overlap integral between effective oscillator wavefunctions and the wavefunctions for the selected fragment vibration, a form that resembles the simple golden rule model for polyatomic dissociation and reaction processes. The full quantum theory can, therefore, be viewed as providing both a rigorous justification for certain generic aspects of the simple golden rule model as well as providing a number of important generalizations thereof. Some of these involve dealing with initial bound state vibrational excitation, explicit molecule, fragment and energy dependence of the effective oscillator, and the incorporation of all isotopic dependence. In certain limiting situations the full quantum theory yields simple, readily usable analytic expressions for the frequency and equilibrium position of the effective oscillator. Specific applications are presented for the direct photodissociation of HCN, DCN, and CO 2 where comparisons between the full theory and the simple golden rule are presented. We also discuss the generalizations of the previous theory to enable the incorporation of effects of distortion in the normal modes as a function of the reaction coordinate on the repulsive potential energy surface
Selective Attention in Inattentional Blindness: Selection is Specific but Suppression is Not
Wood, Katherine; Simons, Daniel J.
2017-01-01
When we selectively attend to one set of objects and ignore another, we often fail to notice unexpected events. The likelihood of noticing varies depending on the similarity of an unexpected object to other items in the display, a process thought to be controlled by the attention set that we create for the attended and ignored objects. It remains unclear, though, how attention sets are formed and structured. Do they enhance features of attended objects (“white”) and suppress features of ignor...
Nuclear structure via isomer tagging of fission fragments
Wu, C. Y.; Cline, D.; Simon, M. W.; Stoyer, M. A.
1997-10-01
The high efficiency for detecting high-fold γ rays by large Ge arrays makes it possible to study the detailed spectroscopy of many neutron-rich nuclei produced by fission. Major progress has been made using sealed spontaneous fission sources. Considerable improvement in selectivity is provided, with an open source, both by gating on isomers and by detection of both fission fragments in coincidence with the deexcitation γ rays (see the preceding contribution). The reconstructed kinematics allows a measure of fragment mass and the Doppler shift correction of γ rays. In a recent experiment, fission fragments were detected using half of the CHICO array and an annular PPAC in coincidence with deexcitation γ rays detected by the Rochester array of eight Compton-suppressed Ge detectors. The annular PPAC was located only 1.0" from a 3.7 μCi ^252Cf source for efficient isomer tagging. The correlation was studied between delayed, within a time window between 150 ns and 10 μs after a fission occurring, and prompt γ rays. Several prominent feeding patterns to isomers in the mass region around 100 and 130 are identified by such correlation study. Experimental details and results will be presented.
Current fragmentation in deep inelastic scattering
International Nuclear Information System (INIS)
Hamer, C.J.
1975-04-01
It is argued that the current fragmentation products in deep inelastic electron scattering will not be distributed in a 'one-dimensional' rapidity plateau as in the parton model picture of Feynman and Bjorken. A reaction mechanism with a multiperipheral topology, but which the above configuration might have been achieved, does not in fact populate the current fragmentation plateau; and unless partons are actually observed in the final state, it cannot lead to Bjorken scaling. The basic reason for this failure is shown to be the fact that when a particle is produced in the current fragmentation plateau, the adjacent momentum transfer in the multiperipheral chain becomes large and negative: such processes are inevitably suppressed. Instead, the current fragmentation products are likely to be generated by a fragmentation, or sequential decay process. (author)
The formation of planets by disc fragmentation
Directory of Open Access Journals (Sweden)
Stamatellos Dimitris
2013-04-01
Full Text Available I discuss the role that disc fragmentation plays in the formation of gas giant and terrestrial planets, and how this relates to the formation of brown dwarfs and low-mass stars, and ultimately to the process of star formation. Protostellar discs may fragment, if they are massive enough and can cool fast enough, but most of the objects that form by fragmentation are brown dwarfs. It may be possible that planets also form, if the mass growth of a proto-fragment is stopped (e.g. if this fragment is ejected from the disc, or suppressed and even reversed (e.g by tidal stripping. I will discuss if it is possible to distinguish whether a planet has formed by disc fragmentation or core accretion, and mention of a few examples of observed exoplanets that are suggestive of formation by disc fragmentation.
Selective suppression of high-order harmonics within phase-matched spectral regions.
Lerner, Gavriel; Diskin, Tzvi; Neufeld, Ofer; Kfir, Ofer; Cohen, Oren
2017-04-01
Phase matching in high-harmonic generation leads to enhancement of multiple harmonics. It is sometimes desired to control the spectral structure within the phase-matched spectral region. We propose a scheme for selective suppression of high-order harmonics within the phase-matched spectral region while weakly influencing the other harmonics. The method is based on addition of phase-mismatched segments within a phase-matched medium. We demonstrate the method numerically in two examples. First, we show that one phase-mismatched segment can significantly suppress harmonic orders 9, 15, and 21. Second, we show that two phase-mismatched segments can efficiently suppress circularly polarized harmonics with one helicity over the other when driven by a bi-circular field. The new method may be useful for various applications, including the generation of highly helical bright attosecond pulses.
Chen, Johnny; Zheng, Gang; Price, William S
2017-02-01
A new 8-pulse Phase Modulated binomial-like selective inversion pulse sequence, dubbed '8PM', was developed by optimizing the nutation and phase angles of the constituent radio-frequency pulses so that the inversion profile resembled a target profile. Suppression profiles were obtained for both the 8PM and W5 based excitation sculpting sequences with equal inter-pulse delays. Significant distortions were observed in both profiles because of the offset effect of the radio frequency pulses. These distortions were successfully reduced by adjusting the inter-pulse delays. With adjusted inter-pulse delays, the 8PM and W5 based excitation sculpting sequences were tested on an aqueous lysozyme solution. The 8 PM based sequence provided higher suppression selectivity than the W5 based sequence. Two-dimensional nuclear Overhauser effect spectroscopy experiments were also performed on the lysozyme sample with 8PM and W5 based water signal suppression. The 8PM based suppression provided a spectrum with significantly increased (~ doubled) cross-peak intensity around the suppressed water resonance compared to the W5 based suppression. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Selective Attention in Inattentional Blindness: Selection is Specific but Suppression is Not
Directory of Open Access Journals (Sweden)
Katherine Wood
2017-08-01
Full Text Available When we selectively attend to one set of objects and ignore another, we often fail to notice unexpected events. The likelihood of noticing varies depending on the similarity of an unexpected object to other items in the display, a process thought to be controlled by the attention set that we create for the attended and ignored objects. It remains unclear, though, how attention sets are formed and structured. Do they enhance features of attended objects (“white” and suppress features of ignored objects (“black”, or do they distinguish objects based on relations or categories (“darker” versus “lighter,” or “dark objects” versus “light objects”? In previous work, these explanations are confounded; the objects would be partitioned into the same groups regardless the structure of the attention set. In the present three experiments, the attended or ignored set of objects was a constant color while the other set was variable. When people attended white and ignored a multicolored set of objects (Experiment 1, novel colors were suppressed just as much as display colors, suggesting nonselective filtering of nonwhite objects. When the color of one set of objects varied across displays but was constant within them (Experiments 2 and 3, we again found as much suppression for task-irrelevant and novel colors as for actively ignored ones. Whenever people ignored a set of objects that varied in color, they suppressed unexpected objects that matched the ignored colors and that differed from the actively ignored items on the critical trial. In contrast, when people attended a varying set, noticing was enhanced only for unexpected objects that matched the currently attended color. In this task, attentional filtering is category-based and did not depend on the features of the individual objects.
Focal Suppression of Distractor Sounds by Selective Attention in Auditory Cortex.
Schwartz, Zachary P; David, Stephen V
2018-01-01
Auditory selective attention is required for parsing crowded acoustic environments, but cortical systems mediating the influence of behavioral state on auditory perception are not well characterized. Previous neurophysiological studies suggest that attention produces a general enhancement of neural responses to important target sounds versus irrelevant distractors. However, behavioral studies suggest that in the presence of masking noise, attention provides a focal suppression of distractors that compete with targets. Here, we compared effects of attention on cortical responses to masking versus non-masking distractors, controlling for effects of listening effort and general task engagement. We recorded single-unit activity from primary auditory cortex (A1) of ferrets during behavior and found that selective attention decreased responses to distractors masking targets in the same spectral band, compared with spectrally distinct distractors. This suppression enhanced neural target detection thresholds, suggesting that limited attention resources serve to focally suppress responses to distractors that interfere with target detection. Changing effort by manipulating target salience consistently modulated spontaneous but not evoked activity. Task engagement and changing effort tended to affect the same neurons, while attention affected an independent population, suggesting that distinct feedback circuits mediate effects of attention and effort in A1. © The Author 2017. Published by Oxford University Press.
Wu, Y; Hayes, VM; Osinga, J; Mulder, IM; Looman, MWG; Buys, CHCM; Hofstra, RMW
1998-01-01
Denaturing gradient gel electrophoresis (DGGE) is one of the most powerful methods for mutation detection currently available. For successful application the appropriate selection of PCR fragments and PCR primers is crucial. The sequence of interest should always be within the domain with the lowest
DEFF Research Database (Denmark)
Nielsen, Kirstine Klitgaard; Ahrens, Peter
2002-01-01
By a suppression subtractive hybridization based method, nine novel Mycobacterium avium subsp. para tuberculosis (M. para tuberculosis) fragments of between 318 and 596 bp have been identified and characterized. Database search revealed little or no similarity with other mycobacteria. The uniquen......By a suppression subtractive hybridization based method, nine novel Mycobacterium avium subsp. para tuberculosis (M. para tuberculosis) fragments of between 318 and 596 bp have been identified and characterized. Database search revealed little or no similarity with other mycobacteria....... The uniqueness and diagnostic potential of seven of these fragments in relation to M. paratuberculosis closest relative Mycobacterium avium subsp. avium (M. avium) was confirmed by species-specific PCR and Southern blot. Furthermore, RT-PCR indicated that eight of the nine fragments originate from areas...
Measurement of charged jet suppression in Pb-Pb collisions at $\\sqrt{s_{NN}}$=2.76TeV
Abelev, B.; Adamova, D.; Aggarwal, M.M.; Aglieri Rinella, G.; Agnello, M.; Agocs, A.G.; Agostinelli, A.; Agrawal, N.; Ahammed, Z.; Ahmad, N.; Masoodi, A.Ahmad; Ahmed, I.; Ahn, S.U.; Ahn, S.A.; Aimo, I.; Aiola, S.; Ajaz, M.; Akindinov, A.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alici, A.; Alkin, A.; Alme, J.; Alt, T.; Altini, V.; Altinpinar, S.; Altsybeev, I.; Garcia Prado, C.Alves; Andrei, C.; Andronic, A.; Anguelov, V.; Anielski, J.; Anticic, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshauser, H.; Arbor, N.; Arcelli, S.; Armesto, N.; Arnaldi, R.; Aronsson, T.; Arsene, I.C.; Arslandok, M.; Augustinus, A.; Averbeck, R.; Awes, T.C.; Azmi, M.D.; Bach, M.; Badala, A.; Baek, Y.W.; Bagnasco, S.; Bailhache, R.; Bairathi, V.; Bala, R.; Baldisseri, A.; Baltasar Dos Santos Pedrosa, F.; Ban, J.; Baral, R.C.; Barbera, R.; Barile, F.; Barnafoldi, G.G.; Barnby, L.S.; Barret, V.; Bartke, J.; Basile, M.; Bastid, N.; Basu, S.; Bathen, B.; Batigne, G.; Batyunya, B.; Batzing, P.C.; Baumann, C.; Bearden, I.G.; Beck, H.; Bedda, C.; Behera, N.K.; Belikov, I.; Bellini, F.; Bellwied, R.; Belmont-Moreno, E.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Berger, M.E.; Bergognon, A.A.E.; Bertens, R.A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhati, A.K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bielcik, J.; Bielcikova, J.; Bilandzic, A.; Bjelogrlic, S.; Blanco, F.; Blau, D.; Blume, C.; Bock, F.; Boehmer, F.V.; Bogdanov, A.; Boggild, H.; Bogolyubsky, M.; Boldizsar, L.; Bombara, M.; Book, J.; Borel, H.; Borissov, A.; Bornschein, J.; Bossu, F.; Botje, M.; Botta, E.; Bottger, S.; Braun-Munzinger, P.; Bregant, M.; Breitner, T.; Broker, T.A.; Browning, T.A.; Broz, M.; Bruna, E.; Bruno, G.E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Caffarri, D.; Cai, X.; Caines, H.; Caliva, A.; Calvo Villar, E.; Camerini, P.; Canoa Roman, V.; Carena, F.; Carena, W.; Carminati, F.; Casanova Diaz, A.; Castillo Castellanos, J.; Casula, E.A.R.; Catanescu, V.; Cavicchioli, C.; Ceballos Sanchez, C.; Cepila, J.; Cerello, P.; Chang, B.; Chapeland, S.; Charvet, J.L.; Chattopadhyay, S.; Chattopadhyay, S.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Chibante Barroso, V.; Chinellato, D.D.; Chochula, P.; Chojnacki, M.; Choudhury, S.; Christakoglou, P.; Christensen, C.H.; Christiansen, P.; Chujo, T.; Chung, S.U.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Conesa Balbastre, G.; Conesa del Valle, Z.; Connors, M.E.; Contin, G.; Contreras, J.G.; Cormier, T.M.; Corrales Morales, Y.; Cortese, P.; Cortes Maldonado, I.; Cosentino, M.R.; Costa, F.; Crochet, P.; Albino, R.Cruz; Cuautle, E.; Cunqueiro, L.; Dainese, A.; Dang, R.; Danu, A.; Das, D.; Das, I.; Das, K.; Das, S.; Dash, A.; Dash, S.; De, S.; Delagrange, H.; Deloff, A.; Denes, E.; D'Erasmo, G.; de Barros, G.O.V.; De Caro, A.; De Cataldo, G.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; de Rooij, R.; Diaz Corchero, M.A.; Dietel, T.; Divia, R.; Di Bari, D.; Di Liberto, S.; Di Mauro, A.; Di Nezza, P.; Djuvsland, O.; Dobrin, A.; Dobrowolski, T.; Domenicis Gimenez, D.; Donigus, B.; Dordic, O.; Dorheim, S.; Dubey, A.K.; Dubla, A.; Ducroux, L.; Dupieux, P.; Dutta Majumdar, A.K.; Elia, D.; Engel, H.; Erazmus, B.; Erdal, H.A.; Eschweiler, D.; Espagnon, B.; Estienne, M.; Esumi, S.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabris, D.; Faivre, J.; Falchieri, D.; Fantoni, A.; Fasel, M.; Fehlker, D.; Feldkamp, L.; Felea, D.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Fernandez Tellez, A.; Ferreiro, E.G.; Ferretti, A.; Festanti, A.; Figiel, J.; Figueredo, M.A.S.; Filchagin, S.; Finogeev, D.; Fionda, F.M.; Fiore, E.M.; Floratos, E.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Frankenfeld, U.; Fuchs, U.; Furget, C.; Fusco Girard, M.; Gaardhoje, J.J.; Gagliardi, M.; Gallio, M.; Gangadharan, D.R.; Ganoti, P.; Garabatos, C.; Garcia-Solis, E.; Gargiulo, C.; Garishvili, I.; Gerhard, J.; Germain, M.; Gheata, A.; Gheata, M.; Ghidini, B.; Ghosh, P.; Ghosh, S.K.; Gianotti, P.; Giubellino, P.; Gladysz-Dziadus, E.; Glassel, P.; Gomez, R.; Gonzalez-Zamora, P.; Gorbunov, S.; Gorlich, L.; Gotovac, S.; Graczykowski, L.K.; Grajcarek, R.; Grelli, A.; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Grosse-Oetringhaus, J.F.; Grossiord, J.Y.; Grosso, R.; Guber, F.; Guernane, R.; Guerzoni, B.; Guilbaud, M.; Gulbrandsen, K.; Gulkanyan, H.; Gunji, T.; Gupta, A.; Gupta, R.; Khan, K.H.; Haake, R.; Haaland, O.; Hadjidakis, C.; Haiduc, M.; Hamagaki, H.; Hamar, G.; Hanratty, L.D.; Hansen, A.; Harris, J.W.; Hartmann, H.; Harton, A.; Hatzifotiadou, D.; Hayashi, S.; Hayrapetyan, A.; Heckel, S.T.; Heide, M.; Helstrup, H.; Herghelegiu, A.; Herrera Corral, G.; Hess, B.A.; Hetland, K.F.; Hicks, B.; Hippolyte, B.; Hladky, J.; Hristov, P.; Huang, M.; Humanic, T.J.; Hutter, D.; Hwang, D.S.; Ianigro, J.C.; Ilkaev, R.; Ilkiv, I.; Inaba, M.; Incani, E.; Innocenti, G.M.; Ionita, C.; Ippolitov, M.; Irfan, M.; Ivanov, M.; Ivanov, V.; Ivanytskyi, O.; Jacholkowski, A.; Jahnke, C.; Jang, H.J.; Janik, M.A.; Jayarathna, P.H.S.Y.; Jena, S.; Jimenez Bustamante, R.T.; Jones, P.G.; Jung, H.; Jusko, A.; Kalcher, S.; Kalinak, P.; Kalweit, A.; Kamin, J.; Kang, J.H.; Kaplin, V.; Kar, S.; Karasu Uysal, A.; Karavichev, O.; Karavicheva, T.; Karpechev, E.; Kebschull, U.; Keidel, R.; Ketzer, B.; Khan, M.Mohisin.; Khan, P.; Khan, S.A.; Khanzadeev, A.; Kharlov, Y.; Kileng, B.; Kim, B.; Kim, D.W.; Kim, D.J.; Kim, J.S.; Kim, M.; Kim, M.; Kim, S.; Kim, T.; Kirsch, S.; Kisel, I.; Kiselev, S.; Kisiel, A.; Kiss, G.; Klay, J.L.; Klein, J.; Klein-Bosing, C.; Kluge, A.; Knichel, M.L.; Knospe, A.G.; Kobdaj, C.; Kohler, M.K.; Kollegger, T.; Kolojvari, A.; Kondratiev, V.; Kondratyeva, N.; Konevskikh, A.; Kovalenko, V.; Kowalski, M.; Kox, S.; Koyithatta Meethaleveedu, G.; Kral, J.; Kralik, I.; Kramer, F.; Kravcakova, A.; Krelina, M.; Kretz, M.; Krivda, M.; Krizek, F.; Krus, M.; Kryshen, E.; Krzewicki, M.; Kucera, V.; Kucheriaev, Y.; Kugathasan, T.; Kuhn, C.; Kuijer, P.G.; Kulakov, I.; Kumar, J.; Kurashvili, P.; Kurepin, A.; Kurepin, A.B.; Kuryakin, A.; Kushpil, S.; Kushpil, V.; Kweon, M.J.; Kwon, Y.; Ladron de Guevara, P.; Lagana Fernandes, C.; Lakomov, I.; Langoy, R.; Lara, C.; Lardeux, A.; Lattuca, A.; La Pointe, S.L.; La Rocca, P.; Lea, R.; Lee, G.R.; Legrand, I.; Lehnert, J.; Lemmon, R.C.; Lenhardt, M.; Lenti, V.; Leogrande, E.; Leoncino, M.; Leon Monzon, I.; Levai, P.; Li, S.; Lien, J.; Lietava, R.; Lindal, S.; Lindenstruth, V.; Lippmann, C.; Lisa, M.A.; Ljunggren, H.M.; Lodato, D.F.; Loenne, P.I.; Loggins, V.R.; Loginov, V.; Lohner, D.; Loizides, C.; Lopez, X.; Lopez Torres, E.; Lu, X.G.; Luettig, P.; Lunardon, M.; Luo, J.; Luparello, G.; Luzzi, C.; Gago, A.M.; Jacobs, P.M.; Ma, R.; Maevskaya, A.; Mager, M.; Mahapatra, D.P.; Maire, A.; Malaev, M.; Maldonado Cervantes, I.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manceau, L.; Manko, V.; Manso, F.; Manzari, V.; Marchisone, M.; Mares, J.; Margagliotti, G.V.; Margotti, A.; Marin, A.; Markert, C.; Marquard, M.; Martashvili, I.; Martin, N.A.; Martinengo, P.; Martinez, M.I.; Martinez Garcia, G.; Blanco, J.Martin; Martynov, Y.; Mas, A.; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Mastroserio, A.; Matyja, A.; Mayer, C.; Mazer, J.; Mazumder, R.; Mazzoni, M.A.; Meddi, F.; Menchaca-Rocha, A.; Mercado Perez, J.; Meres, M.; Miake, Y.; Mikhaylov, K.; Milano, L.; Milosevic, J.; Mischke, A.; Mishra, A.N.; Miskowiec, D.; Mitu, C.M.; Mlynarz, J.; Mohanty, B.; Molnar, L.; Montano Zetina, L.; Montes, E.; Morando, M.; Moreira De Godoy, D.A.; Moretto, S.; Morreale, A.; Morsch, A.; Muccifora, V.; Mudnic, E.; Muhuri, S.; Mukherjee, M.; Muller, H.; Munhoz, M.G.; Murray, S.; Musa, L.; Musinsky, J.; Nandi, B.K.; Nania, R.; Nappi, E.; Nattrass, C.; Nayak, T.K.; Nazarenko, S.; Nedosekin, A.; Nicassio, M.; Niculescu, M.; Nielsen, B.S.; Nikolaev, S.; Nikulin, S.; Nikulin, V.; Nilsen, B.S.; Noferini, F.; Nomokonov, P.; Nooren, G.; Nyanin, A.; Nyatha, A.; Nystrand, J.; Oeschler, H.; Oh, S.; Oh, S.K.; Okatan, A.; Olah, L.; Oleniacz, J.; Oliveira Da Silva, A.C.; Onderwaater, J.; Oppedisano, C.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Pachmayer, Y.; Pachr, M.; Pagano, P.; Paic, G.; Painke, F.; Pajares, C.; Pal, S.K.; Palmeri, A.; Pant, D.; Papikyan, V.; Pappalardo, G.S.; Park, W.J.; Passfeld, A.; Patalakha, D.I.; Paticchio, V.; Paul, B.; Pawlak, T.; Peitzmann, T.; Pereira Da Costa, H.; Pereira De Oliveira Filho, E.; Peresunko, D.; Perez Lara, C.E.; Peryt, W.; Pesci, A.; Pestov, Y.; Petracek, V.; Petran, M.; Petris, M.; Petrovici, M.; Petta, C.; Piano, S.; Pikna, M.; Pillot, P.; Pinazza, O.; Pinsky, L.; Piyarathna, D.B.; Ploskon, M.; Planinic, M.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P.L.M.; Poghosyan, M.G.; Pohjoisaho, E.H.O.; Polichtchouk, B.; Poljak, N.; Pop, A.; Porteboeuf-Houssais, S.; Porter, J.; Pospisil, V.; Potukuchi, B.; Prasad, S.K.; Preghenella, R.; Prino, F.; Pruneau, C.A.; Pshenichnov, I.; Puddu, G.; Pujahari, P.; Punin, V.; Putschke, J.; Qvigstad, H.; Rachevski, A.; Raha, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Raniwala, R.; Raniwala, S.; Rasanen, S.S.; Rascanu, B.T.; Rathee, D.; Rauf, A.W.; Razazi, V.; Read, K.F.; Real, J.S.; Redlich, K.; Reed, R.J.; Rehman, A.; Reichelt, P.; Reicher, M.; Reidt, F.; Renfordt, R.; Reolon, A.R.; Reshetin, A.; Rettig, F.; Revol, J.P.; Reygers, K.; Riabov, V.; Ricci, R.A.; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Rivetti, A.; Rocco, E.; Rodriguez Cahuantzi, M.; Rodriguez Manso, A.; Roed, K.; Rogochaya, E.; Rohni, S.; Rohr, D.; Rohrich, D.; Romita, R.; Ronchetti, F.; Ronflette, L.; Rosnet, P.; Rossegger, S.; Rossi, A.; Roy, A.; Roy, C.; Roy, P.; Rubio Montero, A.J.; Rui, R.; Russo, R.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Sadovsky, S.; Safarik, K.; Sahlmuller, B.; Sahoo, R.; Sahu, P.K.; Saini, J.; Salgado, C.A.; Salzwedel, J.; Sambyal, S.; Samsonov, V.; Sanchez Castro, X.; Sanchez Rodriguez, F.J.; Sandor, L.; Sandoval, A.; Sano, M.; Santagati, G.; Sarkar, D.; Scapparone, E.; Scarlassara, F.; Scharenberg, R.P.; Schiaua, C.; Schicker, R.; Schmidt, C.; Schmidt, H.R.; Schuchmann, S.; Schukraft, J.; Schulc, M.; Schuster, T.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Scott, P.A.; Scott, R.; Segato, G.; Seger, J.E.; Selyuzhenkov, I.; Seo, J.; Serradilla, E.; Sevcenco, A.; Shabetai, A.; Shabratova, G.; Shahoyan, R.; Shangaraev, A.; Sharma, N.; Sharma, S.; Shigaki, K.; Shtejer, K.; Sibiriak, Y.; Siddhanta, S.; Siemiarczuk, T.; Silvermyr, D.; Silvestre, C.; Simatovic, G.; Singaraju, R.; Singh, R.; Singha, S.; Singhal, V.; Sinha, B.C.; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T.B.; Skjerdal, K.; Smakal, R.; Smirnov, N.; Snellings, R.J.M.; Sogaard, C.; Soltz, R.; Song, J.; Song, M.; Soramel, F.; Sorensen, S.; Spacek, M.; Sputowska, I.; Spyropoulou-Stassinaki, M.; Srivastava, B.K.; Stachel, J.; Stan, I.; Stefanek, G.; Steinpreis, M.; Stenlund, E.; Steyn, G.; Stiller, J.H.; Stocco, D.; Stolpovskiy, M.; Strmen, P.; Suaide, A.A.P.; Subieta Vasquez, M.A.; Sugitate, T.; Suire, C.; Suleymanov, M.; Sultanov, R.; Sumbera, M.; Susa, T.; Symons, T.J.M.; Szanto de Toledo, A.; Szarka, I.; Szczepankiewicz, A.; Szymanski, M.; Takahashi, J.; Tangaro, M.A.; J.Tapia Takaki, D.; Peloni, A.Tarantola; Tarazona Martinez, A.; Tauro, A.; Tejeda Munoz, G.; Telesca, A.; Terrevoli, C.; Minasyan, A.Ter; Thader, J.; Thomas, D.; Tieulent, R.; Timmins, A.R.; Toia, A.; Torii, H.; Trubnikov, V.; Trzaska, W.H.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T.S.; Ulery, J.; Ullaland, K.; Ulrich, J.; Uras, A.; Usai, G.L.; Vajzer, M.; Vala, M.; Valencia Palomo, L.; Vallero, S.; Vande Vyvre, P.; Vannucci, L.; Van Hoorne, J.W.; van Leeuwen, M.; Vargas, A.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Vechernin, V.; Veldhoen, M.; Venaruzzo, M.; Vercellin, E.; Limon, S.Vergara; Vernet, R.; Verweij, M.; Vickovic, L.; Viesti, G.; Viinikainen, J.; Vilakazi, Z.; Villalobos Baillie, O.; Vinogradov, A.; Vinogradov, L.; Vinogradov, Y.; Virgili, T.; Viyogi, Y.P.; Vodopyanov, A.; Volkl, M.A.; Voloshin, K.; Voloshin, S.A.; Volpe, G.; von Haller, B.; Vorobyev, I.; Vranic, D.; Vrlakova, J.; Vulpescu, B.; Vyushin, A.; Wagner, B.; Wagner, J.; Wagner, V.; Wang, M.; Wang, Y.; Watanabe, D.; Weber, M.; Wessels, J.P.; Westerhoff, U.; Wiechula, J.; Wikne, J.; Wilde, M.; Wilk, G.; Wilkinson, J.; Williams, M.C.S.; Windelband, B.; Winn, M.; Xiang, C.; Yaldo, C.G.; Yamaguchi, Y.; Yang, H.; Yang, P.; Yang, S.; Yano, S.; Yasnopolskiy, S.; Yi, J.; Yin, Z.; Yoo, I.K.; Yushmanov, I.; Zaccolo, V.; Zach, C.; Zaman, A.; Zampolli, C.; Zaporozhets, S.; Zarochentsev, A.; Zavada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zgura, I.S.; Zhalov, M.; Zhang, F.; Zhang, H.; Zhang, X.; Zhang, Y.; Zhao, C.; Zhou, D.; Zhou, F.; Zhou, Y.; Zhu, H.; Zhu, J.; Zhu, X.; Zichichi, A.; Zimmermann, A.; Zimmermann, M.B.; Zinovjev, G.; Zoccarato, Y.; Zynovyev, M.; Zyzak, M.
2014-01-01
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at $\\sqrt{s_{NN}}$=2.76TeV is reported. Jets are reconstructed from charged particles using the anti-$k_T$ jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |$\\eta$|<0.5. The transverse momentum p_T of charged particles is measured down to 0.15 GeV/c which gives access to the low p_T fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high p_T leading particle, which ...
Fragmentation inside atomic cooling haloes exposed to Lyman-Werner radiation
Regan, John A.; Downes, Turlough P.
2018-04-01
Supermassive stars born in pristine environments in the early Universe hold the promise of being the seeds for the supermassive black holes observed as high redshift quasars shortly after the epoch of reionisation. H2 suppression is thought to be crucial in order to negate normal Population III star formation and allow high accretion rates to drive the formation of supermassive stars. Only in the cases where vigorous fragmentation is avoided will a monolithic collapse be successful, giving rise to a single massive central object. We investigate the number of fragmentation sites formed in collapsing atomic cooling haloes subject to various levels of background Lyman-Werner flux. The background Lyman-Werner flux manipulates the chemical properties of the gas in the collapsing halo by destroying H2. We find that only when the collapsing gas cloud shifts from the molecular to the atomic cooling regime is the degree of fragmentation suppressed. In our particular case, we find that this occurs above a critical Lyman-Werner background of J ˜ 10 J21. The important criterion being the transition to the atomic cooling regime rather than the actual value of J, which will vary locally. Once the temperature of the gas exceeds T ≳ 104 K and the gas transitions to atomic line cooling, then vigorous fragmentation is strongly suppressed.
Burst-Suppression Ratio on Electrocorticography Depends on Interelectrode Distance
DEFF Research Database (Denmark)
Moldovan, Mihai; Calin, Alexandru; Kumaraswamy, Vishakhadatta M.
2016-01-01
Introduction: With deepening of anesthesia-induced comatose states, the EEG becomes fragmented by increasing periods of suppression. When measured from conventional EEG recordings, the binary burst-suppression signal (BS) appears similar across the scalp. As such, the BS ratio (BSR), quantifying...
Jordan, John B; Whittington, Douglas A; Bartberger, Michael D; Sickmier, E Allen; Chen, Kui; Cheng, Yuan; Judd, Ted
2016-04-28
Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, β-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.
Social exclusion impairs distractor suppression but not target enhancement in selective attention.
Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong
2017-11-01
Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.
Karkov, Hanne Sophie; Woo, James; Krogh, Berit Olsen; Ahmadian, Haleh; Cramer, Steven M
2015-12-24
This study describes the in silico design, surface property analyses, production and chromatographic evaluations of a diverse set of antibody Fab fragment variants. Based on previous findings, we hypothesized that the complementarity-determining regions (CDRs) constitute important binding sites for multimodal chromatographic ligands. Given that antibodies are highly diversified molecules and in particular the CDRs, we set out to examine the generality of this result. For this purpose, four different Fab fragments with different CDRs and/or framework regions of the variable domains were identified and related variants were designed in silico. The four Fab variant libraries were subsequently generated by site-directed mutagenesis and produced by recombinant expression and affinity purification to enable examination of their chromatographic retention behavior. The effects of geometric re-arrangement of the functional moieties on the multimodal resin ligands were also investigated with respect to Fab variant retention profiles by comparing two commercially available multimodal cation-exchange ligands, Capto MMC and Nuvia cPrime, and two novel multimodal ligand prototypes. Interestingly, the chromatographic data demonstrated distinct selectivity trends between the four Fab variant libraries. For three of the Fab libraries, the CDR regions appeared as major binding sites for all multimodal ligands. In contrast, the fourth Fab library displayed a distinctly different chromatographic behavior, where Nuvia cPrime and related multimodal ligand prototypes provided markedly improved selectivity over Capto MMC. Clearly, the results illustrate that the discriminating power of multimodal ligands differs between different Fab fragments. The results are promising indications that multimodal chromatography using the appropriate multimodal ligands can be employed in downstream bioprocessing for challenging selective separation of product related variants. Copyright © 2015 Elsevier B
Andersen, S K; Müller, M M
2010-08-03
A central question in the field of attention is whether visual processing is a strictly limited resource, which must be allocated by selective attention. If this were the case, attentional enhancement of one stimulus should invariably lead to suppression of unattended distracter stimuli. Here we examine voluntary cued shifts of feature-selective attention to either one of two superimposed red or blue random dot kinematograms (RDKs) to test whether such a reciprocal relationship between enhancement of an attended and suppression of an unattended stimulus can be observed. The steady-state visual evoked potential (SSVEP), an oscillatory brain response elicited by the flickering RDKs, was measured in human EEG. Supporting limited resources, we observed both an enhancement of the attended and a suppression of the unattended RDK, but this observed reciprocity did not occur concurrently: enhancement of the attended RDK started at 220 ms after cue onset and preceded suppression of the unattended RDK by about 130 ms. Furthermore, we found that behavior was significantly correlated with the SSVEP time course of a measure of selectivity (attended minus unattended) but not with a measure of total activity (attended plus unattended). The significant deviations from a temporally synchronized reciprocity between enhancement and suppression suggest that the enhancement of the attended stimulus may cause the suppression of the unattended stimulus in the present experiment.
Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B
2014-12-01
Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signalled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. Copyright
Duque, Julie; Labruna, Ludovica; Cazares, Christian; Ivry, Richard B.
2014-01-01
Motor behavior requires selecting between potential actions. The role of inhibition in response selection has frequently been examined in tasks in which participants are engaged in some advance preparation prior to the presentation of an imperative signal. Under such conditions, inhibition could be related to processes associated with response selection, or to more general inhibitory processes that are engaged in high states of anticipation. In Experiment 1, we manipulated the degree of anticipatory preparation. Participants performed a choice reaction time task that required choosing between a movement of the left or right index finger, and used transcranial magnetic stimulation (TMS) to elicit motor evoked potentials (MEPs) in the left hand agonist. In high anticipation blocks, a non-informative cue (e.g., fixation marker) preceded the imperative; in low anticipation blocks, there was no cue and participants were required to divide their attention between two tasks to further reduce anticipation. MEPs were substantially reduced before the imperative signal in high anticipation blocks. In contrast, in low anticipation blocks, MEPs remained unchanged before the imperative signal but showed a marked suppression right after the onset of the imperative. This effect occurred regardless of whether the imperative had signaled a left or right hand response. After this initial inhibition, left MEPs increased when the left hand was selected and remained suppressed when the right hand was selected. We obtained similar results in Experiment 2 except that the persistent left MEP suppression when the left hand was not selected was attenuated when the alternative response involved a non-homologous effector (right foot). These results indicate that, even in the absence of an anticipatory period, inhibitory mechanisms are engaged during response selection, possibly to prevent the occurrence of premature and inappropriate responses during a competitive selection process. PMID
Energy Technology Data Exchange (ETDEWEB)
Gaudefroy, L., E-mail: laurent.gaudefroy@cea.fr [CEA, DAM, DIF, F-91297 Arpajon (France); Roger, T., E-mail: roger@ganil.fr [GANIL, CEA/DSM-CNRS/IN2P3, BP 55027, F-14076 Caen (France); Pancin, J., E-mail: pancin@ganil.fr [GANIL, CEA/DSM-CNRS/IN2P3, BP 55027, F-14076 Caen (France); Spitaels, C. [GANIL, CEA/DSM-CNRS/IN2P3, BP 55027, F-14076 Caen (France); Aupiais, J. [CEA, DAM, DIF, F-91297 Arpajon (France); Mottier, J. [Institut de Physique Nucléaire, Université Paris-Sud-11-CNRS-IN2P3, F-91406 Orsay (France)
2017-05-21
We present a twin Frisch-grid ionization chamber. The detector is meant to provide high selective power for the study of delayed gamma-ray spectroscopy of fission fragments produced via {sup 252}Cf spontaneous fission. A mean energy resolution on the kinetic energy of fission fragments of 675 keV (FWHM) is achieved and allows us to resolve masses of fragments for fission events where neutron emission is not energetically possible. The mean mass resolution measured for these particular events amounts to 0.54 mass units (FWHM). For fission events with neutron emission a resolution of 4 mass units (FWHM) is reported. Information on fragment emission angle is measured with a resolution of 0.1 on the difference of the cosines determined for both halves of the detector. A charge resolution of 4.5 charge units (FWHM) is also demonstrated.
Photon-hadron fragmentation: theoretical situation
International Nuclear Information System (INIS)
Peschanski, R.
1983-07-01
Using a selection of new experimental results models of hadronic fragmentation and their phenomenological comparison are presented. Indeed a convenient theory of hadronic fragmentation -for instance based on Q.C.D.- does not exist: low transverse momentum fragmentation involves the badly known hadronic long-range forces. Models should clarify the situation in the prospect of an eventual future theory
Ludwig, Karin; Kathmann, Norbert; Sterzer, Philipp; Hesselmann, Guido
2015-01-01
Recent behavioral and neuroimaging studies using continuous flash suppression (CFS) have suggested that action-related processing in the dorsal visual stream might be independent of perceptual awareness, in line with the "vision-for-perception" versus "vision-for-action" distinction of the influential dual-stream theory. It remains controversial if evidence suggesting exclusive dorsal stream processing of tool stimuli under CFS can be explained by their elongated shape alone or by action-relevant category representations in dorsal visual cortex. To approach this question, we investigated category- and shape-selective functional magnetic resonance imaging-blood-oxygen level-dependent responses in both visual streams using images of faces and tools. Multivariate pattern analysis showed enhanced decoding of elongated relative to non-elongated tools, both in the ventral and dorsal visual stream. The second aim of our study was to investigate whether the depth of interocular suppression might differentially affect processing in dorsal and ventral areas. However, parametric modulation of suppression depth by varying the CFS mask contrast did not yield any evidence for differential modulation of category-selective activity. Together, our data provide evidence for shape-selective processing under CFS in both dorsal and ventral stream areas and, therefore, do not support the notion that dorsal "vision-for-action" processing is exclusively preserved under interocular suppression. © 2014 Wiley Periodicals, Inc.
International Nuclear Information System (INIS)
Arnold, Werner
2002-01-01
Contrary to natural fragmentation, controlled fragmentation offers the possibility to adapt fragment parameters like size and mass to the performance requirements in a very flexible way. Known mechanisms like grooves inside the casing, weaken the structure. This is, however, excluded for applications with high accelerations during launch or piercing requirements for example on a semi armor piercing penetrator. Another method to achieve controlled fragmentation with an additional grid layer is presented with which the required grooves are produced 'just in time' inside the casing during detonation of the high explosive. The process of generating the grooves aided by the grid layer was studied using the hydrocode HULL with respect to varying grid designs and material combinations. Subsequent to this, a large range of these theoretically investigated combinations was contemplated in substantial experimental tests. With an optimised grid design and a suitable material selection, the controlled fragment admits a very flexible adaptation to the set requirements. Additional advantages like the increase of perforation performance or incendiary amplification can be realized with the grid layer
A Compact Band-Pass Filter with High Selectivity and Second Harmonic Suppression.
Hadarig, Ramona Cosmina; de Cos Gomez, Maria Elena; Las-Heras, Fernando
2013-12-03
The design of a novel band-pass filter with narrow-band features based on an electromagnetic resonator at 6.4 GHz is presented. A prototype is manufactured and characterized in terms of transmission and reflection coefficient. The selective passband and suppression of the second harmonic make the filter suitable to be used in a C band frequency range for radar systems and satellite/terrestrial applications. To avoid substantial interference for this kind of applications, passive components with narrow band features and small dimensions are required. Between 3.6 GHz and 4.2 GHz the band-pass filter with harmonic suppression should have an attenuation of at least 35 dB, whereas for a passband, less than 10% is sufficient.
Karkov, Hanne Sophie; Krogh, Berit Olsen; Woo, James; Parimal, Siddharth; Ahmadian, Haleh; Cramer, Steven M
2015-11-01
In this study, a unique set of antibody Fab fragments was designed in silico and produced to examine the relationship between protein surface properties and selectivity in multimodal chromatographic systems. We hypothesized that multimodal ligands containing both hydrophobic and charged moieties would interact strongly with protein surface regions where charged groups and hydrophobic patches were in close spatial proximity. Protein surface property characterization tools were employed to identify the potential multimodal ligand binding regions on the Fab fragment of a humanized antibody and to evaluate the impact of mutations on surface charge and hydrophobicity. Twenty Fab variants were generated by site-directed mutagenesis, recombinant expression, and affinity purification. Column gradient experiments were carried out with the Fab variants in multimodal, cation-exchange, and hydrophobic interaction chromatographic systems. The results clearly indicated that selectivity in the multimodal system was different from the other chromatographic modes examined. Column retention data for the reduced charge Fab variants identified a binding site comprising light chain CDR1 as the main electrostatic interaction site for the multimodal and cation-exchange ligands. Furthermore, the multimodal ligand binding was enhanced by additional hydrophobic contributions as evident from the results obtained with hydrophobic Fab variants. The use of in silico protein surface property analyses combined with molecular biology techniques, protein expression, and chromatographic evaluations represents a previously undescribed and powerful approach for investigating multimodal selectivity with complex biomolecules. © 2015 Wiley Periodicals, Inc.
Universality of fragment shapes.
Domokos, Gábor; Kun, Ferenc; Sipos, András Árpád; Szabó, Tímea
2015-03-16
The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. We performed a thorough experimental study of the problem fragmenting various types of materials by slowly proceeding weathering and by rapid breakup due to explosion and hammering. We demonstrate that the shape of fragments obeys an astonishing universality having the same generic evolution with the fragment size irrespective of materials details and loading conditions. There exists a cutoff size below which fragments have an isotropic shape, however, as the size increases an exponential convergence is obtained to a unique elongated form. We show that a discrete stochastic model of fragmentation reproduces both the size and shape of fragments tuning only a single parameter which strengthens the general validity of the scaling laws. The dependence of the probability of the crack plan orientation on the linear extension of fragments proved to be essential for the shape selection mechanism.
International Nuclear Information System (INIS)
Miyata, Kenichi; Takagi, Satoshi; Sato, Shigeo; Morioka, Hiroshi; Shiba, Kiyotaka; Minamisawa, Tamiko; Takami, Miho; Fujita, Naoya
2014-01-01
Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be identical to the marker protein podoplanin (alternative names, T1α, OTS-8, and others). Aggrus is frequently overexpressed in several types of tumors and enhances platelet aggregation by interacting with the platelet receptor C-type lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody variable region fragment (scFv) by linking the variable regions of heavy and light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed phage display screening and finally obtained a high-affinity scFv, K-11. K-11 scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover, K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is expected to aid in the development of preclinical and clinical examinations of Aggrus-targeted cancer therapies
Selective suppression of antibody production with the aid of radiolabelled birch pollen allergen
International Nuclear Information System (INIS)
Filipp, G.; Biro, G.; Hartung, W.D.; Lehmann, G.
1981-01-01
In accordance with the clonal selection theory we intended to prevent the development of artificially induced birch pollen allergy in rabbits with the aid of of the radiolabelled pollen allergen (75-1000 μCi 125 I-pollen/animal) intravenously administered prior to pollen sensitization. The birch pollen allergen, in accordance with Burnet's working hypothesis, reacts only with a genetically determining B cell subpopulation. The fixation of the radiolabelled birch pollen allergen to the receptors of the competent B cell clone causes the lesion of the latter. Compared with the control group, this group of rabbits showed an extensive suppression of anaphylactic reagin-like PCA-antibodies, and haemagglutinating antibodies in the blood as well as in nasal secretion. In addition, we tried to influence the already ongoing synthesis of the antibodies with the aid of a subsequent intravenously administered radiolabelled birch pollen allergen (750-1000μCi 125 I-pollen/animal). An intensive suppression of the synthesis of antibodies could also be proved in this case. The simultaneous immunization of the control rabbits with birch pollen and egg albumin resulted in the production of antibodies against both antigens, as expected. The hot-labelled birch pollen antigen intravenously injected before or after immunization with egg albumin and birch pollen led selectively to suppression of anti-birch-pollen PCA antibodies. The synthesis of anti-egg albumin PCA antibodies was unaffected. (author)
Bastien, Dominic; Ebert, Maximilian C C J C; Forge, Delphine; Toulouse, Jacynthe; Kadnikova, Natalia; Perron, Florent; Mayence, Annie; Huang, Tien L; Vanden Eynde, Jean Jacques; Pelletier, Joelle N
2012-04-12
The continuously increasing use of trimethoprim as a common antibiotic for medical use and for prophylactic application in terrestrial and aquatic animal farming has increased its prevalence in the environment. This has been accompanied by increased drug resistance, generally in the form of alterations in the drug target, dihydrofolate reductase (DHFR). The most highly resistant variants of DHFR are known as type II DHFR, among which R67 DHFR is the most broadly studied variant. We report the first attempt at designing specific inhibitors to this emerging drug target by fragment-based design. The detection of inhibition in R67 DHFR was accompanied by parallel monitoring of the human DHFR, as an assessment of compound selectivity. By those means, small aromatic molecules of 150-250 g/mol (fragments) inhibiting R67 DHFR selectively in the low millimolar range were identified. More complex, symmetrical bis-benzimidazoles and a bis-carboxyphenyl were then assayed as fragment-based leads, which procured selective inhibition of the target in the low micromolar range (K(i) = 2-4 μM). The putative mode of inhibition is discussed according to molecular modeling supported by in vitro tests. © 2012 American Chemical Society
Souriau, Christelle; Rothacker, Julie; Hoogenboom, Hennie R; Nice, Edouard
2004-09-01
Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (ka and kd). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.
THE FRAGMENTATION OF MAGNETIZED, MASSIVE STAR-FORMING CORES WITH RADIATIVE FEEDBACK
Energy Technology Data Exchange (ETDEWEB)
Myers, Andrew T.; McKee, Christopher F. [Department of Physics, University of California, Berkeley, Berkeley, CA 94720 (United States); Cunningham, Andrew J. [Lawrence Livermore National Laboratory, P.O. Box 808, L-23, Livermore, CA 94550 (United States); Klein, Richard I. [Department of Astronomy, University of California, Berkeley, Berkeley, CA 94720 (United States); Krumholz, Mark R., E-mail: atmyers@berkeley.edu [Department of Astronomy and Astrophysics, University of California, Santa Cruz, CA 95064 (United States)
2013-04-01
We present a set of three-dimensional, radiation-magnetohydrodynamic calculations of the gravitational collapse of massive (300 M{sub Sun }), star-forming molecular cloud cores. We show that the combined effects of magnetic fields and radiative feedback strongly suppress core fragmentation, leading to the production of single-star systems rather than small clusters. We find that the two processes are efficient at suppressing fragmentation in different regimes, with the feedback most effective in the dense, central region and the magnetic field most effective in more diffuse, outer regions. Thus, the combination of the two is much more effective at suppressing fragmentation than either one considered in isolation. Our work suggests that typical massive cores, which have mass-to-flux ratios of about 2 relative to critical, likely form a single-star system, but that cores with weaker fields may form a small star cluster. This result helps us understand why the observed relationship between the core mass function and the stellar initial mass function holds even for {approx}100 M{sub Sun} cores with many thermal Jeans masses of material. We also demonstrate that a {approx}40 AU Keplerian disk is able to form in our simulations, despite the braking effect caused by the strong magnetic field.
Adaptive single-antenna transmit selection with interference suppression
Radaydeh, Redha Mahmoud Mesleh
2011-10-01
This paper studies the performance of adaptive transmit selection with co-channel interference suppression in multipath fading channels. The adaptive selection algorithms are configured for single-antenna bandwidth-efficient or power-efficient transmission with as low transmit channel estimations as possible. Due to the fact that the number of active co-channel interfering signals and their corresponding powers experience random behavior, the adaptation to channels conditions, assuming uniform buffer and traffic loading, is proposed to be jointly based on the transmit channels instantaneous signal-to-noise ratios (SNRs) and signal-to-interference-plus-noise ratios (SINRs). Two interference cancelation algorithms are considered. The first algorithm assumes that the receiver eliminates the impact of the strongest subset of interferers, whereas the second algorithm suggests random cancelation of interferers to further reduce processing complexity. The impact of outdated ordering of interferers powers on the efficiency of interference cancelation, and the effect of imperfect prediction of transmit channels for desired user adaptation are investigated. Analytical formulations for various performance measures and comparisons between the performance and processing complexity of different adaptation schemes are presented. © 2011 IEEE.
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.
Deconstructing continuous flash suppression.
Yang, Eunice; Blake, Randolph
2012-03-08
In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.
Hushmendy, Shazaan; Jayakumar, Lalithapriya; Hahn, Amy B.; Bhoiwala, Devang; Bhoiwala, Dipti L.; Crawford, Dana R.
2009-01-01
We have considered a novel “rational” gene targeting approach for treating pathologies whose genetic bases are defined using select phytochemicals. We reason that one such potential application of this approach would be conditions requiring immunosuppression such as autoimmune disease and transplantation, where the genetic target is clearly defined; i.e., interleukin-2 and associated T-cell activation. Therefore, we hypothesized that select phytochemicals can suppress T-lymphocyte proliferation both in vitro and in vivo. The immunosuppressive effects of berry extract, curcumin, quercetin, sulforaphane, epigallocatechin gallate (EGCG), resveratrol, α-tocopherol, vitamin C and sucrose were tested on anti-CD3 plus anti-CD28-activated primary human T-lymphocytes in culture. Curcumin, sulforaphane, quercetin, berry extract and EGCG all significantly inhibited T-cell proliferation, and this effect was not due to toxicity. IL-2 production was also reduced by these agents, implicating this important T-cell cytokine in proliferation suppression. Except for berry extract, these same agents also inhibited mouse splenic T-cell proliferation and IL-2 production. Subsequent in vivo studies revealed that quercetin (but not sulforaphane) modestly suppressed mouse splenocyte proliferation following supplementation of BALB/c mice diets. This effect was especially prominent if corrected for the loss of supplement “recall” as observed in cultured T-cells. These results suggest the potential use of these select phytochemicals for treating autoimmune and transplant patients, and support our strategy of using select phytochemicals to treat genetically-defined pathologies, an approach that we believe is simple, healthy, and cost-effective. PMID:19761891
International Nuclear Information System (INIS)
Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng
2015-01-01
Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.
Energy Technology Data Exchange (ETDEWEB)
Yang, Ping; Fu, Shilong; Cao, Zhifei; Liao, Huaidong; Huo, Zihe; Pan, Yanyan; Zhang, Gaochuan; Gao, Aidi; Zhou, Quansheng, E-mail: zhouqs@suda.edu.cn
2015-10-15
Cancer cells have both tumor-adaptive and -suppressive endoplasmic reticulum (ER) stress machineries that determine cell fate. In malignant tumors including lymphoma, constant activation of tumor-adaptive ER stress and concurrent reduction of tumor-suppressive ER stress favors cancer cell proliferation and tumor growth. Current ER stress-based anti-tumor drugs typically activate both tumor-adaptive and -suppressive ER stresses, resulting in low anti-cancer efficacy; hence, selective induction of tumor-suppressive ER stress and inhibition of tumor-adaptive ER stress are new strategies for novel anti-cancer drug discovery. Thus far, specific tumor-suppressive ER stress therapeutics have remained absent in clinical settings. In this study, we explored unique tumor-suppressive ER stress agents from the traditional Chinese medicinal herb Oroxylum indicum, and found that a small molecule oroxin B selectively induced tumor-suppressive ER stress in malignant lymphoma cells, but not in normal cells, effectively inhibited lymphoma growth in vivo, and significantly prolonged overall survival of lymphoma-xenografted mice without obvious toxicity. Mechanistic studies have revealed that the expression of key tumor-adaptive ER-stress gene GRP78 was notably suppressed by oroxin B via down-regulation of up-stream key signaling protein ATF6, while tumor-suppressive ER stress master gene DDIT3 was strikingly activated through activating the MKK3-p38 signaling pathway, correcting the imbalance between tumor-suppressive DDIT3 and tumor-adaptive GRP78 in lymphoma. Together, selective induction of unique tumor-suppressive ER stress and concurrent inhibition of tumor-adaptive ER stress in malignant lymphoma are new and feasible approaches for novel anti-lymphoma drug discovery and anti-lymphoma therapy. - Highlights: • Oroxin B selectively induces tumor-suppressive ER stress in B-lymphoma cells. • Oroxin B significantly prolonged overall survival of lymphoma-xenografted mice.
A short synthetic peptide fragment of human C2ORF40 has therapeutic potential in breast cancer
Energy Technology Data Exchange (ETDEWEB)
Lin, Chaoyang [Shandong Univ., Jinan (China); Zhang, Pengju [Shandong Univ., Jinan (China); Jiang, Anli [Shandong Univ., Jinan (China); Mao, Jian-Hua [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wei, Guangwei [Shandong Univ. School of Medicine, Jinan (China)
2017-03-30
C2ORF40 encodes a secreted protein which is cleaved to generate soluble peptides by proteolytic processing and this process is believed to be necessary for C2ORF40 to exert cell type specific biological activity. Here, we reported a short mimic peptide of human C2ORF40 acts potential therapeutic efficacy in human cancer cells in vitro and in vivo. We synthesized a short peptide of human C2ORF40, named C2ORF40 mimic peptide fragment and assessed its biological function on cancer cell growth, migration and tumorigenesis. Cell growth assay showed that C2ORF40 mimic peptide fragment significantly suppressed cell proliferation of breast and lung cancer cells. Moreover, C2ORF40 mimic peptide fragment significantly inhibited the migration and invasion of breast cancer cells. Furthermore, we showed that this peptide suppressed tumorigenesis in breast tumor xenograft model. Cell cycle assay indicated that the C2ORF40 mimic peptide fragment suppressed the growth of tumor cells through inducing mitotic phase arrest. In conclusion, our results firstly suggested that this short synthetic peptide of human C2ORF40 may be a candidate tumor therapeutic agent.
Fragment emission from modestly excited nuclear systems
Energy Technology Data Exchange (ETDEWEB)
Lou, Y. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Souza, R.T. de [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Chen, S.L. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Cornell, E.W. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Davin, B. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Fox, D. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Hamilton, T.M. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Mcdonald, K. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility; Tsang, M.B. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Glasmacher, T. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Dinius, J. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Gelbke, C.K. [Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Handzy, D.O. [Indiana Univ., Bloomington, IN (United States). Dept. of Chemistry]|[Indiana Univ., Bloomington, IN (United States). Cyclotron Facility]|[Michigan State Univ., East Lansing, MI (United States). National Superconducting Cyclotron Lab.; Hsi, W.C.
1996-07-08
Fragment emission patterns occurring in nuclear systems of modest excitation are studied. Exclusive measurement of fragment emission in {sup 14}N+{sup 197}Au reactions at E/A=100, 130 and 156 MeV allows selection of central collisions where a single source dominates the decay. Low threshold measurement of IMF emission for these events allows investigation of the influence of detector threshold effects. The time scale of fragment emission is deduced using fragment-fragment velocity correlations. Comparisons are made to the predictions of a statistical decay model. (orig.).
Directory of Open Access Journals (Sweden)
Devin H. Kehoe
2018-01-01
Full Text Available The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was functionally related to the CIE (x,y color space distances between color stimuli and whether there were hierarchical differences between color categories in the strength and speed of encoding potential saccade goals. We observed that saccade planning was modulated by the CIE (x,y distances between stimuli thus demonstrating that color is encoded in perceptual color space by the oculomotor system. Furthermore, these representations were modulated by (1 cueing attention to a particular color thereby eliciting surround suppression in oculomotor color space and (2 inherent selection and encoding biases based on color category independent of cueing and perceptual discriminability. Since surround suppression emerges from recurrent feedback attenuation of sensory projections, observing oculomotor surround suppression suggested that oculomotor encoding of behavioral relevance results from integrating sensory and cognitive signals that are pre-attenuated based on task demands and that the oculomotor system therefore does not functionally contribute to this process. Second, although perceptual discriminability did partially account for oculomotor processing differences between color categories, we also observed preferential processing of the red color category across various behavioral metrics. This is consistent with numerous previous studies and could not be simply explained by perceptual discriminability. Since we utilized a memory-guided saccade task, this
Kehoe, Devin H; Rahimi, Maryam; Fallah, Mazyar
2018-01-01
The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was functionally related to the CIE ( x , y ) color space distances between color stimuli and whether there were hierarchical differences between color categories in the strength and speed of encoding potential saccade goals. We observed that saccade planning was modulated by the CIE ( x , y ) distances between stimuli thus demonstrating that color is encoded in perceptual color space by the oculomotor system. Furthermore, these representations were modulated by (1) cueing attention to a particular color thereby eliciting surround suppression in oculomotor color space and (2) inherent selection and encoding biases based on color category independent of cueing and perceptual discriminability. Since surround suppression emerges from recurrent feedback attenuation of sensory projections, observing oculomotor surround suppression suggested that oculomotor encoding of behavioral relevance results from integrating sensory and cognitive signals that are pre-attenuated based on task demands and that the oculomotor system therefore does not functionally contribute to this process. Second, although perceptual discriminability did partially account for oculomotor processing differences between color categories, we also observed preferential processing of the red color category across various behavioral metrics. This is consistent with numerous previous studies and could not be simply explained by perceptual discriminability. Since we utilized a memory-guided saccade task, this indicates that
Kehoe, Devin H.; Rahimi, Maryam; Fallah, Mazyar
2018-01-01
The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was...
Topology of White Stars in Relativistic Fragmentation of Light Nuclei
Andreeva, N P; Vokal, S; Vokalova, A; Gaitinov, A Sh; Gerassimov, S G; Goncharova, L A; Dronov, V A; Zarubin, P I; Zarubina, I G; Kovalenko, A D; Kravchakova, A; Larionova, V G; Levitskaja, O V; Lepehin, F G; Malakhov, A I; Moiseenko, A A; Orlova, G I; Peresadko, N G; Polukhina, N G; Rukojatkin, P A; Rusakova, V V; Salmanova, N A; Sarkisian, V R; Simonov, B B; Stan, E; Stanoeva, R; Chernyavsky, M M; Haidue, M; Kharlamov, S P; Tsakov, I; Shchedrina, T V
2004-01-01
In the present paper, experimental observation of the multifragmentation processes of light relativistic nuclei carried out by means of emulsions are reviewed. Events of the type of "white stars" in which the dissociation of relativistic nuclei is not accompanied by the production of mesons and the target-nucleus fragments are considered. A distinctive feature of the charge topology in the dissociation of the Ne, Mg, Si and S nuclei is an almost total suppression of the binary splitting of nuclei to fragments with charges higher than 2. The growth of the nuclear fragmentation degree is revealed in an increase in the multiplicity of singly and doubly charged fragments with decreasing charge of the main non-excited part of the fragmenting nucleus. The processes of dissociation of stable Li, Be, B, C, N, and O isotopes to charged fragments were used to study special features of the formation of systems consisting of the lightest nuclei - alpha, d and t. Clustering of the 3He nucleus can be detected in "white sta...
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
Directory of Open Access Journals (Sweden)
V. L. Levshin
2015-01-01
Full Text Available The previous authors’ works have shown that the system of quasi-optimal linear spatial filtering, due to the restriction of this class of filters, related to the superposition principle, has very limited capacity to suppress the most critical interference spatially inhomogeneous background. Such partial suppression does not meet extreme approach requirements for providing high probability characteristics to detect small targets in the most difficult background conditions.In this regard, there is a conclusion that it is necessary to find a different approach, in which the result of the system operation in complex background does not depend on the level of the background noise at the input. This article performs an engineering synthesis of the system with the artificial visual intelligence elements, which recognizes a class of the small-sized radiating objects with the suppression of the most critical interference through nonlinear topological selection.Consideration of this problem begins with the formation of the filter-discriminator aperture, which is a basis for this theory, «echoing» with the theory of optimal nonlinear filtering spatial Poisson processes. Thus, formation of the optimized nonlinear filter structure is based on the optimal linear filter (Wiener filter structure. As a result, there are three versions of filter apertures (4-, 8- and 16-connected ones, with one of which later providing operations of the object shape discrimination. The focus of the article is, mainly, on the 8-connected aperture, as the average in balance of efficiency and complexity option.The article pays considerable attention to development of signs and algorithms to select the objects by size and shape. It shows that selection on a uniform background is possible by the maximum value of the first derivative and to separate the most critical form of Markov’s field inhomogeneities and background brightness, as the fragments of component boundaries of
Fragment size distribution in viscous bag breakup of a drop
Kulkarni, Varun; Bulusu, Kartik V.; Plesniak, Michael W.; Sojka, Paul E.
2015-11-01
In this study we examine the drop size distribution resulting from the fragmentation of a single drop in the presence of a continuous air jet. Specifically, we study the effect of Weber number, We, and Ohnesorge number, Oh on the disintegration process. The regime of breakup considered is observed between 12 phase Doppler anemometry. Both the number and volume fragment size probability distributions are plotted. The volume probability distribution revealed a bi-modal behavior with two distinct peaks: one corresponding to the rim fragments and the other to the bag fragments. This behavior was suppressed in the number probability distribution. Additionally, we employ an in-house particle detection code to isolate the rim fragment size distribution from the total probability distributions. Our experiments showed that the bag fragments are smaller in diameter and larger in number, while the rim fragments are larger in diameter and smaller in number. Furthermore, with increasing We for a given Ohwe observe a large number of small-diameter drops and small number of large-diameter drops. On the other hand, with increasing Oh for a fixed We the opposite is seen.
Kornilov, Oleg; Toennies, J Peter
2008-05-21
Clusters consisting of normal H2 molecules, produced in a free jet expansion, are size selected by diffraction from a transmission nanograting prior to electron impact ionization. For each neutral cluster (H2)(N) (N=2-40), the relative intensities of the ion fragments Hn+ are measured with a mass spectrometer. H3+ is found to be the most abundant fragment up to N=17. With a further increase in N, the abundances of H3+, H5+, H7+, and H9+ first increase and, after passing through a maximum, approach each other. At N=40, they are about the same and more than a factor of 2 and 3 larger than for H11+ and H13+, respectively. For a given neutral cluster size, the intensities of the ion fragments follow a Poisson distribution. The fragmentation probabilities are used to determine the neutral cluster size distribution produced in the expansion at a source temperature of 30.1 K and a source pressure of 1.50 bar. The distribution shows no clear evidence of a magic number N=13 as predicted by theory and found in experiments with pure para-H2 clusters. The ion fragment distributions are also used to extract information on the internal energy distribution of the H3+ ions produced in the reaction H2+ + H2-->H3+ +H, which is initiated upon ionization of the cluster. The internal energy is assumed to be rapidly equilibrated and to determine the number of molecules subsequently evaporated. The internal energy distribution found in this way is in good agreement with data obtained in an earlier independent merged beam scattering experiment.
De Fusco, Claudia; Brear, Paul; Iegre, Jessica; Georgiou, Kathy Hadje; Sore, Hannah F; Hyvönen, Marko; Spring, David R
2017-07-01
Recently we reported the discovery of a potent and selective CK2α inhibitor CAM4066. This compound inhibits CK2 activity by exploiting a pocket located outside the ATP binding site (αD pocket). Here we describe in detail the journey that led to the discovery of CAM4066 using the challenging fragment linking strategy. Specifically, we aimed to develop inhibitors by linking a high-affinity fragment anchored in the αD site to a weakly binding warhead fragment occupying the ATP site. Moreover, we describe the remarkable impact that molecular modelling had on the development of this novel chemical tool. The work described herein shows potential for the development of a novel class of CK2 inhibitors. Copyright © 2017. Published by Elsevier Ltd.
Molecular markers. Amplified fragment length polymorphism
Directory of Open Access Journals (Sweden)
Pržulj Novo
2005-01-01
Full Text Available Amplified Fragment Length Polymorphism molecular markers (AFLPs has been developed combining procedures of RFLPs and RAPDs molekular markers, i.e. the first step is restriction digestion of the genomic DNA that is followed by selective amplification of the restricted fragments. The advantage of the AFLP technique is that it allows rapid generation of a large number of reproducible markers. The reproducibility of AFLPs markers is assured by the use of restriction site-specific adapters and adapter-specific primers for PCR reaction. Only fragments containing the restriction site sequence plus the additional nucleotides will be amplified and the more selected nucleotides added on the primer sequence the fewer the number of fragments amplified by PCR. The amplified products are normally separated on a sequencing gel and visualized after exposure to X-ray film or by using fluorescent labeled primers. AFLP shave proven to be extremely proficient in revealing diversity at below the species level. A disadvantage of AFLP technique is that AFLPs are essentially a dominant marker system and not able to identify heterozygotes.
International Nuclear Information System (INIS)
Adare, A.; Bickley, A. A.; Ellinghaus, F.; Glenn, A.; Kinney, E.; Kiriluk, K.; Linden Levy, L. A.; Nagle, J. L.; Rosen, C. A.; Seele, J.; Wysocki, M.; Afanasiev, S.; Isupov, A.; Litvinenko, A.; Malakhov, A.; Peresedov, V.; Rukoyatkin, P.; Zolin, L.; Aidala, C.; Datta, A.
2011-01-01
Pair correlations between large transverse momentum neutral pion triggers (p T =4--7 GeV/c) and charged hadron partners (p T =3--7 GeV/c) in central (0%-20%) and midcentral (20%-60%) Au+Au collisions at √(s NN )=200 GeV are presented as a function of trigger orientation with respect to the reaction plane. The particles are at larger momentum than where jet shape modifications have been observed, and the correlations are sensitive to the energy loss of partons traveling through hot dense matter. An out-of-plane trigger particle produces only 26±20% of the away-side pairs that are observed opposite of an in-plane trigger particle for midcentral (20%-60%) collisions. In contrast, near-side jet fragments are consistent with no suppression or dependence on trigger orientation with respect to the reaction plane. These observations are qualitatively consistent with a picture of little near-side parton energy loss either due to surface bias or fluctuations and increased away-side parton energy loss due to a long path through the medium. The away-side suppression as a function of reaction-plane angle is shown to be sensitive to both the energy loss mechanism and the space-time evolution of heavy-ion collisions.
Kruidhof, H.M.; Gallandt, E.R.; Haramoto, E.R.; Bastiaans, L.
2011-01-01
Laboratory bioassays have shown that large-seeded species better tolerate cover crop residue–mediated stress than small-seeded species. This provides the potential for selective suppression of small-seeded weeds in large-seeded crops. We conducted two field experiments in which seedling emergence of
Deconstructing continuous flash suppression
Yang, Eunice; Blake, Randolph
2012-01-01
In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...
Selective epidemic broadcast algorithm to suppress broadcast storm in vehicular ad hoc networks
Directory of Open Access Journals (Sweden)
M. Chitra
2018-03-01
Full Text Available Broadcasting in Vehicular Ad Hoc Networks is the best way to spread emergency messages all over the network. With the dynamic nature of vehicular ad hoc networks, simple broadcast or flooding faces the problem called as Broadcast Storm Problem (BSP. The issue of the BSP will degrade the performance of a message broadcasting process like increased overhead, collision and dissemination delay. The paper is motivated to solve the problems in the existing Broadcast Strom Suppression Algorithms (BSSAs like p-Persistence, TLO, VSPB, G-SAB and SIR. This paper proposes to suppress the Broadcast Storm Problem and to improve the Emergency Safety message dissemination rate through a new BSSA based on Selective Epidemic Broadcast Algorithm (SEB. The simulation results clearly show that the SEB outperforms the existing algorithms in terms of ESM Delivery Ratio, Message Overhead, Collision Ratio, Broadcast Storm Ratio and Redundant Rebroadcast Ratio with decreased Dissemination Delay.
Sobolev, Victor; Arias, Renee; Goodman, Kerestin; Walk, Travis; Orner, Valerie; Faustinelli, Paola; Massa, Alicia
2018-01-10
Aspergillus flavus is a soil fungus that commonly invades peanut seeds and often produces carcinogenic aflatoxins. Under favorable conditions, the fungus-challenged peanut plant produces and accumulates resveratrol and its prenylated derivatives in response to such an invasion. These prenylated stilbenoids are considered peanut antifungal phytoalexins. However, the mechanism of peanut-fungus interaction has not been sufficiently studied. We used pure peanut stilbenoids arachidin-1, arachidin-3, and chiricanine A to study their effects on the viability of and metabolite production by several important toxigenic Aspergillus species. Significant reduction or virtually complete suppression of aflatoxin production was revealed in feeding experiments in A. flavus, Aspergillus parasiticus, and Aspergillus nomius. Changes in morphology, spore germination, and growth rate were observed in A. flavus exposed to the selected peanut stilbenoids. Elucidation of the mechanism of aflatoxin suppression by peanut stilbenoids could provide strategies for preventing plant invasion by the fungi that produce aflatoxins.
Attentional Selection and Suppression in Children With Attention-Deficit/Hyperactivity Disorder.
Wang, Encong; Sun, Li; Sun, Meirong; Huang, Jing; Tao, Ye; Zhao, Xixi; Wu, Zhanliang; Ding, Yulong; Newman, Daniel P; Bellgrove, Mark A; Wang, Yufeng; Song, Yan
2016-07-01
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with prominent impairments in directing and sustaining attention. The aim of this study was to identify the neurophysiologic bases of attention deficits in ADHD, focusing on electroencephalography markers of attentional selection (posterior contralateral N2 [N2pc]) and suppression (distractor positivity [P D ]). The electroencephalography data were collected from 135 children 9-15 years old with and without ADHD while they searched for a shape target in either the absence (experiment 1) or the presence (experiment 2) of a salient but irrelevant color distractor. In experiment 1, the shape target elicited a smaller N2pc in children with ADHD (n = 38) compared with typically developing children (n = 36). The smaller N2pc amplitude predicted higher levels of inattentive symptoms in children with ADHD. Moreover, the target-elicited N2pc was followed by a positivity in typically developing children but not in children with ADHD. In experiment 2, the salient but irrelevant color distractor elicited a smaller P D component in children with ADHD (n = 32) compared with typically developing children (n = 29). The smaller P D predicted higher inattentive symptom severity as well as lower behavioral accuracy in children with ADHD. The correlation between N2pc/P D amplitudes and ADHD symptom severity suggests that these signals of attentional selection and suppression may serve as potential candidates for neurophysiologic markers of ADHD. Our findings provide a neurophysiologic basis for the subjective reports of attention deficits in children with ADHD and highlight the importance of spatial attention impairments in ADHD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
Electron impact fragmentation of size-selected krypton clusters
Czech Academy of Sciences Publication Activity Database
Steinbach, Ch.; Fárník, Michal; Buck, U.; Brindle, C. A.; Janda, K. C.
2006-01-01
Roč. 110, č. 29 (2006), s. 9108-9115 ISSN 1089-5639 Grant - others:Deutsche Forschungsgemeinschaft(DE) GRK 782; US National Science Foundation(US) CHE-0213149 Institutional research plan: CEZ:AV0Z40400503 Keywords : rare-gas cluster * bombardment fragmentation * scattering analysis Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.047, year: 2006
Barban, P S; Minaeva, V M; Pantiukhina, A N; Startseva, M G
1976-06-01
A comparative study was made of the serological properties and virus-neutralizing activity of antiencephalitis gamma-globulin and Fab-fragments isolated from it by gel-filtration. Horse immunoglobulins against the autumno-summer tick-borne encephalitis virus could be disintegrated with the aid of papaine to monovalent Fab-fragments which (according to the complement fixation reaction, the test of suppression of the complement fixation, and the HAIT) retained the serological activity whose level was compared with that of the serological activity of gamma-globulin. Fab-fragments possessed a marked virus-neutralizing activity. The mean value of a logarithm of the neutralization index was 2.65 +/- 0.2 for Fab-fragments and 3.74 +/- 0.38 for gamma-globulin (P less than 0.01).
TURBULENT DISKS ARE NEVER STABLE: FRAGMENTATION AND TURBULENCE-PROMOTED PLANET FORMATION
Energy Technology Data Exchange (ETDEWEB)
Hopkins, Philip F. [TAPIR, Mailcode 350-17, California Institute of Technology, Pasadena, CA 91125 (United States); Christiansen, Jessie L., E-mail: phopkins@caltech.edu [SETI Institute/NASA Ames Research Center, M/S 244-30, Moffett Field, CA 94035 (United States)
2013-10-10
A fundamental assumption in our understanding of disks is that when the Toomre Q >> 1, the disk is stable against fragmentation into self-gravitating objects (and so cannot form planets via direct collapse). But if disks are turbulent, this neglects a spectrum of stochastic density fluctuations that can produce rare, high-density mass concentrations. Here, we use a recently developed analytic framework to predict the statistics of these fluctuations, i.e., the rate of fragmentation and mass spectrum of fragments formed in a turbulent Keplerian disk. Turbulent disks are never completely stable: we calculate the (always finite) probability of forming self-gravitating structures via stochastic turbulent density fluctuations in such disks. Modest sub-sonic turbulence above Mach number M∼0.1 can produce a few stochastic fragmentation or 'direct collapse' events over ∼Myr timescales, even if Q >> 1 and cooling is slow (t{sub cool} >> t{sub orbit}). In transsonic turbulence this extends to Q ∼ 100. We derive the true Q-criterion needed to suppress such events, which scales exponentially with Mach number. We specify to turbulence driven by magneto-rotational instability, convection, or spiral waves and derive equivalent criteria in terms of Q and the cooling time. Cooling times ∼> 50 t{sub dyn} may be required to completely suppress fragmentation. These gravo-turbulent events produce mass spectra peaked near ∼(Q M{sub disk}/M{sub *}){sup 2} M{sub disk} (rocky-to-giant planet masses, increasing with distance from the star). We apply this to protoplanetary disk models and show that even minimum-mass solar nebulae could experience stochastic collapse events, provided a source of turbulence.
TURBULENT DISKS ARE NEVER STABLE: FRAGMENTATION AND TURBULENCE-PROMOTED PLANET FORMATION
International Nuclear Information System (INIS)
Hopkins, Philip F.; Christiansen, Jessie L.
2013-01-01
A fundamental assumption in our understanding of disks is that when the Toomre Q >> 1, the disk is stable against fragmentation into self-gravitating objects (and so cannot form planets via direct collapse). But if disks are turbulent, this neglects a spectrum of stochastic density fluctuations that can produce rare, high-density mass concentrations. Here, we use a recently developed analytic framework to predict the statistics of these fluctuations, i.e., the rate of fragmentation and mass spectrum of fragments formed in a turbulent Keplerian disk. Turbulent disks are never completely stable: we calculate the (always finite) probability of forming self-gravitating structures via stochastic turbulent density fluctuations in such disks. Modest sub-sonic turbulence above Mach number M∼0.1 can produce a few stochastic fragmentation or 'direct collapse' events over ∼Myr timescales, even if Q >> 1 and cooling is slow (t cool >> t orbit ). In transsonic turbulence this extends to Q ∼ 100. We derive the true Q-criterion needed to suppress such events, which scales exponentially with Mach number. We specify to turbulence driven by magneto-rotational instability, convection, or spiral waves and derive equivalent criteria in terms of Q and the cooling time. Cooling times ∼> 50 t dyn may be required to completely suppress fragmentation. These gravo-turbulent events produce mass spectra peaked near ∼(Q M disk /M * ) 2 M disk (rocky-to-giant planet masses, increasing with distance from the star). We apply this to protoplanetary disk models and show that even minimum-mass solar nebulae could experience stochastic collapse events, provided a source of turbulence
High sintering resistance of size-selected platinum cluster catalysts by suppressed ostwald ripening
DEFF Research Database (Denmark)
Wettergren, Kristina; Schweinberger, Florian F.; Deiana, Davide
2014-01-01
on different supports exhibit remarkable intrinsic sintering resistance even under reaction conditions. The observed stability is related to suppression of Ostwald ripening by elimination of its main driving force via size-selection. This study thus constitutes a general blueprint for the rational design...... of sintering resistant catalyst systems and for efficient experimental strategies to determine sintering mechanisms. Moreover, this is the first systematic experimental investigation of sintering processes in nanoparticle systems with an initially perfectly monomodal size distribution under ambient conditions....
Fragment-based approaches to the discovery of kinase inhibitors.
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.
Thangavelu, Bharani; Bhansali, Pravin; Viola, Ronald E
2015-10-15
Aspartate-β-semialdehyde dehydrogenase (ASADH) lies at the first branch point in the aspartate metabolic pathway which leads to the biosynthesis of several essential amino acids and some important metabolites. This pathway is crucial for many metabolic processes in plants and microbes like bacteria and fungi, but is absent in mammals. Therefore, the key microbial enzymes involved in this pathway are attractive potential targets for development of new antibiotics with novel modes of action. The ASADH enzyme family shares the same substrate binding and active site catalytic groups; however, the enzymes from representative bacterial and fungal species show different inhibition patterns when previously screened against low molecular weight inhibitors identified from fragment library screening. In the present study several approaches, including fragment based drug discovery (FBDD), inhibitor docking, kinetic, and structure-activity relationship (SAR) studies have been used to guide ASADH inhibitor development. Elaboration of a core structure identified by FBDD has led to the synthesis of low micromolar inhibitors of the target enzyme, with high selectivity introduced between the Gram-negative and Gram-positive orthologs of ASADH. This new set of structures open a novel direction for the development of inhibitors against this validated drug-target enzyme. Copyright © 2015 Elsevier Ltd. All rights reserved.
[Fragment-based drug discovery: concept and aim].
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.
Production of a phage-displayed single chain variable fragment ...
African Journals Online (AJOL)
Abstract. Purpose: To develop specific single chain variable fragments (scFv) against ... libraries. The binding ability of the selected scFv antibody fragments against the IBDV particles was ..... Hermelink H, Koscielniak E. A human recombinant.
Jet suppression measurement with the ATLAS detector
AUTHOR|(INSPIRE)INSPIRE-00443411; The ATLAS collaboration
2016-01-01
A hot medium with a high density of unscreened color charges is produced in relativistic heavy ion collisions. Jets are produced at the early stages of this collision and are known to become attenuated as they propagate through the hot matter. One manifestation of this energy loss is a lower yield of jets emerging from the medium than expected in the absence of medium effects. Another manifestation of the energy loss is the modification of the dijet balance and the modification of fragmentation functions. In these proceedings, the latest ATLAS results on single jet suppression, dijet suppression, and modification of the jet internal structure in \\PbPb~collisions are presented.
International Nuclear Information System (INIS)
Park, So Jung; Park, Young Jun; Shin, Ji Hyun; Kim, Eun Sung; Hwang, Jung Jin; Jin, Dong-Hoon; Kim, Jin Cheon; Cho, Dong-Hyung
2011-01-01
Highlights: → We screened and identified Tyrphostin A9, a receptor tyrosine kinase inhibitor as a strong mitochondria fission inducer. → Tyrphostin A9 treatment promotes mitochondria dysfunction and contributes to cytotoxicity in cancer cells. → Tyrphostin A9 induces apoptotic cell death through a Drp1-mediated pathway. → Our studies suggest that Tyrphostin A9 induces mitochondria fragmentation and apoptotic cell death via Drp1 dependently. -- Abstract: Mitochondria dynamics controls not only their morphology but also functions of mitochondria. Therefore, an imbalance of the dynamics eventually leads to mitochondria disruption and cell death. To identify specific regulators of mitochondria dynamics, we screened a bioactive chemical compound library and selected Tyrphostin A9, a tyrosine kinase inhibitor, as a potent inducer of mitochondrial fission. Tyrphostin A9 treatment resulted in the formation of fragmented mitochondria filament. In addition, cellular ATP level was decreased and the mitochondrial membrane potential was collapsed in Tyr A9-treated cells. Suppression of Drp1 activity by siRNA or over-expression of a dominant negative mutant of Drp1 inhibited both mitochondrial fragmentation and cell death induced by Tyrpohotin A9. Moreover, treatment of Tyrphostin A9 also evoked mitochondrial fragmentation in other cells including the neuroblastomas. Taken together, these results suggest that Tyrphostin A9 induces Drp1-mediated mitochondrial fission and apoptotic cell death.
Suppression of Cpn10 increases mitochondrial fission and dysfunction in neuroblastoma cells.
Directory of Open Access Journals (Sweden)
So Jung Park
Full Text Available To date, several regulatory proteins involved in mitochondrial dynamics have been identified. However, the precise mechanism coordinating these complex processes remains unclear. Mitochondrial chaperones regulate mitochondrial function and structure. Chaperonin 10 (Cpn10 interacts with heat shock protein 60 (HSP60 and functions as a co-chaperone. In this study, we found that down-regulation of Cpn10 highly promoted mitochondrial fragmentation in SK-N-MC and SH-SY5Y neuroblastoma cells. Both genetic and chemical inhibition of Drp1 suppressed the mitochondrial fragmentation induced by Cpn10 reduction. Reactive oxygen species (ROS generation in 3-NP-treated cells was markedly enhanced by Cpn10 knock down. Depletion of Cpn10 synergistically increased cell death in response to 3-NP treatment. Furthermore, inhibition of Drp1 recovered Cpn10-mediated mitochondrial dysfunction in 3-NP-treated cells. Moreover, an ROS scavenger suppressed cell death mediated by Cpn10 knockdown in 3-NP-treated cells. Taken together, these results showed that down-regulation of Cpn10 increased mitochondrial fragmentation and potentiated 3-NP-mediated mitochondrial dysfunction in neuroblastoma cells.
Yang, Bin; Peng, Yu; Leung, Henry Chi-Ming; Yiu, Siu-Ming; Chen, Jing-Chi; Chin, Francis Yuk-Lun
2010-04-16
With the rapid development of genome sequencing techniques, traditional research methods based on the isolation and cultivation of microorganisms are being gradually replaced by metagenomics, which is also known as environmental genomics. The first step, which is still a major bottleneck, of metagenomics is the taxonomic characterization of DNA fragments (reads) resulting from sequencing a sample of mixed species. This step is usually referred as "binning". Existing binning methods are based on supervised or semi-supervised approaches which rely heavily on reference genomes of known microorganisms and phylogenetic marker genes. Due to the limited availability of reference genomes and the bias and instability of marker genes, existing binning methods may not be applicable in many cases. In this paper, we present an unsupervised binning method based on the distribution of a carefully selected set of l-mers (substrings of length l in DNA fragments). From our experiments, we show that our method can accurately bin DNA fragments with various lengths and relative species abundance ratios without using any reference and training datasets. Another feature of our method is its error robustness. The binning accuracy decreases by less than 1% when the sequencing error rate increases from 0% to 5%. Note that the typical sequencing error rate of existing commercial sequencing platforms is less than 2%. We provide a new and effective tool to solve the metagenome binning problem without using any reference datasets or markers information of any known reference genomes (species). The source code of our software tool, the reference genomes of the species for generating the test datasets and the corresponding test datasets are available at http://i.cs.hku.hk/~alse/MetaCluster/.
Impact failure and fragmentation properties of metals
Energy Technology Data Exchange (ETDEWEB)
Grady, D.E. [Applied Research Associates, Albuquerque, NM (United States); Kipp, M.E. [Sandia National Labs., Albuquerque, NM (United States)
1998-03-01
In the present study we describe the development of an experimental fracture material property test method specific to dynamic fragmentation. Spherical test samples of the metals of interest are subjected to controlled impulsive stress loads by acceleration to high velocities with a light-gas launcher facility and subsequent normal impact on thin plates. Motion, deformation and fragmentation of the test samples are diagnosed with multiple flash radiography methods. The impact plate materials are selected to be transparent to the x-ray method so that only test metal material is imaged. Through a systematic series of such tests both strain-to-failure and fragmentation resistance properties are determined through this experimental method. Fragmentation property data for several steels, copper, aluminum, tantalum and titanium have been obtained to date. Aspects of the dynamic data have been analyzed with computational methods to achieve a better understanding of the processes leading to failure and fragmentation, and to test an existing computational fragmentation model.
Multiple parton scattering in nuclei: heavy quark energy loss and modified fragmentation functions
International Nuclear Information System (INIS)
Zhang Benwei; Wang, Enke; Wang Xinnian
2005-01-01
Multiple scattering, induced radiative energy loss and modified fragmentation functions of a heavy quark in nuclear matter are studied within the framework of generalized factorization in perturbative QCD. Modified heavy quark fragmentation functions and energy loss are derived in detail with illustration of the mass dependencies of the Landau-Pomeranchuk-Migdal interference effects and heavy quark energy loss. Due to the quark mass dependence of the gluon formation time, the nuclear size dependencies of nuclear modification of the heavy quark fragmentation function and heavy quark energy loss are found to change from a linear to a quadratic form when the initial energy and momentum scale are increased relative to the quark mass. The radiative energy loss of the heavy quark is also significantly suppressed due to limited cone of gluon radiation imposed by the mass. Medium modification of the heavy quark fragmentation functions is found to be limited to the large z region due to the form of heavy quark fragmentation functions in vacuum
Andersen, S. K.; Müller, M. M.
2010-01-01
A central question in the field of attention is whether visual processing is a strictly limited resource, which must be allocated by selective attention. If this were the case, attentional enhancement of one stimulus should invariably lead to suppression of unattended distracter stimuli. Here we examine voluntary cued shifts of feature-selective attention to either one of two superimposed red or blue random dot kinematograms (RDKs) to test whether such a reciprocal relationship between enhanc...
Effects of thought suppression on episodic memory.
Rassin, E; Merckelbach, H; Muris, P
1997-11-01
Subjects were shown a short film fragment. Following this, one group of subjects (n = 26) was instructed to suppress their thoughts about the film, while the other group (n = 24) received no instructions. After 5 hrs subjects returned to the laboratory and completed a questionnaire testing their memory about the film. Results showed that suppression subjects reported a higher frequency of thoughts about the film than control subjects. No evidence was obtained for Wegner, Quillian, and Houston's (1996; Journal of Personality and Social Psychology, 71, 680-691) claim that suppression has an undermining effect on memory for chronology. Possible causes for the differences between the results as obtained by Wegner et al., and those found in the present study are discussed. These causes may pertain to the experimental design, but also to differences in emotional impact of the stimulus material that was used in both studies.
Projectile rapidity dependence in target fragmentation
International Nuclear Information System (INIS)
Haustein, P.E.; Cumming, J.B.; Hseuh, H.C.
1979-01-01
The thick-target, thick-catcher technique was used to determine mean kinetic properties of selected products of the fragmentation of Cu by 1 H, 4 He, and 12 C ions (180 to 28,000 MeV/amu). Momentum transfer, as inferred from F/B ratios, is ovserved to occur most efficiently for the lower velocity projectiles. Recoil properties of target fragments vary strongly with product mass, but show only a weak dependence on projectile type. The projectile's rapidity is shown to be a useful variable for quantitative intercomparison of different reactions. These results indicate that E/sub proj//A/sub proj/ is the dominant parameter which governs the mean recoil behavior of target fragments. 20 references
Heightman, Tom D; Berdini, Valerio; Braithwaite, Hannah; Buck, Ildiko M; Cassidy, Megan; Castro, Juan; Courtin, Aurélie; Day, James E H; East, Charlotte; Fazal, Lynsey; Graham, Brent; Griffiths-Jones, Charlotte M; Lyons, John F; Martins, Vanessa; Muench, Sandra; Munck, Joanne M; Norton, David; O'Reilly, Marc; Palmer, Nick; Pathuri, Puja; Reader, Michael; Rees, David C; Rich, Sharna J; Richardson, Caroline; Saini, Harpreet; Thompson, Neil T; Wallis, Nicola G; Walton, Hugh; Wilsher, Nicola E; Woolford, Alison J-A; Cooke, Michael; Cousin, David; Onions, Stuart; Shannon, Jonathan; Watts, John; Murray, Christopher W
2018-05-31
Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signaling through ERK1/2. Here, we describe the fragment-based generation of ERK1/2 inhibitors that block catalytic phosphorylation of downstream substrates such as RSK but also modulate phosphorylation of ERK1/2 by MEK without directly inhibiting MEK. X-ray crystallographic and biophysical fragment screening followed by structure-guided optimization and growth from the hinge into a pocket proximal to the C-α helix afforded highly potent ERK1/2 inhibitors with excellent kinome selectivity. In BRAF mutant cells, the lead compound suppresses pRSK and pERK levels and inhibits proliferation at low nanomolar concentrations. The lead exhibits tumor regression upon oral dosing in BRAF mutant xenograft models, providing a promising basis for further optimization toward clinical pERK1/2 modulating ERK1/2 inhibitors.
Varnes, Jeffrey G; Geschwindner, Stefan; Holmquist, Christopher R; Forst, Janet; Wang, Xia; Dekker, Niek; Scott, Clay W; Tian, Gaochao; Wood, Michael W; Albert, Jeffrey S
2016-01-01
Fragment-based drug design (FBDD) relies on direct elaboration of fragment hits and typically requires high resolution structural information to guide optimization. In fragment-assisted drug discovery (FADD), fragments provide information to guide selection and design but do not serve as starting points for elaboration. We describe FADD and high-throughput screening (HTS) campaign strategies conducted in parallel against PDE10A where fragment hit co-crystallography was not available. The fragment screen led to prioritized fragment hits (IC50's ∼500μM), which were used to generate a hypothetical core scaffold. Application of this scaffold as a filter to HTS output afforded a 4μM hit, which, after preparation of a small number of analogs, was elaborated into a 16nM lead. This approach highlights the strength of FADD, as fragment methods were applied despite the absence of co-crystallographical information to efficiently identify a lead compound for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.
Arimori, Takao; Kitago, Yu; Umitsu, Masataka; Fujii, Yuki; Asaki, Ryoko; Tamura-Kawakami, Keiko; Takagi, Junichi
2017-10-03
Antibody fragments are frequently used as a "crystallization chaperone" to aid structural analysis of complex macromolecules that are otherwise crystallization resistant, but conventional fragment formats have not been designed for this particular application. By fusing an anti-parallel coiled-coil structure derived from the SARAH domain of human Mst1 kinase to the variable region of an antibody, we succeeded in creating a novel chimeric antibody fragment of ∼37 kDa, termed "Fv-clasp," which exhibits excellent crystallization compatibility while maintaining the binding ability of the original IgG molecule. The "clasp" and the engineered disulfide bond at the bottom of the Fv suppressed the internal mobility of the fragment and shielded hydrophobic residues, likely contributing to the high heat stability and the crystallizability of the Fv-clasp. Finally, Fv-clasp antibodies showed superior "chaperoning" activity over conventional Fab fragments, and facilitated the structure determination of an ectodomain fragment of integrin α6β1. Copyright © 2017 Elsevier Ltd. All rights reserved.
Selective serotonin reuptake inhibitor suppression of HIV infectivity and replication.
Benton, Tami; Lynch, Kevin; Dubé, Benoit; Gettes, David R; Tustin, Nancy B; Ping Lai, Jian; Metzger, David S; Blume, Joshua; Douglas, Steven D; Evans, Dwight L
2010-11-01
To test the hypothesis that the selective serotonin reuptake inhibitor (SSRI) citalopram would down-regulate human immunodeficiency virus (HIV) infectivity and that the greatest effects would be seen in people with depression. Depression is a risk factor for morbidity and mortality in HIV/acquired immune deficiency syndrome. Serotonin (5-HT) neurotransmission has been implicated in the pathobiology of depression, and pharmacologic therapies for depression target this system. The 5-HT transporter and 5-HT receptors are widely distributed throughout the central nervous and immune systems. Depression has been associated with suppression of natural killer cells and CD8(+) lymphocytes, key regulators of HIV infection. Ex vivo models for acute and chronic HIV infection were used to study the effects of citalopram on HIV viral infection and replication in 48 depressed and nondepressed women. For both the acute and chronic infection models, HIV reverse transcriptase activity was measured in the citalopram treatment condition and the control condition. The SSRI significantly down-regulated the reverse transcriptase response in both the acute and chronic infection models. Specifically, citalopram significantly decreased the acute HIV infectivity of macrophages. Citalopram also significantly decreased HIV viral replication in the latently infected T-cell line and in the latently infected macrophage cell line. There was no difference in down-regulation by depression status. These studies suggest that an SSRI enhances natural killer/CD8 noncytolytic HIV suppression in HIV/acquired immune deficiency syndrome and decreases HIV viral infectivity of macrophages, ex vivo, suggesting the need for in vivo studies to determine a potential role for agents targeting serotonin in the host defense against HIV.
International Nuclear Information System (INIS)
Palau, Aina; Girart, Josep M.; Estalella, Robert; Fuente, Asunción; Fontani, Francesco; Sánchez-Monge, Álvaro; Commerçon, Benoit; Hennebelle, Patrick; Busquet, Gemma; Bontemps, Sylvain; Zapata, Luis A.; Zhang, Qizhou; Di Francesco, James
2014-01-01
In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 μm (or 1.2 mm in two cases) and the spectral energy distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. Even though the estimated fragmentation level is strictly speaking a lower limit, its relative value is significant and several trends could be explored with our data. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered the effects of rotational-to-gravitational energy ratio, non-thermal velocity dispersion, and turbulence mode on the density structure of the cores, and found that compressive turbulence seems to yield higher central densities. Finally, a possible explanation for the origin of cores with concentrated density profiles, which are the cores showing no fragmentation, could be related with a strong magnetic field, consistent with the outcome of radiation magnetohydrodynamic simulations.
Energy Technology Data Exchange (ETDEWEB)
Palau, Aina; Girart, Josep M. [Institut de Ciències de l' Espai (CSIC-IEEC), Campus UAB-Facultat de Ciències, Torre C5-parell 2, E-08193 Bellaterra, Catalunya (Spain); Estalella, Robert [Departament d' Astronomia i Meteorologia (IEEC-UB), Institut de Ciències del Cosmos, Universitat de Barcelona, Martí i Franquès, 1, E-08028 Barcelona (Spain); Fuente, Asunción [Observatorio Astronómico Nacional, P.O. Box 112, E-28803 Alcalá de Henares, Madrid (Spain); Fontani, Francesco; Sánchez-Monge, Álvaro [Osservatorio Astrofisico di Arcetri, INAF, Lago E. Fermi 5, I-50125 Firenze (Italy); Commerçon, Benoit; Hennebelle, Patrick [Laboratoire de Radioastronomie, UMR CNRS 8112, École Normale Supérieure et Observatoire de Paris, 24 rue Lhomond, F-75231 Paris Cedex 05 (France); Busquet, Gemma [INAF-Istituto di Astrofisica e Planetologia Spaziali, Area di Recerca di Tor Vergata, Via Fosso Cavaliere 100, I-00133 Roma (Italy); Bontemps, Sylvain [Université de Bordeaux, LAB, UMR 5804, F-33270 Floirac (France); Zapata, Luis A. [Centro de Radioastronomía y Astrofísica, Universidad Nacional Autónoma de México, P.O. Box 3-72, 58090 Morelia, Michoacán (Mexico); Zhang, Qizhou [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Di Francesco, James, E-mail: palau@ieec.uab.es [Department of Physics and Astronomy, University of Victoria, P.O. Box 355, STN CSC, Victoria, BC, V8W 3P6 (Canada)
2014-04-10
In order to shed light on the main physical processes controlling fragmentation of massive dense cores, we present a uniform study of the density structure of 19 massive dense cores, selected to be at similar evolutionary stages, for which their relative fragmentation level was assessed in a previous work. We inferred the density structure of the 19 cores through a simultaneous fit of the radial intensity profiles at 450 and 850 μm (or 1.2 mm in two cases) and the spectral energy distribution, assuming spherical symmetry and that the density and temperature of the cores decrease with radius following power-laws. Even though the estimated fragmentation level is strictly speaking a lower limit, its relative value is significant and several trends could be explored with our data. We find a weak (inverse) trend of fragmentation level and density power-law index, with steeper density profiles tending to show lower fragmentation, and vice versa. In addition, we find a trend of fragmentation increasing with density within a given radius, which arises from a combination of flat density profile and high central density and is consistent with Jeans fragmentation. We considered the effects of rotational-to-gravitational energy ratio, non-thermal velocity dispersion, and turbulence mode on the density structure of the cores, and found that compressive turbulence seems to yield higher central densities. Finally, a possible explanation for the origin of cores with concentrated density profiles, which are the cores showing no fragmentation, could be related with a strong magnetic field, consistent with the outcome of radiation magnetohydrodynamic simulations.
Production of a phage-displayed single chain variable fragment ...
African Journals Online (AJOL)
Purpose: To develop specific single chain variable fragments (scFv) against infectious bursal disease virus (IBDV) via phage display technology. Methods: Purified viruses were initially applied for iterative panning rounds of scFv phage display libraries. The binding ability of the selected scFv antibody fragments against the ...
Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival and
Directory of Open Access Journals (Sweden)
Dmytro Starenki
2015-12-01
Full Text Available BackgroundMedullary thyroid carcinoma (MTC is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077, a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria.MethodsThe effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53, and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts.ResultsMKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts.ConclusionMKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC.
Selective suppression of endothelial cytokine production by progesterone receptor.
Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa
2013-01-01
Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
Fragment screening of cyclin G-associated kinase by weak affinity chromatography.
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.
Fragment growing and linking lead to novel nanomolar lactate dehydrogenase inhibitors.
Kohlmann, Anna; Zech, Stephan G; Li, Feng; Zhou, Tianjun; Squillace, Rachel M; Commodore, Lois; Greenfield, Matthew T; Lu, Xiaohui; Miller, David P; Huang, Wei-Sheng; Qi, Jiwei; Thomas, R Mathew; Wang, Yihan; Zhang, Sen; Dodd, Rory; Liu, Shuangying; Xu, Rongsong; Xu, Yongjin; Miret, Juan J; Rivera, Victor; Clackson, Tim; Shakespeare, William C; Zhu, Xiaotian; Dalgarno, David C
2013-02-14
Lactate dehydrogenase A (LDH-A) catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway. Cancer cells rely heavily on glycolysis instead of oxidative phosphorylation to generate ATP, a phenomenon known as the Warburg effect. The inhibition of LDH-A by small molecules is therefore of interest for potential cancer treatments. We describe the identification and optimization of LDH-A inhibitors by fragment-based drug discovery. We applied ligand based NMR screening to identify low affinity fragments binding to LDH-A. The dissociation constants (K(d)) and enzyme inhibition (IC(50)) of fragment hits were measured by surface plasmon resonance (SPR) and enzyme assays, respectively. The binding modes of selected fragments were investigated by X-ray crystallography. Fragment growing and linking, followed by chemical optimization, resulted in nanomolar LDH-A inhibitors that demonstrated stoichiometric binding to LDH-A. Selected molecules inhibited lactate production in cells, suggesting target-specific inhibition in cancer cell lines.
Fragment Length of Circulating Tumor DNA.
Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay
2016-07-01
Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.
Energy Technology Data Exchange (ETDEWEB)
Niu, Mingshan [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Shen, Yangling; Xu, Xiaoyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Yao, Yao; Fu, Chunling [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Yan, Zhiling [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Wu, Qingyun [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Cao, Jiang; Sang, Wei [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Zeng, Lingyu [Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu (China); Jiangsu Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical College, Xuzhou, Jiangsu (China); Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Li, Zhenyu [Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu (China); Liu, Xuejiao, E-mail: liuxuejiao0923@126.com [Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu (China); and others
2015-07-10
Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys{sup 38} to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy.
International Nuclear Information System (INIS)
Niu, Mingshan; Shen, Yangling; Xu, Xiaoyu; Yao, Yao; Fu, Chunling; Yan, Zhiling; Wu, Qingyun; Cao, Jiang; Sang, Wei; Zeng, Lingyu; Li, Zhenyu; Liu, Xuejiao
2015-01-01
Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. - Highlights: • Current NF-κB targeting strategies lack cancer cell specificity. • Piperlongumine inhibits NF-κB p65 subunit nuclear import via directly binding to p65. • Piperlongumine selectively inhibits proliferation of ABC-DLBCL cells. • This study provides a novel approach to ABC-DLBCL target therapy
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.
Fragment-based drug discovery using rational design.
Jhoti, H
2007-01-01
Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.
Computational fragment-based screening using RosettaLigand: the SAMPL3 challenge
Kumar, Ashutosh; Zhang, Kam Y. J.
2012-05-01
SAMPL3 fragment based virtual screening challenge provides a valuable opportunity for researchers to test their programs, methods and screening protocols in a blind testing environment. We participated in SAMPL3 challenge and evaluated our virtual fragment screening protocol, which involves RosettaLigand as the core component by screening a 500 fragments Maybridge library against bovine pancreatic trypsin. Our study reaffirmed that the real test for any virtual screening approach would be in a blind testing environment. The analyses presented in this paper also showed that virtual screening performance can be improved, if a set of known active compounds is available and parameters and methods that yield better enrichment are selected. Our study also highlighted that to achieve accurate orientation and conformation of ligands within a binding site, selecting an appropriate method to calculate partial charges is important. Another finding is that using multiple receptor ensembles in docking does not always yield better enrichment than individual receptors. On the basis of our results and retrospective analyses from SAMPL3 fragment screening challenge we anticipate that chances of success in a fragment screening process could be increased significantly with careful selection of receptor structures, protein flexibility, sufficient conformational sampling within binding pocket and accurate assignment of ligand and protein partial charges.
Shimizu, Akinori; Tani, Haruna; Takibuchi, Gaku; Ishikawa, Kaori; Sakurazawa, Ryota; Inoue, Takafumi; Hashimoto, Tetsuo; Nakada, Kazuto; Takenaga, Keizo; Hayashi, Jun-Ichi
2017-11-04
In a previous study, we generated transmitochondrial P29mtSAMP1 cybrids, which had nuclear DNA from the C57BL6 (referred to as B6) mouse strain-derived P29 tumor cells and mitochondrial DNA (mtDNA) exogenously-transferred from the allogeneic strain SAMP1. Because P29mtSAMP1 cybrids did not form tumors in syngeneic B6 mice, we proposed that allogeneic SAMP1 mtDNA suppressed tumor formation of P29mtSAMP1 cybrids. To test this hypothesis, current study generated P29mt(sp)B6 cybrids carrying all genomes (nuclear DNA and mtDNA) from syngeneic B6 mice by eliminating SAMP1 mtDNA from P29mtSAMP1 cybrids and reintroducing B6 mtDNA. However, the P29mt(sp)B6 cybrids did not form tumors in B6 mice, even though they had no SAMP1 mtDNA, suggesting that SAMP1 mtDNA is not involved in tumor suppression. Then, we examined another possibility of whether SAMP1 mtDNA fragments potentially integrated into the nuclear DNA of P29mtSAMP1 cybrids are responsible for tumor suppression. We generated P29 H (sp)B6 cybrids by eliminating nuclear DNA from P29mt(sp)B6 cybrids and reintroducing nuclear DNA with no integrated SAMP1 mtDNA fragment from mtDNA-less P29 cells resistant to hygromycin in selection medium containing hygromycin. However, the P29 H (sp)B6 cybrids did not form tumors in B6 mice, even though they carried neither SAMP1 mtDNA nor nuclear DNA with integrated SAMP1 mtDNA fragments. Moreover, overproduction of reactive oxygen species (ROS) and bacterial infection were not involved in tumor suppression. These observations suggest that tumor suppression was caused not by mtDNA with polymorphic mutations or infection of cytozoic bacteria but by hypothetical heritable cytoplasmic elements other than mtDNA from SAMP1 mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Developments in SPR Fragment Screening.
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.
Rituximab selectively suppresses specific islet antibodies.
Yu, Liping; Herold, Kevan; Krause-Steinrauf, Heidi; McGee, Paula L; Bundy, Brian; Pugliese, Alberto; Krischer, Jeff; Eisenbarth, George S
2011-10-01
The TrialNet Study Group evaluated rituximab, a B-cell-depleting monoclonal antibody, for its effect in new-onset patients with type 1A diabetes. Rituximab decreased the loss of C-peptide over the first year of follow-up and markedly depleted B lymphocytes for 6 months after administration. This article analyzes the specific effect of rituximab on multiple islet autoantibodies. A total of 87 patients between the ages of 8 and 40 years received either rituximab or a placebo infusion weekly for four doses close to the onset of diabetes. Autoantibodies to insulin (IAAs), GAD65 (GADAs), insulinoma-associated protein 2 (IA2As), and ZnT8 (ZnT8As) were measured with radioimmunoassays. The primary outcome for this autoantibody analysis was the mean level of autoantibodies during follow-up. Rituximab markedly suppressed IAAs compared with the placebo injection but had a much smaller effect on GADAs, IA2As, and ZnT8As. A total of 40% (19 of 48) of rituximab-treated patients who were IAA positive became IAA negative versus 0 of 29 placebo-treated patients (P 1 year in insulin-treated patients. For the patients receiving insulin for >2 weeks prior to rituximab administration, we cannot assess whether rituximab not only blocks the acquisition of insulin antibodies induced by insulin administration and/or also suppresses preformed insulin autoantibodies. Studies in prediabetic non-insulin-treated patients will likely be needed to evaluate the specific effects of rituximab on levels of IAAs.
Directory of Open Access Journals (Sweden)
Luca Ronconi
Full Text Available Neurophysiological findings in the typical population demonstrate that spatial scrutiny for visual selection determines a center-surround profile of the attentional focus, which is the result of recurrent processing in the visual system. Individuals with autism spectrum disorder (ASD manifest several anomalies in their visual selection, with strengths in detail-oriented tasks, but also difficulties in distractor inhibition tasks. Here, we asked whether contradictory aspects of perception in ASD might be due to a different center-surround profile of their attentional focus. In two experiments, we tested two independent samples of children with ASD, comparing them with typically developing (TD peers. In Experiment 1, we used a psychophysical task that mapped the entire spatial profile of the attentional focus. In Experiment 2, we used dense-array electroencephalography (EEG to explore its neurophysiological underpinnings. Experiment 1 results showed that the suppression, surrounding the attentional focus, was markedly reduced in children with ASD. Experiment 2 showed that the center-surround profile in TD children resulted in a modulation of the posterior N2 ERP component, with cortical sources in the lateral-occipital and medial/inferior temporal areas. In contrast, children with ASD did not show modulation of the N2 and related activations in the ventral visual stream. Furthermore, behavioural and neurophysiological measures of weaker suppression predicted more severe autistic symptomatology. The present findings, showing an altered center-surround profile during attentional selection, give an important insight to understand superior visual processing in autism as well as the experiencing of sensory overload. Keywords: EEG, Source analysis, Ventral visual stream, Perception, Rehabilitation
Romero-Carpio, Mariela; Estrada-Jiménez, Rolando
2013-01-01
A partir de la expresión diferencial de ARNm de plántulas in vitro de dos accesiones de Ullucus tuberosus Loz. «olluco» altamente tolerantes a estrés osmótico, fueron seleccionados 31 fragmentos diferenciales de ADNc relacionados con tolerancia a sequía. Thirty-one differential fragments of cDNA related to drought tolerance have been selected from the mRNA differential expression of in vitro plantelets belonging to two accessions of Ullucus tuberosus Loz. «olluco» highly tolerant to osmoti...
High-throughput fragment screening by affinity LC-MS.
Duong-Thi, Minh-Dao; Bergström, Maria; Fex, Tomas; Isaksson, Roland; Ohlson, Sten
2013-02-01
Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K (D)) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.
Simultaneous measurement of neutrons and fission fragments of thermal neutron fission of U-233
International Nuclear Information System (INIS)
Itsuro Kimura; Katsuhisa Nishio; Yoshihiro Nakagome
2000-01-01
The multiplicity and the energy of prompt neutrons from the fragments for 233 U(n th , f) were measured as functions of fragment mass and total kinetic energy. Average neutron energy against the fragment mass showed a nearly symmetric distribution about the half mass division with two valleys at 98 and 145 u. The slope of the neutron multiplicity with total kinetic energy depended on the fragment mass and showed the minimum at about 130 u. The obtained neutron data were applied to determine the total excitation energy of the system, and the resulting value in the typical asymmetric fission lied between 22 and 25 MeV. The excitation energy agreed with that determined by subtracting the total kinetic energy from the Q-value within 1 MeV, thus satisfied the energy conservation. In the symmetric fission, where the mass yield was drastically suppresses, the total excitation energy is significantly large and reaches to about 40 MeV, suggesting that fragment pairs are preferentially formed in a compact configuration at the scission point [ru
Baculovirus display of functional antibody Fab fragments.
Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki
2015-08-01
The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.
Morrison, Kelsey A.; Clowers, Brian H.
2017-06-01
The alternative dissociation pathways initiated by ultraviolet photodissociation (UVPD) compared with collision-induced dissociation (CID) may provide useful diagnostic fragments for biomolecule identification, including glycans. However, underivatized glycans do not commonly demonstrate strong UV absorbance, resulting in low fragmentation yields for UVPD spectra. In contrast to UVPD experiments that leverage covalent modification of glycans, we detail the capacity of metal adduction to yield comparatively rich UVPD fragmentation patterns and enhance separation factors for an isomeric glycan set in a drift tube ion mobility system. Ion mobility and UVPD-MS spectra for two N-acetyl glycan isomers were examined, each adducted with sodium or cobalt cations, with the latter providing fragment yield gains of an order of magnitude versus sodium adducts. Furthermore, our glycan analysis incorporated front-end ion mobility separation such that the structural glycan isomers could still be identified even as a mixture and not simply composite spectra of isomeric standards. Cobalt adduction proved influential in the glycan separation by yielding an isomer resolution of 0.78 when analyzed simultaneously versus no discernable separation obtained with the sodium adducts. It is the combined enhancement of both isomeric drift time separation and isomer distinction with improved UVPD fragment ion yields that further bolster multivalent metal adduction for advancing glycan IM-MS experiments. [Figure not available: see fulltext.
International Nuclear Information System (INIS)
Chen, J.M.; Lu, K.T.; Lee, J.M.; Ho, S.C.; Chang, H.W.; Lee, Y.Y.
2005-01-01
State-selective dissociation dynamics for the excited fragments of gaseous Si(CH 3 ) 2 Cl 2 following Cl 2p and Si 2p core-level excitations have been investigated by resonant photoemission spectroscopy and dispersed UV/optical fluorescence spectroscopy. The main features in the gaseous Si(CH 3 ) 2 Cl 2 fluorescence spectrum are identified as the emission from excited Si*, Si + *, CH* and H*. The core-to-Rydberg excitations at both Si 2p and Cl 2p edges lead to a noteworthy production of not only the excited atomic fragments, neutral and ionic (Si*, Si + *) but also the excited diatomic fragments (CH*). In particular, the excited neutral atomic fragments Si* are significantly reinforced. The experimental results provide deeper insight into the state-selective dissociation dynamics for the excited fragments of molecules via core-level excitation
Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model.
Directory of Open Access Journals (Sweden)
Mimi Cushman-Nick
Full Text Available There are no effective therapeutics that antagonize or reverse the protein-misfolding events underpinning polyglutamine (PolyQ disorders, including Spinocerebellar Ataxia Type-3 (SCA3. Here, we augment the proteostasis network of Drosophila SCA3 models with Hsp104, a powerful protein disaggregase from yeast, which is bafflingly absent from metazoa. Hsp104 suppressed eye degeneration caused by a C-terminal ataxin-3 (MJD fragment containing the pathogenic expanded PolyQ tract, but unexpectedly enhanced aggregation and toxicity of full-length pathogenic MJD. Hsp104 suppressed toxicity of MJD variants lacking a portion of the N-terminal deubiquitylase domain and full-length MJD variants unable to engage polyubiquitin, indicating that MJD-ubiquitin interactions hinder protective Hsp104 modalities. Importantly, in staging experiments, Hsp104 suppressed toxicity of a C-terminal MJD fragment when expressed after the onset of PolyQ-induced degeneration, whereas Hsp70 was ineffective. Thus, we establish the first disaggregase or chaperone treatment administered after the onset of pathogenic protein-induced degeneration that mitigates disease progression.
Khajeh, Shirin; Tohidkia, Mohammad Reza; Aghanejad, Ayuob; Mehdipour, Tayebeh; Fathi, Farzaneh; Omidi, Yadollah
2018-06-09
Glycine-extended gastrin 17 (G17-Gly), a dominant processing intermediate of gastrin gene, has been implicated in the development or maintenance of colorectal cancers (CRCs). Hence, neutralizing G17-Gly activity by antibody entities can provide a potential therapeutic strategy in the patients with CRCs. To this end, we isolated fully human antibody fragments from a phage antibody library through biopanning against different epitopes of G17-Gly in order to obtain the highest possible antibody diversity. ELISA screening and sequence analysis identified 2 scFvs and 4 V L antibody fragments. Kinetic analysis of the antibody fragments by SPR revealed K D values to be in the nanomolar range (87.9-334 nM). The selected anti-G17-Gly antibody fragments were analyzed for growth inhibition and apoptotic assays in a CRC cell line, HCT-116, which is well-characterized for expressing gastrin intermediate species but not amidated gastrin. The antibody fragments exhibited significant inhibition of HCT-116 cells proliferation ranging from 36.5 to 73% of controls. Further, Annexin V/PI staining indicated that apoptosis rates of scFv H8 and V L G8 treated cells were 45.8 and 63%, respectively. Based on these results, we for the first time, demonstrated the isolation of anti-G17-Gly human scFv and V L antibodies with potential therapeutic applications in G17-Gly-responsive tumors.
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.
Deconstructing Interocular Suppression: Attention and Divisive Normalization.
Directory of Open Access Journals (Sweden)
Hsin-Hung Li
2015-10-01
Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.
Deconstructing Interocular Suppression: Attention and Divisive Normalization.
Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J
2015-10-01
In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.
Correlations of intermediate mass fragments from Fe+Ta, Au, and Th collisions
International Nuclear Information System (INIS)
Sangster, T.C.; Begemann-Blaich, M.; Blaich, T.; Britt, H.C.; Hansen, L.F.; Namboodiri, M.N.; Peilert, G.
1995-01-01
Charge, velocity, and angular correlations between intermediate mass fragments (IMF) are presented for 50 and 100 MeV/nucleon Fe bombardments of Ta, Au, and Th targets. Correlation functions generated as a function of the relative velocity and the opening angle between two IMF's are qualitatively independent of the projectile energy and target mass and show a suppression at small relative velocities and opening angles due to the Coulomb repulsion between the fragments. The correlations are consistent with IMF's emitted primarily from a highly excited target residue following a rapid preequilibrium cascade. The correlation data are compared to model calculations using the event generator MENEKA and the quantum molecular dynamics (QMD) code with a statistical deexcitation of residual fragments utilizing the multifragmentation code SMM. All data are consistent with a simultaneous multifragmentation at a freeze-out density of 0.1--0.3 times normal nuclear matter density or a more sequential emission with time constant τ≤500 fm/c
Energy Technology Data Exchange (ETDEWEB)
Bang, K.H.; Kim, M.H. [Univ. of Science and Technology, Pohang (Korea, Republic of)
1995-09-01
Quenching experiments of hot solid spheres in dilute aqueous solutions of polyethylene oxide polymer have been conducted for the purpose of investigating the physical mechanisms of the suppression of vapor explosions in this polymer solutions. Two spheres of 22.2mm and 9.5mm-diameter were tested in the polymer solutions of various concentrations at 30{degrees}C. Minimum film boiling temperature ({Delta}T{sub MFB}) in this highly-subcooled liquid rapidly decreased from over 700{degrees}c for pure water to about 150{degrees}C as the polymer concentration was increased up to 300ppm for 22.2mm sphere, and it decreased to 350{degrees}C for 9.5mm sphere. This rapid reduction of minimum film boiling temperature in the PEO aqueous solutions can explain its ability of the suppression of spontaneous vapor explosions. The ability of suppression of vapor explosions by dilute polyethylene oxide solutions against an external trigger pressure was tested by dropping molten tin into the polymer solutions at 25{degrees}C. It was observed that in 50ppm solutions more mass fragmented than in pure water, but produced weaker explosion pressures. The explosion was completely suppressed in 300ppm solutions with the external trigger. The debris size distributions of fine fragments smaller than 0.7mm were shown almost identical regardless of the polymer concentrations.
International Nuclear Information System (INIS)
Anzai, Yoshimi; Minoshima, Satoshi; Uno, Kimiichi; Arimizu, Noboru; Lufkin, R.B.; Ishihara, Makiko; Yui, Nobuharu.
1994-01-01
Fat suppression MR imaging is a valuable technique mainly used for the orbit, head and neck, and spine, where the high signal from fat can often obscure adjacent pathology. Fat suppression failure artifact manifested as a high signal area without geographic disortion. The purpose of this study was to investigate the frequency and common location of these artifacts in clinical MR imaging and to caution against their misinterpretation. Fat suppression MR imaging of the head and neck was performed in 30 consecutive patients. The artifact was found in the orbital floor (57%), the skull base (10%), and subcutaneous fat (10%), where the air-fat interface is parallel to the static magnetic field direction. The fat signal in the air-fat interface perpendicular to the static magnetic field was well suppressed. This artifact was independent of the duration of TE, frequency/phase encoding direction, and the strength of gradient amplitude, and appeared to be related to the amount of surrounding air. This may simulate pathology if fat suppression is only performed following Gd-DTPA administration. The radiologist should be aware of the presence of artifact by considering the geographic relation to the static magnetic field. (author)
Residual Fragments after Percutaneous Nephrolithotomy
Directory of Open Access Journals (Sweden)
Kaan Özdedeli
2012-09-01
Full Text Available Clinically insignificant residual fragments (CIRFs are described as asymptomatic, noninfectious and nonobstructive stone fragments (≤4 mm remaining in the urinary system after the last session of any intervention (ESWL, URS or PCNL for urinary stones. Their insignificance is questionable since CIRFs could eventually become significant, as their presence may result in recurrent stone growth and they may cause pain and infection due to urinary obstruction. They may become the source of persistent infections and a significant portion of the patients will have a stone-related event, requiring auxilliary interventions. CT seems to be the ultimate choice of assessment. Although there is no concensus about the timing, recent data suggests that it may be performed one month after the procedure. However, imaging can be done in the immediate postoperative period, if there are no tubes blurring the assessment. There is some evidence indicating that selective medical therapy may have an impact on decreasing stone formation rates. Retrograde intrarenal surgery, with its minimally invasive nature, seems to be the best way to deal with residual fragments.
Critical Features of Fragment Libraries for Protein Structure Prediction.
Trevizani, Raphael; Custódio, Fábio Lima; Dos Santos, Karina Baptista; Dardenne, Laurent Emmanuel
2017-01-01
The use of fragment libraries is a popular approach among protein structure prediction methods and has proven to substantially improve the quality of predicted structures. However, some vital aspects of a fragment library that influence the accuracy of modeling a native structure remain to be determined. This study investigates some of these features. Particularly, we analyze the effect of using secondary structure prediction guiding fragments selection, different fragments sizes and the effect of structural clustering of fragments within libraries. To have a clearer view of how these factors affect protein structure prediction, we isolated the process of model building by fragment assembly from some common limitations associated with prediction methods, e.g., imprecise energy functions and optimization algorithms, by employing an exact structure-based objective function under a greedy algorithm. Our results indicate that shorter fragments reproduce the native structure more accurately than the longer. Libraries composed of multiple fragment lengths generate even better structures, where longer fragments show to be more useful at the beginning of the simulations. The use of many different fragment sizes shows little improvement when compared to predictions carried out with libraries that comprise only three different fragment sizes. Models obtained from libraries built using only sequence similarity are, on average, better than those built with a secondary structure prediction bias. However, we found that the use of secondary structure prediction allows greater reduction of the search space, which is invaluable for prediction methods. The results of this study can be critical guidelines for the use of fragment libraries in protein structure prediction.
Yamaguchi, Takeo; Kojima, Hideaki; Kawaguchi, Shiori; Shimada, Maiko; Aso, Haruka
2017-08-01
Human band 3 is a 98-kDa transmembrane (TM) protein comprising 14 TM segments. Papain cleavages band 3 into 38- and 60-kDa fragments. Under vigorous conditions, the cleavage of the loop region between the TM 7 of gate domain and the TM 8 of core domain in the 38-kDa fragment produces 7- and 31-kDa fragments. Conformational changes of the TM 5 segment containing Lys-539 by cleavage of the 38-kDa fragment remain unclear. Pressure-induced haemolysis of erythrocytes was suppressed by binding of 4, 4'-diisothiocyanostilbene-2, 2'-disulfonate (DIDS) to Lys-539. Such effect of DIDS was not observed upon cleavage of the 38-kDa fragment, because of inhibition of DIDS binding to Lys-539. Using fluorescence of DIDS labelled to Lys-539, conformational changes of band 3 were examined. Fluorescence spectra demonstrated that the molecular motion of DIDS is more restricted upon digestion of the 38-kDa fragment. Interestingly, the quenching of DIDS fluorescence showed that Hg2+ is less accessible to DIDS upon digestion of the 38-kDa fragment. Taken together, we propose that the conformational changes of the TM 5 segment characterized by the sequestration and restricted motion of Lys-539 are induced by the cleavage of the loop region between the TM 7 and the TM 8. © The Authors 2017. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
Selective Nonoperative Management of Penetrating Torso Injury From Combat Fragmentation Wounds
2008-02-01
outlines the paradigm of care: “Penetrating inju- ries below the nipples , above the symphysis pubis, and between the posterior axillary lines must be...abdo- men and were hemodynamically stable and without abdom- inal pain or tenderness. CT scan of some of these casualties revealed fragments in the lumen
Determination of factors associated with natural soil suppressivity to potato common scab.
Directory of Open Access Journals (Sweden)
Marketa Sagova-Mareckova
Full Text Available Common scab of potatoes is a disease, which is difficult to manage due to complex interactions of the pathogenic bacteria (Streptomyces spp. with soil, microbial community and potato plants. In Bohemian-Moravian Highlands in the Czech Republic two sites (Vyklantice and Zdirec were selected for a study of common scab disease suppressivity. At both sites, a field with low disease severity occurs next to one with high severity and the situation was regularly observed over four decades although all four fields undergo a crop rotation. In the four fields, quantities of bacteria, actinobacteria and the gene txtB from the biosynthetic gene cluster of thaxtomin, the main pathogenicity factor of common scab, were analyzed by real-time PCR. Microbial community structure was compared by terminal fragment length polymorphism analysis. Soil and potato periderm were characterized by contents of carbon, nitrogen, phosphorus, sulphur, calcium, magnesium, and iron. Quality of organic matter was assessed by high performance liquid chromatography of soil extracts. The study demonstrated that the suppressive character of the fields is locally specific. At Zdirec, the suppressivity was associated with low txtB gene copies in bulk soil, while at Vyklantice site it was associated with low txtB gene copies in the tuberosphere. The differences were discussed with respect to the effect of abiotic conditions at Zdirec and interaction between potato plant and soil microbial community at Vyklantice. Soil pH, Ca soil content or cation concentrations, although different were not in the range to predict the disease severity. Low severity of common scab was associated with low content of soil C, N, C/N, Ca and Fe suggesting that oligotrophic conditions may be favorable to common scab suppression.
Determination of factors associated with natural soil suppressivity to potato common scab.
Sagova-Mareckova, Marketa; Daniel, Ondrej; Omelka, Marek; Kristufek, Vaclav; Divis, Jiri; Kopecky, Jan
2015-01-01
Common scab of potatoes is a disease, which is difficult to manage due to complex interactions of the pathogenic bacteria (Streptomyces spp.) with soil, microbial community and potato plants. In Bohemian-Moravian Highlands in the Czech Republic two sites (Vyklantice and Zdirec) were selected for a study of common scab disease suppressivity. At both sites, a field with low disease severity occurs next to one with high severity and the situation was regularly observed over four decades although all four fields undergo a crop rotation. In the four fields, quantities of bacteria, actinobacteria and the gene txtB from the biosynthetic gene cluster of thaxtomin, the main pathogenicity factor of common scab, were analyzed by real-time PCR. Microbial community structure was compared by terminal fragment length polymorphism analysis. Soil and potato periderm were characterized by contents of carbon, nitrogen, phosphorus, sulphur, calcium, magnesium, and iron. Quality of organic matter was assessed by high performance liquid chromatography of soil extracts. The study demonstrated that the suppressive character of the fields is locally specific. At Zdirec, the suppressivity was associated with low txtB gene copies in bulk soil, while at Vyklantice site it was associated with low txtB gene copies in the tuberosphere. The differences were discussed with respect to the effect of abiotic conditions at Zdirec and interaction between potato plant and soil microbial community at Vyklantice. Soil pH, Ca soil content or cation concentrations, although different were not in the range to predict the disease severity. Low severity of common scab was associated with low content of soil C, N, C/N, Ca and Fe suggesting that oligotrophic conditions may be favorable to common scab suppression.
Learning to ignore: acquisition of sustained attentional suppression.
Dixon, Matthew L; Ruppel, Justin; Pratt, Jay; De Rosa, Eve
2009-04-01
We examined whether the selection mechanisms committed to the suppression of ignored stimuli can be modified by experience to produce a sustained, rather than transient, change in behavior. Subjects repeatedly ignored the shape of stimuli, while attending to their color. On subsequent attention to shape, there was a robust and sustained decrement in performance that was selective to when shape was ignored across multiple-color-target contexts, relative to a single-color-target context. Thus, amount of time ignored was not sufficient to induce a sustained performance decrement. Moreover, in this group, individual differences in initial color target selection were associated with the subsequent performance decrement when attending to previously ignored stimuli. Accompanying this sustained decrement in performance was a transfer in the locus of suppression from an exemplar (e.g., a circle) to a feature (i.e., shape) level of representation. These data suggest that learning can influence attentional selection by sustained attentional suppression of ignored stimuli.
Measurement of charm fragmentation fractions in photoproduction at HERA
Energy Technology Data Exchange (ETDEWEB)
Abramowicz, H. [Tel Aviv Univ. (Israel). School of Physics; Max-Planck-Institute for Physics, Munich (Germany); Abt, I. [Max-Planck-Institute for Physics, Muinch (Germany); Adamczyk, L. [AGH-Univ. of Science and Technology, Krakow (Poland). Faculty of Physics and Applied Computer Science] [and others; Collaboration: ZEUS Collaboration
2013-06-15
The production of D{sup 0}, D{sup *+}, D{sup +}, D{sub s}{sup +} and {Lambda}{sub c}{sup +} charm hadrons and their antiparticles in ep scattering at HERA has been studied with the ZEUS detector, using a total integrated luminosity of 372 pb{sup -1}. The fractions of charm quarks hadronising into a particular charm hadron were derived. In addition, the ratio of neutral to charged D-meson production rates, the fraction of charged D mesons produced in a vector state, and the strangeness-suppression factor have been determined. The measurements have been performed in the photoproduction regime. The charm hadrons were reconstructed in the range of transverse momentum p{sub T} > 3.8GeV and pseudorapidity vertical stroke {eta} vertical stroke <1.6. The charm fragmentation fractions are compared to previous results from HERA and from e{sup +}e{sup -} experiments. The data support the hypothesis that fragmentation is independent of the production process.
Computational Fragment-Based Drug Design: Current Trends, Strategies, and Applications.
Bian, Yuemin; Xie, Xiang-Qun Sean
2018-04-09
Fragment-based drug design (FBDD) has become an effective methodology for drug development for decades. Successful applications of this strategy brought both opportunities and challenges to the field of Pharmaceutical Science. Recent progress in the computational fragment-based drug design provide an additional approach for future research in a time- and labor-efficient manner. Combining multiple in silico methodologies, computational FBDD possesses flexibilities on fragment library selection, protein model generation, and fragments/compounds docking mode prediction. These characteristics provide computational FBDD superiority in designing novel and potential compounds for a certain target. The purpose of this review is to discuss the latest advances, ranging from commonly used strategies to novel concepts and technologies in computational fragment-based drug design. Particularly, in this review, specifications and advantages are compared between experimental and computational FBDD, and additionally, limitations and future prospective are discussed and emphasized.
Pure-Phase Selective Excitation in Fast-Relaxing Systems
Zangger, Klaus; Oberer, Monika; Sterk, Heinz
2001-09-01
Selective pulses have been used frequently for small molecules. However, their application to proteins and other macromolecules has been limited. The long duration of shaped-selective pulses and the short T2 relaxation times in proteins often prohibited the use of highly selective pulses especially on larger biomolecules. A very selective excitation can be obtained within a short time by using the selective excitation sequence presented in this paper. Instead of using a shaped low-intensity radiofrequency pulse, a cluster of hard 90° pulses, delays of free precession, and pulsed field gradients can be used to selectively excite a narrow chemical shift range within a relatively short time. Thereby, off-resonance magnetization, which is allowed to evolve freely during the free precession intervals, is destroyed by the gradient pulses. Off-resonance excitation artifacts can be removed by random variation of the interpulse delays. This leads to an excitation profile with selectivity as well as phase and relaxation behavior superior to that of commonly used shaped-selective pulses. Since the evolution of scalar coupling is inherently suppressed during the double-selective excitation of two different scalar-coupled nuclei, the presented pulse cluster is especially suited for simultaneous highly selective excitation of N-H and C-H fragments. Experimental examples are demonstrated on hen egg white lysozyme (14 kD) and the bacterial antidote ParD (19 kD).
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.
Universal Rim Thickness in Unsteady Sheet Fragmentation
Wang, Y.; Dandekar, R.; Bustos, N.; Poulain, S.; Bourouiba, L.
2018-05-01
Unsteady fragmentation of a fluid bulk into droplets is important for epidemiology as it governs the transport of pathogens from sneezes and coughs, or from contaminated crops in agriculture. It is also ubiquitous in industrial processes such as paint, coating, and combustion. Unsteady fragmentation is distinct from steady fragmentation on which most theoretical efforts have been focused thus far. We address this gap by studying a canonical unsteady fragmentation process: the breakup from a drop impact on a finite surface where the drop fluid is transferred to a free expanding sheet of time-varying properties and bounded by a rim of time-varying thickness. The continuous rim destabilization selects the final spray droplets, yet this process remains poorly understood. We combine theory with advanced image analysis to study the unsteady rim destabilization. We show that, at all times, the rim thickness is governed by a local instantaneous Bond number equal to unity, defined with the instantaneous, local, unsteady rim acceleration. This criterion is found to be robust and universal for a family of unsteady inviscid fluid sheet fragmentation phenomena, from impacts of drops on various surface geometries to impacts on films. We discuss under which viscous and viscoelastic conditions the criterion continues to govern the unsteady rim thickness.
Inner-shell excitation and ionic fragmentation of molecules
International Nuclear Information System (INIS)
Hitchcock, A.P.; Tyliszczak, T.; Cavell, R.G.
1997-01-01
Inner-shell excitation and associated decay spectroscopies are site specific probes of electronic and geometrical structure and photoionization dynamics. X-ray absorption probes the geometric and electronic structure, while time-of-flight mass spectrometry with multi-coincidence detection provides information on the photofragmentation dynamics of the initially produced inner-shell state. Auger decay of inner-shell excited and ionised states is an efficient source of multiply charged ions. The charge separation and fragmentation of these species, studied by photoelectron-photoion-photoion coincidence (also called charge separation mass spectrometry) gives insights into bonding and electronic structure. In molecules, the dependence of the fragmentation process on the X-ray energy can reveal cases of site and/or state selective fragmentation. At the ALS the authors have examined the soft X-ray spectroscopy and ionic fragmentation of a number of molecules, including carboranes, silylenes, phosphorus halides, SF 6 and CO 2 . Their work is illustrated using results from the carborane and PF 3 studies
Inner-shell excitation and ionic fragmentation of molecules
Energy Technology Data Exchange (ETDEWEB)
Hitchcock, A.P.; Tyliszczak, T. [McMaster Univ., Hamilton, Ontario (Canada); Cavell, R.G. [Univ. of Alberta, Edmonton (Canada)] [and others
1997-04-01
Inner-shell excitation and associated decay spectroscopies are site specific probes of electronic and geometrical structure and photoionization dynamics. X-ray absorption probes the geometric and electronic structure, while time-of-flight mass spectrometry with multi-coincidence detection provides information on the photofragmentation dynamics of the initially produced inner-shell state. Auger decay of inner-shell excited and ionised states is an efficient source of multiply charged ions. The charge separation and fragmentation of these species, studied by photoelectron-photoion-photoion coincidence (also called charge separation mass spectrometry) gives insights into bonding and electronic structure. In molecules, the dependence of the fragmentation process on the X-ray energy can reveal cases of site and/or state selective fragmentation. At the ALS the authors have examined the soft X-ray spectroscopy and ionic fragmentation of a number of molecules, including carboranes, silylenes, phosphorus halides, SF{sub 6} and CO{sub 2}. Their work is illustrated using results from the carborane and PF{sub 3} studies.
Habitat Fragmentation and Native Bees: a Premature Verdict?
Directory of Open Access Journals (Sweden)
James H. Cane
2001-06-01
Full Text Available Few studies directly address the consequences of habitat fragmentation for communities of pollinating insects, particularly for the key pollinator group, bees (Hymenoptera: Apiformes. Bees typically live in habitats where nesting substrates and bloom are patchily distributed and spatially dissociated. Bee studies have all defined habitat fragments as remnant patches of floral hosts or forests, overlooking the nesting needs of bees. Several authors conclude that habitat fragmentation is broadly deleterious, but their own data show that some native species proliferate in sampled fragments. Other studies report greater densities and comparable diversities of native bees at flowers in some fragment size classes relative to undisrupted habitats, but find dramatic shifts in species composition. Insightful studies of habitat fragmentation and bees will consider fragmentation, alteration, and loss of nesting habitats, not just patches of forage plants, as well as the permeability of the surrounding matrix to interpatch movement. Inasmuch as the floral associations and nesting habits of bees are often attributes of species or subgenera, ecological interpretations hinge on authoritative identifications. Study designs must accommodate statistical problems associated with bee community samples, especially non-normal data and frequent zero values. The spatial scale of fragmentation must be appreciated: bees of medium body size can regularly fly 1-2 km from nest site to forage patch. Overall, evidence for prolonged persistence of substantial diversity and abundances of native bee communities in habitat fragments of modest size promises practical solutions for maintaining bee populations. Provided that reserve selection, design, and management can address the foraging and nesting needs of bees, networks of even small reserves may hold hope for sustaining considerable pollinator diversity and the ecological services pollinators provide.
Evolutions in fragment-based drug design: the deconstruction–reconstruction approach
Chen, Haijun; Zhou, Xiaobin; Wang, Ailan; Zheng, Yunquan; Gao, Yu; Zhou, Jia
2014-01-01
Recent advances in the understanding of molecular recognition and protein–ligand interactions have facilitated rapid development of potent and selective ligands for therapeutically relevant targets. Over the past two decades, a variety of useful approaches and emerging techniques have been developed to promote the identification and optimization of leads that have high potential for generating new therapeutic agents. Intriguingly, the innovation of a fragment-based drug design (FBDD) approach has enabled rapid and efficient progress in drug discovery. In this critical review, we focus on the construction of fragment libraries and the advantages and disadvantages of various fragment-based screening (FBS) for constructing such libraries. We also highlight the deconstruction–reconstruction strategy by utilizing privileged fragments of reported ligands. PMID:25263697
Dooley, Helen; Flajnik, Martin F; Porter, Andrew J
2003-09-01
The novel immunoglobulin isotype novel antigen receptor (IgNAR) is found in cartilaginous fish and is composed of a heavy-chain homodimer that does not associate with light chains. The variable regions of IgNAR function as independent domains similar to those found in the heavy-chain immunoglobulins of Camelids. Here, we describe the successful cloning and generation of a phage-displayed, single-domain library based upon the variable domain of IgNAR. Selection of such a library generated from nurse sharks (Ginglymostoma cirratum) immunized with the model antigen hen egg-white lysozyme (HEL) enabled the successful isolation of intact antigen-specific binders matured in vivo. The selected variable domains were shown to be functionally expressed in Escherichia coli, extremely stable, and bind to antigen specifically with an affinity in the nanomolar range. This approach can therefore be considered as an alternative route for the isolation of minimal antigen-binding fragments with favorable characteristics.
Accentuation-suppression and scaling
DEFF Research Database (Denmark)
Sørensen, Thomas Alrik; Bundesen, Claus
2012-01-01
The limitations of the visual short-term memory (VSTM) system have become an increasingly popular field of study. One line of inquiry has focused on the way attention selects objects for encoding into VSTM. Using the framework of the Theory of Visual Attention (TVA; Bundesen, 1990 Psychological...... a scaling mechanism modulating the decision bias of the observer and also through an accentuation-suppression mechanism that modulates the degree of subjective relevance of objects, contracting attention around fewer, highly relevant objects while suppressing less relevant objects. These mechanisms may...
International Nuclear Information System (INIS)
Kazama, Toshiki; Nasu, Katsuhiro; Kuroki, Yoshifumi; Nawano, Shigeru; Ito, Hisao
2009-01-01
Fat suppression is essential for diffusion-weighted imaging (DWI) in the body. However, the chemical shift selective (CHESS) pulse often fails to suppress fat signals in the breast. The purpose of this study was to compare DWI using CHESS and DWI using short inversion time inversion recovery (STIR) in terms of fat suppression and the apparent diffusion coefficient (ADC) value. DWI using STIR, DWI using CHESS, and contrast-enhanced T1-weighted images were obtained in 32 patients with breast carcinoma. Uniformity of fat suppression, ADC, signal intensity, and visualization of the breast tumors were evaluated. In 44% (14/32) of patients there was insufficient fat suppression in the breasts on DWI using CHESS, whereas 0% was observed on DWI using STIR (P<0.0001). The ADCs obtained for DWI using STIR were 4.3% lower than those obtained for DWI using CHESS (P<0.02); there was a strong correlation of the ADC measurement (r=0.93, P<0.001). DWI using STIR may be excellent for fat suppression; and the ADC obtained in this sequence was well correlated with that obtained with DWI using CHESS. DWI using STIR may be useful when the fat suppression technique in DWI using CHESS does not work well. (author)
International Nuclear Information System (INIS)
Saxon, D.H.
1985-10-01
The paper reviews studies on jet fragmentation. The subject is discussed under the topic headings: fragmentation models, charged particle multiplicity, bose-einstein correlations, identified hadrons in jets, heavy quark fragmentation, baryon production, gluon and quark jets compared, the string effect, and two successful models. (U.K.)
[Effects of habitat fragmentation on nesting site selection of red-crowned crane].
Wan, Dongmei; Gao, Wei; Wang, Qiuyu; Wang, Haitao; Liu, Mingyu
2002-05-01
During April and May of 1985, 1995 and 1998, red-crowned crane's nesting and variation of breeding population quantities in Shuangtaihekou National Natural Reserve in Liaoning, and also the habitat fragmentation there were investigated. Associated with previous data of the reserve, red-crowned crane's nesting habitat had been seriously fragmentated into 91 patches from one integrated reed wetland. The area of the smallest patch was 0.37 km2, and the minimum distance of two nests was 304 m. Compared with records of previous data, the minimum area of nesting habitat reduced by 0.72 km2. However, the breeding population quantities of red-crowned crane had maintained at about 30 pairs for a long period. The red-crowned crane adapted to the changed environment by the ecological adaptation strategy of reducing area of nesting habitat.
Fragmentation of high-energy ionic hydrogen clusters by single collision with helium
International Nuclear Information System (INIS)
Ouaskit, S.; Farizon, B.; Farizon, M.; Gaillard, M.J.; Chevarier, A.; Chevarier, N.; Gerlic, E.; Stern, M.
1994-09-01
Fragmentation of mass-selected 60-keV/amu-H n + induced by single collision with helium has been studied for various cluster sizes n (9, 13,21, 25, and 31). The absolute cross sections of the charged fragments H p + are measured from p equal to n-2. The deduced mass distributions are strongly different from those obtained at lower collision energy (where molecular evaporation is mainly involved) due to a strong production of ionic fragments with a size of p/n -τ , where A is the normalized fragment mass (p/n) and τ an exponent close to 2.6. (authors)
Chen, Wei; Shin, Ki-Hyuk; Kim, Sangjae; Shon, Won-Jun; Kim, Reuben H; Park, No-Hee; Kang, Mo K
2018-06-01
GV1001 is a 16‑amino acid peptide derived from the human telomerase reverse transcriptase (hTERT) protein (616‑626; EARPALLTSRLRFIPK), which lies within the reverse transcriptase domain. Originally developed as an anticancer vaccine, GV1001 demonstrates diverse cellular effects, including anti‑inflammatory, tumor suppressive and antiviral effects. In the present study, the radioprotective and antifibrotic effects of GV1001 were demonstrated through suppressing transforming growth factor‑β (TGF‑β) signaling. Proliferating human keratinocytes underwent premature senescence upon exposure to ionizing radiation (IR), however, treatment of cells with GV1001 allowed the cells to proliferate and showed a reduction in senescent phenotype. GV1001 treatment notably increased the levels of Grainyhead‑like 2 and phosphorylated (p‑)Akt (Ser473), and reduced the activation of p53 and the level of p21/WAF1 in irradiated keratinocytes. It also markedly suppressed the level of TGF‑β signaling molecules, including p‑small mothers against decapentaplegic (Smad)2/3 and Smad4, and TGF‑β target genes, including zinc finger E‑box binding homeobox 1, fibronectin, N‑cadharin and Snail, in irradiated keratinocytes. Furthermore, GV1001 suppressed TGF‑β signaling in primary human fibroblasts and inhibited myofibroblast differentiation. Chromatin immunoprecipitation revealed that GV1001 suppressed the binding of Smad2 on the promoter regions of collagen type III α1 chain (Col3a1) and Col1a1. In a dermal fibrosis model in vivo, GV1001 treatment notably reduced the thickness of fibrotic lesions and the synthesis of Col3a1. These data indicated that GV1001 ameliorated the IR‑induced senescence phenotype and tissue fibrosis by inhibiting TGF‑β signaling and may have therapeutic effects on radiation‑induced tissue damage.
Missing Fragments: Detecting Cooperative Binding in Fragment-Based Drug Design
2012-01-01
The aim of fragment-based drug design (FBDD) is to identify molecular fragments that bind to alternate subsites within a given binding pocket leading to cooperative binding when linked. In this study, the binding of fragments to human phenylethanolamine N-methyltransferase is used to illustrate how (a) current protocols may fail to detect fragments that bind cooperatively, (b) theoretical approaches can be used to validate potential hits, and (c) apparent false positives obtained when screening against cocktails of fragments may in fact indicate promising leads. PMID:24900472
Zedek, František; Bureš, Petr
2016-12-01
The centromere drive theory explains diversity of eukaryotic centromeres as a consequence of the recurrent conflict between centromeric repeats and centromeric histone H3 (CenH3), in which selfish centromeres exploit meiotic asymmetry and CenH3 evolves adaptively to counterbalance deleterious consequences of driving centromeres. Accordingly, adaptively evolving CenH3 has so far been observed only in eukaryotes with asymmetric meiosis. However, if such evolution is a consequence of centromere drive, it should depend not only on meiotic asymmetry but also on monocentric or holokinetic chromosomal structure. Selective pressures acting on CenH3 have never been investigated in organisms with holokinetic meiosis despite the fact that holokinetic chromosomes have been hypothesized to suppress centromere drive. Therefore, the present study evaluates selective pressures acting on the CenH3 gene in holokinetic organisms for the first time, specifically in the representatives of the plant genus Luzula (Juncaceae), in which the kinetochore formation is not co-localized with any type of centromeric repeat. PCR, cloning and sequencing, and database searches were used to obtain coding CenH3 sequences from Luzula species. Codon substitution models were employed to infer selective regimes acting on CenH3 in Luzula KEY RESULTS: In addition to the two previously published CenH3 sequences from L. nivea, 16 new CenH3 sequences have been isolated from 12 Luzula species. Two CenH3 isoforms in Luzula that originated by a duplication event prior to the divergence of analysed species were found. No signs of positive selection acting on CenH3 in Luzula were detected. Instead, evidence was found that selection on CenH3 of Luzula might have been relaxed. The results indicate that holokinetism itself may suppress centromere drive and, therefore, holokinetic chromosomes might have evolved as a defence against centromere drive. © The Author 2016. Published by Oxford University Press on behalf of
Duarte, Carlos; Núñez, Víctor; Wong, Yat; Vivar, Carlos; Benites, Elder; Rodriguez, Urso; Vergara, Carlos; Ponce, Jorge
2017-12-01
In assisted reproduction procedures, we need to develop and enhance new protocols to optimize sperm selection. The aim of this study is to evaluate the ability of the Z potential technique to select sperm with intact DNA in non-normospermic patients and evaluate the impact of this selection on embryonic development. We analyzed a total of 174 human seminal samples with at least one altered parameter. We measured basal, post density gradients, and post density gradients + Z potential DNA fragmentation index. To evaluate the impact of this technique on embryo development, 54 cases were selected. The embryo development parameters evaluated were fertilization rate, cleavage rate, top quality embryos at the third day and blastocysts rate. We found significant differences in the study groups when we compared the sperm fragmentation index by adding the Z potential technique to density gradient selection vs. density gradients alone. Furthermore, there was no significant difference in the embryo development parameters between the low sperm fragmentation index group vs. the moderate and high sperm fragmentation index groups, when selecting sperms with this new technique. The Z potential technique is a very useful tool for sperm selection; it significantly reduces the DNA fragmentation index and improves the parameters of embryo development. This technique could be considered routine for its simplicity and low cost.
Formation and fragmentation of quadruply charged molecular ions by intense femtosecond laser pulses.
Yatsuhashi, Tomoyuki; Nakashima, Nobuaki
2010-07-22
We investigated the formation and fragmentation of multiply charged molecular ions of several aromatic molecules by intense nonresonant femtosecond laser pulses of 1.4 mum with a 130 fs pulse duration (up to 2 x 10(14) W cm(-2)). Quadruply charged states were produced for 2,3-benzofluorene and triphenylene molecular ion in large abundance, whereas naphthalene and 1,1'-binaphthyl resulted only in up to triply charged molecular ions. The laser wavelength was nonresonant with regard to the electronic transitions of the neutral molecules, and the degree of fragmentation was strongly correlated with the absorption of the singly charged cation radical. Little fragmentation was observed for naphthalene (off-resonant with cation), whereas heavy fragmentation was observed in the case of 1,1'-binaphthyl (resonant with cation). The degree of H(2) (2H) and 2H(2) (4H) elimination from molecular ions increased as the charge states increased in all the molecules examined. A striking difference was found between triply and quadruply charged 2,3-benzofluorene: significant suppression of molecular ions with loss of odd number of hydrogen was observed in the quadruply charged ions. The Coulomb explosion of protons in the quadruply charged state and succeeding fragmentation resulted in the formation of triply charged molecular ions with an odd number of hydrogens. The hydrogen elimination mechanism in the highly charged state is discussed.
Energy Technology Data Exchange (ETDEWEB)
Hjort, K.; Bergstrom, M.; Adesina, M.F.; Jansson, J.K.; Smalla, K.; Sjoling, S.
2009-09-01
Soil that is suppressive to disease caused by fungal pathogens is an interesting source to target for novel chitinases that might be contributing towards disease suppression. In this study we screened for chitinase genes, in a phytopathogen-suppressive soil in three ways: (1) from a metagenomic library constructed from microbial cells extracted from soil, (2) from directly extracted DNA and (3) from bacterial isolates with antifungal and chitinase activities. Terminal-restriction fragment length polymorphism (T-RFLP) of chitinase genes revealed differences in amplified chitinase genes from the metagenomic library and the directly extracted DNA, but approximately 40% of the identified chitinase terminal-restriction fragments (TRFs) were found in both sources. All of the chitinase TRFs from the isolates were matched to TRFs in the directly extracted DNA and the metagenomic library. The most abundant chitinase TRF in the soil DNA and the metagenomic library corresponded to the TRF{sup 103} of the isolate, Streptomyces mutomycini and/or Streptomyces clavifer. There were good matches between T-RFLP profiles of chitinase gene fragments obtained from different sources of DNA. However, there were also differences in both the chitinase and the 16S rRNA gene T-RFLP patterns depending on the source of DNA, emphasizing the lack of complete coverage of the gene diversity by any of the approaches used.
The influence of articulatory suppression on the control of implicit sequence knowledge
Directory of Open Access Journals (Sweden)
Vinciane eGaillard
2012-07-01
Full Text Available The present study investigated the consciousness-control relationship by suppressing the possibility to exert executive control on incidentally acquired knowledge. Participants performed a serial reaction time (SRT task, followed by a sequence generation task under inclusion and exclusion instructions and a sequence recognition task. The generation task requires control on the sequential knowledge that has been incidentally acquired. We manipulated the possibility for participants to recruit control processes in the generation task in three different conditions. In addition to a control condition, participants generated sequences under inclusion and exclusion concurrently with either articulatory suppression or foot tapping. Results suggest that articulatory suppression specifically impairs exclusion performance by interfering with inner speech. Because participants were nevertheless able to successfully recognize fragments of the training sequence in a final recognition task, this is suggestive of a dissociation between control and recognition memory.
Energy Technology Data Exchange (ETDEWEB)
Koh, Dow-Mu; Hughes, J. [Royal Marsden Hospital, Department of Radiology, Sutton (United Kingdom); Blackledge, M.; Leach, M.O.; Collins, D.J. [Institute of Cancer Research, CR UK-EPSRC Cancer Imaging Centre, Sutton (United Kingdom); Burns, S. [Nuada 3T MRI Centre, London (United Kingdom); Stemmer, A.; Kiefer, B. [Siemens Healthcare, Erlangen (Germany)
2012-12-15
Silicone breast prostheses prove technically challenging when performing diffusion-weighted MR imaging in the breasts. We describe a combined fat and chemical suppression scheme to achieve dual suppression of fat and silicone, thereby improving the quality of diffusion-weighted images in women with breast implants. MR imaging was performed at 3.0 and 1.5 T in women with silicone breast implants using short-tau inversion recovery (STIR) fat-suppressed echo-planar (EPI) diffusion-weighted MR imaging (DWI) on its own and combined with the slice-select gradient-reversal (SSGR) technique. Imaging was performed using dedicated breast imaging coils. Complete suppression of the fat and silicone signal was possible at 3.0 T using EPI DWI with STIR and SSGR, evaluated with dedicated breast coils. However, a residual silicone signal was still perceptible at 1.5 T using this combined approach. Nevertheless, a further reduction in silicone signal at 1.5 T could be achieved by employing thinner slice partitions and the addition of the chemical-selective fat-suppression (CHESS) technique. DWI using combined STIR and SSGR chemical suppression techniques is feasible to eliminate or reduce silicone signal from prosthetic breast implants. (orig.)
International Nuclear Information System (INIS)
Kim, Hye Yeon; Son, Seok Hyun; Eun, Choong Ki; Han, Sang Suk
2001-01-01
To compare the usefulness of combined fat- and fluid-suppressed selective partial inversion recovery-fluid attenuated inversion recovery(SPIR-FLAIR) images in the detection of high signal intensity of the optic nerve in optic neuritis with that of fat-suppressed selective partial inversion recovery(SPIR) or short inversion time inversion recovery(STIR) images. Two radiologists independently analyzed randomly mixed MR images of 16 lesions in 14 patients (M:F=7:7; mean age, 40 years) in whom optic neuritis had been clinically diagnosed. All subjects underwent both SPIR-FLAIR and fat-suppressed SPIR or STIR imaging, in a blind fashion. In order to evaluate the optic nerve, coronal images perpendicular to its long axis were obtained. The detection rate of high signal intensity of the optic nerve, the radiologists preferred imaging sequences, and intersubject consistency of detection were evaluated. 'High signal intensity' was defined as the subjective visual evaluation of increased signal intensity compared with that of the contralateral optic nerve or that of white matter. The mean detection rate of high signal intensity of the optic nerve was 90% for combined fat- and fluid-suppressed SPIR-FLAIR images, and 59% for fat-suppressed SPIR or STIR images. In all cases in which the signal intensity observed on SPIR-FLAIR images was normal, that on fat-suppressed SPIR or STIR images was also normal. The radiologists preferred the contrast properties of SPIR-FLAIR to those of fat-suppressed SPIR or STIR images. In the diagnosis of optic neuritis using MRI, combined fat- and fluid-suppressed SPIR-FLAIR images were more useful for the detection of high signal intensity of the optic nerve than fat-suppressed SPIR or STIR images. For the evaluation of optic neuritis, combined fat- and fluid-suppressed SPIR-FLAIR imaging is superior to fat-suppressed SPIR or STIR imaging
Forgan, D. H.; Hall, C.; Meru, F.; Rice, W. K. M.
2018-03-01
It is likely that most protostellar systems undergo a brief phase where the protostellar disc is self-gravitating. If these discs are prone to fragmentation, then they are able to rapidly form objects that are initially of several Jupiter masses and larger. The fate of these disc fragments (and the fate of planetary bodies formed afterwards via core accretion) depends sensitively not only on the fragment's interaction with the disc, but also with its neighbouring fragments. We return to and revise our population synthesis model of self-gravitating disc fragmentation and tidal downsizing. Amongst other improvements, the model now directly incorporates fragment-fragment interactions while the disc is still present. We find that fragment-fragment scattering dominates the orbital evolution, even when we enforce rapid migration and inefficient gap formation. Compared to our previous model, we see a small increase in the number of terrestrial-type objects being formed, although their survival under tidal evolution is at best unclear. We also see evidence for disrupted fragments with evolved grain populations - this is circumstantial evidence for the formation of planetesimal belts, a phenomenon not seen in runs where fragment-fragment interactions are ignored. In spite of intense dynamical evolution, our population is dominated by massive giant planets and brown dwarfs at large semimajor axis, which direct imaging surveys should, but only rarely, detect. Finally, disc fragmentation is shown to be an efficient manufacturer of free-floating planetary mass objects, and the typical multiplicity of systems formed via gravitational instability will be low.
Kinoshita, S
2001-03-01
In this article I argue that an awareness of the study episode that arises involuntarily during an implicit stem/fragment completion test can under some conditions lead to enhanced repetition priming effects, even though subjects are not engaged in intentional retrieval. I review findings that are consistent with this possibility, which include the effects of depth of processing, and of typography match and new association priming following deep encoding. A theoretical account of involuntary aware memory couched within Moscovitch's (1995b) memory systems framework which suggests that the medial-temporal lobe/hippocampal (MTL/H) complex functions as a memory module is outlined. A putative mechanism is proposed in which involuntary aware memory of a studied item enhances the size of repetition priming effects by guiding its selection in preference to the competitors.
Fragmentation of molecular ions in slow electron collisions
International Nuclear Information System (INIS)
Novotny, Steffen
2008-01-01
The fragmentation of positively charged hydrogen molecular ions by the capture of slow electrons, the so called dissociative recombination (DR), has been investigated in storage ring experiments at the TSR, Heidelberg, where an unique twin-electron-beam arrangement was combined with high resolution fragment imaging detection. Provided with well directed cold electrons the fragmentation kinematics were measured down to meV collision energies where pronounced rovibrational Feshbach resonances appear in the DR cross section. For thermally excited HD + the fragmentation angle and the kinetic energy release were studied at variable precisely controlled electron collision energies on a dense energy grid from 10 to 80 meV. The anisotropy described for the first time by Legendre polynomials higher 2 nd order and the extracted rotational state contributions were found to vary on a likewise narrow energy scale as the rotationally averaged DR rate coefficient. Ro-vibrationally resolved DR experiments were performed on H 2 + produced in distinct internal excitations by a novel ion source. Both the low-energy DR rate as well as the fragmentation dynamics at selected resonances were measured individually in the lowest two vibrational and first three excited rotational states. State-specific DR rates and angular dependences are reported. (orig.)
Fragmentation of molecular ions in slow electron collisions
Energy Technology Data Exchange (ETDEWEB)
Novotny, Steffen
2008-06-25
The fragmentation of positively charged hydrogen molecular ions by the capture of slow electrons, the so called dissociative recombination (DR), has been investigated in storage ring experiments at the TSR, Heidelberg, where an unique twin-electron-beam arrangement was combined with high resolution fragment imaging detection. Provided with well directed cold electrons the fragmentation kinematics were measured down to meV collision energies where pronounced rovibrational Feshbach resonances appear in the DR cross section. For thermally excited HD{sup +} the fragmentation angle and the kinetic energy release were studied at variable precisely controlled electron collision energies on a dense energy grid from 10 to 80 meV. The anisotropy described for the first time by Legendre polynomials higher 2{sup nd} order and the extracted rotational state contributions were found to vary on a likewise narrow energy scale as the rotationally averaged DR rate coefficient. Ro-vibrationally resolved DR experiments were performed on H{sub 2}{sup +} produced in distinct internal excitations by a novel ion source. Both the low-energy DR rate as well as the fragmentation dynamics at selected resonances were measured individually in the lowest two vibrational and first three excited rotational states. State-specific DR rates and angular dependences are reported. (orig.)
Fragment-Based Drug Discovery of Potent Protein Kinase C Iota Inhibitors.
Kwiatkowski, Jacek; Liu, Boping; Tee, Doris Hui Ying; Chen, Guoying; Ahmad, Nur Huda Binte; Wong, Yun Xuan; Poh, Zhi Ying; Ang, Shi Hua; Tan, Eldwin Sum Wai; Ong, Esther Hq; Nurul Dinie; Poulsen, Anders; Pendharkar, Vishal; Sangthongpitag, Kanda; Lee, May Ann; Sepramaniam, Sugunavathi; Ho, Soo Yei; Cherian, Joseph; Hill, Jeffrey; Keller, Thomas H; Hung, Alvin W
2018-05-24
Protein kinase C iota (PKC-ι) is an atypical kinase implicated in the promotion of different cancer types. A biochemical screen of a fragment library has identified several hits from which an azaindole-based scaffold was chosen for optimization. Driven by a structure-activity relationship and supported by molecular modeling, a weakly bound fragment was systematically grown into a potent and selective inhibitor against PKC-ι.
Universal elements of fragmentation
International Nuclear Information System (INIS)
Yanovsky, V. V.; Tur, A. V.; Kuklina, O. V.
2010-01-01
A fragmentation theory is proposed that explains the universal asymptotic behavior of the fragment-size distribution in the large-size range, based on simple physical principles. The basic principles of the theory are the total mass conservation in a fragmentation process and a balance condition for the energy expended in increasing the surface of fragments during their breakup. A flux-based approach is used that makes it possible to supplement the basic principles and develop a minimal theory of fragmentation. Such a supplementary principle is that of decreasing fragment-volume flux with increasing energy expended in fragmentation. It is shown that the behavior of the decreasing flux is directly related to the form of a power-law fragment-size distribution. The minimal theory is used to find universal asymptotic fragment-size distributions and to develop a natural physical classification of fragmentation models. A more general, nonlinear theory of strong fragmentation is also developed. It is demonstrated that solutions to a nonlinear kinetic equation consistent with both basic principles approach a universal asymptotic size distribution. Agreement between the predicted asymptotic fragment-size distributions and experimental observations is discussed.
Harms caused by China's 1906-17 opium suppression intervention.
Windle, James
2013-09-01
Between 1906 and 1917 China (under the Imperial and then Republican regimes) enacted a highly effective intervention to suppress the production of opium. Evidence from British Foreign Office records suggest that the intervention was centred, in many areas, upon a highly repressive incarnation of law enforcement in which rural populations had their property destroyed, their land confiscated and/or were publically tortured, humiliated and executed. Crops were forcefully eradicated and resistance was often brutally suppressed by the military. As few farmers received compensation or support for alternative livelihood creation the intervention pushed many deeper into poverty. Importantly, the repressive nature of the opium ban appears to have been a contributing factor to the fragmentation of China, highlighting the counter-productivity of repressive interventions to reduce drug crop production. Copyright © 2013 Elsevier B.V. All rights reserved.
Fragmentation of a Filamentary Cloud Permeated by a Perpendicular Magnetic Field
Energy Technology Data Exchange (ETDEWEB)
Hanawa, Tomoyuki [Center for Frontier Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, Chiba 263-8522 (Japan); Kudoh, Takahiro [Faculty of Education, Nagasaki University, 1-14 Bonkyo-machi, Nagasaki, Nagasaki 852-8521 (Japan); Tomisaka, Kohji [Division of Theoretical Astronomy, National Astronomical Observatory of Japan, Mitaka, Tokyo 181-8588 (Japan)
2017-10-10
We examine the linear stability of an isothermal filamentary cloud permeated by a perpendicular magnetic field. Our model cloud is assumed to be supported by gas pressure against self-gravity in the unperturbed state. For simplicity, the density distribution is assumed to be symmetric around the axis. Also for simplicity, the initial magnetic field is assumed to be uniform, and turbulence is not taken into account. The perturbation equation is formulated to be an eigenvalue problem. The growth rate is obtained as a function of the wavenumber for fragmentation along the axis and the magnetic field strength. The growth rate depends critically on the outer boundary. If the displacement vanishes in regions very far from the cloud axis (fixed boundary), cloud fragmentation is suppressed by a moderate magnetic field, which means the plasma beta is below 1.67 on the cloud axis. If the displacement is constant along the magnetic field in regions very far from the cloud, the cloud is unstable even when the magnetic field is infinitely strong. The cloud is deformed by circulation in the plane perpendicular to the magnetic field. The unstable mode is not likely to induce dynamical collapse, since it is excited even when the whole cloud is magnetically subcritical. For both boundary conditions, the magnetic field increases the wavelength of the most unstable mode. We find that the magnetic force suppresses compression perpendicular to the magnetic field especially in regions of low density.
DEFF Research Database (Denmark)
Rocha, Nuno M; Bulger, David A; Frontini, Andrea
2017-01-01
body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial...... network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were...
Thermodynamical string fragmentation
Energy Technology Data Exchange (ETDEWEB)
Fischer, Nadine [Theoretical Particle Physics, Department of Astronomy and Theoretical Physics, Lund University,Sölvegatan 14A, Lund, SE-223 62 (Sweden); School of Physics and Astronomy, Monash University,Wellington Road, Clayton, VIC-3800 (Australia); Sjöstrand, Torbjörn [Theoretical Particle Physics, Department of Astronomy and Theoretical Physics, Lund University,Sölvegatan 14A, Lund, SE-223 62 (Sweden)
2017-01-31
The observation of heavy-ion-like behaviour in pp collisions at the LHC suggests that more physics mechanisms are at play than traditionally assumed. The introduction e.g. of quark-gluon plasma or colour rope formation can describe several of the observations, but as of yet there is no established paradigm. In this article we study a few possible modifications to the Pythia event generator, which describes a wealth of data but fails for a number of recent observations. Firstly, we present a new model for generating the transverse momentum of hadrons during the string fragmentation process, inspired by thermodynamics, where heavier hadrons naturally are suppressed in rate but obtain a higher average transverse momentum. Secondly, close-packing of strings is taken into account by making the temperature or string tension environment-dependent. Thirdly, a simple model for hadron rescattering is added. The effect of these modifications is studied, individually and taken together, and compared with data mainly from the LHC. While some improvements can be noted, it turns out to be nontrivial to obtain effects as big as required, and further work is called for.
Incorporation of rapid thermodynamic data in fragment-based drug discovery.
Kobe, Akihiro; Caaveiro, Jose M M; Tashiro, Shinya; Kajihara, Daisuke; Kikkawa, Masato; Mitani, Tomoya; Tsumoto, Kouhei
2013-03-14
Fragment-based drug discovery (FBDD) has enjoyed increasing popularity in recent years. We introduce SITE (single-injection thermal extinction), a novel thermodynamic methodology that selects high-quality hits early in FBDD. SITE is a fast calorimetric competitive assay suitable for automation that captures the essence of isothermal titration calorimetry but using significantly fewer resources. We describe the principles of SITE and identify a novel family of fragment inhibitors of the enzyme ketosteroid isomerase displaying high values of enthalpic efficiency.
International Nuclear Information System (INIS)
Smith, Rowan J.; Glover, Simon C. O.; Klessen, Ralf S.; Iocco, Fabio; Schleicher, Dominik R. G.; Hirano, Shingo; Yoshida, Naoki
2012-01-01
We present the first three-dimensional simulations to include the effects of dark matter annihilation feedback during the collapse of primordial minihalos. We begin our simulations from cosmological initial conditions and account for dark matter annihilation in our treatment of the chemical and thermal evolution of the gas. The dark matter is modeled using an analytical density profile that responds to changes in the peak gas density. We find that the gas can collapse to high densities despite the additional energy input from the dark matter. No objects supported purely by dark matter annihilation heating are formed in our simulations. However, we find that dark matter annihilation heating has a large effect on the evolution of the gas following the formation of the first protostar. Previous simulations without dark matter annihilation found that protostellar disks around Population III stars rapidly fragmented, forming multiple protostars that underwent mergers or ejections. When dark matter annihilation is included, however, these disks become stable to radii of 1000 AU or more. In the cases where fragmentation does occur, it is a wide binary that is formed.
Adams, J; Adler, C; Aggarwal, M M; Ahammed, Z; Amonett, J; Anderson, B D; Anderson, M; Arkhipkin, D; Averichev, G S; Badyal, S K; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Bekele, S; Belaga, V V; Bellwied, R; Berger, J; Bezverkhny, B I; Bhardwaj, S; Bhaskar, P; Bhati, A K; Bichsel, H; Billmeier, A; Bland, L C; Blyth, C O; Bonner, B E; Botje, M; Boucham, A; Brandin, A; Bravar, A; Cadman, R V; Cai, X Z; Caines, H; Calderón de la Barca Sánchez, M; Carroll, J; Castillo, J; Castro, M; Cebra, D; Chaloupka, P; Chattopadhyay, S; Chen, H F; Chen, Y; Chernenko, S P; Cherney, M; Chikanian, A; Choi, B; Christie, W; Coffin, J P; Cormier, T M; Cramer, J G; Crawford, H J; Das, D; Das, S; Derevschikov, A A; Didenko, L; Dietel, T; Dong, X; Draper, J E; Drees, K A; Du, F; Dubey, A K; Dunin, V B; Dunlop, J C; Dutta Majumdar, M R; Eckardt, V; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Fachini, P; Faine, V; Faivre, J; Fatemi, R; Filimonov, K; Filip, P; Finch, E; Fisyak, Y; Flierl, D; Foley, K J; Fu, J; Gagliardi, C A; Ganti, M S; Gagunashvili, N; Gans, J; Gaudichet, L; Germain, M; Geurts, F; Ghazikhanian, V; Ghosh, P; Gonzalez, J E; Grachov, O; Grigoriev, V; Gronstal, S; Grosnick, D; Guedon, M; Guertin, S M; Gupta, A; Gushin, E; Gutierrez, T D; Hallman, T J; Hardtke, D; Harris, J W; Heinz, M; Henry, T W; Heppelmann, S; Herston, T; Hippolyte, B; Hirsch, A; Hjort, E; Hoffmann, G W; Horsley, M; Huang, H Z; Huang, S L; Humanic, T J; Igo, G; Ishihara, A; Jacobs, P; Jacobs, W W; Janik, M; Johnson, I; Jones, P G; Judd, E G; Kabana, S; Kaneta, M; Kaplan, M; Keane, D; Kiryluk, J; Kisiel, A; Klay, J; Klein, S R; Klyachko, A; Kollegger, T; Konstantinov, A S; Kopytine, M; Kotchenda, L; Kovalenko, A D; Kramer, M; Kravtsov, P; Krueger, K; Kuhn, C; Kulikov, A I; Kumar, A; Kunde, G J; Kunz, C L; Kutuev, R Kh; Kuznetsov, A A; Lamont, M A C; Landgraf, J M; Lange, S; Lansdell, C P; Lasiuk, B; Laue, F; Lauret, J; Lebedev, A; Lednický, R; Leontiev, V M; LeVine, M J; Li, C; Li, Q; Lindenbaum, S J; Lisa, M A; Liu, F; Liu, L; Liu, Z; Liu, Q J; Ljubicic, T; Llope, W J; Long, H; Longacre, R S; Lopez-Noriega, M; Love, W A; Ludlam, T; Lynn, D; Ma, J; Ma, Y G; Magestro, D; Mahajan, S; Mangotra, L K; Mahapatra, D P; Majka, R; Manweiler, R; Margetis, S; Markert, C; Martin, L; Marx, J; Matis, H S; Matulenko, Yu A; McShane, T S; Meissner, F; Melnick, Yu; Meschanin, A; Messer, M; Miller, M L; Milosevich, Z; Minaev, N G; Mironov, C; Mishra, D; Mitchell, J; Mohanty, B; Molnar, L; Moore, C F; Mora-Corral, M J; Morozov, V; de Moura, M M; Munhoz, M G; Nandi, B K; Nayak, S K; Nayak, T K; Nelson, J M; Nevski, P; Nikitin, V A; Nogach, L V; Norman, B; Nurushev, S B; Odyniec, G; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Paic, G; Pandey, S U; Pal, S K; Panebratsev, Y; Panitkin, S Y; Pavlinov, A I; Pawlak, T; Perevoztchikov, V; Peryt, W; Petrov, V A; Phatak, S C; Picha, R; Planinic, M; Pluta, J; Porile, N; Porter, J; Poskanzer, A M; Potekhin, M; Potrebenikova, E; Potukuchi, B V K S; Prindle, D; Pruneau, C; Putschke, J; Rai, G; Rakness, G; Raniwala, R; Raniwala, S; Ravel, O; Ray, R L; Razin, S V; Reichhold, D; Reid, J G; Renault, G; Retiere, F; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevski, O V; Romero, J L; Rose, A; Roy, C; Ruan, L J; Rykov, V; Sahoo, R; Sakrejda, I; Salur, S; Sandweiss, J; Savin, I; Schambach, J; Scharenberg, R P; Schmitz, N; Schroeder, L S; Schweda, K; Seger, J; Seliverstov, D; Seyboth, P; Shahaliev, E; Shao, M; Sharma, M; Shestermanov, K E; Shimanskii, S S; Singaraju, R N; Simon, F; Skoro, G; Smirnov, N; Snellings, R; Sood, G; Sorensen, P; Sowinski, J; Spinka, H M; Srivastava, B; Stanislaus, S; Stock, R; Stolpovsky, A; Strikhanov, M; Stringfellow, B; Struck, C; Suaide, A A P; Sugarbaker, E; Suire, C; Sumbera, M; Surrow, B; Symons, T J M; Szanto de Toledo, A; Szarwas, P; Tai, A; Takahashi, J; Tang, A H; Thein, D; Thomas, J H; Tikhomirov, V; Tokarev, M; Tonjes, M B; Trainor, T A; Trentalange, S; Tribble, R E; Trivedi, M D; Trofimov, V; Tsai, O; Ullrich, T; Underwood, D G; Van Buren, G; VanderMolen, A M; Vasiliev, A N; Vasiliev, M; Vigdor, S E; Viyogi, Y P; Voloshin, S A; Waggoner, W; Wang, F; Wang, G; Wang, X L; Wang, Z M; Ward, H; Watson, J W; Wells, R; Westfall, G D; Whitten, C; Wieman, H; Willson, R; Wissink, S W; Witt, R; Wood, J; Wu, J; Xu, N; Xu, Z; Xu, Z Z; Yakutin, A E; Yamamoto, E; Yang, J; Yepes, P; Yurevich, V I; Zanevski, Y V; Zborovský, I; Zhang, H; Zhang, H Y; Zhang, W M; Zhang, Z P; Zołnierczuk, P A; Zoulkarneev, R; Zoulkarneeva, J; Zubarev, A N
2003-10-24
We report high statistics measurements of inclusive charged hadron production in Au+Au and p+p collisions at sqrt[s(NN)]=200 GeV. A large, approximately constant hadron suppression is observed in central Au+Au collisions for 5
suppression provide stringent constraints on theoretical models of suppression. Models incorporating initial-state gluon saturation or partonic energy loss in dense matter are largely consistent with observations. We observe no evidence of p(T)-dependent suppression, which may be expected from models incorporating jet attenuation in cold nuclear matter or scattering of fragmentation hadrons.
International Nuclear Information System (INIS)
Kalay, Z; Ben-Naim, E
2015-01-01
We study fragmentation of a random recursive tree into a forest by repeated removal of nodes. The initial tree consists of N nodes and it is generated by sequential addition of nodes with each new node attaching to a randomly-selected existing node. As nodes are removed from the tree, one at a time, the tree dissolves into an ensemble of separate trees, namely, a forest. We study statistical properties of trees and nodes in this heterogeneous forest, and find that the fraction of remaining nodes m characterizes the system in the limit N→∞. We obtain analytically the size density ϕ s of trees of size s. The size density has power-law tail ϕ s ∼s −α with exponent α=1+(1/m). Therefore, the tail becomes steeper as further nodes are removed, and the fragmentation process is unusual in that exponent α increases continuously with time. We also extend our analysis to the case where nodes are added as well as removed, and obtain the asymptotic size density for growing trees. (paper)
Energy Technology Data Exchange (ETDEWEB)
Diamant, M.; Henricks, P.A.J.; Nijkamp, F.P.; de Wied, D. (Univ. of Utrecht (Netherlands))
1989-01-01
In the present study, the immunomodulatory effect of {beta}-endorphin ({beta}-E) and shorter pro-opiomelancortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity and their non-opioid derivatives were tested. With the exception of {alpha}-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10{sup {minus}17}M and higher than 10{sup {minus}8}M were without effect. {beta}-E and dT{beta}E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations. {gamma}-E and dT{gamma}E proved to be less potent inhibitors, reaching maximal effect at higher concentrations. DE{gamma}E exerted an even less pronounced but still significant suppressive effect at the concentration of 10{sup {minus}10}M. None of the endorphins tested was shown to affect resting oxidative metabolism in the PMN. The modulatory effects of the opioid peptides could not be blocked by the opioid antagonist naloxone.
Czech Academy of Sciences Publication Activity Database
Fárník, Michal; Weimann, M.; Steinbach, Ch.; Buck, U.; Borho, N.; Adler, T. B.; Suhm, M. A.
2006-01-01
Roč. 8, č. 10 (2006), s. 1148-1158 ISSN 1463-9076 Grant - others:Deutsche Forschungsgemeinschaft(DE) SFB 357; Deutsche Forschungsgemeinschaft(DE) GRK 782 Institutional research plan: CEZ:AV0Z40400503 Keywords : electron-bombardment fragmentation * methanol clusters * methanol clusters * water clusters Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.892, year: 2006
Göth, Melanie; Badock, Volker; Weiske, Jörg; Pagel, Kevin; Kuropka, Benno
2017-08-08
Fragment-based screening presents a promising alternative to high-throughput screening and has gained great attention in recent years. So far, only a few studies have discussed mass spectrometry as a screening technology for fragments. Herein, we report the application of native electrospray ionization mass spectrometry (MS) for screening defined sets of fragments against four different target proteins. Fragments were selected from a primary screening conducted with a thermal shift assay (TSA) and represented different binding categories. Our data indicated that, beside specific complex formation, many fragments show extensive multiple binding and also charge-state shifts. Both of these factors complicate automated data analysis and decrease the attractiveness of native MS as a primary screening tool for fragments. A comparison of the hits identified by native MS and TSA showed good agreement for two of the proteins. Furthermore, we discuss general challenges, including the determination of an optimal fragment concentration and the question of how to rank fragment hits according to their affinity. In conclusion, we consider native MS to be a highly valuable tool for the validation and deeper investigation of promising fragment hits rather than a method for primary screening. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Sultan, Sébastien; Rey, Nolwen; Sacquet, Joelle; Mandairon, Nathalie; Didier, Anne
2011-10-19
A role for newborn neurons in olfactory memory has been proposed based on learning-dependent modulation of olfactory bulb neurogenesis in adults. We hypothesized that if newborn neurons support memory, then they should be suppressed by memory erasure. Using an ecological approach in mice, we showed that behaviorally breaking a previously learned odor-reward association prematurely suppressed newborn neurons selected to survive during initial learning. Furthermore, intrabulbar infusions of the caspase pan-inhibitor ZVAD (benzyloxycarbonyl-Val-Ala-Asp) during the behavioral odor-reward extinction prevented newborn neurons death and erasure of the odor-reward association. Newborn neurons thus contribute to the bulbar network plasticity underlying long-term memory.
Fragmentation cross sections outside the limiting-fragmentation regime
Sümmerer, K
2003-01-01
The empirical parametrization of fragmentation cross sections, EPAX, has been successfully applied to estimate fragment production cross sections in reactions of heavy ions at high incident energies. It is checked whether a similar parametrization can be found for proton-induced spallation around 1 GeV, the range of interest for ISOL-type RIB facilities. The validity of EPAX for medium-energy heavy-ion induced reactions is also checked. Only a few datasets are available, but in general EPAX predicts the cross sections rather well, except for fragments close to the projectile, where the experimental cross sections are found to be larger.
Cheng, Xin; Ivessa, Andreas S
2012-10-01
Translocation of mitochondrial DNA (mtDNA) fragments to the nucleus and insertion of those fragments into nuclear DNA has been observed in several organisms ranging from yeast to plants and mammals. Disruption of specific nuclear genes by de novo insertions of mtDNA fragments has even been linked to the initiation of several human diseases. Recently, we demonstrated that baker's yeast strains with high rates of mtDNA fragments migrating to the nucleus (yme1-1 mutant) exhibit short chronological life spans (CLS). The yeast CLS is determined by the survival of non-dividing cell populations. Here, we show that lack of the non-homologous-end-joining enzyme DNA ligase IV (DNL4) can rescue the short CLS of the yme1-1 mutant. In fission yeast, DNA ligase IV has been shown to be required for the capture of mtDNA fragments during the repair of double-stranded DNA breaks in nuclear DNA. In further analyses using pulse field gel and 2D gel electrophoresis we demonstrate that linear mtDNA fragments with likely nuclear localization accumulate in the yme1-1 mutant. The accumulation of the linear mtDNA fragments in the yme1-1 mutant is suppressed when Dnl4 is absent. We propose that the linear nuclear mtDNA fragments accelerate the aging process in the yme1-1 mutant cells by possibly affecting nuclear processes including DNA replication, recombination, and repair as well as transcription of nuclear genes. We speculate further that Dnl4 protein has besides its function as a ligase also a role in DNA protection. Dnl4 protein may stabilize the linear mtDNA fragments in the nucleus by binding to their physical ends. In the absence of Dnl4 protein the linear fragments are therefore unprotected and possibly degraded by nuclear nucleases. Copyright © 2012 Elsevier GmbH. All rights reserved.
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
Directory of Open Access Journals (Sweden)
Chung-Hung Shih
2012-01-01
Full Text Available Hesperetin, a selective phosphodiesterase (PDE4 inhibitor, is present in the traditional Chinese medicine, “Chen Pi.” Therefore, we were interested in investigating its effects on ovalbumin- (OVA- induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD. Hesperetin was revealed to have a therapeutic (PDE4H/PDE4L ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p. dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF. It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation.
Effects of the fragmentation models on the determination of αsub(S) in e+e- annihilation
International Nuclear Information System (INIS)
Lavagne, Y.
1982-06-01
Jet phenomenology is presented and quantum chromodynamic notions necessary to this study comprehension are given. Device is described, together with data acquisition and different steps of hadronic event selection. Three jet topology events are selected from presented variables and methods. Two models with different fragmentation processes are used to determine αsub(S). Results for each model are gathered and display the fragmentation process influence on αsub(S) value [fr
Leptin Suppresses Mouse Taste Cell Responses to Sweet Compounds.
Yoshida, Ryusuke; Noguchi, Kenshi; Shigemura, Noriatsu; Jyotaki, Masafumi; Takahashi, Ichiro; Margolskee, Robert F; Ninomiya, Yuzo
2015-11-01
Leptin is known to selectively suppress neural and behavioral responses to sweet-tasting compounds. However, the molecular basis for the effect of leptin on sweet taste is not known. Here, we report that leptin suppresses sweet taste via leptin receptors (Ob-Rb) and KATP channels expressed selectively in sweet-sensitive taste cells. Ob-Rb was more often expressed in taste cells that expressed T1R3 (a sweet receptor component) than in those that expressed glutamate-aspartate transporter (a marker for Type I taste cells) or GAD67 (a marker for Type III taste cells). Systemically administered leptin suppressed taste cell responses to sweet but not to bitter or sour compounds. This effect was blocked by a leptin antagonist and was absent in leptin receptor-deficient db/db mice and mice with diet-induced obesity. Blocking the KATP channel subunit sulfonylurea receptor 1, which was frequently coexpressed with Ob-Rb in T1R3-expressing taste cells, eliminated the effect of leptin on sweet taste. In contrast, activating the KATP channel with diazoxide mimicked the sweet-suppressing effect of leptin. These results indicate that leptin acts via Ob-Rb and KATP channels that are present in T1R3-expressing taste cells to selectively suppress their responses to sweet compounds. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Neutronics and radiation field studies for the RIA fragmentation target area
Energy Technology Data Exchange (ETDEWEB)
Reyes, Susana [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States)]. E-mail: reyes20@llnl.gov; Boles, Jason L. [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States); Ahle, Larry E. [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States); Stein, Werner [Lawrence Livermore National Laboratory, P.O. Box 808, L-446, Livermore, CA 94550 (United States)
2006-06-23
Neutronics simulations and activation evaluations are currently in progress as part of the pre-conceptual research and development effort for the Rare Isotope Accelerator (RIA). The RIA project involves generating heavy element ion beams with powers up to 400 kw for use in a fragmentation target line to produce selected ion beams for physics research experiments. Designing a fragmentation beam dump for RIA is one of the most critical challenges for such a facility. Here, we present the results from neutronics and radiation field assessments for various beam dump concepts that can meet requirements for the RIA fragmentation line. Preliminary results from heavy ion transport including radiation damage evaluations for the RIA fragmentation beam dump are also presented. Initial neutronics and activation studies will be incorporated with other target area considerations to identify important challenges and explore possible solutions.
Neutronics and radiation field studies for the RIA fragmentation target area
Reyes, Susana; Boles, Jason L.; Ahle, Larry E.; Stein, Werner
2006-06-01
Neutronics simulations and activation evaluations are currently in progress as part of the pre-conceptual research and development effort for the Rare Isotope Accelerator (RIA). The RIA project involves generating heavy element ion beams with powers up to 400 kW for use in a fragmentation target line to produce selected ion beams for physics research experiments. Designing a fragmentation beam dump for RIA is one of the most critical challenges for such a facility. Here, we present the results from neutronics and radiation field assessments for various beam dump concepts that can meet requirements for the RIA fragmentation line. Preliminary results from heavy ion transport including radiation damage evaluations for the RIA fragmentation beam dump are also presented. Initial neutronics and activation studies will be incorporated with other target area considerations to identify important challenges and explore possible solutions.
Two-Step Mechanism of Membrane Disruption by Aβ through Membrane Fragmentation and Pore Formation
Sciacca, Michele F.M.; Kotler, Samuel A.; Brender, Jeffrey R.; Chen, Jennifer; Lee, Dong-kuk; Ramamoorthy, Ayyalusamy
2012-01-01
Disruption of cell membranes by Aβ is believed to be one of the key components of Aβ toxicity. However, the mechanism by which this occurs is not fully understood. Here, we demonstrate that membrane disruption by Aβ occurs by a two-step process, with the initial formation of ion-selective pores followed by nonspecific fragmentation of the lipid membrane during amyloid fiber formation. Immediately after the addition of freshly dissolved Aβ1–40, defects form on the membrane that share many of the properties of Aβ channels originally reported from single-channel electrical recording, such as cation selectivity and the ability to be blockaded by zinc. By contrast, subsequent amyloid fiber formation on the surface of the membrane fragments the membrane in a way that is not cation selective and cannot be stopped by zinc ions. Moreover, we observed that the presence of ganglioside enhances both the initial pore formation and the fiber-dependent membrane fragmentation process. Whereas pore formation by freshly dissolved Aβ1–40 is weakly observed in the absence of gangliosides, fiber-dependent membrane fragmentation can only be observed in their presence. These results provide insights into the toxicity of Aβ and may aid in the design of specific compounds to alleviate the neurodegeneration of Alzheimer’s disease. PMID:22947931
VAAs as sources of volatility and fragmentation: self-selection effects and genuine effects
Kleinnijenhuis, J.; van de Pol, J.; van Hoof, A.; Krouwel, A.
2017-01-01
Recent studies show that using Voting Advice Applications (VAAs) affects party preferences of voters, and hence leads to party switching. Party switching is a necessary but insufficient condition for volatility (a net switch of voters to other parties) and fragmentation (more parties gaining seats)
International Nuclear Information System (INIS)
Chung, K.C.
1989-01-01
An introduction to nuclear fragmentation, with emphasis in percolation ideas, is presented. The main theoretical models are discussed and as an application, the uniform expansion approximation is presented and the statistical multifragmentation model is used to calculate the fragment energy spectra. (L.C.)
International Nuclear Information System (INIS)
Kaneko Mikami, Wakako; Kazama, Toshiki; Sato, Hirotaka
2013-01-01
The purpose of this study was to compare two fat suppression methods in contrast-enhanced MR imaging of breast cancer at 3.0 T: the two-point Dixon method and the frequency selective inversion method. Forty female patients with breast cancer underwent contrast-enhanced three-dimensional T1-weighted MR imaging at 3.0 T. Both the two-point Dixon method and the frequency selective inversion method were applied. Quantitative analyses of the residual fat signal-to-noise ratio and the contrast noise ratio (CNR) of lesion-to-breast parenchyma, lesion-to-fat, and parenchyma-to-fat were performed. Qualitative analyses of the uniformity of fat suppression, image contrast, and the visibility of breast lesions and axillary metastatic adenopathy were performed. The signal-to-noise ratio was significantly lower in the two-point Dixon method (P<0.001). All CNR values were significantly higher in the two-point Dixon method (P<0.001 and P=0.001, respectively). According to qualitative analysis, both the uniformity of fat suppression and image contrast with the two-point Dixon method were significantly higher (P<0.001 and P=0.002, respectively). Visibility of breast lesions and metastatic adenopathy was significantly better in the two-point Dixon method (P<0.001 and P=0.03, respectively). The two-point Dixon method suppressed the fat signal more potently and improved contrast and visibility of the breast lesions and axillary adenopathy. (author)
Fragmentation of acetic acid ions with selected internal energies
Zha, Qingmei; Nishimura, Toshihide; Bertrand, Michel J.; Meisels, G. G.
1991-08-01
The unimolecular dissociation of acetic acid ion in the photon energy range 10.5-17.0 eV was studied using threshold photoelectron photoion coincidence mass spectrometry. The detailed breakdown graph was obtained and the fragmentation pathways were elucidated. The breakdown graph calculated using statistical theories was found to be consistent with the experimental data up to a photon energy of about 12.5 eV. The average kinetic energy release observed is higher than that calculated on the basis of quasi-equilibrium theory for the formation of COOH+ while it seems to be statistical for the formation of CH3CO+. The origin of kinetic energy release accompanying the formation of these two ions is discussed. The structure of [COH3]+ ion (m/z 31) is determined to be hydroxymethyl cation, CH2OH+, which could be formed by a two-step rearrangement prior to dissociation.
Impact of pulse duration on Ho:YAG laser lithotripsy: fragmentation and dusting performance.
Bader, Markus J; Pongratz, Thomas; Khoder, Wael; Stief, Christian G; Herrmann, Thomas; Nagele, Udo; Sroka, Ronald
2015-04-01
In vitro investigations of Ho:YAG laser-induced stone fragmentation were performed to identify potential impacts of different pulse durations on stone fragmentation characteristics. A Ho:YAG laser system (Swiss LaserClast, EMS S.A., Nyon, Switzerland) with selectable long or short pulse mode was tested with regard to its fragmentation and laser hardware compatibility properties. The pulse duration is depending on the specific laser parameters. Fragmentation tests (hand-held, hands-free, single-pulse-induced crater) on artificial BEGO stones were performed under reproducible experimental conditions (fibre sizes: 365 and 200 µm; laser settings: 10 W through combinations of 0.5, 1, 2 J/pulse and 20, 10, 5 Hz, respectively). Differences in fragmentation rates between the two pulse duration regimes were detected with statistical significance for defined settings. Hand-held and motivated Ho:YAG laser-assisted fragmentation of BEGO stones showed no significant difference between short pulse mode and long pulse mode, neither in fragmentation rates nor in number of fragments and fragment sizes. Similarly, the results of the hands-free fragmentation tests (with and without anti-repulsion device) showed no statistical differences between long pulse and short pulse modes. The study showed that fragmentation rates for long and short pulse durations at identical power settings remain at a comparable level. Longer holmium laser pulse duration reduces stone pushback. Therefore, longer laser pulses may result in better clinical outcome of laser lithotripsy and more convenient handling during clinical use without compromising fragmentation effectiveness.
Fine-scale movement decisions of tropical forest birds in a fragmented landscape.
Gillies, Cameron S; Beyer, Hawthorne L; St Clair, Colleen Cassady
2011-04-01
The persistence of forest-dependent species in fragmented landscapes is fundamentally linked to the movement of individuals among subpopulations. The paths taken by dispersing individuals can be considered a series of steps built from individual route choices. Despite the importance of these fine-scale movement decisions, it has proved difficult to collect such data that reveal how forest birds move in novel landscapes. We collected unprecedented route information about the movement of translocated forest birds from two species in the highly fragmented tropical dry forest of Costa Rica. In this pasture-dominated landscape, forest remains in patches or riparian corridors, with lesser amounts of living fencerows and individual trees or "stepping stones." We used step selection functions to quantify how route choice was influenced by these habitat elements. We found that the amount of risk these birds were willing to take by crossing open habitat was context dependent. The forest-specialist Barred Antshrike (Thamnophilus doliatus) exhibited stronger selection for forested routes when moving in novel landscapes distant from its territory relative to locations closer to its territory. It also selected forested routes when its step originated in forest habitat. It preferred steps ending in stepping stones when the available routes had little forest cover, but avoided them when routes had greater forest cover. The forest-generalist Rufous-naped Wren (Campylorhynchus rufinucha) preferred steps that contained more pasture, but only when starting from non-forest habitats. Our results showed that forested corridors (i.e., riparian corridors) best facilitated the movement of a sensitive forest specialist through this fragmented landscape. They also suggested that stepping stones can be important in highly fragmented forests with little remaining forest cover. We expect that naturally dispersing birds and species with greater forest dependence would exhibit even stronger
Borysko, Petro; Moroz, Yurii S; Vasylchenko, Oleksandr V; Hurmach, Vasyl V; Starodubtseva, Anastasia; Stefanishena, Natalia; Nesteruk, Kateryna; Zozulya, Sergey; Kondratov, Ivan S; Grygorenko, Oleksandr O
2018-05-09
A combination approach of a fragment screening and "SAR by catalog" was used for the discovery of bromodomain-containing protein 4 (BRD4) inhibitors. Initial screening of 3695-fragment library against bromodomain 1 of BRD4 using thermal shift assay (TSA), followed by initial hit validation, resulted in 73 fragment hits, which were used to construct a follow-up library selected from available screening collection. Additionally, analogs of inactive fragments, as well as a set of randomly selected compounds were also prepared (3 × 3200 compounds in total). Screening of the resulting sets using TSA, followed by re-testing at several concentrations, counter-screen, and TR-FRET assay resulted in 18 confirmed hits. Compounds derived from the initial fragment set showed better hit rate as compared to the other two sets. Finally, building dose-response curves revealed three compounds with IC 50 = 1.9-7.4 μM. For these compounds, binding sites and conformations in the BRD4 (4UYD) have been determined by docking. Copyright © 2018 Elsevier Ltd. All rights reserved.
De novo analysis of electron impact mass spectra using fragmentation trees
International Nuclear Information System (INIS)
Hufsky, Franziska; Rempt, Martin; Rasche, Florian; Pohnert, Georg; Böcker, Sebastian
2012-01-01
Highlights: ► We present a method for de novo analysis of accurate mass EI mass spectra of small molecules. ► This method identifies the molecular ion and thus the molecular formula where the molecular ion is present in the spectrum. ► Fragmentation trees are constructed by automated signal extraction and evaluation. ► These trees explain relevant fragmentation reactions. ► This method will be very helpful in the automated analysis of unknown metabolites. - Abstract: The automated fragmentation analysis of high resolution EI mass spectra based on a fragmentation tree algorithm is introduced. Fragmentation trees are constructed from EI spectra by automated signal extraction and evaluation. These trees explain relevant fragmentation reactions and assign molecular formulas to fragments. The method enables the identification of the molecular ion and the molecular formula of a metabolite if the molecular ion is present in the spectrum. These identifications are independent of existing library knowledge and, thus, support assignment and structural elucidation of unknown compounds. The method works even if the molecular ion is of very low abundance or hidden under contaminants with higher masses. We apply the algorithm to a selection of 50 derivatized and underivatized metabolites and demonstrate that in 78% of cases the molecular ion can be correctly assigned. The automatically constructed fragmentation trees correspond very well to published mechanisms and allow the assignment of specific relevant fragments and fragmentation pathways even in the most complex EI-spectra in our dataset. This method will be very helpful in the automated analysis of metabolites that are not included in common libraries and it thus has the potential to support the explorative character of metabolomics studies.
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.
New fat suppression RF pulse with shorter duration
International Nuclear Information System (INIS)
Yamaguchi, Kojiro; Ukai, Hiroyuki
2010-01-01
The fat suppression radio frequency pulse currently employed for MRI, which selectively saturates the frequency of the fat, has the narrow-band frequency characteristics. Therefore, the application duration for the pulse employed tends to be prolonged. In the present study, we designed a new fat suppression radiofrequency (RF) pulse using the Laguerre function in order to shorten the duration for fat suppression RF pulse and conducted an evaluation with the clinical equipment. The length of the RF pulse that we created allowed to reduce the duration by 47.3% compared with that employed for the clinical equipment. In addition, in the MR imaging evaluation, the new pulse was confirmed to have the fat suppression effect equivalent to that employed for the clinical equipment. (author)
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
Diebolder, Philipp; Keller, Armin; Haase, Stephanie; Schlegelmilch, Anne; Kiefer, Jonathan D; Karimi, Tamana; Weber, Tobias; Moldenhauer, Gerhard; Kehm, Roland; Eis-Hübinger, Anna M; Jäger, Dirk; Federspil, Philippe A; Herold-Mende, Christel; Dyckhoff, Gerhard; Kontermann, Roland E; Arndt, Michaela A E; Krauss, Jürgen
2014-01-01
The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro,the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.
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)
Fujita, Mitsugu; Ohnishi, Katsunori; Takaoka, Shinsaku; Ogasawara, Kazuya; Fukuyama, Ryo; Nakamuta, Hiromichi
2011-01-01
To determine whether the antihypertensive effect of nattokinase is associated with the protease activity of this enzyme, we compared nattokinase with the fragments derived from nattokinase, which possessed no protease activity, in terms of the effect on hypertension in spontaneously hypertensive rats (SHR). In the continuous oral administration test, the groups were given a basic diet alone (control), the basic diet containing nattokinase (0.2, 2.6 mg/g diet) or the basic diet containing the fragments derived from nattokinase (0.2, 0.6 mg/g diet). The group fed the basic diet containing high-dosage nattokinase (2.6 mg/g diet) showed significant reductions in systolic blood pressure (SBP), diastolic blood pressure (DBP) and plasma fibrinogen level, compared with control group and no influence on activities of renin and angiotensin-converting enzyme (ACE, EC 3.4.15.1), and plasma angiotensin II level in the renin-angiotensin system. The treatment of the basic diet containing high-dosage fragments (0.6 mg/g diet) significantly decreased SBP, DBP and plasma angiotensin II level in plasma but the treatment did not influence on plasma fibrinogen level. These results suggest that nattokinase and its fragments are different from each other in the mechanism to reduce hypertension. Nattokinase, retained its protease activity after absorbance across the intestines, may decrease blood pressure through cleavage of fibrinogen in plasma. The fragments, which absorbed as nattokinase-degradation products, prevents the elevation of plasma angiotensin II level to suppress hypertension.
Hypoxia, Radiosensitizers and high-LET radiation - Nimorazole fragmentation using mass spectrometry
DEFF Research Database (Denmark)
Feketeova, Linda; Bassler, Niels
(s): Fragmentation experiments have been performed using a Finnigan- LTQ-FT mass spectrometer equipped with an electrospray ionisation source. Collision-induced dissociation (CID) and electron-induced dissociation (EID) have been carried out by mass selecting the desired ions and subjecting them to activation energy...... using mass spectrometry. Understanding the fragmentation of radiosensitizers is crucial in evaluating the radiosensitization potential and developing new and more effective drugs, which may improve TCP in hypoxic tumours when using ion beams such as carbon-12 along with LET-painting techniques. Method...
Reflection/suppression coatings for 900 - 1200 A radiation
Edelstein, Jerry
1989-01-01
The design and performance of multiple-layer, selective-reflection, selective-suppression coatings for the 900 - 1200 A band are described. These coatings are designed to optimize both high reflectivity at a desirable wavelength and low reflectivity at an undesirable wavelength. The minimum structure for a selective coating consists of a thin metal or metal oxide layer (50 - 150 A thickness) over an aluminum substrate protected with a semi-transparent dielectric (100 - 1000 A thickness). Predicted coating performance is strongly effected by varying the layer combination and thickness. A graphical method of optimizing the coating layer structure is developed. Aluminum, silicon, their oxides, and gold have been investigated as coating layer materials. A very simple coating with a 1026 to 1216 A reflectivity ratio greater than 100 was fabricated. Such reflection/suppression coatings may be of great utility to spaceborne EUV spectrographs.
Woods, Lucy A; Dolezal, Olan; Ren, Bin; Ryan, John H; Peat, Thomas S; Poulsen, Sally-Ann
2016-03-10
Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery.
Jet suppression and the flavor dependence of partonic energy loss with ATLAS
Energy Technology Data Exchange (ETDEWEB)
Kosek, Tomas
2016-12-15
In relativistic heavy ion collisions, a hot medium with a high density of unscreened color charges is produced. One manifestation of the energy loss of jets propagating through the medium is a lower yield of jets and hadrons emerging from this medium than expected in the absence of medium effects. Therefore modifications of the jet yield are directly sensitive to the energy loss mechanism. Furthermore, jets with different flavor content are expected to be affected by the medium in different ways. In this publication, the latest ATLAS results on single hadron suppression along with the complementary measurements of single jet suppression are presented. Rapidity dependence, which is sensitive to the relative energy loss between quark and gluon jets, is discussed. Finally, a new measurement of jet fragmentation functions is presented.
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.)
Threshold Switching Induced by Controllable Fragmentation in Silver Nanowire Networks.
Wan, Tao; Pan, Ying; Du, Haiwei; Qu, Bo; Yi, Jiabao; Chu, Dewei
2018-01-24
Silver nanowire (Ag NW) networks have been widely studied because of a great potential in various electronic devices. However, nanowires usually undergo a fragmentation process at elevated temperatures due to the Rayleigh instability that is a result of reduction of surface/interface energy. In this case, the nanowires become completely insulating due to the formation of randomly distributed Ag particles with a large distance and further applications are hindered. Herein, we demonstrate a novel concept based on the combination of ultraviolet/ozone irradiation and a low-temperature annealing process to effectively utilize and control the fragmentation behavior to realize the resistive switching performances. In contrast to the conventional fragmentation, the designed Ag/AgO x interface facilitates a unique morphology of short nanorod-like segments or chains of tiny Ag nanoparticles with a very small spacing distance, providing conduction paths for achieving the tunneling process between the isolated fragments under the electric field. On the basis of this specific morphology, the Ag NW network has a tunable resistance and shows volatile threshold switching characteristics with a high selectivity, which is the ON/OFF current ratio in selector devices. Our concept exploits a new function of Ag NW network, i.e., resistive switching, which can be developed by designing a controllable fragmentation.
Gouge, Michael F.
2011-01-01
Hypervelocity impact tests on test satellites are performed by members of the orbital debris scientific community in order to understand and typify the on-orbit collision breakup process. By analysis of these test satellite fragments, the fragment size and mass distributions are derived and incorporated into various orbital debris models. These same fragments are currently being put to new use using emerging technologies. Digital models of these fragments are created using a laser scanner. A group of computer programs referred to as the Fragment Rotation Analysis and Lightcurve code uses these digital representations in a multitude of ways that describe, measure, and model on-orbit fragments and fragment behavior. The Dynamic Rotation subroutine generates all of the possible reflected intensities from a scanned fragment as if it were observed to rotate dynamically while in orbit about the Earth. This calls an additional subroutine that graphically displays the intensities and the resulting frequency of those intensities as a range of solar phase angles in a Probability Density Function plot. This document reports the additions and modifications to the subset of the Fragment Rotation Analysis and Lightcurve concerned with the Dynamic Rotation and Probability Density Function plotting subroutines.
ANGULAR MOMENTUM TRANSFER AND LACK OF FRAGMENTATION IN SELF-GRAVITATING ACCRETION FLOWS
International Nuclear Information System (INIS)
Begelman, Mitchell C.; Shlosman, Isaac
2009-01-01
Rapid inflows associated with early galaxy formation lead to the accumulation of self-gravitating gas in the centers of proto-galaxies. Such gas accumulations are prone to nonaxisymmetric instabilities, as in the well known Maclaurin sequence of rotating ellipsoids, which are accompanied by a catastrophic loss of angular momentum (J). Self-gravitating gas is also intuitively associated with star formation. However, recent simulations of the infall process display highly turbulent continuous flows. We propose that J-transfer, which enables the inflow, also suppresses fragmentation. Inefficient J loss by the gas leads to decay of turbulence, triggering global instabilities and renewed turbulence driving. Flow regulated in this way is stable against fragmentation, while staying close to the instability threshold for bar formation-thick self-gravitating disks are prone to global instabilities before they become unstable locally. On smaller scales, the fraction of gravitationally unstable matter swept up by shocks in such a flow is a small and decreasing function of the Mach number. We conclude counterintuitively that gas able to cool down to a small fraction of its virial temperature will not fragment as it collapses. This provides a venue for supermassive black holes to form via direct infall, without the intermediary stage of forming a star cluster. Some black holes could have formed or grown in massive halos at low redshifts. Thus the fragmentation is intimately related to J redistribution within the system: it is less dependent on the molecular/metal cooling but is conditioned by the ability of the flow to develop virial, supersonic turbulence.
Payne, Lloyd R.; Cole, David L.
2010-03-30
A fragment capture device for use in explosive containment. The device comprises an assembly of at least two rows of bars positioned to eliminate line-of-sight trajectories between the generation point of fragments and a surrounding containment vessel or asset. The device comprises an array of at least two rows of bars, wherein each row is staggered with respect to the adjacent row, and wherein a lateral dimension of each bar and a relative position of each bar in combination provides blockage of a straight-line passage of a solid fragment through the adjacent rows of bars, wherein a generation point of the solid fragment is located within a cavity at least partially enclosed by the array of bars.
Peñaloza-Ramírez, Juan Manuel; Aguilar-Amezquita, Bernardo; Núñez-Farfán, Juan; Pérez-Nasser, Nidia; Albarrán-Lara, Ana Luisa; Oyama, Ken
2016-01-01
Abstract: Chamaedorea alternans is a palm species that has suffered from selective extraction, and habitat loss. We collected 11 populations from fragmented and conserved forest. We assess genetic variation of C. alternans, genetic exchange, differentiation, bottlenecks, effective population size and signals of natural selection. Genetic diversity was higher in conserved than in fragmented forest but not significant. Fragmentation did not play a significant role in genetic diversity, possibly...
The evolution of urban sprawl: evidence of spatial heterogeneity and increasing land fragmentation.
Irwin, Elena G; Bockstael, Nancy E
2007-12-26
We investigate the dynamics and spatial distribution of land use fragmentation in a rapidly urbanizing region of the United States to test key propositions regarding the evolution of sprawl. Using selected pattern metrics and data from 1973 and 2000 for the state of Maryland, we find significant increases in developed and undeveloped land fragmentation but substantial spatial heterogeneity as well. Estimated fragmentation gradients that describe mean fragmentation as a function of distance from urban centers confirm the hypotheses that fragmentation rises and falls with distance and that the point of maximum fragmentation shifted outward over time. However, rather than outward increases in sprawl balanced by development infill, we find substantial and significant increases in mean fragmentation values along the entire urban-rural gradient. These findings are in contrast to the results of Burchfield et al. [Burchfield M, Overman HG, Puga D, Turner MA (2006) Q J Econ 121:587-633], who conclude that the extent of sprawl remained roughly unchanged in the Unites States between 1976 and 1992. As demonstrated here, both the data and pattern measure used in their study are systematically biased against recording low-density residential development, the very land use that we find is most strongly associated with fragmentation. Other results demonstrate the association between exurban growth and increasing fragmentation and the systematic variation of fragmentation with nonurban factors. In particular, proximity to the Chesapeake Bay is negatively associated with fragmentation, suggesting that an attraction effect associated with this natural amenity has concentrated development.
Szaszkó, Mária; Hajdú, István; Flachner, Beáta; Dobi, Krisztina; Magyar, Csaba; Simon, István; Lőrincz, Zsolt; Kapui, Zoltán; Pázmány, Tamás; Cseh, Sándor; Dormán, György
2017-02-01
A glutaminyl cyclase (QC) fragment library was in silico selected by disconnection of the structure of known QC inhibitors and by lead-like 2D virtual screening of the same set. The resulting fragment library (204 compounds) was acquired from commercial suppliers and pre-screened by differential scanning fluorimetry followed by functional in vitro assays. In this way, 10 fragment hits were identified ([Formula: see text]5 % hit rate, best inhibitory activity: 16 [Formula: see text]). The in vitro hits were then docked to the active site of QC, and the best scoring compounds were analyzed for binding interactions. Two fragments bound to different regions in a complementary manner, and thus, linking those fragments offered a rational strategy to generate novel QC inhibitors. Based on the structure of the virtual linked fragment, a 77-membered QC target focused library was selected from vendor databases and docked to the active site of QC. A PubChem search confirmed that the best scoring analogues are novel, potential QC inhibitors.
Directory of Open Access Journals (Sweden)
S. C. Oukouomi Noutchie
2014-01-01
Full Text Available We make use of Laplace transform techniques and the method of characteristics to solve fragmentation equations explicitly. Our result is a breakthrough in the analysis of pure fragmentation equations as this is the first instance where an exact solution is provided for the fragmentation evolution equation with general fragmentation rates. This paper is the key for resolving most of the open problems in fragmentation theory including “shattering” and the sudden appearance of infinitely many particles in some systems with initial finite particles number.
Land fragmentation and production diversification
Ciaian, Pavel; Guri, Fatmir; Rajcaniova, Miroslava; Drabik, Dusan; Paloma, Sergio Gomez Y.
2018-01-01
We analyze the impact of land fragmentation on production diversification in rural Albania. Albania represents a particularly interesting case for studying land fragmentation as the fragmentation is a direct outcome of land reforms. The results indicate that land fragmentation is an important driver
Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug Discovery Campaigns.
Luise, Nicola; Wyatt, Paul
2018-05-07
Synthesising polar semi-saturated bicyclic heterocycles can lead to better starting points for fragment-based drug discovery (FBDD) programs. This communication highlights the application of diverse chemistry to construct bicyclic systems from a common intermediate, where pyrazole, a privileged heteroaromatic able to bind effectively to biological targets, is fused to diverse saturated counterparts. The generated fragments can be further developed either after confirmation of their binding pose or early in the process, as their synthetic intermediates. Essential quality control (QC) for selection of small molecules to add to a fragment library is discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
International Nuclear Information System (INIS)
Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu
2014-01-01
Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS
Energy Technology Data Exchange (ETDEWEB)
Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)
2014-05-01
Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin
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
Selective inhibition of distracting input.
Noonan, MaryAnn P; Crittenden, Ben M; Jensen, Ole; Stokes, Mark G
2017-10-16
We review a series of studies exploring distractor suppression. It is often assumed that preparatory distractor suppression is controlled via top-down mechanisms of attention akin to those that prepare brain areas for target enhancement. Here, we consider two alternative mechanisms: secondary inhibition and expectation suppression within a predictive coding framework. We draw on behavioural studies, evidence from neuroimaging and some animal studies. We conclude that there is very limited evidence for selective top-down control of preparatory inhibition. By contrast, we argue that distractor suppression often relies secondary inhibition of non-target items (relatively non-selective inhibition) and on statistical regularities of the environment, learned through direct experience. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.
Georgescu, Roxana E; Schauer, Grant D; Yao, Nina Y; Langston, Lance D; Yurieva, Olga; Zhang, Dan; Finkelstein, Jeff; O'Donnell, Mike E
2015-01-01
We have reconstituted a eukaryotic leading/lagging strand replisome comprising 31 distinct polypeptides. This study identifies a process unprecedented in bacterial replisomes. While bacteria and phage simply recruit polymerases to the fork, we find that suppression mechanisms are used to position the distinct eukaryotic polymerases on their respective strands. Hence, Pol ε is active with CMG on the leading strand, but it is unable to function on the lagging strand, even when Pol δ is not present. Conversely, Pol δ-PCNA is the only enzyme capable of extending Okazaki fragments in the presence of Pols ε and α. We have shown earlier that Pol δ-PCNA is suppressed on the leading strand with CMG (Georgescu et al., 2014). We propose that CMG, the 11-subunit helicase, is responsible for one or both of these suppression mechanisms that spatially control polymerase occupancy at the fork. DOI: http://dx.doi.org/10.7554/eLife.04988.001 PMID:25871847
International Nuclear Information System (INIS)
Sasano, Nakashi; Shiraishi, Kenshiro; Igaki, Hiroshi; Nakagawa, Keiichi; Enomoto, Atsushi; Hosoi, Yoshio; Matsumoto, Yoshihisa; Miyagawa, Kiyoshi; Katsumura, Yosuke
2007-01-01
Edaravone, a clinical drug used widely for the treatment of acute cerebral infarction, is reported to scavenge free radicals. In the present study, we investigated the radioprotective effect of edaravone on X-ray-induced apoptosis in MOLT-4 cells. Apoptosis was determined by the dye exclusion test, Annexin V binding assay, cleavage of caspase, and DNA fragmentation. We found that edaravone significantly suppressed the X-ray-induced apoptosis. The amount of intracellular reactive oxygen species (ROS) production was determined by the chloromethyl-2', 7'-dichlorodihydro-fluorescein diacetate system. We found that the intracellular ROS production by X-irradiation was completely suppressed by the addition of edaravone. The accumulation and phosphorylation of p53 and the expression of p21 WAF1 , a target protein of p53, which were induced by X-irradiation, were also suppressed by adding edaravone. We conclude that the free radical scavenger edaravone suppresses X-ray-induced apoptosis in MOLT-4 cells by inhibiting p53. (author)
Energy Technology Data Exchange (ETDEWEB)
Sasano, Nakashi; Shiraishi, Kenshiro; Igaki, Hiroshi; Nakagawa, Keiichi [Tokyo Univ., Graduate School of Medicine, Tokyo (Japan); Enomoto, Atsushi; Hosoi, Yoshio; Matsumoto, Yoshihisa; Miyagawa, Kiyoshi [Tokyo Univ., Faculty of Medicine, Tokyo (Japan); Katsumura, Yosuke [Tokyo Univ., Graduate School of Engineering, Tokyo (Japan)
2007-11-15
Edaravone, a clinical drug used widely for the treatment of acute cerebral infarction, is reported to scavenge free radicals. In the present study, we investigated the radioprotective effect of edaravone on X-ray-induced apoptosis in MOLT-4 cells. Apoptosis was determined by the dye exclusion test, Annexin V binding assay, cleavage of caspase, and DNA fragmentation. We found that edaravone significantly suppressed the X-ray-induced apoptosis. The amount of intracellular reactive oxygen species (ROS) production was determined by the chloromethyl-2', 7'-dichlorodihydro-fluorescein diacetate system. We found that the intracellular ROS production by X-irradiation was completely suppressed by the addition of edaravone. The accumulation and phosphorylation of p53 and the expression of p21{sup WAF1}, a target protein of p53, which were induced by X-irradiation, were also suppressed by adding edaravone. We conclude that the free radical scavenger edaravone suppresses X-ray-induced apoptosis in MOLT-4 cells by inhibiting p53. (author)
Twenty years on: the impact of fragments on drug discovery.
Erlanson, Daniel A; Fesik, Stephen W; Hubbard, Roderick E; Jahnke, Wolfgang; Jhoti, Harren
2016-09-01
After 20 years of sometimes quiet growth, fragment-based drug discovery (FBDD) has become mainstream. More than 30 drug candidates derived from fragments have entered the clinic, with two approved and several more in advanced trials. FBDD has been widely applied in both academia and industry, as evidenced by the large number of papers from universities, non-profit research institutions, biotechnology companies and pharmaceutical companies. Moreover, FBDD draws on a diverse range of disciplines, from biochemistry and biophysics to computational and medicinal chemistry. As the promise of FBDD strategies becomes increasingly realized, now is an opportune time to draw lessons and point the way to the future. This Review briefly discusses how to design fragment libraries, how to select screening techniques and how to make the most of information gleaned from them. It also shows how concepts from FBDD have permeated and enhanced drug discovery efforts.
Selective SWS suppression does not affect the time course of core body temperature in men
Beersma, Domien G.M.; Dijk, Derk-Jan
1992-01-01
In eight healthy middle-aged men, sleep and core body temperature were recorded under baseline conditions, during all-night SWS suppression by acoustic stimulation, and during undisturbed recovery sleep. SWS suppression resulted in a marked reduction of sleep stages 3 and 4 but did not affect the
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.
Amplified-fragment length polymorphism fingerprinting of Mycoplasma species
DEFF Research Database (Denmark)
Kokotovic, Branko; Friis, N.F.; Jensen, J.S.
1999-01-01
Amplified-fragment length polymorphism (AFLP) is a whole-genome fingerprinting method based on selective amplification of restriction fragments. The potential of the method for the characterization of mycoplasmas was investigated in a total of 50 strains of human and animal origin, including...... Mycoplasma genitalium (n = 11), Mycoplasma pneumoniae (n = 5), Mycoplasma hominis (n = 5), Mycoplasma hyopneunmoniae (n = 9), Myco plasma flocculare (n = 5), Mycoplasma hyosynoviae (n = 10), and Mycoplasma dispar (n = 5), AFLP templates were prepared by the digestion of mycoplasmal DNA with BglII and Mfe...... to discriminate the analyzed strains at species and intraspecies levels as well, Each of the tested Mycoplasma species developed a banding pattern entirely different from those obtained from other species under analysis, Subtle intraspecies genomic differences were detected among strains of all of the Mycoplasma...
Fragment Screening of Human Kynurenine Aminotransferase-II.
Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, W Bret
2018-03-01
Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors. Surface plasmon resonance (SPR) was used to screen a fragment library containing 1000 compounds, of which 41 hits were identified. These hits were further evaluated with SPR, and 18 were selected for inhibition studies. From these hits, two fragments, F6037-0164 and F0037-7280, were pursued and determined to have an IC 50 of 524.5 (± 25.6) μM and 115.2 (± 4.5) μM, respectively. This strategy shows the viability of using FBDD in gleaning knowledge about KAT-II inhibition and generating leads for the production of KAT-II inhibitors.
Sankar, Punnaivanam; Alain, Krief; Aghila, Gnanasekaran
2010-05-24
We have developed a model structure-editing tool, ChemEd, programmed in JAVA, which allows drawing chemical structures on a graphical user interface (GUI) by selecting appropriate structural fragments defined in a fragment library. The terms representing the structural fragments are organized in fragment ontology to provide a conceptual support. ChemEd describes the chemical structure in an XML document (ChemFul) with rich semantics explicitly encoding the details of the chemical bonding, the hybridization status, and the electron environment around each atom. The document can be further processed through suitable algorithms and with the support of external chemical ontologies to generate understandable reports about the functional groups present in the structure and their specific environment.
Energy Technology Data Exchange (ETDEWEB)
Benlliure, J
1995-03-01
The study of moments of fragments charge distributions produced in heavy ions collisions can give us evidence of a critical behavior of nuclear matter which could explain the multifragmentation pattern. From an experimental point of view, in order to perform this capabilities of the INDRA detector has made it possible to identify all these particles and to reconstruct the initial projectile-like fragment coming from binary collisions in the reaction Xe+Sn at 50 MeV/A. We have selected events where the initial projectile-like fragments keep their entire charge in a large range of excitation energy. The study of these fragment`s characteristics show clearly a change in the deexcitation pattern. The evolution of moments of the fragment charge distributions has been reproduced within a percolation model, in this sense we can interpreter this change in the deexcitation pattern as a function of the initial projectile-like fragment`s size shows the existence of finite-size effects. However, the signature of a phase transition remains independent on the projectile-like fragment`s size. (author). 74 refs., 58 figs., 9 tabs.
Feyfant, Eric; Cross, Jason B; Paris, Kevin; Tsao, Désirée H H
2011-01-01
Fragment-based drug design (FBDD), which is comprised of both fragment screening and the use of fragment hits to design leads, began more than 15 years ago and has been steadily gaining in popularity and utility. Its origin lies on the fact that the coverage of chemical space and the binding efficiency of hits are directly related to the size of the compounds screened. Nevertheless, FBDD still faces challenges, among them developing fragment screening libraries that ensure optimal coverage of chemical space, physical properties and chemical tractability. Fragment screening also requires sensitive assays, often biophysical in nature, to detect weak binders. In this chapter we will introduce the technologies used to address these challenges and outline the experimental advantages that make FBDD one of the most popular new hit-to-lead process.
Fragment informatics and computational fragment-based drug design: an overview and update.
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.
Adaptive transmit selection with interference suppression
Radaydeh, Redha Mahmoud Mesleh
2010-01-01
This paper studies the performance of adaptive transmit channel selection in multipath fading channels. The adaptive selection algorithms are configured for single-antenna bandwidth-efficient or power-efficient transmission with as low transmit channel estimations as possible. Due to the fact that the number of active co-channel interfering signals and their corresponding powers experience random behavior, the adaptation to channels conditions, assuming uniform buffer and traffic loading, is proposed to be jointly based on the transmit channels instantaneous signal-to-noise ratios (SNRs) and signal-to- interference-plus- noise ratios (SINRs). Two interference cancelation algorithms, which are the dominant cancelation and the less complex arbitrary cancelation, are considered, for which the receive antenna array is assumed to have small angular spread. Analytical formulation for some performance measures in addition to several processing complexity and numerical comparisons between various adaptation schemes are presented. ©2010 IEEE.
Lei, Hao; Jones, Christopher; Zhu, Tian; Patel, Kavankumar; Wolf, Nina M; Fung, Leslie W-M; Lee, Hyun; Johnson, Michael E
2016-02-15
The de novo purine biosynthesis pathway is an attractive target for antibacterial drug design, and PurE from this pathway has been identified to be crucial for Bacillus anthracis survival in serum. In this study we adopted a fragment-based hit discovery approach, using three screening methods-saturation transfer difference nucleus magnetic resonance (STD-NMR), water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR, and surface plasmon resonance (SPR), against B. anthracis PurE (BaPurE) to identify active site binding fragments by initially testing 352 compounds in a Zenobia fragment library. Competition STD NMR with the BaPurE product effectively eliminated non-active site binding hits from the primary hits, selecting active site binders only. Binding affinities (dissociation constant, KD) of these compounds varied between 234 and 301μM. Based on test results from the Zenobia compounds, we subsequently developed and applied a streamlined fragment screening strategy to screen a much larger library consisting of 3000 computationally pre-selected fragments. Thirteen final fragment hits were confirmed to exhibit binding affinities varying from 14μM to 700μM, which were categorized into five different basic scaffolds. All thirteen fragment hits have ligand efficiencies higher than 0.30. We demonstrated that at least two fragments from two different scaffolds exhibit inhibitory activity against the BaPurE enzyme. Published by Elsevier Ltd.
Wexels, Fredrik; Dahl, Ola E; Pripp, Are H; Seljeflot, Ingebjørg; Borris, Lars C; Haslund, Anniken; Gudmundsen, Tor E; Lauritzen, Trine; Lassen, Michael R
2014-07-01
We have recently reported that increased levels of urine prothrombin fragment 1+2 reflected radiologically verified deep vein thrombosis. In this study we evaluated whether urine prothrombin fragment 1+2 was associated with pulmonary embolism in non-selected patients. Patients with clinical suspected pulmonary embolism were interviewed on comorbidities and medications. Urine was collected from each patient before radiological examination and snap frozen until analysed on urine prothrombin fragment 1+2 with an ELISA kit. Imaging of the pulmonary arteries were conducted with contrast enhanced computer tomography. Pulmonary embolism was diagnosed in 44/197 patients. Non-significantly higher urine prothrombin fragment 1+2 levels were found in non-selected patients with pulmonary embolism vs. those without (p=0.324). Significantly higher urine prothrombin fragment 1+2 levels were found in the pulmonary embolism positive patients without comorbidities (n=13) compared to the control group (n=28) (p=0.009). The calculated sensitivity, specificity and negative predictive value using the lowest detectable urine prothrombin fragment 1+2 level was 82%, 34% and 87%, respectively. There was no significant urine prothrombin fragment 1+2 level difference in patients with and without pulmonary embolism. In non-comorbide pulmonary embolism positive patients the urine prothrombin fragment 1+2 levels were significantly higher compared to the control group. The negative predictive value found in this study indicates that uF1+2 has the potential to identify patients with a low risk of PE. Copyright © 2014 Elsevier Ltd. All rights reserved.
Ambardekar, Vishakha V; Han, Huai-Yun; Varney, Michelle L; Vinogradov, Serguei V; Singh, Rakesh K; Vetro, Joseph A
2011-02-01
Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. Copyright © 2010 Elsevier Ltd. All rights reserved.
DEFF Research Database (Denmark)
Halling, Jens Frey; Jørgensen, Stine Ringholm; Olesen, Jesper
2017-01-01
Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effect...... evidence that exercise training rescues aging-induced mitochondrial fragmentation in skeletal muscle by suppressing mitochondrial fission protein expression in a PGC-1α dependent manner....
Fragmentation of chromatin with 125I radioactive disintegrations
International Nuclear Information System (INIS)
Turner, G.N.; Nobis, P.; Dewey, W.C.
1976-01-01
The DNA in Chinese hamster cells was labeled first for 3 h with [ 3 H]TdR and then for 3 h with [ 125 I]UdR. Chromatin was extracted, frozen, and stored at -30 0 C until 1.0 x 10 17 and 1.25 x 10 17 disintegrations/g of labeled DNA occurred for 125 I and 3 H, respectively. Velocity sedimentation of chromatin (DNA with associated chromosomal proteins) in neutral sucrose gradients indicated that the localized energy from the 125 I disintegrations, which gave about 1 double-strand break/disintegration plus an additional 1.3 single strand breaks, selectively fragmented the [ 125 I] chromatin into pieces smaller than the [ 3 H] chromatin. In other words, 125 I disintegrations caused much more localized damage in the chromatin labeled with 125 I than in the chromatin labeled with 3 H, and fragments induced in DNA by 125 I disintegrations were not held together by the associated chromosomal proteins. Use of this 125 I technique for studying chromosomal proteins associated with different regions in the cellular DNA is discussed. For these studies, the number of disintegrations required for fragmenting DNA molecules of different sizes is illustrated
Boiling and fragmentation behaviour during fuel-sodium interactions
International Nuclear Information System (INIS)
Schins, H.; Gunnerson, F.S.
1986-01-01
A selection of the results and subsequent analysis of molten fuel-sodium interaction experiments conducted within the JRC BETULLA I and II facilities are reported. The fuels were copper and stainless steel, at initial temperatures far above their melting points; or urania and alumina, initially at their melting points. For each test, the molten fuel masses were in lower kilogram range and the subcooled pool mass was either 160 or 4 kg. The sodium pool was instrumented continually monitor the system temperature and pressure. Post-test examination results of the fragmented fuel debris sizes, shape and crystalline structure are given. The results of this study suggest the following: Transition boiling is the dominant boiling mode for the tested fuels in subcooled sodium. Two fragmentation mechanisms, vapour bubble formation/collapse and thermal stress shrinkage cracking prevailed for the oxide fuels. This was evidenced by the presence of both smooth and fractured particulate. In contrast, all metal fuel debris was smooth, suggesting fragmentation by the vapour bubble formation/collapse mechanism only during the molten state and for each test, there was no evidence of an energetic fuel-coolant interaction. (orig.)
Tugnoli, Alessandro; Gubinelli, Gianfilippo; Landucci, Gabriele; Cozzani, Valerio
2014-08-30
The evaluation of the initial direction and velocity of the fragments generated in the fragmentation of a vessel due to internal pressure is an important information in the assessment of damage caused by fragments, in particular within the quantitative risk assessment (QRA) of chemical and process plants. In the present study an approach is proposed to the identification and validation of probability density functions (pdfs) for the initial direction of the fragments. A detailed review of a large number of past accidents provided the background information for the validation procedure. A specific method was developed for the validation of the proposed pdfs. Validated pdfs were obtained for both the vertical and horizontal angles of projection and for the initial velocity of the fragments. Copyright © 2014 Elsevier B.V. All rights reserved.
Knowledge-based Fragment Binding Prediction
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
Chen, Haijun; Yang, Zhengduo; Ding, Chunyong; Chu, Lili; Zhang, Yusong; Terry, Kristin; Liu, Huiling; Shen, Qiang; Zhou, Jia
2013-01-01
Fragment-based drug design (FBDD) is a promising approach for the generation of lead molecules with enhanced activity and especially drug-like properties against therapeutic targets. Herein, we report the fragment-based drug design, systematic chemical synthesis and pharmacological evaluation of novel scaffolds as potent anticancer agents by utilizing six privileged fragments from known STAT3 inhibitors. Several new molecules such as compounds 5, 12, and 19 that may act as advanced chemical leads have been identified. The most potent compound 5 (HJC0123) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. Furthermore, compound 5 significantly suppressed estrogen receptor (ER)-negative breast cancer MDA-MB-231 xenograft tumor growth in vivo (p.o.), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy. PMID:23416191
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....
Two-pulse laser control of bond-selective fragmentation
DEFF Research Database (Denmark)
Amstrup, Bjarne; Henriksen, Niels Engholm
1996-01-01
We elaborate on a two-pulse (pump-pump) laser control scheme for selective bond-breaking in molecules [Amstrup and Henriksen, J. Chem. Phys. 97, 8285 (1992)]. We show, in particular, that with this scheme one can overcome the obstacle of intramolecular vibrational relaxation. As an example, we...... consider an ozone molecule with isotopic substitution, that is, (OOO)-O-16-O-16-O-18. It is shown that asymmetric bond stretching can be created in simple (intense) laser fields. We predict that an alternating high selectivity between the channels O-16+(OO)-O-16-O-18 and (OO)-O-16-O-16+ O-18 can...
Separation and implantation of relativistic 86Kr-fragments at the FRS
International Nuclear Information System (INIS)
Czajkowski, S.; Bernas, M.; Dessagne, Ph.; Miehe, Ch.; Audi, G.; Lee, J.K.P.
1993-01-01
Neutron-rich Co and Fe isotopes produced by 86 Kr projectile fragmentation at 500 MeV/u have been separated and identified using the Fragment Separator (FRS) in a bunched energy mode. 66 Co and 65 Fe ions were selectively implanted in a double PIN-diode array where the β-decay signals were measured. The half-lives were deduced from time correlations between implantation and β-decay signals. The re-measurement of the 66 Co half-life confirms the isotope identification. The value of 65 Fe half-life was found to be 0.45±0.15 s. (authors). 18 refs., 5 figs
International Nuclear Information System (INIS)
Walker, K.Z.; Seymour-Munn, K.; Axiak, S.M.; Raison, R.L.; Basten, A.; Towson, J.E.; Bautovitch, G.J.; Morris, J.
1988-01-01
Monoclonal antibody (MoAb) fragments are known to have advantages over intact immunoglobulins for radioimmunoscintigraphy. It is less clear whether they are as effective in the delivery of radioimmunotherapy. The imaging and dosimetric properties of an intact MoAb, K-1-21, reactive against human kappa light chains (LC) were compared with that of its F(ab') 2 and Fab fragments using a normal rat model system. Two days after injection of 131 I-K-1-21 into rats bearing antigen-sepharose implants, gamma camera images showed specific localization of the MoAb to the target (kappa LC) but not to the control (lambda LC) implant. Better images were obtained with K-1-21 F(ab') 2 than with Fab or intact antibody. Mean kappa implant: blood ratios were 8.6 ± 3.9 for Fab, 7.9 ± 1.8 for F(ab') 2 and 2.0 ± 0.3 for intact K-1-21. The improvement associated with the use of 131 I-K-1-21 fragments was, however, achieved at the expense of lower absolute values of activity at the target site. Thus the absorbed dose delivered to the implant by the intact K-1-21 was double that delivered with F(ab') 2 and six times that delivered with Fab. As intact K-1-21 also delivered a greater radiation dose to normal tissues, F(ab') 2 fragments may have the greatest overall advantages for therapy with radionuclide MoAb conjugates. (author)
Lirman
2000-08-23
Acropora palmata, a branching coral abundant on shallow reef environments throughout the Caribbean, is susceptible to physical disturbance caused by storms. Accordingly, the survivorship and propagation of this species are tied to its capability to recover after fragmentation. Fragments of A. palmata comprised 40% of ramets within populations that had experienced recent storms. While the survivorship of A. palmata fragments was not directly related to the size of fragments, removal of fragments from areas where they settled was influenced by size. Survivorship of fragments was also affected by type of substratum; the greatest mortality (58% loss within the first month) was observed on sand, whereas fragments placed on top of live colonies of A. palmata fused to the underlying tissue and did not experience any losses. Fragments created by Hurricane Andrew on a Florida reef in August 1992 began developing new growth (proto-branches) 7 months after the storm. The number of proto-branches on fragments was dependent on size, but growth was not affected by the size of fragments. Growth-rates of proto-branches increased exponentially with time (1.7 cm year(-1) for 1993-1994, 2.7 cm year(-1) for 1994-1995, 4.2 cm year(-1) for 1995-1996, and 6.5 cm year(-1) for 1996-1997), taking over 4 years for proto-branches to achieve rates comparable to those of adult colonies on the same reef (6.9 cm year(-1)). In addition to the initial mortality and reduced growth-rates, fragmentation resulted in a loss of reproductive potential. Neither colonies that experienced severe fragmentation nor fragments contained gametes until 4 years after the initial damage. Although A. palmata may survive periodic fragmentation, the long-term effects of this process will depend ultimately on the balance between the benefits and costs of this process.
Plasminogen fragments K 1-3 and K 5 bind to different sites in fibrin fragment DD.
Grinenko, T V; Kapustianenko, L G; Yatsenko, T A; Yusova, O I; Rybachuk, V N
2016-01-01
Specific plasminogen-binding sites of fibrin molecule are located in Аα148-160 regions of C-terminal domains. Plasminogen interaction with these sites initiates the activation process of proenzyme and subsequent fibrin lysis. In this study we investigated the binding of plasminogen fragments K 1-3 and K 5 with fibrin fragment DD and their effect on Glu-plasminogen interaction with DD. It was shown that the level of Glu-plasminogen binding to fibrin fragment DD is decreased by 50-60% in the presence of K 1-3 and K 5. Fragments K 1-3 and K 5 have high affinity to fibrin fragment DD (Kd is 0.02 for K 1-3 and 0.054 μМ for K 5). K 5 interaction is independent and K 1-3 is partly dependent on C-terminal lysine residues. K 1-3 interacts with complex of fragment DD-immobilized K 5 as well as K 5 with complex of fragment DD-immobilized K 1-3. The plasminogen fragments do not displace each other from binding sites located in fibrin fragment DD, but can compete for the interaction. The results indicate that fibrin fragment DD contains different binding sites for plasminogen kringle fragments K 1-3 and K 5, which can be located close to each other. The role of amino acid residues of fibrin molecule Аα148-160 region in interaction with fragments K 1-3 and K 5 is discussed.
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.
How to inhibit a distractor location? Statistical learning versus active, top-down suppression.
Wang, Benchi; Theeuwes, Jan
2018-05-01
Recently, Wang and Theeuwes (Journal of Experimental Psychology: Human Perception and Performance, 44(1), 13-17, 2018a) demonstrated the role of lingering selection biases in an additional singleton search task in which the distractor singleton appeared much more often in one location than in all other locations. For this location, there was less capture and selection efficiency was reduced. It was argued that statistical learning induces plasticity within the spatial priority map such that particular locations that are high likely to contain a distractor are suppressed relative to all other locations. The current study replicated these findings regarding statistical learning (Experiment 1) and investigated whether similar effects can be obtained by cueing the distractor location in a top-down way on a trial-by-trial basis. The results show that top-down cueing of the distractor location with long (1,500 ms; Experiment 2) and short stimulus-onset symmetries (SOAs) (600 ms; Experiment 3) does not result in suppression: The amount of capture nor the efficiency of selection was affected by the cue. If anything, we found an attentional benefit (instead of the suppression) for the short SOA. We argue that through statistical learning, weights within the attentional priority map are changed such that one location containing a salient distractor is suppressed relative to all other locations. Our cueing experiments show that this effect cannot be accomplished by active, top-down suppression. Consequences for recent theories of distractor suppression are discussed.
Directory of Open Access Journals (Sweden)
Yang You-Lan
2011-11-01
Full Text Available Abstract Background Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4. While hesperetin-7,3'-O-dimethylether (HDME is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD. Methods PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th1/Th2 cytokine CBA kits, and total immunoglobulin (IgE or IgG2a levels were done using ELISA method. Xylazine (10 mg/kg/ketamine (70 mg/kg-induced anesthesia was performed. Results HDME revealed selective phosphodiesterase 4 (PDE4 inhibition with a therapeutic (PDE4H/PDE4L ratio of 35.5 in vitro. In vivo, HDME (3~30 μmol/kg, orally (p.o. dose-dependently and significantly attenuated the airway resistance (RL and increased lung dynamic compliance (Cdyn, and decreased enhanced pause (Penh values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF of these mice. In addition, HDME (3~30 μmol/kg, p.o. dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (IgE levels in the BALF and serum, and enhanced IgG2a level in the serum of these mice. Conclusions HDME exerted anti
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.
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
International Nuclear Information System (INIS)
Rettori, V.; Aguila, M.C.; McCann, S.M.; Gimeno, M.F.; Franchi, A.M.
1990-01-01
Previous in vivo studies have shown that Δ 9 -tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E 2 (PGE 2 ) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE 2 suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE 2 synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release
International Nuclear Information System (INIS)
Eitenmueller, K.
1977-01-01
75 patients with suspected hormone-producing autonomous adenoma were examined by the extended TRH assay (BTSH determination, TSH rise 30 min. p.i., and T3 rise 120 min. p.i. 400 μg TRH i.v.) and selective uptake measurements of three different areas of the thyroid using 132 I. The TRH stimulation test alone or the 132 I uptake test alone before and after suppression do not give a clear diagnosis. A clear differentiation of thyroid diseases is only possible if both tests are applied and their results combined. For a differential diagnosis of nodular hyperthyroidism resp. autonomous adenoma, also the TSH stimulation test is necessary in addition to the combination of TRH test and suppression test. (orig./AJ) [de
DEFF Research Database (Denmark)
Wang, Bijue; Chen, Pingping; Jensen, Anne-Christine Bay
2009-01-01
BACKGROUND: Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggreca......BACKGROUND: Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP......- and aggrecanase-derived fragments of aggrecan and type II collagen into the supernatant of bovine cartilage explants cultures using neo-epitope specific immunoassays, and to associate the release of these fragments with the activity of proteolytic enzymes using inhibitors. FINDINGS: Bovine cartilage explants were...... cultured in the presence or absence of the catabolic cytokines oncostatin M (OSM) and tumor necrosis factor alpha (TNFalpha). In parallel, explants were co-cultured with protease inhibitors such as GM6001, TIMP1, TIMP2 and TIMP3. Fragments released into the supernatant were determined using a range of neo...
DEFF Research Database (Denmark)
Connolly, Brian M; Choi, Eun Young; Gårdsvoll, Henrik
2010-01-01
the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure...... a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor....
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
Rieger, S.; Fischedick, M.; Boller, Klaus J.; Fallnich, Carsten
2016-01-01
We report on the first experimental demonstration of the suppression of spontaneous Raman scattering via ground state depletion. The concept of Raman suppression can be used to achieve sub-diffraction-limited resolution in label-free microscopy by exploiting spatially selective signal suppression
International Nuclear Information System (INIS)
Demartis, S.; Tarli, L.; Neri, D.; Borsi, L.; Zardi, L.
2001-01-01
Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211 At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse. (orig.)
The K0/π- ratio and strangeness suppression in νp and anti νp charged current interactions
International Nuclear Information System (INIS)
Jones, G.T.; Kennedy, O.W.; O'Neale, S.W.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.; Towers, S.; Shotton, P.
1984-10-01
Neutral kaon to negative pion production ratios from νp and anti νp charged current interactions in BEBC are presented and compared with LUND fragmentation model predictions. Good agreement is obtained with a strangeness suppression factor lambda = 0.203 +- 0.014(stat) +- 0.010(sys). No evidence is seen for an energy dependence of lambda in our kinematic region. (orig.)
The K0/π- ratio and strangeness suppression in νp and anti νp charged current interactions
International Nuclear Information System (INIS)
Jones, G.T.; Kennedy, O.W.; O'Neale, S.W.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.; Towers, S.; Shotton, P.
1985-01-01
Neutral kaon to negative pion production ratios from νp and anti νp charged current interactions in BEBC are presented and compared with LUND fragmentation model predictions. Good agreement is obtained with a strangeness suppression factor lambda=0.203+-0.014(stat)+-0.010(sys). No evidence is seen for an energy dependence of lambda in our kinematic region. (orig.)
Effective Fragment Potential Method for H-Bonding: How To Obtain Parameters for Nonrigid Fragments.
Dubinets, Nikita; Slipchenko, Lyudmila V
2017-07-20
Accuracy of the effective fragment potential (EFP) method was explored for describing intermolecular interaction energies in three dimers with strong H-bonded interactions, formic acid, formamide, and formamidine dimers, which are a part of HBC6 database of noncovalent interactions. Monomer geometries in these dimers change significantly as a function of intermonomer separation. Several EFP schemes were considered, in which fragment parameters were prepared for a fragment in its gas-phase geometry or recomputed for each unique fragment geometry. Additionally, a scheme in which gas-phase fragment parameters are shifted according to relaxed fragment geometries is introduced and tested. EFP data are compared against the coupled cluster with single, double, and perturbative triple excitations (CCSD(T)) method in a complete basis set (CBS) and the symmetry adapted perturbation theory (SAPT). All considered EFP schemes provide a good agreement with CCSD(T)/CBS for binding energies at equilibrium separations, with discrepancies not exceeding 2 kcal/mol. However, only the schemes that utilize relaxed fragment geometries remain qualitatively correct at shorter than equilibrium intermolecular distances. The EFP scheme with shifted parameters behaves quantitatively similar to the scheme in which parameters are recomputed for each monomer geometry and thus is recommended as a computationally efficient approach for large-scale EFP simulations of flexible systems.
Ambardekar, Vishakha V.; Han, Huai-Yun; Varney, Michelle L.; Vinogradov, Serguei V.; Singh, Rakesh K.; Vetro, Joseph A.
2010-01-01
Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3′ cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. PMID:21047680
Functional imaging correlates of impaired distractor suppression following sleep deprivation.
Kong, Danyang; Soon, Chun Siong; Chee, Michael W L
2012-05-15
Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived. Copyright © 2012 Elsevier Inc. All rights reserved.
Suppression of phase synchronisation in network based on cat's brain.
Lameu, Ewandson L; Borges, Fernando S; Borges, Rafael R; Iarosz, Kelly C; Caldas, Iberê L; Batista, Antonio M; Viana, Ricardo L; Kurths, Jürgen
2016-04-01
We have studied the effects of perturbations on the cat's cerebral cortex. According to the literature, this cortex structure can be described by a clustered network. This way, we construct a clustered network with the same number of areas as in the cat matrix, where each area is described as a sub-network with a small-world property. We focus on the suppression of neuronal phase synchronisation considering different kinds of perturbations. Among the various controlling interventions, we choose three methods: delayed feedback control, external time-periodic driving, and activation of selected neurons. We simulate these interventions to provide a procedure to suppress undesired and pathological abnormal rhythms that can be associated with many forms of synchronisation. In our simulations, we have verified that the efficiency of synchronisation suppression by delayed feedback control is higher than external time-periodic driving and activation of selected neurons of the cat's cerebral cortex with the same coupling strengths.
Energies and Yields of Prompt Gamma Rays from Fragments in Slow-Neutron Induced Fission of 235U
Energy Technology Data Exchange (ETDEWEB)
Albinsson, H [Chalmers Univ. of Technology, Goeteborg (SE)
1971-04-15
Measurements were made on the gamma radiation emitted from fission fragments in slow-neutron induced fission of 235U. The fragments were detected with solid state detectors of the surface barrier type and the gamma radiation with a Nal(Tl) scintillator. Mass selection was used so that the gamma radiation could be measured as a function of fragment mass. Time discrimination between the fission gammas and the prompt neutrons released in the fission process was employed to reduce the background. The gamma radiation emitted during different time intervals after the fission event was studied with the help of a collimator, the position of which was changed along the path of the fission fragments. In this way it was possible to select various collimator settings and let gamma radiation of different half-lives be enhanced. Gamma-ray energy spectra from these time components were then recorded as function of mass. The spectrum shape differed greatly depending on the half-life of the radiation and the fragment from which it was emitted. The results of the present measurements were discussed in the light of existing fission models, and comparisons were made with prompt gamma-ray and neutron data from other fission experiments
Energies and Yields of Prompt Gamma Rays from Fragments in Slow-Neutron Induced Fission of 235U
International Nuclear Information System (INIS)
Albinsson, H.
1971-04-01
Measurements were made on the gamma radiation emitted from fission fragments in slow-neutron induced fission of 235 U. The fragments were detected with solid state detectors of the surface barrier type and the gamma radiation with a Nal(Tl) scintillator. Mass selection was used so that the gamma radiation could be measured as a function of fragment mass. Time discrimination between the fission gammas and the prompt neutrons released in the fission process was employed to reduce the background. The gamma radiation emitted during different time intervals after the fission event was studied with the help of a collimator, the position of which was changed along the path of the fission fragments. In this way it was possible to select various collimator settings and let gamma radiation of different half-lives be enhanced. Gamma-ray energy spectra from these time components were then recorded as function of mass. The spectrum shape differed greatly depending on the half-life of the radiation and the fragment from which it was emitted. The results of the present measurements were discussed in the light of existing fission models, and comparisons were made with prompt gamma-ray and neutron data from other fission experiments
DEFF Research Database (Denmark)
Duan, Zhi; Siegumfeldt, Henrik
2010-01-01
We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....
The effects of habitat fragmentation on extinction risk: Mechanisms and synthesis
Directory of Open Access Journals (Sweden)
David H. Reed
2006-01-01
Full Text Available Across the globe, much current research reflects concerns over the effect of habitat fragmentation on the viability of species and populations. This is an immediate and important concern for the Kingdom of Thailand, where decisions about land use are at a critical juncture. Thailand is in danger of losing species that play a special role in Thai culture and history such as the Asian elephant (Elephas maximus and the tiger (Panthera tigris. We provide a selective review and synthesis of the effects of habitat fragmentation on extinction risk. Our emphasis is on objectives, causal mechanisms, and the validity of some of the arguments that have been made in the debate. Heuristic models are explored to elucidate mechanisms that may affect populations in fragmented landscapes and we point out gaps in our knowledge of this important and complicated question. Our synthesis of the current evidence suggests that fragmenting landscapes usually increases the risk of extinction, especially as the isolation of patches increases or the size of patches decreases. The Kingdom of Thailand, and other countries facing similar circumstances, should seek to connect isolated patches of habitat in order to better protect their remaining biodiversity.
Self-organized criticality in fragmenting
DEFF Research Database (Denmark)
Oddershede, L.; Dimon, P.; Bohr, J.
1993-01-01
The measured mass distributions of fragments from 26 fractured objects of gypsum, soap, stearic paraffin, and potato show evidence of obeying scaling laws; this suggests the possibility of self-organized criticality in fragmenting. The probability of finding a fragment scales inversely to a power...
Segall-Shapiro, Thomas H; Nguyen, Peter Q; Dos Santos, Edgardo D; Subedi, Saurav; Judd, Justin; Suh, Junghae; Silberg, Jonathan J
2011-02-11
The extent to which thermostability influences the location of protein fragmentation sites that allow retention of function is not known. To evaluate this, we used a novel transposase-based approach to create libraries of vectors that express structurally-related fragments of Bacillus subtilis adenylate kinase (BsAK) and Thermotoga neapolitana adenylate kinase (TnAK) with identical modifications at their termini, and we selected for variants in each library that complement the growth of Escherichia coli with a temperature-sensitive adenylate kinase (AK). Mutants created using the hyperthermophilic TnAK were found to support growth with a higher frequency (44%) than those generated from the mesophilic BsAK (6%), and selected TnAK mutants complemented E. coli growth more strongly than homologous BsAK variants. Sequencing of functional clones from each library also identified a greater dispersion of fragmentation sites within TnAK. Nondisruptive fission sites were observed within the AMP binding and core domains of both AK homologs. However, only TnAK contained sites within the lid domain, which undergoes dynamic fluctuations that are critical for catalysis. These findings implicate the flexible lid domain as having an increased sensitivity to fission events at physiological temperatures. In addition, they provide evidence that comparisons of nondisruptive fission sites in homologous proteins could be useful for finding dynamic regions whose conformational fluctuations are important for function, and they show that the discovery of protein fragments that cooperatively function in mesophiles can be aided by the use of thermophilic enzymes as starting points for protein design. Copyright © 2010 Elsevier Ltd. All rights reserved.
Energy production using fission fragment rockets
International Nuclear Information System (INIS)
Chapline, G.; Matsuda, Y.
1991-08-01
Fission fragment rockets are nuclear reactors with a core consisting of thin fibers in a vacuum, and which use magnetic fields to extract the fission fragments from the reactor core. As an alternative to ordinary nuclear reactors, fission fragment rockets would have the following advantages: Approximately twice as efficient if one can directly convert the fission fragment energy into electricity; by reducing the buildup of a fission fragment inventory in the reactor one could avoid a Chernobyl type disaster; and collecting the fission fragments outside the reactor could simplify the waste disposal problem. 6 refs., 4 figs., 2 tabs
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)
Energy Technology Data Exchange (ETDEWEB)
Audias, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires
1965-07-01
This fission fragment detecting apparatus is based on the principle that fragments traversing a thin foil will cause emission of secondary electrons. These electrons are then accelerated (10 kV) and directly detected by means of a plastic scintillator and associated photomultiplier. Some of the advantages of such a detector are, its rapidity, its discriminating power between alpha particles and fission fragments, its small energy loss in detecting the fragments and the relatively great amount of fissionable material which it can contain. This paper is subdivided as follows: a) theoretical considerations b) constructional details of apparatus and some experimental details and c) a study of the secondary emission effect itself. (author) [French] Le detecteur de fragments de fission que nous avons realise est base sur le principe de l'emission secondaire produite par les fragments de fission traversant une feuille mince: les electrons secondaires emis sont acceleres a des tensions telles (de l'ordre de 10 kV), qu'ils soient directement detectables par un scintillateur plastique associe a un photomultiplicateur. L'interet d'un tel detecteur reside: dans sa rapidite, sa tres bonne discrimination alpha, fission, la possibilite de detecter les fragments de fission avec une perte d'energie pouvant rester relativement faible, et la possibilite d'introduire des quantites de matiere fissile plus importantes que dans les autres types de detecteurs. Ce travail comporte: -) un apercu bibliographique de la theorie du phenomene, -) realisation et mise au point du detecteur avec etude experimentale de quelques parametres intervenant dans l'emission secondaire, -) etude de l'emission secondaire (sur la face d'emergence des fragments de fission) en fonction de l'energie du fragment et en fonction de l'epaisseur de matiere traversee avant emission secondaire, et -) une etude comparative de l'emission secondaire sur la face d'incidence et sur la face d'emergence des fragments de
Older Adults Can Suppress Unwanted Memories When Given an Appropriate Strategy
2015-01-01
Memory suppression refers to the ability to exclude distracting memories from conscious awareness, and this ability can be assessed with the think/no-think paradigm. Recent research with older adults has provided evidence suggesting both intact and deficient memory suppression. The present studies seek to understand the conditions contributing to older adults’ ability to suppress memories voluntarily. We report 2 experiments indicating that the specificity of the think/no-think task instructions contributes to older adults’ suppression success: When older adults receive open-ended instructions that require them to develop a retrieval suppression strategy on their own, they show diminished memory suppression compared with younger adults. Conversely, when older adults receive focused instructions directing them to a strategy thought to better isolate inhibitory control, they show suppression-induced forgetting similar to that exhibited by younger adults. Younger adults demonstrate memory suppression regardless of the specificity of the instructions given, suggesting that the ability to select a successful suppression strategy spontaneously may be compromised in older adults. If so, this deficit may be associated with diminished control over unwanted memories in naturalistic settings if impeded strategy development reduces the successful deployment of inhibitory control. PMID:25602491
Thermodynamics of the fuel fragmentation gas
International Nuclear Information System (INIS)
Perez, R.B.; Alsmiller, R.G. Jr.
1977-01-01
In the context of nuclear reactor safety studies, a program is in progress at ORNL whereby fuel-fragmentation situations are mocked up by the application of high-current capacitor discharges through solid UO 2 samples. The goal of the present work is to predict such quantities as the number of gas and liquid fragments and their energy distributions. The point of view adopted is that upon fragmentation, a cloud of UO 2 vapor is formed containing ''primeval'' liquid fragments which act as condensation centers. In the evolution of time, fragment growth is controlled by nucleation, coagulation and evaporation processes. Eventually, the vapor-droplet system will reach a situation in which clusters (fragments) of various sizes and UO 2 vapor will coexist in an ''association-disassociation'' equilibrium. Thus, the physical model considered here consists of the identification of the fragmentation gas with an ''imperfect'' vapor, made up of interacting UO 2 vapor and liquid fragments. The results of the study are presented
Chen, Chao; Zhao, Xinqing; Jin, Yingyu; Zhao, Zongbao Kent; Suh, Joo-Won
2014-11-01
Bacterial artificial chromosomal (BAC) vectors are increasingly being used in cloning large DNA fragments containing complex biosynthetic pathways to facilitate heterologous production of microbial metabolites for drug development. To express inserted genes using Streptomyces species as the production hosts, an integration expression cassette is required to be inserted into the BAC vector, which includes genetic elements encoding a phage-specific attachment site, an integrase, an origin of transfer, a selection marker and a promoter. Due to the large sizes of DNA inserted into the BAC vectors, it is normally inefficient and time-consuming to assemble these fragments by routine PCR amplifications and restriction-ligations. Here we present a rapid method to insert fragments to construct BAC-based expression vectors. A DNA fragment of about 130 bp was designed, which contains upstream and downstream homologous sequences of both BAC vector and pIB139 plasmid carrying the whole integration expression cassette. In-Fusion cloning was performed using the designer DNA fragment to modify pIB139, followed by λ-RED-mediated recombination to obtain the BAC-based expression vector. We demonstrated the effectiveness of this method by rapid construction of a BAC-based expression vector with an insert of about 120 kb that contains the entire gene cluster for biosynthesis of immunosuppressant FK506. The empty BAC-based expression vector constructed in this study can be conveniently used for construction of BAC libraries using either microbial pure culture or environmental DNA, and the selected BAC clones can be directly used for heterologous expression. Alternatively, if a BAC library has already been constructed using a commercial BAC vector, the selected BAC vectors can be manipulated using the method described here to get the BAC-based expression vectors with desired gene clusters for heterologous expression. The rapid construction of a BAC-based expression vector facilitates
The dual role of fragments in fragment-assembly methods for de novo protein structure prediction
Handl, Julia; Knowles, Joshua; Vernon, Robert; Baker, David; Lovell, Simon C.
2013-01-01
In fragment-assembly techniques for protein structure prediction, models of protein structure are assembled from fragments of known protein structures. This process is typically guided by a knowledge-based energy function and uses a heuristic optimization method. The fragments play two important roles in this process: they define the set of structural parameters available, and they also assume the role of the main variation operators that are used by the optimiser. Previous analysis has typically focused on the first of these roles. In particular, the relationship between local amino acid sequence and local protein structure has been studied by a range of authors. The correlation between the two has been shown to vary with the window length considered, and the results of these analyses have informed directly the choice of fragment length in state-of-the-art prediction techniques. Here, we focus on the second role of fragments and aim to determine the effect of fragment length from an optimization perspective. We use theoretical analyses to reveal how the size and structure of the search space changes as a function of insertion length. Furthermore, empirical analyses are used to explore additional ways in which the size of the fragment insertion influences the search both in a simulation model and for the fragment-assembly technique, Rosetta. PMID:22095594
Molecular-Simulation-Driven Fragment Screening for the Discovery of New CXCL12 Inhibitors.
Martinez-Rosell, Gerard; Harvey, Matt J; De Fabritiis, Gianni
2018-03-26
Fragment-based drug discovery (FBDD) has become a mainstream approach in drug design because it allows the reduction of the chemical space and screening libraries while identifying fragments with high protein-ligand efficiency interactions that can later be grown into drug-like leads. In this work, we leverage high-throughput molecular dynamics (MD) simulations to screen a library of 129 fragments for a total of 5.85 ms against the CXCL12 monomer, a chemokine involved in inflammation and diseases such as cancer. Our in silico binding assay was able to recover binding poses, affinities, and kinetics for the selected library and was able to predict 8 mM-affinity fragments with ligand efficiencies higher than 0.3. All of the fragment hits present a similar chemical structure, with a hydrophobic core and a positively charged group, and bind to either sY7 or H1S68 pockets, where they share pharmacophoric properties with experimentally resolved natural binders. This work presents a large-scale screening assay using an exclusive combination of thousands of short MD adaptive simulations analyzed with a Markov state model (MSM) framework.
Models of fragmentation with composite power laws
Tavassoli, Z.; Rodgers, G. J.
1999-06-01
Some models for binary fragmentation are introduced in which a time dependent transition size produces two regions of fragment sizes above and below the transition size. In the first model we assume a fixed rate of fragmentation for the largest fragment and two different rates of fragmentation in the two regions of sizes above and below the transition size. The model is solved exactly in the long time limit to reveal stable time-invariant solutions for the fragment size and mass distributions. These solutions exhibit composite power law behaviours; power laws with two different exponents for fragments in smaller and larger regions. A special case of the model with no fragmentation in the smaller size region is also examined. Another model is also introduced which have three regions of fragment sizes with different rates of fragmentation. The similarities between the stable distributions in our models and composite power law distributions from experimental work on shock fragmentation of long thin glass rods and thick clay plates are discussed.
Kinetics of fragmentation-annihilation processes
Filipe, JAN; Rodgers, GJ
1996-01-01
We investigate the kinetics of systems in which particles of one species undergo binary fragmentation and pair annihilation. In the latter, nonlinear process, fragments react at collision to produce an inert species, causing loss of mass. We analyze these systems in the reaction-limited regime by solving a continuous model within the mean-field approximation. The rate of fragmentation for a particle of mass x to break into fragments of masses y and x-y has the form x(lambda-1) (lambda > 0), a...
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
Zella, Julia B; Plum, Lori A; Plowchalk, David R; Potochoiba, Michael; Clagett-Dame, Margaret; DeLuca, Hector F
2014-01-01
The use of 1α-hydroxylated vitamin D therapy to control secondary hyperparathyroidism in renal failure patients has been a success story, culminating with the demonstration of increased life expectancy in patients treated with these compounds. However, hypercalcemic episodes have been a recurrent problem with these therapies and have resulted in the added use of calcium mimetics. Clearly there is good reason to search for improved vitamin D therapy. In our inventory of vitamin D compounds, 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 (2MD) surfaced as a potential candidate. This was based on its preferential localization in the parathyroid gland and a clear suppression of serum parathyroid hormone (PTH) levels without a change in serum calcium in a clinical trial in postmenopausal women. 2MD has now been tested in the rat 5/6-nephrectomy model of renal failure, and in postmenopausal women to determine if it can suppress serum PTH at doses that do not elevate serum calcium and serum phosphorus concentrations. Daily oral treatment of uremic rats on 2.5 ng/bw/day of 2MD dramatically suppressed PTH without a change in serum calcium or serum phosphorus. Further, PTH was suppressed in postmenopausal women after only 3 daily oral doses of 2MD that continued for 4 weeks with no change in serum calcium or serum phosphorus. These results coupled with a pharmacokinetic half-life of ~24 h suggest that 2MD given either daily or at the time of dialysis may be a superior therapy for secondary hyperparathyroidism in chronic renal failure patients.
Feature-selective attention in healthy old age: a selective decline in selective attention?
Quigley, Cliodhna; Müller, Matthias M
2014-02-12
Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.
Performances of Different Fragment Sizes for Reduced Representation Bisulfite Sequencing in Pigs.
Yuan, Xiao-Long; Zhang, Zhe; Pan, Rong-Yang; Gao, Ning; Deng, Xi; Li, Bin; Zhang, Hao; Sangild, Per Torp; Li, Jia-Qi
2017-01-01
Reduced representation bisulfite sequencing (RRBS) has been widely used to profile genome-scale DNA methylation in mammalian genomes. However, the applications and technical performances of RRBS with different fragment sizes have not been systematically reported in pigs, which serve as one of the important biomedical models for humans. The aims of this study were to evaluate capacities of RRBS libraries with different fragment sizes to characterize the porcine genome. We found that the Msp I-digested segments between 40 and 220 bp harbored a high distribution peak at 74 bp, which were highly overlapped with the repetitive elements and might reduce the unique mapping alignment. The RRBS library of 110-220 bp fragment size had the highest unique mapping alignment and the lowest multiple alignment. The cost-effectiveness of the 40-110 bp, 110-220 bp and 40-220 bp fragment sizes might decrease when the dataset size was more than 70, 50 and 110 million reads for these three fragment sizes, respectively. Given a 50-million dataset size, the average sequencing depth of the detected CpG sites in the 110-220 bp fragment size appeared to be deeper than in the 40-110 bp and 40-220 bp fragment sizes, and these detected CpG sties differently located in gene- and CpG island-related regions. In this study, our results demonstrated that selections of fragment sizes could affect the numbers and sequencing depth of detected CpG sites as well as the cost-efficiency. No single solution of RRBS is optimal in all circumstances for investigating genome-scale DNA methylation. This work provides the useful knowledge on designing and executing RRBS for investigating the genome-wide DNA methylation in tissues from pigs.
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.
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.
Fragmentation of atomic clusters: A theoretical study
International Nuclear Information System (INIS)
Lopez, M.J.; Jellinek, J.
1994-01-01
Collisionless fragmentation of nonrotating model n-atom metal clusters (n=12, 13, and 14) is studied using isoergic molecular-dynamics simulations. Minimum-energy paths for fragmentation are mapped out as functions of the distance between the centers of mass of the fragments. These paths provide information on the fragmentation energies for the different fragmentation channels. Fragmentation patterns (distributions of the fragmentation channel probabilities) and global and channel-specific fragmentation rate constants are computed and analyzed as functions of the internal energy and of the size of the clusters. The trends derived from the dynamics are compared with those obtained using the RRK and TST statistical approaches. The dynamics of the fragmentation process is analyzed in terms of characteristic quantities such as the distance between the centers of mass of the fragments, their relative translational energy, and their interaction energy, all considered as functions of time
How does methylation suppress the electron-induced decomposition of 1-methyl-nitroimidazoles?
Kossoski, F.; Varella, M. T. do N.
2017-10-01
The efficient decomposition of nitroimidazoles (NIs) by low energy electrons is believed to underlie their radiosensitizing properties. Recent dissociative electron attachment (DEA) measurements showed that methylation at the N1 site unexpectedly suppresses the electron-induced reactions in 4(5)-NI. We report theoretical results that provide a clear interpretation of that astounding finding. Around 1.5 eV, DEA reactions into several fragments are initiated by a π* resonance, not considered in previous studies. The autoionization lifetime of this anion state, which limits the predissociation dynamics, is considerably shorter in the methylated species, thereby suppressing the DEA signals. On the other hand, the lifetime of the π* resonance located around 3 eV is less affected by methylation, which explains why DEA is still observed at these energies. Our results demonstrate how even a simple methylation can significantly modify the probabilities for DEA reactions, which may be significant for NI-based cancer therapy.
Klocko, Amy L.; Borejsza-Wysocka, Ewa; Brunner, Amy M.; Shevchenko, Olga; Aldwinckle, Herb; Strauss, Steven H.
2016-01-01
We investigated the ability of RNA interference (RNAi) directed against two co-orthologs of AGAMOUS (AG) from Malus domestica (domestic apple, MdAG) to reduce the risks of invasiveness and provide genetic containment of transgenes, while also promoting the attractiveness of flowers for ornamental usage. Suppression of two MdAG-like genes, MdMADS15 and MdMADS22, led to the production of trees with highly showy, polypetalous flowers. These “double-flowers” had strongly reduced expression of both MdAG-like genes. Members of the two other clades within in the MdAG subfamily showed mild to moderate differences in gene expression, or were unchanged, with the level of suppression approximately proportional to the level of sequence identity between the gene analyzed and the RNAi fragment. The double-flowers also exhibited reduced male and female fertility, had few viable pollen grains, a decreased number of stigmas, and produced few viable seeds after cross-pollination. Despite these floral alterations, RNAi-AG trees with double-flowers set full-sized fruit. Suppression or mutation of apple AG-like genes appears to be a promising method for combining genetic containment with improved floral attractiveness. PMID:27500731
Harel, Assaf; Ullman, Shimon; Harari, Danny; Bentin, Shlomo
2011-07-28
Visual expertise is usually defined as the superior ability to distinguish between exemplars of a homogeneous category. Here, we ask how real-world expertise manifests at basic-level categorization and assess the contribution of stimulus-driven and top-down knowledge-based factors to this manifestation. Car experts and novices categorized computer-selected image fragments of cars, airplanes, and faces. Within each category, the fragments varied in their mutual information (MI), an objective quantifiable measure of feature diagnosticity. Categorization of face and airplane fragments was similar within and between groups, showing better performance with increasing MI levels. Novices categorized car fragments more slowly than face and airplane fragments, while experts categorized car fragments as fast as face and airplane fragments. The experts' advantage with car fragments was similar across MI levels, with similar functions relating RT with MI level for both groups. Accuracy was equal between groups for cars as well as faces and airplanes, but experts' response criteria were biased toward cars. These findings suggest that expertise does not entail only specific perceptual strategies. Rather, at the basic level, expertise manifests as a general processing advantage arguably involving application of top-down mechanisms, such as knowledge and attention, which helps experts to distinguish between object categories. © ARVO
Compton suppression through rise-time analysis
International Nuclear Information System (INIS)
Selvi, S.; Celiktas, C.
2007-01-01
We studied Compton suppression for 60 Co and 137 Cs radioisotopes using a signal selection criterion based on contrasting the fall time of the signals composing the photo peak with those composing the Compton continuum. The fall time criterion is employed by using the pulse shape analysis observing the change in the fall times of the gamma-ray pulses. This change is determined by measuring the changes in the rise times related to the fall time of the scintillator and the timing signals related to the fall time of the input signals. We showed that Compton continuum suppression is achieved best via the precise timing adjustment of an analog rise-time analyzer connected to a NaI(Tl) scintillation spectrometer
DNA fragmentation in spermatozoa
DEFF Research Database (Denmark)
Rex, A S; Aagaard, J.; Fedder, J
2017-01-01
Sperm DNA Fragmentation has been extensively studied for more than a decade. In the 1940s the uniqueness of the spermatozoa protein complex which stabilizes the DNA was discovered. In the fifties and sixties, the association between unstable chromatin structure and subfertility was investigated....... In the seventies, the impact of induced DNA damage was investigated. In the 1980s the concept of sperm DNA fragmentation as related to infertility was introduced as well as the first DNA fragmentation test: the Sperm Chromatin Structure Assay (SCSA). The terminal deoxynucleotidyl transferase nick end labelling...... (TUNEL) test followed by others was introduced in the nineties. The association between DNA fragmentation in spermatozoa and pregnancy loss has been extensively investigated spurring the need for a therapeutic tool for these patients. This gave rise to an increased interest in the aetiology of DNA damage...
Valjakka, J; Hemminki, A; Teerinen, T; Takkinen, K; Rouvinen, J
2000-02-01
Recombinant anti-testosterone wild-type Fab fragment and mutant Fab fragments with high binding selectivity developed by protein engineering have been crystallized with and without ligands. Crystals of these Fab fragments were obtained by the vapour-diffusion technique at room temperature using solutions of PEG 3350 with various biological buffers and with a wide pH range. So far, five data sets have been collected from crystals of three Fab-antigen complexes and from two uncomplexed Fab fragments, with resolutions ranging from 2.10 to 3.1 A. Crystallization conditions for Fab fragments were found by using modifications of the low ionic strength PEG 3350 series. Suitable concentrations of PEG 400, MPD and glycerol solutions for use as cryoprotectants in PEG 3350 solutions have been determined. One useful observation was that PEG 3350 is able to work alone as a cryoprotectant. The screening protocol used requires a smaller amount of protein material to achieve auspicious pre-crystals than previously. Results support the claim that PEG 3350 is more suitable for the crystallization of Fab fragments than higher molecular weight PEGs.
Directory of Open Access Journals (Sweden)
Rashmi Choudhary
2010-03-01
Full Text Available Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ inhibits transformed growth of non-small cell lung cancer (NSCLC cell lines in vitro and in vivo. We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1, Slug (Snail2, and ZEB1, is an important regulator of epithelial-mesenchymal transition, as well as cell survival. The goal of this study was to determine whether the biological responses to rosiglitazone, a member of the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 and matrix metaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal-regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators.
Wehrmann, A; Eggeling, L; Sahm, H
1994-12-01
In Corynebacterium glutamicum L-lysine is synthesized simultaneously via the succinylase and dehydrogenase variant of the diaminopimelate pathway. Starting from a strain with a disrupted dehydrogenase gene, three different-sized DNA fragments were isolated which complemented defective Escherichia coli mutants in the succinylase pathway. Enzyme studies revealed that in one case the dehydrogenase gene had apparently been reconstituted in the heterologous host. The two other fragments resulted in desuccinylase activity; one of them additionally in succinylase activity. However, the physical analysis showed that structural changes had taken place in all fragments. Using a probe derived from one of the fragments we isolated a 3.4 kb BamHI DNA fragment without selective pressure (by colony hybridization). This was structurally intact and proved functionally to result in tenfold desuccinylase overexpression. The nucleotide sequence of a 1966 bp fragment revealed the presence of one truncated open reading frame of unknown function and that of dapE encoding N-succinyl diaminopimelate desuccinylase (EC 3.5.1.18). The deduced amino acid sequence of the dapE gene product shares 23% identical residues with that from E. coli. The C. glutamicum gene now available is the first gene from the succinylase branch of lysine synthesis of this biotechnologically important organism.
Zhen, Junfeng; Castellanos, Pablo; Linnartz, Harold; Tielens, Alexander G. G. M.
2016-11-01
A systematic study, using ion trap time-of-flight mass spectrometry, is presented for the photo-fragmentation of methyl- and methoxy-substituted derivatives of HBC cations, (OCH3)6HBC+ and (CH3)4(OCH3)2HBC+. Both substituted HBC cations fragment through sequential loss of CH3CO units upon laser (595nm) irradiation, resulting in a PAH-like derivative C36H12+ and a methyl-substituted PAH derivative C44H24+ , respectively. Upon ongoing irradiation, these species further fragment. For lower laser energy C44H24+ dehydrogenates and photo-fragments through CH3 and CHCH2 unit losses; for higher laser energy isomerization takes place, yielding a regular PAH-like configuration, and both stepwise dehydrogenation and C2/C2H2 loss pathways are found. C36H12+ follows largely this latter fragmentation scheme upon irradiation. It is concluded that the photo-dissociation mechanism of the substituted PAH cations studied here is site selective in the substituted subunit. This work also shows experimental evidence that photo-fragmentation of substituted PAHs may contribute to the formation in space of smaller species that are normally considered to form by merging atoms and molecules.
Recent progress on perturbative QCD fragmentation functions
International Nuclear Information System (INIS)
Cheung, K.
1995-05-01
The recent development of perturbative QCD (PQCD) fragmentation functions has strong impact on quarkonium production. I shall summarize B c meson production based on these PQCD fragmentation functions, as well as, the highlights of some recent activities on applying these PQCD fragmentation functions to explain anomalous J/ψ and ψ' production at the Tevatron. Finally, I discuss a fragmentation model based on the PQCD fragmentation functions for heavy quarks fragmenting into heavy-light mesons
Spatial- and Time-Correlated Detection of Fission Fragments
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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.
Fragmentation and flow in central collisions
International Nuclear Information System (INIS)
Jacak, B.V.; Doss, K.G.R.; Gustafsson, H.A.
1987-01-01
Investigation of the fragmentation mechanism requires the measurement of complicated observables. To identify what part of the reacting system gives rise to the fragments, it would be useful to tag them as participants or spectators. A large acceptance for all the reaction products and an event-by-event measurement of the fragment multiplicity is required to distinguish fragment formation via sequential emission from a large equilibrated system and multifragmentation. In order to address whether fragments are formed early or late in the collision, information about the dynamical evolution of the reaction is necessary. This can be provided by study of the global properties of the events. This paper discusses experimental techniques applicable to studying fragmentation processes. 25 refs., 8 figs
David J. Flaspohler; Christian P. Giardina; Gregory P. Asner; Patrick Hart; Jonathan Price; Cassie Ka’apu Lyons; Xeronimo. Castaneda
2010-01-01
Forest fragmentation is a common disturbance affecting biological diversity, yet the impacts of fragmentation on many forest processes remain poorly understood. Forest restoration is likely to be more successful when it proceeds with an understanding of how native and exotic vertebrates utilize forest patches of different size. We used a system of forest fragments...
Mass spectrometry for fragment screening.
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.
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.
Physics of projectile fragments
International Nuclear Information System (INIS)
Minamisono, Tadanori
1982-01-01
This is a study report on the polarization phenomena of the projectile fragments produced by heavy ion reactions, and the beta decay of fragments. The experimental project by using heavy ions with the energy from 50 MeV/amu to 250 MeV/amu was designed. Construction of an angle-dispersion spectrograph for projectile fragments was proposed. This is a two-stage spectrograph. The first stage is a QQDQQ type separator, and the second stage is QDQD type. Estimation shows that Co-66 may be separated from the nuclei with mass of 65 and 67. The orientation of fragments can be measured by detecting beta-ray. The apparatus consists of a uniform field magnet, an energy absorber, a stopper, a RF coil and a beta-ray hodoscope. This system can be used for not only this purpose but also for the measurement of hyperfine structure. (Kato, T.)
Fragment-Based Drug Discovery in the Bromodomain and Extra-Terminal Domain Family.
Radwan, Mostafa; Serya, Rabah
2017-08-01
Bromodomain and extra-terminal domain (BET) inhibition has emerged recently as a potential therapeutic target for the treatment of many human disorders such as atherosclerosis, inflammatory disorders, chronic obstructive pulmonary disease (COPD), some viral infections, and cancer. Since the discovery of the two potent inhibitors, I-BET762 and JQ1, different research groups have used different techniques to develop novel potent and selective inhibitors. In this review, we will be concerned with the trials that used fragment-based drug discovery (FBDD) approaches to discover or optimize BET inhibitors, also showing fragments that can be further optimized in future projects to reach novel potent BET inhibitors. © 2017 Deutsche Pharmazeutische Gesellschaft.
Prompt Gamma Radiation from Fragments in the Thermal Fission of 235U
International Nuclear Information System (INIS)
Albinsson, H.; Lindow, L.
1970-06-01
Measurements were made on the gamma radiation emitted from fission fragments in slow neutron induced fission of 235 U. The fragments were detected with solid state detectors of the surface barrier type and the gamma radiation with a Nal(Tl) scintillator. Mass selection was used so that the gamma radiation could be measured as a function of fragment mass. Time discrimination between the fission gammas and the prompt neutrons released in the fission process was employed to reduce the background. The gamma radiation emitted during different time intervals after the fission event was studied with the help of a collimator, the position of which was changed along the path of the fission fragments. In this way a decay curve was obtained from which the life-time of one of the gamma-emitting states could be estimated. The relative yield of the gamma-rays was determined as a function of mass for different gamma-ray energy portions and two specific time intervals after the fission events. Comparisons were made with data obtained from 252 Cf-fission. Attention is drawn to some features which seem to be the same in 235 U and 252 Cf-fission
Directory of Open Access Journals (Sweden)
Elsharkawy Karim
2017-01-01
Full Text Available This paper describes formulations of plastic bonded explosives (PBXs based on three highly brisant explosives, namely 1,3,5-trinitro-1,3,5-triazinane (RDX, 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX and pentaerythritoltetranitrate (PETN with polyurethane (PU based on Glycidyl azide polymer (GAP as an energetic binder in comparison with composition-B, which used in the fragmentation warheads. The sensitivity and performance properties of different types of PBXs were evaluated by experimental results of prepared selected PBX compositions. Casting technique was used to prepare the selected compositions containing 14% PU based on GAP. It has been observed that the brisance of the PBX based on HMX was higher than that of comp-B by 21.3 %, the detonation velocity showed a remarkable increase of the order of 8480 (m/s while that of comp-B was 7638 (m/s. A controlled fragmentation warhead with an outer grooving warhead case of dimensions 100x35x4 mm was used and arena test was carried out to determine the lethal zone of the fragmentation warhead. The lethal zone obtained from arena test for PBX composition based on HMX named PBXHG4 was higher than that based on RDX or PETN, and than that of comp-B by 40%.
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.
MRI of displaced meniscal fragments
International Nuclear Information System (INIS)
Dunoski, Brian; Zbojniewicz, Andrew M.; Laor, Tal
2012-01-01
A torn meniscus frequently requires surgical fixation or debridement as definitive treatment. Meniscal tears with associated fragment displacement, such as bucket handle and flap tears, can be difficult to recognize and accurately describe on MRI, and displaced fragments can be challenging to identify at surgery. A displaced meniscal fragment can be obscured by synovium or be in a location not usually evaluated at arthroscopy. We present a pictorial essay of meniscal tears with displaced fragments in patients referred to a pediatric hospital in order to increase recognition and accurate interpretation by the radiologist, who in turn can help assist the surgeon in planning appropriate therapy. (orig.)
MRI of displaced meniscal fragments
Energy Technology Data Exchange (ETDEWEB)
Dunoski, Brian [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Children' s Hospital of Michigan, Department of Radiology, Detroit, MI (United States); Zbojniewicz, Andrew M.; Laor, Tal [University of Cincinnati College of Medicine, Department of Radiology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States)
2012-01-15
A torn meniscus frequently requires surgical fixation or debridement as definitive treatment. Meniscal tears with associated fragment displacement, such as bucket handle and flap tears, can be difficult to recognize and accurately describe on MRI, and displaced fragments can be challenging to identify at surgery. A displaced meniscal fragment can be obscured by synovium or be in a location not usually evaluated at arthroscopy. We present a pictorial essay of meniscal tears with displaced fragments in patients referred to a pediatric hospital in order to increase recognition and accurate interpretation by the radiologist, who in turn can help assist the surgeon in planning appropriate therapy. (orig.)
Dimensional crossover in fragmentation
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.
Directory of Open Access Journals (Sweden)
Yiming Liu
2016-10-01
Full Text Available Agrobacterium overgrowth is a common problem in Agrobacterium-mediated plant transfor-mation. To suppress the Agrobacterium overgrowth, various antibiotics have been used during plant tissue culture steps. The antibiotics are expensive and may adversely affect plant cell differentiation and reduce plant transformation efficiency. The SacB-SacR proteins are toxic to most Agrobacterium tumefaciens strains when they are grown on culture medium sup¬plemented with sucrose. Therefore, SacB-SacR genes can be used as negative selection markers to suppress the overgrowth of Agrobacterium tumefaciens in the plant tissue culture process. We generated a mutant Agrobacterium tumefaciens strain GV2260 (recA-SacB/R that has the SacB-SacR cassette inserted into the bacterial genome at the recA gene locus. The mutant Agrobacterium strain is sensitive to sucrose but maintains its ability to transform plant cells in both transient and stable transformation assays. We demonstrated that the mutant strain GV2260 (recA-SacB/R can be inhibited by sucrose that reduces the overgrowth of Agrobacterium and therefore improves the plant transformation efficiency. We employed GV2260 (recA-SacB/R to generate stable transgenic N. benthamiana plants expressing a CRISPR-Cas9 for knocking out a WRKY transcrip¬tion factor.
Measuring colour rivalry suppression in amblyopia.
Hofeldt, T S; Hofeldt, A J
1999-11-01
To determine if the colour rivalry suppression is an index of the visual impairment in amblyopia and if the stereopsis and fusion evaluator (SAFE) instrument is a reliable indicator of the difference in visual input from the two eyes. To test the accuracy of the SAFE instrument for measuring the visual input from the two eyes, colour rivalry suppression was measured in six normal subjects. A test neutral density filter (NDF) was placed before one eye to induce a temporary relative afferent defect and the subject selected the NDF before the fellow eye to neutralise the test NDF. In a non-paediatric private practice, 24 consecutive patients diagnosed with unilateral amblyopia were tested with the SAFE. Of the 24 amblyopes, 14 qualified for the study because they were able to fuse images and had no comorbid disease. The relation between depth of colour rivalry suppression, stereoacuity, and interocular difference in logMAR acuity was analysed. In normal subjects, the SAFE instrument reversed temporary defects of 0.3 to 1. 8 log units to within 0.6 log units. In amblyopes, the NDF to reverse colour rivalry suppression was positively related to interocular difference in logMAR acuity (beta=1.21, psuppression as measured with the SAFE was found to agree closely with the degree of visual acuity impairment in non-paediatric patients with amblyopia.
Directory of Open Access Journals (Sweden)
Eric Wajnberg
Full Text Available Expansion and intensification of human land use represents the major cause of habitat fragmentation. Such fragmentation can have dramatic consequences on species richness and trophic interactions within food webs. Although the associated ecological consequences have been studied by several authors, the evolutionary effects on interacting species have received little research attention. Using a genetic algorithm, we quantified how habitat fragmentation and environmental variability affect the optimal reproductive strategies of parasitic wasps foraging for hosts. As observed in real animal species, the model is based on the existence of a negative trade-off between survival and reproduction resulting from competitive allocation of resources to either somatic maintenance or egg production. We also asked to what degree plasticity along this trade-off would be optimal, when plasticity is costly. We found that habitat fragmentation can indeed have strong effects on the reproductive strategies adopted by parasitoids. With increasing habitat fragmentation animals should invest in greater longevity with lower fecundity; yet, especially in unpredictable environments, some level of phenotypic plasticity should be selected for. Other consequences in terms of learning ability of foraging animals were also observed. The evolutionary consequences of these results are discussed.
Wu, Te-Haw; Liu, Ching-Ping; Chien, Chih-Te; Lin, Shu-Yi
2013-08-26
Herein, a promising sensing approach based on the structure fragmentation of poly(amidoamine) (PAMAM) dendrimers for the selective detection of intracellular hypochlorite (OCl(-)) is reported. PAMAM dendrimers were easily disrupted by a cascade of oxidations in the tertiary amines of the dendritic core to produce an unsaturated hydroxylamine with blue fluorescence. Specially, the novel fluorophore was only sensitive to OCl(-), one of reactive oxygen species (ROS), resulting in an irreversible fluorescence turn-off. The fluorescent hydroxylamine was selectively oxidised by OCl(-) to form a labile oxoammonium cation that underwent further degradation. Without using any troublesomely synthetic steps, the novel sensing platform based on the fragmentation of PAMAM dendrimers, can be applied to detect OCl(-) in macrophage cells. The results suggest that the sensing approach may be useful for the detection of intracellular OCl(-) with minimal interference from biological matrixes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Energy Technology Data Exchange (ETDEWEB)
Ogawa, T., E-mail: ogawa.tatsuhiko@jaea.go.jp [Research Group for Radiation Protection, Division of Environment and Radiation Sciences, Nuclear Science and Engineering Directorate, Japan Atomic Energy Agency, Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Sato, T.; Hashimoto, S. [Research Group for Radiation Protection, Division of Environment and Radiation Sciences, Nuclear Science and Engineering Directorate, Japan Atomic Energy Agency, Shirakata-Shirane, Tokai, Ibaraki 319-1195 (Japan); Niita, K. [Research Organization for Information Science and Technology, Shirakata-shirane, Tokai, Ibaraki 319-1188 (Japan)
2013-09-21
The fragmentation cross-sections of relativistic energy nucleus–nucleus collisions were analyzed using the statistical multi-fragmentation model (SMM) incorporated with the Monte-Carlo radiation transport simulation code particle and heavy ion transport code system (PHITS). Comparison with the literature data showed that PHITS-SMM reproduces fragmentation cross-sections of heavy nuclei at relativistic energies better than the original PHITS by up to two orders of magnitude. It was also found that SMM does not degrade the neutron production cross-sections in heavy ion collisions or the fragmentation cross-sections of light nuclei, for which SMM has not been benchmarked. Therefore, SMM is a robust model that can supplement conventional nucleus–nucleus reaction models, enabling more accurate prediction of fragmentation cross-sections.
International Nuclear Information System (INIS)
Ogawa, T.; Sato, T.; Hashimoto, S.; Niita, K.
2013-01-01
The fragmentation cross-sections of relativistic energy nucleus–nucleus collisions were analyzed using the statistical multi-fragmentation model (SMM) incorporated with the Monte-Carlo radiation transport simulation code particle and heavy ion transport code system (PHITS). Comparison with the literature data showed that PHITS-SMM reproduces fragmentation cross-sections of heavy nuclei at relativistic energies better than the original PHITS by up to two orders of magnitude. It was also found that SMM does not degrade the neutron production cross-sections in heavy ion collisions or the fragmentation cross-sections of light nuclei, for which SMM has not been benchmarked. Therefore, SMM is a robust model that can supplement conventional nucleus–nucleus reaction models, enabling more accurate prediction of fragmentation cross-sections
Energy Technology Data Exchange (ETDEWEB)
Rettori, V.; Aguila, M.C.; McCann, S.M. (Univ. of Texas Southwestern Medical Center at Dallas (United States)); Gimeno, M.F.; Franchi, A.M. (Centro de Estudios Farmacologicos y de Principios Naturales, Buenos Aires (Argentina))
1990-12-01
Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.
International Nuclear Information System (INIS)
Takahashi, Hideo; Igarashi, Takako; Shimada, Ichio; Arata, Yoji
1991-01-01
The Fv fragment, a univalent antigen-binding unit with a molecular weight of 25,000, has successfully been prepared in high yield by limited proteolysis with clostripain of a short-chain mouse IgG2a anti-dansyl monoclonal antibody in which the entire C H 1 domain is deleted. The Fv fragment obtained is stable at room temperature and retains its full antigen-binding capability. It has been shown that selective deuterium labeling of the Fv fragment, which is half the size of the Fab fragment, provides 1 H NMR spectral data at a sufficient resolution for a detailed structural analysis of the antigen-combining site. NOESY spectra of an Fv analogue, in which all aromatic protons except for His C2'-H and Tyr C3',5'-H had been deuterated, were measured in the presence of varying amounts of dansyl-L-lysine. On the basis of the NOESY data obtained, it was possible to assign all the ring proton resonances for the dansly group that is bound to the Fv fragment. It was also possible to obtain information about His and Tyr residues of the Fv fragment in the absence and presence of the antigen. On the basis of the NMR data obtained, the authors have shown that at least two Tyr residues along with one of the amide groups are directly involved in antigen binding. The mode of interaction of the dansyl ring with these residues in the Fv fragment has briefly been discussed
Fat suppression applied to MR imaging of the pathologic orbit
International Nuclear Information System (INIS)
Simon, J.H.; Kido, D.K.; Ekholm, S.E.; Totterman, S.; Szumowski, J.; Manzione, J.V. Jr.; Joy, S.E.
1987-01-01
Previous MR studies of the normal orbit have shown that fat suppression sequences applied at the proper T1-T2 weighting will decrease artifacts from chemical shift, and can be used to enhance contrast in selected anatomic regions. The purpose of this study was to evaluate the clinical application of fat suppression to studies of the pathologic orbit. The studies included conventional imaging sequences and comparative fat suppression sequences through a range of T1-T2 weighting (repetition time [TR] 400 msec, echo time [TE]20 msec, to TR 2,000 msec, TE 90 msec), using the chopper fat suppression technique developed by J. Szumowski and D. Plewes, which requires no postprocessing and no increased scan time to achieve relatively linear fat suppression. Fat suppression was advantageous in determining tumor margins (extension through sclera); increasing diagnostic specificity (fat vs. water content); detailing anatomic relationships along bony margins (particularly in the orbital apex); and for demonstrating true thickness of optic nerve separate from adjacent cerebrospinal fluid and fibrous sheath. Disadvantages included susceptibility to motion artifact and a perception of lower quality due to lower overall orbital signal
Du, Qi-Shi; Huang, Ri-Bo; Wei, Yu-Tuo; Pang, Zong-Wen; Du, Li-Qin; Chou, Kuo-Chen
2009-01-30
In cooperation with the fragment-based design a new drug design method, the so-called "fragment-based quantitative structure-activity relationship" (FB-QSAR) is proposed. The essence of the new method is that the molecular framework in a family of drug candidates are divided into several fragments according to their substitutes being investigated. The bioactivities of molecules are correlated with the physicochemical properties of the molecular fragments through two sets of coefficients in the linear free energy equations. One coefficient set is for the physicochemical properties and the other for the weight factors of the molecular fragments. Meanwhile, an iterative double least square (IDLS) technique is developed to solve the two sets of coefficients in a training data set alternately and iteratively. The IDLS technique is a feedback procedure with machine learning ability. The standard Two-dimensional quantitative structure-activity relationship (2D-QSAR) is a special case, in the FB-QSAR, when the whole molecule is treated as one entity. The FB-QSAR approach can remarkably enhance the predictive power and provide more structural insights into rational drug design. As an example, the FB-QSAR is applied to build a predictive model of neuraminidase inhibitors for drug development against H5N1 influenza virus. (c) 2008 Wiley Periodicals, Inc.
Polarization dependent effects in photo-fragmentation dynamics of free molecules
International Nuclear Information System (INIS)
Mocellin, A.; Marinho, R.R.T.; Coutinho, L.H.; Burmeister, F.; Wiesner, K.; Naves de Brito, A.
2003-01-01
We present multicoincidence spectra of nitrogen, formic acid and methyl methacrylate. We demonstrate how to probe the local symmetry of molecular orbitals from molecules core excited with linearly polarized synchrotron radiation. The intensity distribution of the photoelectron photo-ion photo-ion coincidence (PEPIPICO) spectrum reflects the selectivity and localization of core excitation by polarized light. By simulating the spectra the angular dependence of the fragmentation is determined
Polarization dependent effects in photo-fragmentation dynamics of free molecules
Energy Technology Data Exchange (ETDEWEB)
Mocellin, A.; Marinho, R.R.T.; Coutinho, L.H.; Burmeister, F.; Wiesner, K.; Naves de Brito, A
2003-04-01
We present multicoincidence spectra of nitrogen, formic acid and methyl methacrylate. We demonstrate how to probe the local symmetry of molecular orbitals from molecules core excited with linearly polarized synchrotron radiation. The intensity distribution of the photoelectron photo-ion photo-ion coincidence (PEPIPICO) spectrum reflects the selectivity and localization of core excitation by polarized light. By simulating the spectra the angular dependence of the fragmentation is determined.
From leading hadron suppression to jet quenching at RHIC and at the LHC
International Nuclear Information System (INIS)
Wiedemann, U.A.
2005-01-01
In nucleus-nucleus collisions at the Relativistic Heavy Ion Collider (RHIC), one generically observes a strong medium-induced suppression of high- p T hadron production. This suppression is accounted for in models which assume a significant medium-induced radiative energy loss of high- p T parent partons produced in the collision. How can we further test the microscopic dynamics conjectured to underlie this abundant high- p T phenomenon? What can we learn about the dynamics of parton fragmentation, and what can we learn about the properties of the medium which modifies it? Given that inelastic parton scattering is expected to be the dominant source of partonic equilibration processes, can we use hard processes as an experimentally well-controlled window into QCD non-equilibrium dynamics? Here I review what has been achieved so far, and which novel opportunities open up with higher luminosity at RHIC, and with the wider kinematical range accessible soon at the LHC. (orig.)
Formation and suppression of acoustic memories during human sleep.
Andrillon, Thomas; Pressnitzer, Daniel; Léger, Damien; Kouider, Sid
2017-08-08
Sleep and memory are deeply related, but the nature of the neuroplastic processes induced by sleep remains unclear. Here, we report that memory traces can be both formed or suppressed during sleep, depending on sleep phase. We played samples of acoustic noise to sleeping human listeners. Repeated exposure to a novel noise during Rapid Eye Movements (REM) or light non-REM (NREM) sleep leads to improvements in behavioral performance upon awakening. Strikingly, the same exposure during deep NREM sleep leads to impaired performance upon awakening. Electroencephalographic markers of learning extracted during sleep confirm a dissociation between sleep facilitating memory formation (light NREM and REM sleep) and sleep suppressing learning (deep NREM sleep). We can trace these neural changes back to transient sleep events, such as spindles for memory facilitation and slow waves for suppression. Thus, highly selective memory processes are active during human sleep, with intertwined episodes of facilitative and suppressive plasticity.Though memory and sleep are related, it is still unclear whether new memories can be formed during sleep. Here, authors show that people could learn new sounds during REM or light non-REM sleep, but that learning was suppressed when sounds were played during deep NREM sleep.
Reframing landscape fragmentation's effects on ecosystem services.
Mitchell, Matthew G E; Suarez-Castro, Andrés F; Martinez-Harms, Maria; Maron, Martine; McAlpine, Clive; Gaston, Kevin J; Johansen, Kasper; Rhodes, Jonathan R
2015-04-01
Landscape structure and fragmentation have important effects on ecosystem services, with a common assumption being that fragmentation reduces service provision. This is based on fragmentation's expected effects on ecosystem service supply, but ignores how fragmentation influences the flow of services to people. Here we develop a new conceptual framework that explicitly considers the links between landscape fragmentation, the supply of services, and the flow of services to people. We argue that fragmentation's effects on ecosystem service flow can be positive or negative, and use our framework to construct testable hypotheses about the effects of fragmentation on final ecosystem service provision. Empirical efforts to apply and test this framework are critical to improving landscape management for multiple ecosystem services. Copyright © 2015 Elsevier Ltd. All rights reserved.
Fragment Size Distribution of Blasted Rock Mass
Jug, Jasmin; Strelec, Stjepan; Gazdek, Mario; Kavur, Boris
2017-12-01
Rock mass is a heterogeneous material, and the heterogeneity of rock causes sizes distribution of fragmented rocks in blasting. Prediction of blasted rock mass fragmentation has a significant role in the overall economics of opencast mines. Blasting as primary fragmentation can significantly decrease the cost of loading, transport, crushing and milling operations. Blast fragmentation chiefly depends on the specific blast design (geometry of blast holes drilling, the quantity and class of explosive, the blasting form, the timing and partition, etc.) and on the properties of the rock mass (including the uniaxial compressive strength, the rock mass elastic Young modulus, the rock discontinuity characteristics and the rock density). Prediction and processing of blasting results researchers can accomplish by a variety of existing software’s and models, one of them is the Kuz-Ram model, which is possibly the most widely used approach to estimating fragmentation from blasting. This paper shows the estimation of fragmentation using the "SB" program, which was created by the authors. Mentioned program includes the Kuz-Ram model. Models of fragmentation are confirmed and calibrated by comparing the estimated fragmentation with actual post-blast fragmentation from image processing techniques. In this study, the Kuz-Ram fragmentation model has been used for an open-pit limestone quarry in Dalmatia, southern Croatia. The resulting calibrated value of the rock factor enables the quality prognosis of fragmentation in further blasting works, with changed drilling geometry and blast design parameters. It also facilitates simulation in the program to optimize blasting works and get the desired fragmentations of the blasted rock mass.
Amano, Yasushi; Tanabe, Eiki; Yamaguchi, Tomohiko
2015-05-15
Soluble epoxide hydrolase (sEH) is a potential target for the treatment of inflammation and hypertension. X-ray crystallographic fragment screening was used to identify fragment hits and their binding modes. Eight fragment hits were identified via soaking of sEH crystals with fragment cocktails, and the co-crystal structures of these hits were determined via individual soaking. Based on the binding mode, N-ethylmethylamine was identified as a promising scaffold that forms hydrogen bonds with the catalytic residues of sEH, Asp335, Tyr383, and Tyr466. Compounds containing this scaffold were selected from an in-house chemical library and assayed. Although the starting fragment had a weak inhibitory activity (IC50: 800μM), we identified potent inhibitors including 2-({[2-(adamantan-1-yl)ethyl]amino}methyl)phenol exhibiting the highest inhibitory activity (IC50: 0.51μM). This corresponded to a more than 1500-fold increase in inhibitory activity compared to the starting fragment. Co-crystal structures of the hit compounds demonstrate that the binding of N-ethylmethylamine to catalytic residues is similar to that of the starting fragment. We therefore consider crystallographic fragment screening to be appropriate for the identification of weak but promising fragment hits. Copyright © 2015 Elsevier Ltd. All rights reserved.
Magmatic and fragmentation controls on volcanic ash surface chemistry
Ayris, Paul M.; Diplas, Spyros; Damby, David E.; Hornby, Adrian J.; Cimarelli, Corrado; Delmelle, Pierre; Scheu, Bettina; Dingwell, Donald B.
2016-04-01
The chemical effects of silicate ash ejected by explosive volcanic eruptions on environmental systems are fundamentally mediated by ash particle surfaces. Ash surfaces are a composite product of magmatic properties and fragmentation mechanisms, as well as in-plume and atmospheric alteration processes acting upon those surfaces during and after the eruption. Recent attention has focused on the capacity of alteration processes to shape ash surfaces; most notably, several studies have utilised X-ray photoelectron spectroscopy (XPS), a technique probing the elemental composition and coordination state of atoms within the top 10 nm of ash surfaces, to identify patterns of elemental depletions and enrichments relative to bulk ash chemical composition. Under the presumption of surface and bulk equivalence, any disparities have been previously attributed to surface alteration processes, but the ubiquity of some depletions (e.g., Ca, Fe) across multiple ash studies, irrespective of eruptive origin, could suggest these to be features of the surface produced at the instant of magma fragmentation. To investigate this possibility further, we conducted rapid decompression experiments at different pressure conditions and at ambient and magmatic temperature on porous andesitic rocks. These experiments produced fragmented ash material untouched by secondary alteration, which were compared to particles produced by crushing of large clasts from the same experiments. We investigated a restricted size fraction (63-90 μm) from both fragmented and crushed materials, determining bulk chemistry and mineralogy via XRF, SEM-BSE and EPMA, and investigated the chemical composition of the ash surface by XPS. Analyses suggest that fragmentation under experimental conditions partitioned a greater fraction of plagioclase-rich particles into the selected size fraction, relative to particles produced by crushing. Trends in surface chemical composition in fragmented and crushed particles mirror that
Origin of complex fragments from 32S + natAg reaction at 37.5 A.MeV
International Nuclear Information System (INIS)
Benchekroun, D.; Cheynis, B.; Demeyer, A.; Gerlic, E.; Guinet, D.; Lautesse, P.; Lebreton, L.; Magda, M.T.; Stern, M.; Chabane, A.; Desesquelles, P.; Giorni, A.; Heuer, D.; Lleres, A.; Viano, J.B.
1996-08-01
Fragment emission from collisions of 32 S with nat Ag at 37.5 A.MeV has been studied with the 4π multidetector AMPHORA. Production of intermediate mass and heavy fragments as well as of light charged particles has been measured. The total charged particle multiplicity and polar angular distributions have been used to select various classes of collisions. Analysis of angular and energy distributions of fragments and light particles in central collisions indicates the formation of a hot source (excitation energy of ∼ 4.4 A.MeV) with an additional contribution from a preequilibrium process at more forward angles. Azimuthal angle correlations of He - Li, Li - Li, B - B, and C - C pairs have been used as a tool to study the origin of complex fragments. Data at backward angles are well described by considering a thermalized emitter with an angular momentum around 70 h and a fragment emission time of the order of 200 fm/c. A microscopic approach of BNV type confirms these emission times and angular momenta indicating the persistence of an incomplete fusion process responsible for the emission of complex fragments at backward angles
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
Verlinde, Christophe L. M. J.; Rudenko, Gabrielle; Hol, Wim G. J.
1992-04-01
A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness.
Evolutionary Agroecology: the potential for cooperative, high density, weed-suppressing cereals.
Weiner, Jacob; Andersen, Sven B; Wille, Wibke K-M; Griepentrog, Hans W; Olsen, Jannie M
2010-09-01
Evolutionary theory can be applied to improve agricultural yields and/or sustainability, an approach we call Evolutionary Agroecology. The basic idea is that plant breeding is unlikely to improve attributes already favored by millions of years of natural selection, whereas there may be unutilized potential in selecting for attributes that increase total crop yield but reduce plants' individual fitness. In other words, plant breeding should be based on group selection. We explore this approach in relation to crop-weed competition, and argue that it should be possible to develop high density cereals that can utilize their initial size advantage over weeds to suppress them much better than under current practices, thus reducing or eliminating the need for chemical or mechanical weed control. We emphasize the role of density in applying group selection to crops: it is competition among individuals that generates the 'Tragedy of the Commons', providing opportunities to improve plant production by selecting for attributes that natural selection would not favor. When there is competition for light, natural selection of individuals favors a defensive strategy of 'shade avoidance', but a collective, offensive 'shading' strategy could increase weed suppression and yield in the high density, high uniformity cropping systems we envision.
International Nuclear Information System (INIS)
Weckenmann, J.; Hanelt, E.; Schmidt, K.H.
1990-07-01
The fragment separator is a magnetic spectrometer, in which an especially-shaped layer of matter is applied as ion-optical element. The energy loss occurring there is accompanied by a series of unwanted effects like nuclear reaction, elecromagnetic dissociation, energy and angle straggling. These effects reduce on the one hand the total resolution of the separator and on the other hand the number of the fragments, which reach the exit of the separator. In the present study it was stated that the influence of these effects exhibits in most of the cases only a weak dependence on the material of the stopper. The ideal stopper material has a mass number, which corresponds nearly to the mass number of the selected fragment. If only one single stopper material will be applied, a material with low mass number seems to be the best compromise. Therefore for the universal stopper equipment of the fragment separator aluminium was selected. A further object of this study was the profile of the stopper. In a symmetrically constructed magnet spectrometer as the fragment separator the highest resolution is then reached, when the required particles are stopped in the whole width of their momentum distribution by a constant factor. This requirement leads to a curved profile of the stopper. It was stated that the profile can be approached by a linear wedge shape without a disadvantageous change of the resolution of the separator. The technical realization of the universal stopping equipment for the fragment separator consists mainly of very accurately manufactured, shiftable, and rotatable wedge-shaped layers. By means of a step-motor guiding the profiles required for the isotope separation can thus be obtained in a wide range. (orig.) [de
Dual Fragment Impact of PBX Charges
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.
Influence of spin on fission fragments anisotropy
Directory of Open Access Journals (Sweden)
Ghodsi Omid N.
2005-01-01
Full Text Available An analysis of selected fission fragment angular distribution when at least one of the spins of the projectile or target is appreciable in induced fission was made by using the statistical scission model. The results of this model predicate that the spins of the projectile or target are affected on the nuclear level density of the compound nucleus. The experimental data was analyzed by means of the couple channel spin effect formalism. This formalism suggests that the projectile spin is more effective on angular anisotropies within the limits of energy near the fusion barrier.
Directory of Open Access Journals (Sweden)
Maaike evan Agtmaal
2015-07-01
Full Text Available There is increasing evidence that microbial volatiles (VOCs play an important role in natural suppression of soil-borne diseases, but little is known on the factors that influence production of suppressing VOCs. In the current study we examined whether a stress-induced change in soil microbial community composition would affect the production by soils of VOCs suppressing the plant-pathogenic oomycete Pythium. Using pyrosequencing of 16S ribosomal gene fragments we compared the composition of bacterial communities in sandy soils that had been exposed to anaerobic disinfestation (AD, a treatment used to kill harmful soil organisms, with the composition in untreated soils. Three months after the AD treatment had been finished, there was still a clear legacy effect of the former anaerobic stress on bacterial community composition with a strong increase in relative abundance of the phylum Bacteroidetes and a significant decrease of the phyla Acidobacteria, Planctomycetes, Nitrospirae, Chloroflexi and Chlorobi. This change in bacterial community composition coincided with loss of production of Pythium suppressing soil volatiles (VOCs and of suppression of Pythium impacts on Hyacinth root development. One year later, the composition of the bacterial community in the AD soils was reflecting that of the untreated soils. In addition, both production of Pythium-suppressing VOCs and suppression of Pythium in Hyacinth bioassays had returned to the levels of the untreated soil. GC/MS analysis identified several VOCs, among which compounds known to be antifungal, that were produced in the untreated soils but not in the AD soils. These compounds were again produced 15 months after the AD treatment. Our data indicate that soils exposed to a drastic stress can temporarily lose pathogen suppressive characteristics and that both loss and return of these suppressive characteristics coincides with shifts in the soil bacterial community composition. Our data are
Wyss, Daniel F; Wang, Yu-Sen; Eaton, Hugh L; Strickland, Corey; Voigt, Johannes H; Zhu, Zhaoning; Stamford, Andrew W
2012-01-01
Fragment-based drug discovery (FBDD) has become increasingly popular over the last decade. We review here how we have used highly structure-driven fragment-based approaches to complement more traditional lead discovery to tackle high priority targets and those struggling for leads. Combining biomolecular nuclear magnetic resonance (NMR), X-ray crystallography, and molecular modeling with structure-assisted chemistry and innovative biology as an integrated approach for FBDD can solve very difficult problems, as illustrated in this chapter. Here, a successful FBDD campaign is described that has allowed the development of a clinical candidate for BACE-1, a challenging CNS drug target. Crucial to this achievement were the initial identification of a ligand-efficient isothiourea fragment through target-based NMR screening and the determination of its X-ray crystal structure in complex with BACE-1, which revealed an extensive H-bond network with the two active site aspartate residues. This detailed 3D structural information then enabled the design and validation of novel, chemically stable and accessible heterocyclic acylguanidines as aspartic acid protease inhibitor cores. Structure-assisted fragment hit-to-lead optimization yielded iminoheterocyclic BACE-1 inhibitors that possess desirable molecular properties as potential therapeutic agents to test the amyloid hypothesis of Alzheimer's disease in a clinical setting.
Gallstone fragmentation by control electrohydraulic lithotripsy
International Nuclear Information System (INIS)
Tung, G.A.; Mueller, P.R.; Brink, J.A.; Saini, S.; Picus, D.; Simeone, J.F.; Ferrucci, J.T.
1989-01-01
The authors have performed in vitro contact electrohydraulic lithotripsy (EHL) of 100 gallstones > 10 mm in diameter to identify physical and technical factors that affect fragmentation success. Ninety-one of 100 stones were fragmented with a 3-F electrode (average, seven shocks; range, 1--42); only 12 stones were fragmented with a single shock. Of the nine stones refractory to 50 shocks, four were > 30 mm in diameter and five stones were densely calcified. The most important variable determining power requirements for fragmentation was gallstone size (R = .58), but radiographic calcification of gallstones was also important (R = .47). Stones < 15 mm tended to produce fragments of left-angle 2 mm; stones right-angle 20 mm tended to produce two to five large discrete fragments (P , .05). In addition, lithotripsy could be conducted equally well in 1:1 dilute diatrizoate contrast agent as in 1:6 normal saline, suggesting that contact EHL could be performed under fluoroscopy
Fragmentation functions approach in pQCD fragmentation phenomena
International Nuclear Information System (INIS)
Rolli, S.
1996-07-01
Next-to-leading order parton fragmentation functions into light mesons are presented. They have been extracted from real and simulated e + e - data and used to predict inclusive single particle distributions at different machines
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.)
Energy Technology Data Exchange (ETDEWEB)
Nyarko, B.J.B. [SLOWPOKE-2 Facility, Trace Analysis Research Centre, Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada); National Nuclear Research Institute, Ghana Atomic Energy Commission, P.O. Box LG 80, Legon-Accra (Ghana)], E-mail: bjbnyarko@yahoo.co.uk; Bredwa-Mensah, Y. [Department of Archaeology, University of Ghana, Legon-Accra (Ghana); Serfor-Armah, Y. [SLOWPOKE-2 Facility, Trace Analysis Research Centre, Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada); National Nuclear Research Institute, Ghana Atomic Energy Commission, P.O. Box LG 80, Legon-Accra (Ghana); Dampare, S.B. [National Nuclear Research Institute, Ghana Atomic Energy Commission, P.O. Box LG 80, Legon-Accra (Ghana); Department of Earth Sciences, Okayama University, 3-1-1 Tsushima, Okayama 700-8530 (Japan); Akaho, E.H.K.; Osae, S. [National Nuclear Research Institute, Ghana Atomic Energy Commission, P.O. Box LG 80, Legon-Accra (Ghana); Perbi, A. [Department of Archaeology, University of Ghana, Legon-Accra (Ghana); Chatt, A. [SLOWPOKE-2 Facility, Trace Analysis Research Centre, Department of Chemistry, Dalhousie University, Halifax, Nova Scotia, B3H 4J3 (Canada)
2007-10-15
Concentrations of trace elements in ancient pottery excavated from Jenini in the Brong Ahafo region of Ghana were determined using instrumental neutron activation analysis (INAA) in conjunction with both conventional and Compton suppression counting. Jenini was a slave Camp of Samory Toure during the indigenous slavery and the Trans-Atlantic slave trade. Pottery fragments found during the excavation of the grave tombs of the slaves who died in the slave camps were analysed. In all, 26 trace elements were determined in 40 pottery fragments. These elemental concentrations were processed using multivariate statistical methods, cluster, factor and discriminant analyses in order to determine similarities and correlation between the various samples. The suitability of the two counting systems for determination of trace elements in pottery objects has been evaluated.
International Nuclear Information System (INIS)
Nyarko, B.J.B.; Bredwa-Mensah, Y.; Serfor-Armah, Y.; Dampare, S.B.; Akaho, E.H.K.; Osae, S.; Perbi, A.; Chatt, A.
2007-01-01
Concentrations of trace elements in ancient pottery excavated from Jenini in the Brong Ahafo region of Ghana were determined using instrumental neutron activation analysis (INAA) in conjunction with both conventional and Compton suppression counting. Jenini was a slave Camp of Samory Toure during the indigenous slavery and the Trans-Atlantic slave trade. Pottery fragments found during the excavation of the grave tombs of the slaves who died in the slave camps were analysed. In all, 26 trace elements were determined in 40 pottery fragments. These elemental concentrations were processed using multivariate statistical methods, cluster, factor and discriminant analyses in order to determine similarities and correlation between the various samples. The suitability of the two counting systems for determination of trace elements in pottery objects has been evaluated
Directory of Open Access Journals (Sweden)
Paula Eveline Ribeiro D’Anunciação
2013-01-01
Full Text Available In recent years, there has been increasing interest in matrix-type influence on forest fragments. Terrestrial amphibians are good bioindicators for this kind of research because of low vagility and high philopatry. This study compared richness, abundance, and species composition of terrestrial amphibians through pitfall traps in two sets of semideciduous seasonal forest fragments in southeastern Brazil, according to the predominant surrounding matrix (sugar cane and pasture. There were no differences in richness, but fragments surrounded by sugar cane had the lowest abundance of amphibians, whereas fragments surrounded by pastures had greater abundance. The most abundant species, Rhinella ornata, showed no biometric differences between fragment groups but like many other amphibians sampled showed very low numbers of individuals in fragments dominated by sugar cane fields. Our data indicate that the sugar cane matrix negatively influences the community of amphibians present in fragments surrounded by this type of land use.
Fragmentation of Ceramics in Rapid Expansion Mode
Maiti, Spandan; Geubelle, Philippe H.; Rangaswamy, Krishnan
The study of the fragmentation process goes back to more than a century, motivated primarily by problems related to mining and ore handling (Grady and Kipp, 1985). Various theories have been proposed to predict the fragmentation stress and the fragment size and distribution. But the investigations are generally case specific and relate to only a narrow set of fragmentation processes. A number of theoretical studies of dynamic fragmentation in a rapidly expanding body can be found in the literature. For example, the study summarized in (Grady, 1982) presents a model based on a simple energy balance concept between the surface energy released due to fracture and the kinetic energy of the fragments. Subsequent refinements of the energy balance model have been proposed by (Glenn and Chudnovsky, 1986), which take into account the strain energy of the fragments and specify a threshold stress below which no fragmentation occurs. These models assume that the fracture events are instantaneous and occur simultaneously. Evidently, these assumptions are quite restrictive and these models can not take into account the transient nature of the fragmentation process after the onset of fracture in the material. A more recent model proposed by (Miller et al., 1999) however takes into account this time-dependent nature of the fragmentation event and the distribution of flaws of various strengths in the original material.
Characterization of a recombinant humanized anti-cocaine monoclonal antibody and its Fab fragment.
Kirley, Terence L; Norman, Andrew B
2015-01-01
Variations of post-translational modifications are important for stability and in vivo behavior of therapeutic antibodies. A recombinant humanized anti-cocaine monoclonal antibody (h2E2) was characterized for heterogeneity of N-linked glycosylation and disulfide bonds. In addition, charge heterogeneity, which is partially due to the presence or absence of C-terminal lysine on the heavy chains, was examined. For cocaine overdose therapy, Fab fragments may be therapeutic, and thus, a simplified method of generation, purification, and characterization of the Fab fragment generated by Endoproteinase Lys-C digestion was devised. Both the intact h2E2 antibody and purified Fab fragments were analyzed for their affinities for cocaine and 2 of its metabolites, benzoylecgonine and cocaethylene, by fluorescence quenching of intrinsic antibody tyrosine and tryptophan fluorescence resulting from binding of these drugs. Binding constants obtained from fluorescence quenching measurements are in agreement with recently published radioligand and ELISA binding assays. The dissociation constants determined for the h2E2 monoclonal and its Fab fragment are approximately 1, 5, and 20 nM for cocaethylene, cocaine, and benzoylecgonine, respectively. Tryptophan fluorescence quenching (emission at 330 nm) was measured after either excitation of tyrosine and tryptophan (280 nm) or selective excitation of tryptophan alone (295 nm). More accurate binding constants are obtained using tryptophan selective excitation at 295 nm, likely due to interfering absorption of cocaine and metabolites at 280 nm. These quenching results are consistent with multiple tryptophan and tyrosine residues in or near the predicted binding location of cocaine in a previously published 3-D model of this antibody's variable region.
International Nuclear Information System (INIS)
Jaqaman, H.R.; Birzeit Univ.; Papp, G.; Eoetvoes Lorand Tudomanyegyetem, Budapest; Gross, D.H.E.; Freie Univ. Berlin
1990-01-01
The distributions of fragments produced by microcanonical multifragmentation of hot nuclei are compared with the cluster distributions predicted by a bond percolation model on a finite lattice. The conditional moments of these distributions are used together with the correlations between the largest three fragments in each event. Whereas percolation and statistical nuclear fragmentation agree in many details as in the usual plots of the averaged moments of the fragment distributions which yield the critical exponents, they turn out to be essentially different when less averaged quantities or correlations are considered. The differences between the predictions of the two models are mainly due to the particularities of the nuclear problem, especially the effect of the long-range Coulomb force which favours the break-up of the highly excited nucleus into two large fragments (pseudo-fission) and, to a somewhat lesser extent, enhances the possibility for the cracking of the nucleus into more than two large fragments. The fission events are, however, clearly separated from a second branch of critical correlations which shows up clearly in both nuclear fragmentation and percolation. We think that this critical correlation branch is due to the liquid-gas phase transition in finite nuclei. (orig.)
Directory of Open Access Journals (Sweden)
Andrea Kirmaier
2010-08-01
Full Text Available Simian immunodeficiency viruses of sooty mangabeys (SIVsm are the source of multiple, successful cross-species transmissions, having given rise to HIV-2 in humans, SIVmac in rhesus macaques, and SIVstm in stump-tailed macaques. Cellular assays and phylogenetic comparisons indirectly support a role for TRIM5alpha, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Here, we investigate the in vivo role of TRIM5 directly, focusing on transmission of primate immunodeficiency viruses between outbred primate hosts. Specifically, we retrospectively analyzed experimental cross-species transmission of SIVsm in two cohorts of rhesus macaques and found a significant effect of TRIM5 genotype on viral replication levels. The effect was especially pronounced in a cohort of animals infected with SIVsmE543-3, where TRIM5 genotype correlated with approximately 100-fold to 1,000-fold differences in viral replication levels. Surprisingly, transmission occurred even in individuals bearing restrictive TRIM5 genotypes, resulting in attenuation of replication rather than an outright block to infection. In cell-culture assays, the same TRIM5 alleles associated with viral suppression in vivo blocked infectivity of two SIVsm strains, but not the macaque-adapted strain SIVmac239. Adaptations appeared in the viral capsid in animals with restrictive TRIM5 genotypes, and similar adaptations coincide with emergence of SIVmac in captive macaques in the 1970s. Thus, host TRIM5 can suppress viral replication in vivo, exerting selective pressure during the initial stages of cross-species transmission.
Energy Technology Data Exchange (ETDEWEB)
Takahashi, Hideo; Igarashi, Takako; Shimada, Ichio; Arata, Yoji (Univ. of Tokyo (Japan))
1991-03-19
The Fv fragment, a univalent antigen-binding unit with a molecular weight of 25,000, has successfully been prepared in high yield by limited proteolysis with clostripain of a short-chain mouse IgG2a anti-dansyl monoclonal antibody in which the entire C{sub H}1 domain is deleted. The Fv fragment obtained is stable at room temperature and retains its full antigen-binding capability. It has been shown that selective deuterium labeling of the Fv fragment, which is half the size of the Fab fragment, provides {sup 1}H NMR spectral data at a sufficient resolution for a detailed structural analysis of the antigen-combining site. NOESY spectra of an Fv analogue, in which all aromatic protons except for His C2{prime}-H and Tyr C3{prime},5{prime}-H had been deuterated, were measured in the presence of varying amounts of dansyl-L-lysine. On the basis of the NOESY data obtained, it was possible to assign all the ring proton resonances for the dansly group that is bound to the Fv fragment. It was also possible to obtain information about His and Tyr residues of the Fv fragment in the absence and presence of the antigen. On the basis of the NMR data obtained, the authors have shown that at least two Tyr residues along with one of the amide groups are directly involved in antigen binding. The mode of interaction of the dansyl ring with these residues in the Fv fragment has briefly been discussed.
Selective Memories: Infants' Encoding Is Enhanced in Selection via Suppression
Markant, Julie; Amso, Dima
2013-01-01
The present study examined the hypothesis that inhibitory visual selection mechanisms play a vital role in memory by limiting distractor interference during item encoding. In Experiment 1a we used a modified spatial cueing task in which 9-month-old infants encoded multiple category exemplars in the contexts of an attention orienting mechanism…
Extraction of 16th Century Calender Fragments
DEFF Research Database (Denmark)
Holck, Jakob Povl; Etheridge, Christian
at the Cultural Heritage & Archaeometric Research Team, SDU. Upon finding medieval manuscript fragments in the university library’s special collections, scholars at the Centre for Medieval Literature are consulted. In most cases, digital pictures of the finds will circulate in the international community...... fragments may require extensive use of Big Data and other forms of analysis in order to be identified. Usually, the university library prefers not to remove the fragments from their “fragment carriers”. In order to read fragments that are only partially visible or invisible, x-ray technology may be deployed...... of medieval scholars. Thousands of 16th and 17th Century books are stored in the University Library of Southern Denmark. One out of five of these books is expected to contain medieval manuscript fragments or fragments of rare prints, e.g. incunabula....
Rymarczuk, George N; Davidson, Laurence; Severson, Meryl A; Armonda, Rocco A
2015-10-01
Wartime penetrating brain injury can result in deep-seated parenchymal and intraventicular shrapnel, bullets, and bone. Large fragments pose a risk of secondary injury from migration, infection, and metal toxicity. It has been recommended that aggressive removal of fragments be avoided. The goal of this study is to report our technique of minimally invasive removal of select deep-seated fragments using a tubular retractor system. A retrospective review of our database of service members presenting with penetrating traumatic brain injuries incurred during Operations Iraqi Freedom and Enduring Freedom and treated at the Walter Reed Army Medical Center and the National Naval Medical Center was performed. Six individuals were identified in which the Vycor ViewSite retractor system (Vycor Medical, Boca Raton, Florida, USA) was used to remove a ventricular or deep intraparenchymal fragment. All patients were male and ranged in age from 21 to 29 years. Fragment location included the foramen of Monro; the atrium of the right lateral ventricle; parasagittally within the right occipital lobe; the occipital horn of the right lateral ventricle; the deep white matter of the dominant temporal lobe; and within the posterior right temporal lobe deep to the junction of the transverse and sigmoid dural venous sinuses. Fragments included in-driven bone, shrapnel from improvised explosive devices, and bullets. In all cases the fragment was successfully removed. No patient had worsening of their neurologic condition following surgery. Deep parenchymal and intraventricular fragments can be safely removed using a tubular retractor system. Published by Elsevier Inc.
Prescher, Horst; Koch, Guido; Schuhmann, Tim; Ertl, Peter; Bussenault, Alex; Glick, Meir; Dix, Ina; Petersen, Frank; Lizos, Dimitrios E
2017-02-01
A fragment library consisting of 3D-shaped, natural product-like fragments was assembled. Library construction was mainly performed by natural product degradation and natural product diversification reactions and was complemented by the identification of 3D-shaped, natural product like fragments available from commercial sources. In addition, during the course of these studies, novel rearrangements were discovered for Massarigenin C and Cytochalasin E. The obtained fragment library has an excellent 3D-shape and natural product likeness, covering a novel, unexplored and underrepresented chemical space in fragment based drug discovery (FBDD). Copyright © 2016 Elsevier Ltd. All rights reserved.
Prevention and suppression of metal packing fires.
Roberts, Mark; Rogers, William J; Sam Mannan, M; Ostrowski, Scott W
2003-11-14
Structured packing has been widely used because of large surface area that makes possible columns with high capacity and efficiency. The large surface area also contributes to fire hazards because of hydrocarbon deposits that can easily combust and promote combustion of the thin metal packing materials. Materials of high surface area that can fuel fires include reactive metals, such as titanium, and materials that are not considered combustible, such as stainless steel. Column design and material selection for packing construction is discussed together with employee training and practices for safe column maintenance and operations. Presented also are methods and agents for suppression of metal fires. Guidance for prevention and suppression of metal fires is related to incidents involving packing fires in columns.
Energy Technology Data Exchange (ETDEWEB)
Le Fevre, A. [Paris-7 Univ., 75 (France)
1997-05-14
This work is focused on the study of fragment and light particle production mechanisms in the multifragmentation process of hot nuclei, which are formed in the central collisions of Xe+Sn at 50 MeV/u. The experiment has been performed with the INDRA multidetector. The central collision events, selected via the flow angle variable, exhibit the presence of a heavy (Z=90) and highly excited (E{sup *}=12.5 MeV/u) isotropic emission source. The comparison of the data with a statistical multifragmentation model (MMMC) and a dynamical model (BNV) makes us conclude that the multifragmentation can only be explained in the frame of a relatively cold process, around 6 MeV/u of thermal excitation energy, preceded by a primary emission stage of the expanding source, during which nearly one third of the excitation energy is dissipated. In addition, it appears that the fragment energy spectra are not explained by a purely thermal process, and that one has to put forward an expansion collective motion, of 2 MeV/u of energy, following the compression of the compound system. In order to precise the existence of a two-step particle emission (primary and secondary), we have developed and applied an original method of reduced velocity correlations between particles and fragments. It has allowed us to underline two distinct origins for the particle production: one corresponding to secondary emissions, coming from the fragments, and the other one, associated with emissions which occur prior to the fragment production. At last, it has allowed us, also to bring out a hierarchy in the emission time in the decay process, with respect to the particle type. (author) 90 refs.
Fluctuations in the fragmentation process
International Nuclear Information System (INIS)
Botet, R.; Ploszajczak, M.
1993-01-01
Some general framework of sequential fragmentation is presented, as provided by the newly proposed Fragmentation - Inactivation - Binary model, and to study briefly its basic and universal features. This model includes as particular cases most of the previous kinetic fragmentation models. In particular it is discussed how one arrives in this framework to the critical behaviour, called the shattering transition. This model is then compared to recent data on gold multifragmentation at 600 MeV/nucl. (authors) 20 refs., 5 figs
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)
Prompt Gamma Radiation from Fragments in the Thermal Fission of {sup 235}U
Energy Technology Data Exchange (ETDEWEB)
Albinsson, H [Chalmers Univ. of Technology, Goteborg (Sweden); Lindow, L [AB Atomenergi, Nykoeping (Sweden)
1970-06-15
Measurements were made on the gamma radiation emitted from fission fragments in slow neutron induced fission of {sup 235}U. The fragments were detected with solid state detectors of the surface barrier type and the gamma radiation with a Nal(Tl) scintillator. Mass selection was used so that the gamma radiation could be measured as a function of fragment mass. Time discrimination between the fission gammas and the prompt neutrons released in the fission process was employed to reduce the background. The gamma radiation emitted during different time intervals after the fission event was studied with the help of a collimator, the position of which was changed along the path of the fission fragments. In this way a decay curve was obtained from which the life-time of one of the gamma-emitting states could be estimated. The relative yield of the gamma-rays was determined as a function of mass for different gamma-ray energy portions and two specific time intervals after the fission events. Comparisons were made with data obtained from {sup 252} Cf-fission. Attention is drawn to some features which seem to be the same in {sup 235}U and {sup 252} Cf-fission.
Directory of Open Access Journals (Sweden)
Edward C. Mader Jr.
2017-02-01
Full Text Available Drug-induced burst suppression (DIBS is bihemispheric and bisymmetric in adults and older children. However, asymmetric DIBS may occur if a pathological process is affecting one hemisphere only or both hemispheres disproportionately. The usual suspect is a destructive lesion; an irritative or epileptogenic lesion is usually not invoked to explain DIBS asymmetry. We report the case of a 66-year-old woman with new-onset seizures who was found to have a hemorrhagic cavernoma and periodic lateralized epileptiform discharges (PLEDs in the right temporal region. After levetiracetam and before anesthetic antiepileptic drugs (AEDs were administered, the electroencephalogram (EEG showed continuous PLEDs over the right hemisphere with maximum voltage in the posterior temporal region. Focal electrographic seizures also occurred occasionally in the same location. Propofol resulted in bihemispheric, but not in bisymmetric, DIBS. Remnants or fragments of PLEDs that survived anesthesia increased the amplitude and complexity of the bursts in the right hemisphere leading to asymmetric DIBS. Phenytoin, lacosamide, ketamine, midazolam, and topiramate were administered at various times in the course of EEG monitoring, resulting in suppression of seizures but not of PLEDs. Ketamine and midazolam reduced the rate, amplitude, and complexity of PLEDs but only after producing substantial attenuation of all burst components. When all anesthetics were discontinued, the EEG reverted to the original preanesthesia pattern with continuous non-fragmented PLEDs. The fact that PLEDs can survive anesthesia and affect DIBS symmetry is a testament to the robustness of the neurodynamic processes underlying PLEDs.
Farcaş, E; Bouckaert, C; Servais, A-C; Hanson, J; Pochet, L; Fillet, M
2017-09-01
With the emergence of more challenging targets, a relatively new approach, fragment-based drug discovery (FBDD), proved its efficacy and gained increasing importance in the pharmaceutical industry. FBDD identifies low molecular-weight (MW) ligands (fragments) that bind to biologically important macromolecules, then a structure-guided fragment growing or merging approach is performed, contributing to the quality of the lead. However, to select the appropriate fragment to be evolved, sensitive analytical screening methods must be used to measure the affinity in the μM or even mM range. In this particular context, we developed a robust and selective partial filling affinity CE (ACE) method for the direct binding screening of a small fragment library in order to identify new thrombin inhibitors. To demonstrate the accuracy of our assay, the complex dissociation constants of three known thrombin inhibitors, namely benzamidine, p-aminobenzamidine and nafamostat were determined and found to be in good concordance with the previously reported values. Finally, the screening of a small library was performed and demonstrated the high discriminatory power of our method towards weak binders compared to classical spectrophotometric activity assay, proving the interest of our method in the context of FBDD. Copyright © 2017 Elsevier B.V. All rights reserved.
Velocity distribution of fragments of catastrophic impacts
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 in DNA double-strand breaks
International Nuclear Information System (INIS)
Wei Zhiyong; Suzhou Univ., Suzhou; Zhang Lihui; Li Ming; Fan Wo; Xu Yujie
2005-01-01
DNA double strand breaks are important lesions induced by irradiations. Random breakage model or quantification supported by this concept is suitable to analyze DNA double strand break data induced by low LET radiation, but deviation from random breakage model is more evident in high LET radiation data analysis. In this work we develop a new method, statistical fragmentation model, to analyze the fragmentation process of DNA double strand breaks. After charged particles enter the biological cell, they produce ionizations along their tracks, and transfer their energies to the cells and break the cellular DNA strands into fragments. The probable distribution of the fragments is obtained under the condition in which the entropy is maximum. Under the approximation E≅E 0 + E 1 l + E 2 l 2 , the distribution functions are obtained as exp(αl + βl 2 ). There are two components, the one proportional to exp(βl 2 ), mainly contributes to the low mass fragment yields, the other component, proportional to exp(αl), decreases slowly as the mass of the fragments increases. Numerical solution of the constraint equations provides parameters α and β. Experimental data, especially when the energy deposition is higher, support the statistical fragmentation model. (authors)
Fission fragment yields from heavy-ion-induced reactions measured with a fragment separator
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.
Assessing the lipophilicity of fragments and early hits
Mortenson, Paul N.; Murray, Christopher W.
2011-07-01
A key challenge in many drug discovery programs is to accurately assess the potential value of screening hits. This is particularly true in fragment-based drug design (FBDD), where the hits often bind relatively weakly, but are correspondingly small. Ligand efficiency (LE) considers both the potency and the size of the molecule, and enables us to estimate whether or not an initial hit is likely to be optimisable to a potent, druglike lead. While size is a key property that needs to be controlled in a small molecule drug, there are a number of additional properties that should also be considered. Lipophilicity is amongst the most important of these additional properties, and here we present a new efficiency index (LLEAT) that combines lipophilicity, size and potency. The index is intuitively defined, and has been designed to have the same target value and dynamic range as LE, making it easily interpretable by medicinal chemists. Monitoring both LE and LLEAT should help both in the selection of more promising fragment hits, and controlling molecular weight and lipophilicity during optimisation.
Ligand deconstruction: Why some fragment binding positions are conserved and others are not
Kozakov, Dima; Hall, David R.; Jehle, Stefan; Luo, Lingqi; Ochiana, Stefan O.; Jones, Elizabeth V.; Pollastri, Michael; Allen, Karen N.; Whitty, Adrian; Vajda, Sandor
2015-01-01
Fragment-based drug discovery (FBDD) relies on the premise that the fragment binding mode will be conserved on subsequent expansion to a larger ligand. However, no general condition has been established to explain when fragment binding modes will be conserved. We show that a remarkably simple condition can be developed in terms of how fragments coincide with binding energy hot spots—regions of the protein where interactions with a ligand contribute substantial binding free energy—the locations of which can easily be determined computationally. Because a substantial fraction of the free energy of ligand binding comes from interacting with the residues in the energetically most important hot spot, a ligand moiety that sufficiently overlaps with this region will retain its location even when other parts of the ligand are removed. This hypothesis is supported by eight case studies. The condition helps identify whether a protein is suitable for FBDD, predicts the size of fragments required for screening, and determines whether a fragment hit can be extended into a higher affinity ligand. Our results show that ligand binding sites can usefully be thought of in terms of an anchor site, which is the top-ranked hot spot and dominates the free energy of binding, surrounded by a number of weaker satellite sites that confer improved affinity and selectivity for a particular ligand and that it is the intrinsic binding potential of the protein surface that determines whether it can serve as a robust binding site for a suitably optimized ligand. PMID:25918377
Ligand deconstruction: Why some fragment binding positions are conserved and others are not.
Kozakov, Dima; Hall, David R; Jehle, Stefan; Jehle, Sefan; Luo, Lingqi; Ochiana, Stefan O; Jones, Elizabeth V; Pollastri, Michael; Allen, Karen N; Whitty, Adrian; Vajda, Sandor
2015-05-19
Fragment-based drug discovery (FBDD) relies on the premise that the fragment binding mode will be conserved on subsequent expansion to a larger ligand. However, no general condition has been established to explain when fragment binding modes will be conserved. We show that a remarkably simple condition can be developed in terms of how fragments coincide with binding energy hot spots--regions of the protein where interactions with a ligand contribute substantial binding free energy--the locations of which can easily be determined computationally. Because a substantial fraction of the free energy of ligand binding comes from interacting with the residues in the energetically most important hot spot, a ligand moiety that sufficiently overlaps with this region will retain its location even when other parts of the ligand are removed. This hypothesis is supported by eight case studies. The condition helps identify whether a protein is suitable for FBDD, predicts the size of fragments required for screening, and determines whether a fragment hit can be extended into a higher affinity ligand. Our results show that ligand binding sites can usefully be thought of in terms of an anchor site, which is the top-ranked hot spot and dominates the free energy of binding, surrounded by a number of weaker satellite sites that confer improved affinity and selectivity for a particular ligand and that it is the intrinsic binding potential of the protein surface that determines whether it can serve as a robust binding site for a suitably optimized ligand.
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
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.
Kesselman, Andrew J; Hoang, Nam Sao; Sheu, Alexander Y; Kuo, William T
2018-06-01
To evaluate the safety and efficacy of attempted percutaneous filter fragment removal during retrieval of fractured inferior vena cava (IVC) filters and to report outcomes associated with retained filter fragments. Over a 5-year period, 82 consecutive patients presenting with a fractured IVC filter were prospectively enrolled into an institutional review board-approved registry. There were 27 men and 55 women (mean, 47 y; range, 19-85 y). After main filter removal, percutaneous removal of fragments was attempted if they were deemed intravascular and accessible on preprocedural computed tomography (CT), cone-beam CT, and/or intravascular ultrasound; distal pulmonary artery (PA) fragments were left alone. A total of 185 fragments were identified (81 IVC, 33 PA, 16 cardiac, 2 hepatic vein, 1 renal vein, 1 aorta, 51 retroperitoneal). Mean filter dwell time was 2,183 days (range, 59-9,936 d). Eighty-seven of 185 fragments (47%) were deemed amenable to attempted removal: 65 IVC, 11 PA, 8 cardiac, 2 hepatic, and 1 aortic. Primary safety outcomes were major procedure-related complications. Fragment removal was successful in 78 of 87 cases (89.7%; 95% confidence interval [CI], 81.3-95.2). There were 6 minor complications with no consequence (6.9%; 95% CI, 2.6-14.4) involving intraprocedural fragment embolization and 1 major complication (1.1%; 95% CI, 0.0-6.2), a cardiac tamponade that was successfully treated. The complication rate from attempted cardiac fragment removal was 12.5% (1 of 8; 95% CI, 0.3-52.7). Among patients with retained cardiopulmonary fragments (n = 19), 81% remained asymptomatic during long-term clinical follow-up of 845 days (range, 386-2,071 d). Percutaneous removal of filter fragments from the IVC and proximal PAs is safe and effective overall, but attempted intracardiac fragment removal carries a higher risk of complication. Most residual filter fragments not amenable to percutaneous removal remain asymptomatic and may be monitored clinically
The importance of ignoring: Alpha oscillations protect selectivity
Payne, Lisa; Sekuler, Robert
2014-01-01
Selective attention is often thought to entail an enhancement of some task-relevant stimulus or attribute. We discuss the perspective that ignoring irrelevant, distracting information plays a complementary role in information processing. Cortical oscillations within the alpha (8–14 Hz) frequency band have emerged as a marker of sensory suppression. This suppression is linked to selective attention for visual, auditory, somatic, and verbal stimuli. Inhibiting processing of irrelevant input mak...
Fragger: a protein fragment picker for structural queries.
Berenger, Francois; Simoncini, David; Voet, Arnout; Shrestha, Rojan; Zhang, Kam Y J
2017-01-01
Protein modeling and design activities often require querying the Protein Data Bank (PDB) with a structural fragment, possibly containing gaps. For some applications, it is preferable to work on a specific subset of the PDB or with unpublished structures. These requirements, along with specific user needs, motivated the creation of a new software to manage and query 3D protein fragments. Fragger is a protein fragment picker that allows protein fragment databases to be created and queried. All fragment lengths are supported and any set of PDB files can be used to create a database. Fragger can efficiently search a fragment database with a query fragment and a distance threshold. Matching fragments are ranked by distance to the query. The query fragment can have structural gaps and the allowed amino acid sequences matching a query can be constrained via a regular expression of one-letter amino acid codes. Fragger also incorporates a tool to compute the backbone RMSD of one versus many fragments in high throughput. Fragger should be useful for protein design, loop grafting and related structural bioinformatics tasks.
Kaon fragmentation function from NJL-jet model
International Nuclear Information System (INIS)
Matevosyan, Hrayr H.; Thomas, Anthony W.; Bentz, Wolfgang
2010-01-01
The NJL-jet model provides a sound framework for calculating the fragmentation functions in an effective chiral quark theory, where the momentum and isospin sum rules are satisfied without the introduction of ad hoc parameters [1]. Earlier studies of the pion fragmentation functions using the Nambu-Jona-Lasinio (NJL) model within this framework showed good qualitative agreement with the empirical parameterizations. Here we extend the NJL-jet model by including the strange quark. The corrections to the pion fragmentation function and corresponding kaon fragmentation functions are calculated using the elementary quark to quark-meson fragmentation functions from NJL. The results for the kaon fragmentation function exhibit a qualitative agreement with the empirical parameterizations, while the unfavored strange quark fragmentation to pions is shown to be of the same order of magnitude as the unfavored light quark's. The results of these studies are expected to provide important guidance for the analysis of a large variety of semi-inclusive data.
Study of fragmentation potential for doubly magic 208Pb daughter cluster radioactivity
International Nuclear Information System (INIS)
Sukhmanpreet Kaur; Kaur, Mandeep; Singh, BirBikram
2017-01-01
In present work, the selected CR decays of different trans-lead parent nuclei are investigated within the collective clusterisation approach of quantum mechanical fragmentation theory (QMFT), specifically, which lead to 208 Pb daughter nucleus, always, through emission of clusters 14 C, 18,20 O, 22 Ne, 23 F, 24,26 Ne, 28,30 Mg and 34 Si
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
Fragmentation of rotating protostellar clouds
International Nuclear Information System (INIS)
Tohline, J.E.
1980-01-01
We examine, with a three-dimensional hydrodynamic computer code, the behavior of rotating, isothermal gas clouds as they collapse from Jeans unstable configurations, in order to determine whether they are susceptible to fragmentation during the initial dynamic collapse phase of their evolution. We find that a gas cloud will not fragment unless (a) it begins collapsing from a radius much smaller than the Jeans radius (i.e., the cloud initially encloses many Jeans masses) and (b) irregularities in the cloud's initial structure (specifically, density inhomogeneities) enclose more than one Jeans mass of material. Gas pressure smooths out features that are not initially Jeans unstable while rotation plays no direct role in damping inhomogeneities. Instead of fragmenting, most of our models collapse to a ring configuration (as has been observed by other investigators in two-dimensional, axisymmetric models). The rings appear to be less susceptible to gragmentation from arbitrary perturbations in their structure than has previously been indicated in other work. Because our models, which include the effects of gas pressure, do not readily fragment during a phase of dynamic collapse, we suggest that gas clouds in the galactic disk undergo fragmentation only during quasi-equilibrium phases of their evolution
Fragment-based approaches to TB drugs.
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.
The Zero-Degree Detector system for fragmentation studies
International Nuclear Information System (INIS)
Adams, J.H.; Christl, M.J.; Howell, L.W.; Kuznetsov, E.
2007-01-01
The measurement of nuclear fragmentation cross-sections requires the detection and identification of individual projectile fragments. If light and heavy fragments are recorded in the same detector, it may be impossible to distinguish the signal from the light fragment. To overcome this problem, we have developed the Zero-degree Detector System (ZDDS). The ZDDS enables the measurement of cross-sections for light fragment production by using pixelated detectors to separately measure the signals of each fragment. The system has been used to measure the fragmentation of beams as heavy as Fe at the NASA Space Radiation Laboratory at Brookhaven National Laboratory and the Heavy Ion Medical Accelerator in Chiba, Japan
Lomakin, Ya A; Shmidt, A A; Bobik, T V; Chernov, A S; Pyrkov, A Yu; Aleksandrova, N M; Okunola, D O; Vaskina, M I; Ponomarenko, N A; Telegin, G B; Dubina, M V; Belogurov, A A
2017-10-01
Intracellular fragments of latent phase protein LMP1 of Epstein-Barr virus, denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to the transforming potential of the virus. Generation of recombinant proteins CTAR1/2/3 is expected to yield more ample data on functional and immunogenic characteristics of LMP1. We created genetic constructs for prokaryotic expression of LMP1 CTAR fragments and selected optimal conditions for their production and purification. Using a new library of LMP1 CTAR fragments, we carried out epitope mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of CTAR elements comparable with that of full-length protein.
Introduction to fragment-based drug discovery.
Erlanson, Daniel A
2012-01-01
Fragment-based drug discovery (FBDD) has emerged in the past decade as a powerful tool for discovering drug leads. The approach first identifies starting points: very small molecules (fragments) that are about half the size of typical drugs. These fragments are then expanded or linked together to generate drug leads. Although the origins of the technique date back some 30 years, it was only in the mid-1990s that experimental techniques became sufficiently sensitive and rapid for the concept to be become practical. Since that time, the field has exploded: FBDD has played a role in discovery of at least 18 drugs that have entered the clinic, and practitioners of FBDD can be found throughout the world in both academia and industry. Literally dozens of reviews have been published on various aspects of FBDD or on the field as a whole, as have three books (Jahnke and Erlanson, Fragment-based approaches in drug discovery, 2006; Zartler and Shapiro, Fragment-based drug discovery: a practical approach, 2008; Kuo, Fragment based drug design: tools, practical approaches, and examples, 2011). However, this chapter will assume that the reader is approaching the field with little prior knowledge. It will introduce some of the key concepts, set the stage for the chapters to follow, and demonstrate how X-ray crystallography plays a central role in fragment identification and advancement.
Directory of Open Access Journals (Sweden)
Bergerot Benjamin
2012-04-01
Full Text Available Abstract Background Theory predicts a nonlinear response of dispersal evolution to habitat fragmentation. First, dispersal will be favoured in line with both decreasing area of habitat patches and increasing inter-patch distances. Next, once these inter-patch distances exceed a critical threshold, dispersal will be counter-selected, unless essential resources no longer co-occur in compact patches but are differently scattered; colonization of empty habitat patches or rescue of declining populations are then increasingly overruled by dispersal costs like mortality risks and loss of time and energy. However, to date, most empirical studies mainly document an increase of dispersal associated with habitat fragmentation. We analyzed dispersal kernels for males and females of the common, widespread woodland butterfly Pararge aegeria in highly fragmented landscape, and for males in landscapes that differed in their degree of habitat fragmentation. Results The male and female probabilities of moving were considerably lower in the highly fragmented landscapes compared to the male probability of moving in fragmented agricultural and deciduous oak woodland landscapes. We also investigated whether, and to what extent, daily dispersal distance in the highly fragmented landscape was influenced by a set of landscape variables for both males and females, including distance to the nearest woodland, area of the nearest woodland, patch area and abundance of individuals in the patch. We found that daily movement distance decreased with increasing distance to the nearest woodland in both males and females. Daily distances flown by males were related to the area of the woodland capture site, whereas no such effect was observed for females. Conclusion Overall, mobility was strongly reduced in the highly fragmented landscape, and varied considerably among landscapes with different spatial resource distributions. We interpret the results relative to different cost
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
International Nuclear Information System (INIS)
Noh, Eunyoung; Yoon, Chang-Yong; Lee, Ji Hyun; Baek, Sun-Young; Do, Jung-Ah; Lee, Jung-min; Oh, Han Bin
2016-01-01
Corticosteroids have been often found to be added to a dietary supplement for the purpose of illegally improving the effect of their products. Thus, it is imperative to develop or improve a method that enables one to rapidly and reliably analyze corticosteroids in health or dietary supplements, for the safety management purpose. In the present study, results from liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) experiments for the selected 35 corticosteroid compounds are presented, which can be useful for the qualitative screening of corticosteroids in health or dietary supplements. Specifically, retention times, accurate mass data of the protonated steroids, m/z values of major fragment ions are given for the 35 corticosteroids. Further, fragmentation pathways for the selected steroids are also suggested. Based on the suggested fragmentation pathways, it was shown that an unknown steroid compound can be readily identified using the knowledge of a group of unique and specific common skeletal fragments. The high selectivity and sensitivity of the LC-Q-TOF-MS/MS results combined with the knowledge of the fragmentation pathways can offer a new opportunity for rapid and accurate screening of corticosteroids, thus preventing health-related incidents involving adulterated products and clamping down on illegally circulated health products.
Energy Technology Data Exchange (ETDEWEB)
Noh, Eunyoung; Yoon, Chang-Yong; Lee, Ji Hyun; Baek, Sun-Young; Do, Jung-Ah [Ministry of Food and Drug Safety, Cheongju (Korea, Republic of); Lee, Jung-min; Oh, Han Bin [Sogang University, Seoul (Korea, Republic of)
2016-07-15
Corticosteroids have been often found to be added to a dietary supplement for the purpose of illegally improving the effect of their products. Thus, it is imperative to develop or improve a method that enables one to rapidly and reliably analyze corticosteroids in health or dietary supplements, for the safety management purpose. In the present study, results from liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) experiments for the selected 35 corticosteroid compounds are presented, which can be useful for the qualitative screening of corticosteroids in health or dietary supplements. Specifically, retention times, accurate mass data of the protonated steroids, m/z values of major fragment ions are given for the 35 corticosteroids. Further, fragmentation pathways for the selected steroids are also suggested. Based on the suggested fragmentation pathways, it was shown that an unknown steroid compound can be readily identified using the knowledge of a group of unique and specific common skeletal fragments. The high selectivity and sensitivity of the LC-Q-TOF-MS/MS results combined with the knowledge of the fragmentation pathways can offer a new opportunity for rapid and accurate screening of corticosteroids, thus preventing health-related incidents involving adulterated products and clamping down on illegally circulated health products.
Selective suppression of in situ proliferation of scyphozoan polyps by biofouling
International Nuclear Information System (INIS)
Feng, Song; Wang, Shi-Wei; Zhang, Guang-Tao; Sun, Song; Zhang, Fang
2017-01-01
An increase in marine artificial constructions has been proposed as a major cause of jellyfish blooms, because these constructions provide additional substrates for organisms at the benthic stage (polyps), which proliferate asexually and release a large amount of free-swimming medusae. These hard surfaces are normally covered by fouling communities, the components of which have the potential to impede the proliferation of polyps. In this study, we report an in situ experiment of polyp survival of four large scyphozoan species found in East Asian marginal seas that were exposed to biofouling, a universal phenomenon occurring on marine artificial constructions. Our results showed that the polyps of three species (Nemopilema nomurai, Cyanea nozaki, and Rhopilema esculentum) attached to the artificial surfaces were completely eliminated by biofouling within 7–8 months, and only those of moon jellyfish (Aurelia sp.1) in the upper layers could multiply on both artificial materials and other organisms (e.g., ascidians and bryozoans). Fouling-associated competition and predation and suppressed asexual reproduction of podocysts were observed to contribute to the loss of polyps. This study shows that the natural distribution of polyps is defined by the biofouling community that colonizes the surfaces of artificial constructions. Consequently, the contribution of marine constructions to jellyfish bloom is limited only to the ability of the jellyfish species to reproduce asexually through budding and inhabit solid surfaces of fouling organisms in addition to inhabiting original artificial materials. We anticipate that fragile polyps will colonize and proliferate in harsh environments that are deleterious to biofouling, and we propose special attention to polyps in antifouling practices for excluding the possibility that they occupy the available ecological space. - Highlights: • Biofouling selectively controls in situ proliferation of scyphozoan polyps • The contribution
Quark fragmentation in e+e- collisions
International Nuclear Information System (INIS)
Oddone, P.
1984-12-01
This brief review of new results in quark and gluon fragmentation observed in e + e - collisions concentrates mostly on PEP results and, within PEP, mostly on TPC results. The new PETRA results have been reported at this conference by M. Davier. It is restricted to results on light quark fragmentation since the results on heavy quark fragmentation have been reported by J. Chapman
International Nuclear Information System (INIS)
Lee, Hoo Min; Kim, Ham Gyum; Kong, Seok Kyo
2009-01-01
The purpose of this research is to seek SPAIR's reversal time (TI) which satisfies two conditions ; maintaining the suppression ability of fat tissue and simultaneously minimizing the inhomogeneity of fat tissue in T2 high-speed spin echo 3.0T magnetic resonance image (MRI) of the brain, and to compare SPAIR with STIR which is fat-suppression technique. The reversal times (TI) of SPAIR protocol are set to 1/2, 1/3, 1/6 and 1/12 of SPAIR TR (420 msec), namely 210 msec (8 people), 140 msec (26 people), 70 msec (26 people) and 35 msec (18 people) and STIR TI is set with 250 msec (26 people). With these parameter sets, we acquired the axis direction 104 images of the brain. In ROI (50 mm 2 ) of output image, signal intensities of the fatty tissue, the muscular tissue, and the background were measured and the CNRs of fatty tissue and the muscular tissue were calculated. The inhomogeneity of the fatty tissue is SD/mean, where SD is the standard deviation and 'mean' is a average fatty tissue signal. Consequently, SPAIR TI is determined on either 1/3 or 1/6 of TR (420 ms) ; 140 ms or 70 ms. Because the difference of statistics in fat-suppression ability and inhomogeneity of fatty tissue is very small (p < 0.001), Selecting 140 ms seems to be better choice for the image quality. Meanwhile, Comparing SPAIR (TI : 140 ms) with STIR, the fat-suppression is not able to be considered statistically (p < 0.252), but the image quality is able to be considered statistically (p < 0.01). In conclusion, SPAIR is better than STIR in the image quality.
Headey, Stephen J.; Vazirani, Mansha; Shouldice, Stephen R.; Coinçon, Mathieu; Tay, Stephanie; Morton, Craig J.; Simpson, Jamie S.; Martin, Jennifer L.
2017-01-01
At a time when the antibiotic drug discovery pipeline has stalled, antibiotic resistance is accelerating with catastrophic implications for our ability to treat bacterial infections. Globally we face the prospect of a future when common infections can once again kill. Anti-virulence approaches that target the capacity of the bacterium to cause disease rather than the growth or survival of the bacterium itself offer a tantalizing prospect of novel antimicrobials. They may also reduce the propensity to induce resistance by removing the strong selection pressure imparted by bactericidal or bacteriostatic agents. In the human pathogen Pseudomonas aeruginosa, disulfide bond protein A (PaDsbA1) plays a central role in the oxidative folding of virulence factors and is therefore an attractive target for the development of new anti-virulence antimicrobials. Using a fragment-based approach we have identified small molecules that bind to PaDsbA1. The fragment hits show selective binding to PaDsbA1 over the DsbA protein from Escherichia coli, suggesting that developing species-specific narrow-spectrum inhibitors of DsbA enzymes may be feasible. Structures of a co-complex of PaDsbA1 with the highest affinity fragment identified in the screen reveal that the fragment binds on the non-catalytic surface of the protein at a domain interface. This biophysical and structural data represent a starting point in the development of higher affinity compounds, which will be assessed for their potential as selective PaDsbA1 inhibitors. PMID:28346540
Directory of Open Access Journals (Sweden)
Hust Michael
2008-09-01
Full Text Available Abstract Background Venezuelan equine encephalitis virus (VEEV belongs to the Alphavirus group. Several species of this family are also pathogenic to humans and are recognized as potential agents of biological warfare and terrorism. The objective of this work was the generation of recombinant antibodies for the detection of VEEV after a potential bioterrorism assault or an natural outbreak of VEEV. Results In this work, human anti-VEEV single chain Fragments variable (scFv were isolated for the first time from a human naïve antibody gene library using optimized selection processes. In total eleven different scFvs were identified and their immunological specificity was assessed. The specific detection of the VEEV strains TC83, H12/93 and 230 by the selected antibody fragments was proved. Active as well as formalin inactivated virus particles were recognized by the selected antibody fragments which could be also used for Western blot analysis of VEEV proteins and immunohistochemistry of VEEV infected cells. The anti-VEEV scFv phage clones did not show any cross-reactivity with Alphavirus species of the Western equine encephalitis virus (WEEV and Eastern equine encephalitis virus (EEEV antigenic complex, nor did they react with Chikungunya virus (CHIKV, if they were used as detection reagent. Conclusion For the first time, this study describes the selection of antibodies against a human pathogenic virus from a human naïve scFv antibody gene library using complete, active virus particles as antigen. The broad and sensitive applicability of scFv-presenting phage for the immunological detection and diagnosis of Alphavirus species was demonstrated. The selected antibody fragments will improve the fast identification of VEEV in case of a biological warfare or terroristic attack or a natural outbreak.
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.)
Ternary-fragmentation-driving potential energies of 252Cf
Karthikraj, C.; Ren, Zhongzhou
2017-12-01
Within the framework of a simple macroscopic model, the ternary-fragmentation-driving potential energies of 252Cf are studied. In this work, all possible ternary-fragment combinations of 252Cf are generated by the use of atomic mass evaluation-2016 (AME2016) data and these combinations are minimized by using a two-dimensional minimization approach. This minimization process can be done in two ways: (i) with respect to proton numbers (Z1, Z2, Z3) and (ii) with respect to neutron numbers (N1, N2, N3) of the ternary fragments. In this paper, the driving potential energies for the ternary breakup of 252Cf are presented for both the spherical and deformed as well as the proton-minimized and neutron-minimized ternary fragments. From the proton-minimized spherical ternary fragments, we have obtained different possible ternary configurations with a minimum driving potential, in particular, the experimental expectation of Sn + Ni + Ca ternary fragmentation. However, the neutron-minimized ternary fragments exhibit a driving potential minimum in the true-ternary-fission (TTF) region as well. Further, the Q -value energy systematics of the neutron-minimized ternary fragments show larger values for the TTF fragments. From this, we have concluded that the TTF region fragments with the least driving potential and high Q values have a strong possibility in the ternary fragmentation of 252Cf. Further, the role of ground-state deformations (β2, β3, β4, and β6) in the ternary breakup of 252Cf is also studied. The deformed ternary fragmentation, which involves Z3=12 -19 fragments, possesses the driving potential minimum due to the larger oblate deformations. We also found that the ground-state deformations, particularly β2, strongly influence the driving potential energies and play a major role in determining the most probable fragment combinations in the ternary breakup of 252Cf.
DEFF Research Database (Denmark)
Bang, Jacob Sebastian
2018-01-01
I have created a large collection of plaster models: a collection of Obstructions, errors and opportunities that may develop into architecture. The models are fragments of different complex shapes as well as more simple circular models with different profiling and diameters. In this contect I have....... I try to invent the ways of drawing the models - that decode and unfold them into architectural fragments- into future buildings or constructions in the landscape. [1] Luigi Moretti: Italian architect, 1907 - 1973 [2] Man Ray: American artist, 1890 - 1976. in 2015, I saw the wonderful exhibition...... "Man Ray - Human Equations" at the Glyptotek in Copenhagen, organized by the Philips Collection in Washington D.C. and the Israel Museum in Jerusalem (in 2013). See also: "Man Ray - Human Equations" catalogue published by Hatje Cantz Verlag, Germany, 2014....
The multiple facets of Peto's paradox: a life-history model for the evolution of cancer suppression.
Brown, Joel S; Cunningham, Jessica J; Gatenby, Robert A
2015-07-19
Large animals should have higher lifetime probabilities of cancer than small animals because each cell division carries an attendant risk of mutating towards a tumour lineage. However, this is not observed--a (Peto's) paradox that suggests large and/or long-lived species have evolved effective cancer suppression mechanisms. Using the Euler-Lotka population model, we demonstrate the evolutionary value of cancer suppression as determined by the 'cost' (decreased fecundity) of suppression verses the 'cost' of cancer (reduced survivorship). Body size per se will not select for sufficient cancer suppression to explain the paradox. Rather, cancer suppression should be most extreme when the probability of non-cancer death decreases with age (e.g. alligators), maturation is delayed, fecundity rates are low and fecundity increases with age. Thus, the value of cancer suppression is predicted to be lowest in the vole (short lifespan, high fecundity) and highest in the naked mole rat (long lived with late female sexual maturity). The life history of pre-industrial humans likely selected for quite low levels of cancer suppression. In modern humans that live much longer, this level results in unusually high lifetime cancer risks. The model predicts a lifetime risk of 49% compared with the current empirical value of 43%. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression
Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.
2013-10-01
Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.
Chemical Production using Fission Fragments
International Nuclear Information System (INIS)
Dawson, J. K.; Moseley, F.
1960-01-01
Some reactor design considerations of the use of fission recoil fragment energy for the production of chemicals of industrial importance have been discussed previously in a paper given at the Second United Nations International Conference on the Peaceful Uses of Atomic Energy [A/Conf. 15/P.76]. The present paper summarizes more recent progress made on this topic at AERE, Harwell. The range-energy relationship for fission fragments is discussed in the context of the choice of fuel system for a chemical production reactor, and the experimental observation of a variation of chemical effect along the length of a fission fragment track is described for the irradiation of nitrogen-oxygen mixtures. Recent results are given on the effect of fission fragments on carbon monoxide-hydrogen gas mixtures and on water vapour. No system investigated to date shows any outstanding promise for large-scale chemical production. (author) [fr
The dynamics of fragment formation
International Nuclear Information System (INIS)
Keane, D.
1994-09-01
We demonstrate that in the Quantum Molecular Dynamics model, dynamical correlations can result in the production rate for final state nucleon clusters (and hence composite fragments) being higher than would be expected if statistics and the available phase space were dominant in determining composite formation. An intranuclear cascade or a Boltzmann-Uehling-Uhlenbeck model, combined with a statistical approach in the late stage of the collision to determine composites, provides an equivalent description only under limited conditions of centrality and beam energy. We use data on participant fragment production in Au + Au collisions in the Bevalac's BOS time projection chamber to map out the parameter space where statistical clustering provides a good description. In particular, we investigate momentum-space densities of fragments up to 4 He as a function of fragment transverse momentum, azimuth relative to the reaction plane, rapidity, multiplicity and beam energy
Hands as markers of fragmentation
Directory of Open Access Journals (Sweden)
A. Barnard
2005-07-01
Full Text Available Margaret Atwood is an internationally read, translated, and critiqued writer whose novels have established her as one of the most esteemed authors in English (McCombs & Palmer, 1991:1. Critical studies of her work deal mainly with notions of identity from psychoanalytical perspectives. This study has identified a gap in current critical studies on Atwood’s works, namely the challenging of textual unity which is paralleled in the challenging of the traditional (single narrative voice. The challenging of textual unity and the single narrative voice brings about the fragmentation of both. This article will focus on the role that hands play as markers of fragmentation in “The Blind Assassin” (2000. In the novel, the writing hand destabilises the narrative voice, since it is not connected to the voice of a single author. If the author of the text – the final signified – is eliminated, the text becomes fragmentary and open, inviting the reader to contribute to the creation of meaning. Hands play a signficant role in foregrounding the narrator’s fragmented identity, and consequently, the fragmentation of the text. We will investigate this concept in the light of Roland Barthes’ notion of the scriptor, whose hand is metaphorically severed from his or her “voice”. Instead of the text being a unified entity, it becomes unstable and it displays the absence of hierarchical textual levels. Based mainly on Barthes’ writings, this article concludes that hands foreground the narrator’s fragmented identity, which is paralleled in the fragmented text.
International Nuclear Information System (INIS)
Silisteanu, I.
1991-06-01
The effect of collective mode excitation in heavy fragment radioactivity (HFR) is explored and discussed in the light of current experimental data. It is found that the coupling and resonance effects in fragment interaction and also the proper angular momentum effects may lead to an important enhancing of the emission process. New useful procedures are proposed for the study of nuclear decay properties. The relations between different decay processes are investigated in detail. We are also trying to understand and explain in a unified way the reaction mechanisms in decay phenomena. (author). 17 refs, 4 figs, 3 tabs
An Algebra for Program Fragments
DEFF Research Database (Denmark)
Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger
1985-01-01
Program fragments are described either by strings in the concrete syntax or by constructor applications in the abstract syntax. By defining conversions between these forms, both may be intermixed. Program fragments are constructed by terminal and nonterminal symbols from the grammar and by variab...
Energy Technology Data Exchange (ETDEWEB)
Shevitz, Daniel Wolf [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Key, Brian P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Garcia, Daniel B. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
2017-09-05
The Fragment Impact Toolkit (FIT) is a software package used for probabilistic consequence evaluation of fragmenting sources. The typical use case for FIT is to simulate an exploding shell and evaluate the consequence on nearby objects. FIT is written in the programming language Python and is designed as a collection of interacting software modules. Each module has a function that interacts with the other modules to produce desired results.
A model for projectile fragmentation
International Nuclear Information System (INIS)
Chaudhuri, G; Mallik, S; Gupta, S Das
2013-01-01
A model for projectile fragmentation is developed whose origin can be traced back to the Bevalac era. The model positions itself between the phenomenological EPAX parametrization and transport models like 'Heavy Ion Phase Space Exploration' (HIPSE) model and antisymmetrised molecular dynamics (AMD) model. A very simple impact parameter dependence of input temperature is incorporated in the model which helps to analyze the more peripheral collisions. The model is applied to calculate the charge, isotopic distributions, average number of intermediate mass fragments and the average size of largest cluster at different Z bound of different projectile fragmentation reactions at different energies.
Gamma Radiation from Fission Fragments
International Nuclear Information System (INIS)
Higbie, Jack
1969-10-01
The gamma radiation from the fragments of the thermal neutron fission of 235 U has been investigated, and the preliminary data are presented here with suggestions for further lines of research and some possible interpretations of the data. The data have direct bearing on the fission process and the mode of fragment de-excitation. The parameters measured are the radiation decay curve for the time interval (1 - 7) x 10 -10 sec after fission, the photon yield, the total gamma ray energy yield, and the average photon energy. The last three quantities are measured as a function of the fragment mass
Gamma Radiation from Fission Fragments
Energy Technology Data Exchange (ETDEWEB)
Higbie, Jack
1969-10-15
The gamma radiation from the fragments of the thermal neutron fission of {sup 235}U has been investigated, and the preliminary data are presented here with suggestions for further lines of research and some possible interpretations of the data. The data have direct bearing on the fission process and the mode of fragment de-excitation. The parameters measured are the radiation decay curve for the time interval (1 - 7) x 10{sup -10} sec after fission, the photon yield, the total gamma ray energy yield, and the average photon energy. The last three quantities are measured as a function of the fragment mass.
Almeida, C S; Cristaldo, P F; Florencio, D F; Ribeiro, E J M; Cruz, N G; Silva, E A; Costa, D A; Araújo, A P A
2017-01-01
Habitat fragmentation is considered to be one of the biggest threats to tropical ecosystem functioning. In this region, termites perform an important ecological role as decomposers and ecosystem engineers. In the present study, we tested whether termite community is negatively affected by edge effects on three fragments of Brazilian Atlantic Rainforest. Termite abundance and vegetation structure were sampled in 10 transects (15 × 2 m), while termite richness, activity, and soil litter biomass were measured in 16 quadrants (5 × 2 m) at forest edge and interior of each fragment. Habitat structure (i.e. number of tree, diameter at breast height and soil litter biomass) did not differ between forest edge and interior of fragments. Termite richness, abundance and activity were not affected by edge effect. However, differences were observed in the β diversity between forest edge and interior as well as in the fragments sampled. The β diversity partitioning indicates that species turnover is the determinant process of termite community composition under edge effect. Our results suggest that conservation strategies should be based on the selection of several distinct sites instead of few rich sites (e.g. nesting).
de Souza, Mirian S; Pepinelli, Mateus; de Almeida, Eduardo C; Ochoa-Quintero, Jose M; Roque, Fabio O
2016-01-01
Given the general expectation that forest loss can alter biodiversity patterns, we hypothesize that blow fly species abundances differ in a gradient of native vegetation cover. This study was conducted in 17 fragments across different landscapes in central Brazil. Different land cover type proportions were used to represent landscape structure. In total, 2334 specimens of nine species of Calliphoridae were collected. We used principal component analysis (PCA) to reduce dimensionality and multicollinearity of the landscape data. The first component explained 70%, and it represented a gradient of forest-pasture land uses. Alien species showed a wide distribution in different fragments with no clear relationship between the abundance values and the scores of PCA axes, whereas native species occurred only in areas with a predominance of forest cover. Our study revealed that certain native species may be sensitive to forest loss at the landscape scale, and they represent a bioindicator in forensic entomology. © 2015 American Academy of Forensic Sciences.
Anisotropy in highly charged ion induced molecule fragmentation
International Nuclear Information System (INIS)
Juhasz, Z.; Sulik, B.; Fremont, F.; Chesnel, J.Y.; Hajaji, A.
2006-01-01
Complete text of publication follows. Studying fragmentation processes of biologically relevant molecules due to highly charged ion impact is important to understand radiation damage in biological tissues. Energy spectra of the charged molecule fragments may reveal the different fragmentation patterns meanwhile the angular distributions of the fragments characterize the dependence of fragmentation probability on the initial orientation of the molecule. The research to explore the angular distribution of the molecule fragments has only recently been started[1]. In 2006 we performed measurements at ARIBE facility at GANIL, Caen (France), in order to investigate orientation effects in molecule fragmentation. Fragmentation of H 2 O, C 6 H 6 and CH 4 , which represent different level of symmetry, have been studied by 60 keV N 6+ ion impact. Energy spectra of the charged fragments at different observation angles have been taken. As our example spectra show the different protonic peaks can be attributed to different fragmentation processes. Significant anisotropy can be seen in the different processes. The strongest evidence for the anisotropy can be seen in the spectra of C 6 H 6 , where the spectra appear isotropic in almost the whole observed energy range except one peak, which has a strong angular dependence and is maximal around 90 deg. (author)
Energy Technology Data Exchange (ETDEWEB)
Chen, T.; Gatchell, M.; Stockett, M. H.; Alexander, J. D.; Schmidt, H. T.; Cederquist, H.; Zettergren, H., E-mail: henning@fysik.su.se [Department of Physics, Stockholm University, S-106 91 Stockholm (Sweden); Zhang, Y. [Department of Mathematics, Faculty of Physics, M. V. Lomonosov Moscow State University, Leninskie Gory, 119991 Moscow (Russian Federation); Rousseau, P.; Maclot, S.; Delaunay, R.; Adoui, L. [CIMAP, UMR 6252, CEA/CNRS/ENSICAEN/Université de Caen Basse-Normandie, bd Henri Becquerel, BP 5133, F-14070 Caen Cedex 05 (France); Université de Caen Basse-Normandie, Esplanade de la Paix, F-14032 Caen (France); Domaracka, A.; Huber, B. A. [CIMAP, UMR 6252, CEA/CNRS/ENSICAEN/Université de Caen Basse-Normandie, bd Henri Becquerel, BP 5133, F-14070 Caen Cedex 05 (France); Schlathölter, T. [Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747AG Groningen (Netherlands)
2014-06-14
We present scaling laws for absolute cross sections for non-statistical fragmentation in collisions between Polycyclic Aromatic Hydrocarbons (PAH/PAH{sup +}) and hydrogen or helium atoms with kinetic energies ranging from 50 eV to 10 keV. Further, we calculate the total fragmentation cross sections (including statistical fragmentation) for 110 eV PAH/PAH{sup +} + He collisions, and show that they compare well with experimental results. We demonstrate that non-statistical fragmentation becomes dominant for large PAHs and that it yields highly reactive fragments forming strong covalent bonds with atoms (H and N) and molecules (C{sub 6}H{sub 5}). Thus nonstatistical fragmentation may be an effective initial step in the formation of, e.g., Polycyclic Aromatic Nitrogen Heterocycles (PANHs). This relates to recent discussions on the evolution of PAHNs in space and the reactivities of defect graphene structures.
Remarks about the hypothesis of limiting fragmentation
International Nuclear Information System (INIS)
Chou, T.T.; Yang, C.N.
1987-01-01
Remarks are made about the hypothesis of limiting fragmentation. In particular, the concept of favored and disfavored fragment distribution is introduced. Also, a sum rule is proved leading to a useful quantity called energy-fragmentation fraction. (author). 11 refs, 1 fig., 2 tabs
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
Nuclear energy release from fragmentation
Energy Technology Data Exchange (ETDEWEB)
Li, Cheng [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Souza, S.R. [Instituto de Física, Universidade Federal do Rio de Janeiro Cidade Universitária, Caixa Postal 68528, 21945-970 Rio de Janeiro (Brazil); Tsang, M.B. [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); National Superconducting Cyclotron Laboratory and Physics and Astronomy Department, Michigan State University, East Lansing, MI 48824 (United States); Zhang, Feng-Shou, E-mail: fszhang@bnu.edu.cn [The Key Laboratory of Beam Technology and Material Modification of Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, Beijing 100875 (China); Beijing Radiation Center, Beijing 100875 (China); Center of Theoretical Nuclear Physics, National Laboratory of Heavy Ion Accelerator of Lanzhou, Lanzhou 730000 (China)
2016-08-15
It is well known that binary fission occurs with positive energy gain. In this article we examine the energetics of splitting uranium and thorium isotopes into various numbers of fragments (from two to eight) with nearly equal size. We find that the energy released by splitting {sup 230,232}Th and {sup 235,238}U into three equal size fragments is largest. The statistical multifragmentation model (SMM) is applied to calculate the probability of different breakup channels for excited nuclei. By weighing the probability distributions of fragment multiplicity at different excitation energies, we find the peaks of energy release for {sup 230,232}Th and {sup 235,238}U are around 0.7–0.75 MeV/u at excitation energy between 1.2 and 2 MeV/u in the primary breakup process. Taking into account the secondary de-excitation processes of primary fragments with the GEMINI code, these energy peaks fall to about 0.45 MeV/u.
Multiple H3+ fragment production in single collision of fast Hn+ clusters with He atoms
International Nuclear Information System (INIS)
Farizon, B.; Farizon, M.; Gaillard, M.J.; Gerlic, E.; Ouaskit, S.
1994-09-01
The production of H 3 + ions resulting from single collisions of mass-selected ionic hydrogen clusters, H n + (n=9,25,31), with helium at high velocity (1.55 times the Bohr velocity) has been studied. A strong double H 3 + ion production resulting from one incident cluster is observed. Moreover, evidence for a triple H 3 + fragment production is presented for n=25 and 31. Thus, in this energy range, the collision gives rise to multifragmentation processes. The formation of H 3 + ions takes place in the fragmentation of the multicharged cluster resulting from the collision. (authors)
Dihadron fragmentation function and its evolution
International Nuclear Information System (INIS)
Majumder, A.; Wang Xinnian
2004-01-01
Dihadron fragmentation functions and their evolution are studied in the process of e + e - annihilation. Under the collinear factorization approximation and facilitated by the cut-vertex technique, the two hadron inclusive cross section at leading order is shown to factorize into a short distance parton cross section and a long distance dihadron fragmentation function. We provide the definition of such a dihadron fragmentation function in terms of parton matrix elements and derive its Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution equation at leading log. The evolution equation for the nonsinglet quark fragmentation function is solved numerically with a simple ansatz for the initial condition and results are presented for cases of physical interest
SCEDS: protein fragments for molecular replacement in Phaser
Energy Technology Data Exchange (ETDEWEB)
McCoy, Airlie J., E-mail: ajm201@cam.ac.uk [University of Cambridge, Hills Road, Cambridge CB2 0XY (United Kingdom); Nicholls, Robert A. [MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH (United Kingdom); Schneider, Thomas R. [Hamburg Unit c/o DESY, Notkestrasse 85, 22603 Hamburg (Germany); University of Cambridge, Hills Road, Cambridge CB2 0XY (United Kingdom)
2013-11-01
Protein fragments suitable for use in molecular replacement can be generated by normal-mode perturbation, analysis of the difference distance matrix of the original versus normal-mode perturbed structures, and SCEDS, a score that measures the sphericity, continuity, equality and density of the resulting fragments. A method is described for generating protein fragments suitable for use as molecular-replacement (MR) template models. The template model for a protein suspected to undergo a conformational change is perturbed along combinations of low-frequency normal modes of the elastic network model. The unperturbed structure is then compared with each perturbed structure in turn and the structurally invariant regions are identified by analysing the difference distance matrix. These fragments are scored with SCEDS, which is a combined measure of the sphericity of the fragments, the continuity of the fragments with respect to the polypeptide chain, the equality in number of atoms in the fragments and the density of C{sup α} atoms in the triaxial ellipsoid of the fragment extents. The fragment divisions with the highest SCEDS are then used as separate template models for MR. Test cases show that where the protein contains fragments that undergo a change in juxtaposition between template model and target, SCEDS can identify fragments that lead to a lower R factor after ten cycles of all-atom refinement with REFMAC5 than the original template structure. The method has been implemented in the software Phaser.
SCEDS: protein fragments for molecular replacement in Phaser
International Nuclear Information System (INIS)
McCoy, Airlie J.; Nicholls, Robert A.; Schneider, Thomas R.
2013-01-01
Protein fragments suitable for use in molecular replacement can be generated by normal-mode perturbation, analysis of the difference distance matrix of the original versus normal-mode perturbed structures, and SCEDS, a score that measures the sphericity, continuity, equality and density of the resulting fragments. A method is described for generating protein fragments suitable for use as molecular-replacement (MR) template models. The template model for a protein suspected to undergo a conformational change is perturbed along combinations of low-frequency normal modes of the elastic network model. The unperturbed structure is then compared with each perturbed structure in turn and the structurally invariant regions are identified by analysing the difference distance matrix. These fragments are scored with SCEDS, which is a combined measure of the sphericity of the fragments, the continuity of the fragments with respect to the polypeptide chain, the equality in number of atoms in the fragments and the density of C α atoms in the triaxial ellipsoid of the fragment extents. The fragment divisions with the highest SCEDS are then used as separate template models for MR. Test cases show that where the protein contains fragments that undergo a change in juxtaposition between template model and target, SCEDS can identify fragments that lead to a lower R factor after ten cycles of all-atom refinement with REFMAC5 than the original template structure. The method has been implemented in the software Phaser
Designer genes. Recombinant antibody fragments for biological imaging
Energy Technology Data Exchange (ETDEWEB)
Wu, A.M.; Yazaki, P.J. [Beckman Research Institute of the City of Hope, Duarte, CA (United States). Dept. of Molecular Biology
2000-09-01
Monoclonal antibodies (MAbs), with high specificity and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C{sub H}3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering
Designer genes. Recombinant antibody fragments for biological imaging
International Nuclear Information System (INIS)
Wu, A.M.; Yazaki, P.J.
2000-01-01
Monoclonal antibodies (MAbs), with high specificy and high affinity for their target antigens, can be utilized for delivery of agents such as radionuclides, enzymes, drugs or toxins in vivo. However, the implementation of radiolabeled antibodies as magic bullets for detection and treatment of diseases such as cancer has required addressing several shortcomings of murine MAbs. These include their immunogenicity, sub-optimal targeting and pharmacokinetic properties, and practical issues of production and radiolabeling. Genetic engineering provides a powerful approach for redesigning antibodies for use in oncologic applications in vivo. Recombinant fragments have been produced that retain high affinity for target antigens, and display a combination of rapid, high-level tumor targeting with concomitant clearance from normal tissues and the circulation in animal models. An important first step was cloning and engineering of antibody heavy and light chain variable domains into single-chain Fvs (molecular weight, 25-17 kDa), in which the variable regions are joined via a synthetic linker peptide sequence. Although scFvs themselves showed limited tumor uptake in preclinical and clinical studies, they provide a useful building block for intermediate sized recombinant fragments. Covalently linked dimers or non-covalent dimers of scFvs (also known as diabodies) show improved targeting and clearance properties due to their higher molecular weight (55kDa) and increased avidity. Further gains can be made by generation of larger recombinant fragments, such as the minibody, an scFv-C H 3 fusion protein that self-assembles into a bivalent dimer of 80 kDa. A systematic evaluation of scFv, diabody, minibody, and intact antibody (based on comparison of tumor uptakes, tumor: blood activity ratios, and calculation of an Imaging Figure of Merit) can form the basis for selection of combinations of recombinant fragments and radionuclides for imaging applications. Ease of engineering and
Evolution equations for extended dihadron fragmentation functions
International Nuclear Information System (INIS)
Ceccopieri, F.A.; Bacchetta, A.
2007-03-01
We consider dihadron fragmentation functions, describing the fragmentation of a parton in two unpolarized hadrons, and in particular extended dihadron fragmentation functions, explicitly dependent on the invariant mass, M h , of the hadron pair. We first rederive the known results on M h -integrated functions using Jet Calculus techniques, and then we present the evolution equations for extended dihadron fragmentation functions. Our results are relevant for the analysis of experimental measurements of two-particle-inclusive processes at different energies. (orig.)
Quantitative experimental modelling of fragmentation during explosive volcanism
Thordén Haug, Ø.; Galland, O.; Gisler, G.
2012-04-01
Phreatomagmatic eruptions results from the violent interaction between magma and an external source of water, such as ground water or a lake. This interaction causes fragmentation of the magma and/or the host rock, resulting in coarse-grained (lapilli) to very fine-grained (ash) material. The products of phreatomagmatic explosions are classically described by their fragment size distribution, which commonly follows power laws of exponent D. Such descriptive approach, however, considers the final products only and do not provide information on the dynamics of fragmentation. The aim of this contribution is thus to address the following fundamental questions. What are the physics that govern fragmentation processes? How fragmentation occurs through time? What are the mechanisms that produce power law fragment size distributions? And what are the scaling laws that control the exponent D? To address these questions, we performed a quantitative experimental study. The setup consists of a Hele-Shaw cell filled with a layer of cohesive silica flour, at the base of which a pulse of pressurized air is injected, leading to fragmentation of the layer of flour. The fragmentation process is monitored through time using a high-speed camera. By varying systematically the air pressure (P) and the thickness of the flour layer (h) we observed two morphologies of fragmentation: "lift off" where the silica flour above the injection inlet is ejected upwards, and "channeling" where the air pierces through the layer along sub-vertical conduit. By building a phase diagram, we show that the morphology is controlled by P/dgh, where d is the density of the flour and g is the gravitational acceleration. To quantify the fragmentation process, we developed a Matlab image analysis program, which calculates the number and sizes of the fragments, and so the fragment size distribution, during the experiments. The fragment size distributions are in general described by power law distributions of
International Nuclear Information System (INIS)
Vojtsitskij, V.M.; Fedorov, A.N.; Lugovskoj, Eh.B.; Derzskaya, S.G.; Khizhnyak, S.V.; Kurskij, M.D.; Kucherenko, N.E.
1990-01-01
Early (1 and 24 h) after X-irradiation with a dose of 0.21 C/kg changes occurred in the acceptibility of the polypeptide chain parts of sarcoplasmic reticulum Ca-ATPase for the effect of trypsin. The analysis of the results of studying the structural and functional properties of a hydrophobic fragment of this enzyme in the control and after irradiation permitted to define the part of the Ca-ATPase polypeptide chain that provided ion selectivity of the fragment
AutoDrug: fully automated macromolecular crystallography workflows for fragment-based drug discovery
International Nuclear Information System (INIS)
Tsai, Yingssu; McPhillips, Scott E.; González, Ana; McPhillips, Timothy M.; Zinn, Daniel; Cohen, Aina E.; Feese, Michael D.; Bushnell, David; Tiefenbrunn, Theresa; Stout, C. David; Ludaescher, Bertram; Hedman, Britt; Hodgson, Keith O.; Soltis, S. Michael
2013-01-01
New software has been developed for automating the experimental and data-processing stages of fragment-based drug discovery at a macromolecular crystallography beamline. A new workflow-automation framework orchestrates beamline-control and data-analysis software while organizing results from multiple samples. AutoDrug is software based upon the scientific workflow paradigm that integrates the Stanford Synchrotron Radiation Lightsource macromolecular crystallography beamlines and third-party processing software to automate the crystallography steps of the fragment-based drug-discovery process. AutoDrug screens a cassette of fragment-soaked crystals, selects crystals for data collection based on screening results and user-specified criteria and determines optimal data-collection strategies. It then collects and processes diffraction data, performs molecular replacement using provided models and detects electron density that is likely to arise from bound fragments. All processes are fully automated, i.e. are performed without user interaction or supervision. Samples can be screened in groups corresponding to particular proteins, crystal forms and/or soaking conditions. A single AutoDrug run is only limited by the capacity of the sample-storage dewar at the beamline: currently 288 samples. AutoDrug was developed in conjunction with RestFlow, a new scientific workflow-automation framework. RestFlow simplifies the design of AutoDrug by managing the flow of data and the organization of results and by orchestrating the execution of computational pipeline steps. It also simplifies the execution and interaction of third-party programs and the beamline-control system. Modeling AutoDrug as a scientific workflow enables multiple variants that meet the requirements of different user groups to be developed and supported. A workflow tailored to mimic the crystallography stages comprising the drug-discovery pipeline of CoCrystal Discovery Inc. has been deployed and successfully
Age-related decline in global form suppression
DEFF Research Database (Denmark)
Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas
2015-01-01
. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global...... differences in the subsequent (250–500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanisza, as compared to non-Kanisza, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative...... to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages – indicative of older observers having difficulties with disengaging from a global default selection mode...
International Nuclear Information System (INIS)
Chen, J M; Lu, K T; Lee, J M; Chou, T L; Chen, H C; Chen, S A; Haw, S C; Chen, T H
2008-01-01
The state-selective dissociation dynamics for anionic and excited neutral fragments of gaseous SiCl 4 following Cl 2p and Si 2p core-level excitations were characterized by combining measurements of the photon-induced anionic dissociation, x-ray absorption and UV/visible dispersed fluorescence. The transitions of core electrons to high Rydberg states/doubly excited states in the vicinity of both Si 2p and Cl 2p ionization thresholds of gaseous SiCl 4 lead to a remarkably enhanced production of anionic, Si - and Cl - , fragments and excited neutral atomic, Si*, fragments. This enhancement via core-level excitation near the ionization threshold of gaseous SiCl 4 is explained in terms of the contributions from the Auger decay of doubly excited states, shake-modified resonant Auger decay, or/and post-collision interaction. These complementary results provide insight into the state-selective anionic and excited neutral fragmentation of gaseous molecules via core-level excitation.
Predicting "Hot" and "Warm" Spots for Fragment Binding.
Rathi, Prakash Chandra; Ludlow, R Frederick; Hall, Richard J; Murray, Christopher W; Mortenson, Paul N; Verdonk, Marcel L
2017-05-11
Computational fragment mapping methods aim to predict hotspots on protein surfaces where small fragments will bind. Such methods are popular for druggability assessment as well as structure-based design. However, to date researchers developing or using such tools have had no clear way of assessing the performance of these methods. Here, we introduce the first diverse, high quality validation set for computational fragment mapping. The set contains 52 diverse examples of fragment binding "hot" and "warm" spots from the Protein Data Bank (PDB). Additionally, we describe PLImap, a novel protocol for fragment mapping based on the Protein-Ligand Informatics force field (PLIff). We evaluate PLImap against the new fragment mapping test set, and compare its performance to that of simple shape-based algorithms and fragment docking using GOLD. PLImap is made publicly available from https://bitbucket.org/AstexUK/pli .
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
The politics of municipal fragmentation in Ghana
Directory of Open Access Journals (Sweden)
Abdulai Kuyini Mohammed
2015-06-01
Full Text Available The scholarly debate over the rival merits of local government consolidation and fragmentation is an old but enduring one. However, in this debate very little attention has been focused on the political dimension of council amalgamation and fragmentation – yet political considerations play a central role in both the formulation and outcomes of de-concentration policy. The purpose of this article is to fill a gap in the literature by examining local government fragmentation in Ghana from 1988 to 2014. The article does this by identifying the key players and analysing their interests and gains, as well as the tensions arising from the fragmentation exercise. The implications from the Ghanaian case for more general theories of fragmentation are drawn out.
Heart Rate Fragmentation: A Symbolic Dynamical Approach
Directory of Open Access Journals (Sweden)
Madalena D. Costa
2017-11-01
Full Text Available Background: We recently introduced the concept of heart rate fragmentation along with a set of metrics for its quantification. The term was coined to refer to an increase in the percentage of changes in heart rate acceleration sign, a dynamical marker of a type of anomalous variability. The effort was motivated by the observation that fragmentation, which is consistent with the breakdown of the neuroautonomic-electrophysiologic control system of the sino-atrial node, could confound traditional short-term analysis of heart rate variability.Objective: The objectives of this study were to: (1 introduce a symbolic dynamical approach to the problem of quantifying heart rate fragmentation; (2 evaluate how the distribution of the different dynamical patterns (“words” varied with the participants' age in a group of healthy subjects and patients with coronary artery disease (CAD; and (3 quantify the differences in the fragmentation patterns between the two sample populations.Methods: The symbolic dynamical method employed here was based on a ternary map of the increment NN interval time series and on the analysis of the relative frequency of symbolic sequences (words with a pre-defined set of features. We analyzed annotated, open-access Holter databases of healthy subjects and patients with CAD, provided by the University of Rochester Telemetric and Holter ECG Warehouse (THEW.Results: The degree of fragmentation was significantly higher in older individuals than in their younger counterparts. However, the fragmentation patterns were different in the two sample populations. In healthy subjects, older age was significantly associated with a higher percentage of transitions from acceleration/deceleration to zero acceleration and vice versa (termed “soft” inflection points. In patients with CAD, older age was also significantly associated with higher percentages of frank reversals in heart rate acceleration (transitions from acceleration to
The Assessment of Selectivity in Different Quadrupole-Orbitrap Mass Spectrometry Acquisition Modes
Berendsen, Bjorn J. A.; Wegh, Robin S.; Meijer, Thijs; Nielen, Michel W. F.
2015-02-01
Selectivity of the confirmation of identity in liquid chromatography (tandem) mass spectrometry using Q-Orbitrap instrumentation was assessed using different acquisition modes based on a representative experimental data set constructed from 108 samples, including six different matrix extracts and containing over 100 analytes each. Single stage full scan, all ion fragmentation, and product ion scanning were applied. By generating reconstructed ion chromatograms using unit mass window in targeted MS2, selected reaction monitoring (SRM), regularly applied using triple-quadrupole instruments, was mimicked. This facilitated the comparison of single stage full scan, all ion fragmentation, (mimicked) SRM, and product ion scanning applying a mass window down to 1 ppm. Single factor Analysis of Variance was carried out on the variance (s2) of the mass error to determine which factors and interactions are significant parameters with respect to selectivity. We conclude that selectivity is related to the target compound (mainly the mass defect), the matrix, sample clean-up, concentration, and mass resolution. Selectivity of the different instrumental configurations was quantified by counting the number of interfering peaks observed in the chromatograms. We conclude that precursor ion selection significantly contributes to selectivity: monitoring of a single product ion at high mass accuracy with a 1 Da precursor ion window proved to be equally selective or better to monitoring two transition products in mimicked SRM. In contrast, monitoring a single fragment in all ion fragmentation mode results in significantly lower selectivity versus mimicked SRM. After a thorough inter-laboratory evaluation study, the results of this study can be used for a critical reassessment of the current identification points system and contribute to the next generation of evidence-based and robust performance criteria in residue analysis and sports doping.
International Nuclear Information System (INIS)
Le Fevre, A.
1997-01-01
This work is focused on the study of fragment and light particle production mechanisms in the multifragmentation process of hot nuclei, which are formed in the central collisions of Xe+Sn at 50 MeV/u. The experiment has been performed with the INDRA multidetector. The central collision events, selected via the flow angle variable, exhibit the presence of a heavy (Z=90) and highly excited (E * =12.5 MeV/u) isotropic emission source. The comparison of the data with a statistical multifragmentation model (MMMC) and a dynamical model (BNV) makes us conclude that the multifragmentation can only be explained in the frame of a relatively cold process, around 6 MeV/u of thermal excitation energy, preceded by a primary emission stage of the expanding source, during which nearly one third of the excitation energy is dissipated. In addition, it appears that the fragment energy spectra are not explained by a purely thermal process, and that one has to put forward an expansion collective motion, of 2 MeV/u of energy, following the compression of the compound system. In order to precise the existence of a two-step particle emission (primary and secondary), we have developed and applied an original method of reduced velocity correlations between particles and fragments. It has allowed us to underline two distinct origins for the particle production: one corresponding to secondary emissions, coming from the fragments, and the other one, associated with emissions which occur prior to the fragment production. At last, it has allowed us, also to bring out a hierarchy in the emission time in the decay process, with respect to the particle type. (author)
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
Simulations of High Speed Fragment Trajectories
Yeh, Peter; Attaway, Stephen; Arunajatesan, Srinivasan; Fisher, Travis
2017-11-01
Flying shrapnel from an explosion are capable of traveling at supersonic speeds and distances much farther than expected due to aerodynamic interactions. Predicting the trajectories and stable tumbling modes of arbitrary shaped fragments is a fundamental problem applicable to range safety calculations, damage assessment, and military technology. Traditional approaches rely on characterizing fragment flight using a single drag coefficient, which may be inaccurate for fragments with large aspect ratios. In our work we develop a procedure to simulate trajectories of arbitrary shaped fragments with higher fidelity using high performance computing. We employ a two-step approach in which the force and moment coefficients are first computed as a function of orientation using compressible computational fluid dynamics. The force and moment data are then input into a six-degree-of-freedom rigid body dynamics solver to integrate trajectories in time. Results of these high fidelity simulations allow us to further understand the flight dynamics and tumbling modes of a single fragment. Furthermore, we use these results to determine the validity and uncertainty of inexpensive methods such as the single drag coefficient model.
Agarose gel electrophoresis for the separation of DNA fragments.
Lee, Pei Yun; Costumbrado, John; Hsu, Chih-Yuan; Kim, Yong Hoon
2012-04-20
concentration for their needs Prepare an agarose gel for electrophoresis of DNA samples Set up the gel electrophoresis apparatus and power supply Select an appropriate voltage for the separation of DNA fragments Understand the mechanism by which ethidium bromide allows for the visualization of DNA bands Determine the sizes of separated DNA fragments.
Microstructural characterization of pipe bomb fragments
International Nuclear Information System (INIS)
Gregory, Otto; Oxley, Jimmie; Smith, James; Platek, Michael; Ghonem, Hamouda; Bernier, Evan; Downey, Markus; Cumminskey, Christopher
2010-01-01
Recovered pipe bomb fragments, exploded under controlled conditions, have been characterized using scanning electron microscopy, optical microscopy and microhardness. Specifically, this paper examines the microstructural changes in plain carbon-steel fragments collected after the controlled explosion of galvanized, schedule 40, continuously welded, steel pipes filled with various smokeless powders. A number of microstructural changes were observed in the recovered pipe fragments: deformation of the soft alpha-ferrite grains, deformation of pearlite colonies, twin formation, bands of distorted pearlite colonies, slip bands, and cross-slip bands. These microstructural changes were correlated with the relative energy of the smokeless powder fillers. The energy of the smokeless powder was reflected in a reduction in thickness of the pipe fragments (due to plastic strain prior to fracture) and an increase in microhardness. Moreover, within fragments from a single pipe, there was a radial variation in microhardness, with the microhardness at the outer wall being greater than that at the inner wall. These findings were consistent with the premise that, with the high energy fillers, extensive plastic deformation and wall thinning occurred prior to pipe fracture. Ultimately, the information collected from this investigation will be used to develop a database, where the fragment microstructure and microhardness will be correlated with type of explosive filler and bomb design. Some analyses, specifically wall thinning and microhardness, may aid in field characterization of explosive devices.
Cryobiology of coral fragments.
Hagedorn, Mary; Farrell, Ann; Carter, Virginia L
2013-02-01
Around the world, coral reefs are dying due to human influences, and saving habitat alone may not stop this destruction. This investigation focused on the biological processes that will provide the first steps in understanding the cryobiology of whole coral fragments. Coral fragments are a partnership of coral tissue and endosymbiotic algae, Symbiodinium sp., commonly called zooxanthellae. These data reflected their separate sensitivities to chilling and a cryoprotectant (dimethyl sulfoxide) for the coral Pocillopora damicornis, as measured by tissue loss and Pulse Amplitude Modulated fluorometry 3weeks post-treatment. Five cryoprotectant treatments maintained the viability of the coral tissue and zooxanthellae at control values (1M dimethyl sulfoxide at 1.0, 1.5 and 2.0h exposures, and 1.5M dimethyl sulfoxide at 1.0 and 1.5h exposures, P>0.05, ANOVA), whereas 2M concentrations did not (Pzooxanthellae. During the winter when the fragments were chilled, the coral tissue remained relatively intact (∼25% loss) post-treatment, but the zooxanthellae numbers in the tissue declined after 5min of chilling (Pzooxanthellae numbers declined in response to chilling alone (P0.05, ANOVA), but it did not protect against the loss of zooxanthellae (Pzooxanthellae are the most sensitive element in the coral fragment complex and future cryopreservation protocols must be guided by their greater sensitivity. Copyright © 2012 Elsevier Inc. All rights reserved.
MaRaCluster: A Fragment Rarity Metric for Clustering Fragment Spectra in Shotgun Proteomics.
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).
SPR-based fragment screening with neurotensin receptor 1 generates novel small molecule ligands
Huber, Sylwia; Casagrande, Fabio; Hug, Melanie N.; Wang, Lisha; Heine, Philipp; Kummer, Lutz; Plückthun, Andreas; Hennig, Michael
2017-01-01
The neurotensin receptor 1 represents an important drug target involved in various diseases of the central nervous system. So far, the full exploitation of potential therapeutic activities has been compromised by the lack of compounds with favorable physicochemical and pharmacokinetic properties which efficiently penetrate the blood-brain barrier. Recent progress in the generation of stabilized variants of solubilized neurotensin receptor 1 and its subsequent purification and successful structure determination presents a solid starting point to apply the approach of fragment-based screening to extend the chemical space of known neurotensin receptor 1 ligands. In this report, surface plasmon resonance was used as primary method to screen 6369 compounds. Thereby 44 hits were identified and confirmed in competition as well as dose-response experiments. Furthermore, 4 out of 8 selected hits were validated using nuclear magnetic resonance spectroscopy as orthogonal biophysical method. Computational analysis of the compound structures, taking the known crystal structure of the endogenous peptide agonist into consideration, gave insight into the potential fragment-binding location and interactions and inspires chemistry efforts for further exploration of the fragments. PMID:28510609
Kostetskiĭ, P V; Dobrova, I E
1988-04-01
An algorithm for reconstructing long DNA sequences, i.e. arranging all overlapping gel readings in the contigs, and the corresponding BASIC programme for personal computer "Iskra-226" (USSR) are described. The contig construction begins with the search for all fragments overlapping the basic (longest) one follower by determination of coordinates of 5' ends of the overlapping fragments. Then the gel reading with minimal 5' end coordinate and the gel reading with maximal 3' end coordinate are selected and used as basic ones at the next assembly steps. The procedure is finished when no gel reading overlapping the basic one can be found. All gel readings entered the contig are ignored at the next steps of the assembly. Finally, one or several contigs consisted of DNA fragments are obtained. Effectiveness of the algorithm was tested on a model based on the multiple assembly of the nucleotide sequence, encoding the Na, K-ATPase alpha-subunit of pig kidney. The programme does not call for user's participation and can comprise contigs up to 10,000 nucleotides long.
Harris, Christopher; Stace, Anthony J
2018-03-15
A series of experiments have been undertaken on the fragmentation of multiply charged ammonia clusters, (NH 3 ) n z+ , where z ≤ 8 and n ≤ 850, to establish Rayleigh instability limits, whereby clusters at certain critical sizes become unstable due to Coulomb repulsion between the resident charges. Experimental results on size-selected clusters are found to be in excellent agreement with theoretical predictions of Rayleigh instability limits at all values of the charge. Electrostatic theory has been used to help identify fragmentation patterns on the assumption that the clusters separate into two dielectric spheres, and the predicted Coulomb repulsion energies used to establish pathways and the sizes of cluster fragments. The results show that fragmentation is very asymmetric in terms of both the numbers of molecules involved and the amount of charge each fragment accommodates. For clusters carrying a charge ≤+4, the results show that fragmentation proceeds via the loss of small, singly charged clusters. When clusters carry a charge of +5 or more, the experimental observations suggest a marked switch in behavior. Although the laboratory measurements equate to fragmentation via the loss of a large dication cluster, electrostatic theory supports an interpretation that involves the sequential loss of two smaller, singly charged clusters possibly accompanied by the extensive evaporation of neutral molecules. It is suggested that this change in fragmentation pattern is driven by the channelling of Coulomb repulsion energy into intermolecular modes within these larger clusters. Overall, the results appear to support the ion evaporation model that is frequently used to interpret electrospray experiments.
Vuilleumier, Patrik; Schwartz, Sophie; Duhoux, Stéphanie; Dolan, Raymond J; Driver, Jon
2005-08-01
Attention can enhance processing for relevant information and suppress this for ignored stimuli. However, some residual processing may still arise without attention. Here we presented overlapping outline objects at study, with subjects attending to those in one color but not the other. Attended objects were subsequently recognized on a surprise memory test, whereas there was complete amnesia for ignored items on such direct explicit testing; yet reliable behavioral priming effects were found on indirect testing. Event-related fMRI examined neural responses to previously attended or ignored objects, now shown alone in the same or mirror-reversed orientation as before, intermixed with new items. Repetition-related decreases in fMRI responses for objects previously attended and repeated in the same orientation were found in the right posterior fusiform, lateral occipital, and left inferior frontal cortex. More anterior fusiform regions also showed some repetition decreases for ignored objects, irrespective of orientation. View-specific repetition decreases were found in the striate cortex, particularly for previously attended items. In addition, previously ignored objects produced some fMRI response increases in the bilateral lingual gyri, relative to new objects. Selective attention at exposure can thus produce several distinct long-term effects on processing of stimuli repeated later, with neural response suppression stronger for previously attended objects, and some response enhancement for previously ignored objects, with these effects arising in different brain areas. Although repetition decreases may relate to positive priming phenomena, the repetition increases for ignored objects shown here for the first time might relate to processes that can produce "negative priming" in some behavioral studies. These results reveal quantitative and qualitative differences between neural substrates of long-term repetition effects for attended versus unattended objects.
Fragmentation properties of 6Li
International Nuclear Information System (INIS)
Lovas, R.G.; Kruppa, A.T.; Beck, R.; Dickmann, F.
1987-01-01
The α+d and t+τ cluster structure of 6 Li is described in a microscopic α+d cluster model through quantities that enter into the description of cluster fragmentation processes. The states of the separate clusters α, d, t and τ are described as superpositions of Os Slater determinants belonging to different potential size parameters. To describe both the 6 Li and fragment state realistically, nucleon-nucleon forces optimized for the used model state spaces were constructed. The fragmentation properties predicted by them slightly differ from those calculated with some forces of common use provided the latter are modified so as to reproduce the α, d and 6 Li energies. (author) 61 refs.; 9 figs
Geometrical scaling of jet fragmentation photons
Energy Technology Data Exchange (ETDEWEB)
Hattori, Koichi, E-mail: koichi.hattori@riken.jp [RIKEN BNL Research Center, Brookhaven National Laboratory, Upton NY 11973 (United States); Theoretical Research Division, Nishina Center, RIKEN, Wako, Saitama 351-0198 (Japan); McLerran, Larry, E-mail: mclerran@bnl.gov [RIKEN BNL Research Center, Brookhaven National Laboratory, Upton NY 11973 (United States); Physics Dept., Bdg. 510A, Brookhaven National Laboratory, Upton, NY-11973 (United States); Physics Dept., China Central Normal University, Wuhan (China); Schenke, Björn, E-mail: bschenke@bnl.gov [Physics Dept., Bdg. 510A, Brookhaven National Laboratory, Upton, NY-11973 (United States)
2016-12-15
We discuss jet fragmentation photons in ultrarelativistic heavy-ion collisions. We argue that, if the jet distribution satisfies geometrical scaling and an anisotropic spectrum, these properties are transferred to photons during the jet fragmentation.
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...
March, Raymond E.; Miao, Xiu-Sheng
2004-02-01
A mass spectrometric method based on the combined use of electrospray ionization, collision-induced dissociation and tandem mass spectrometry at high mass resolution has been applied to an investigation of the structural characterization of protonated and deprotonated kaempferol (3,5,7,4'-tetrahydroxyflavone). Low-energy product ion mass spectra of [M+H]+ ions showed simple fragmentations of the C ring that permitted characterization of the substituents in the A and B rings. In addition, four rearrangement reactions accompanied by losses of C2H2O, CHO[radical sign], CO, and H2O were observed. Low-energy product ion mass spectra of [M-H]- ions showed only four rearrangement reactions accompanied by losses of OH[radical sign], CO, CH2O, and C2H2O. The use of elevated cone voltages permitted observation of product ion mass spectra of selected primary and secondary fragment ions so that each fragment ion reported was observed as a direct product of its immediate precursor ion. Product ion mass spectra examined at high mass resolution allowed unambiguous determination of the elemental composition of fragment ions and resolution of two pairs of isobars. Fragmentation mechanisms and ion structures have been proposed.
A new location to split Cre recombinase for protein fragment complementation.
Rajaee, Maryam; Ow, David W
2017-11-01
We have previously described a recombinase-mediated gene stacking system in which the Cre recombinase is used to remove lox-site flanked DNA no longer needed after each round of Bxb1 integrase-mediated site-specific integration. The Cre recombinase can be conveniently introduced by hybridization with a cre-expressing plant. However, maintaining an efficient cre-expressing line over many generations can be a problem, as high production of this DNA-binding protein might interfere with normal chromosome activities. To counter this selection against high Cre activity, we considered a split-cre approach, in which Cre activity is reconstituted after separate parts of Cre are brought into the same genome by hybridization. To insure that the recombinase-mediated gene stacking system retains its freedom to operate, we tested for new locations to split Cre into complementing fragments. In this study, we describe testing four new locations for splitting the Cre recombinase for protein fragment complementation and show that the two fragments of Cre split between Lys244 and Asn245 can reconstitute activity that is comparable to that of wild-type Cre. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.
Fracture mechanics model of fragmentation
International Nuclear Information System (INIS)
Glenn, L.A.; Gommerstadt, B.Y.; Chudnovsky, A.
1986-01-01
A model of the fragmentation process is developed, based on the theory of linear elastic fracture mechanics, which predicts the average fragment size as a function of strain rate and material properties. This approach permits a unification of previous results, yielding Griffith's solution in the low-strain-rate limit and Grady's solution at high strain rates
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.
Heavy-Quark Production in the Target Fragmentation Region
Graudenz, Dirk
1997-01-01
Fixed-target experiments permit the study of hadron production in the target fragmentation region. It is expected that the tagging of specific particles in the target fragments can be employed to introduce a bias in the hard scattering process towards a specific flavour content. The case of hadrons containing a heavy quark is particularly attractive because of the clear experimental signatures and the applicability of perturbative QCD. The standard approach to one-particle inclusive processes based on fragmentation functions is valid in the current fragmentation region and for large transverse momenta $p_T$ in the target fragmentation region, but it fails for particle production at small $p_T$ in the target fragmentation region. A collinear singularity, which cannot be absorbed in the standard way into the phenomenological distribution functions, prohibits the application of this procedure. This situation is remedied by the introduction of a new set of distribution functions, the target fragmentation function...
Structure-guided evolution of potent and selective CHK1 inhibitors through scaffold morphing.
Reader, John C; Matthews, Thomas P; Klair, Suki; Cheung, Kwai-Ming J; Scanlon, Jane; Proisy, Nicolas; Addison, Glynn; Ellard, John; Piton, Nelly; Taylor, Suzanne; Cherry, Michael; Fisher, Martin; Boxall, Kathy; Burns, Samantha; Walton, Michael I; Westwood, Isaac M; Hayes, Angela; Eve, Paul; Valenti, Melanie; de Haven Brandon, Alexis; Box, Gary; van Montfort, Rob L M; Williams, David H; Aherne, G Wynne; Raynaud, Florence I; Eccles, Suzanne A; Garrett, Michelle D; Collins, Ian
2011-12-22
Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice.
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
Experimental modelling of fragmentation applied to volcanic explosions
Haug, Øystein Thordén; Galland, Olivier; Gisler, Galen R.
2013-12-01
Explosions during volcanic eruptions cause fragmentation of magma and host rock, resulting in fragments with sizes ranging from boulders to fine ash. The products can be described by fragment size distributions (FSD), which commonly follow power laws with exponent D. The processes that lead to power-law distributions and the physical parameters that control D remain unknown. We developed a quantitative experimental procedure to study the physics of the fragmentation process through time. The apparatus consists of a Hele-Shaw cell containing a layer of cohesive silica flour that is fragmented by a rapid injection of pressurized air. The evolving fragmentation of the flour is monitored with a high-speed camera, and the images are analysed to obtain the evolution of the number of fragments (N), their average size (A), and the FSD. Using the results from our image-analysis procedure, we find transient empirical laws for N, A and the exponent D of the power-law FSD as functions of the initial air pressure. We show that our experimental procedure is a promising tool for unravelling the complex physics of fragmentation during phreatomagmatic and phreatic eruptions.
Directory of Open Access Journals (Sweden)
Komarine Romdenh-Romluc
2009-12-01
Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.
Neighbouring charge fragmentations in low energy fission
International Nuclear Information System (INIS)
Montoya, M.
1986-10-01
Shell and odd-even effects in fission have been largely studied until now. The structure in fragment mass, charge and kinetic energy distributions of fragments were interpreted as shell and even-odd effects. In this paper, we want to show that the discret change of fragment charge symmetry should produce also structures in those distribution. 19 refs
Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.
The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in
Aspect Ratio Dependence of Impact Fragmentation
International Nuclear Information System (INIS)
Inaoka, H.; Toyosawa, E.; Takayasu, H.; Inaoka, H.
1997-01-01
A numerical model of three-dimensional impact fragmentation produces a power-law cumulative fragment mass distribution followed by a flat tail. The result is consistent with an experimental result in a recent paper by Meibom and Balslev [Phys. Rev. Lett. 76, 2492 (1996)]. Our numerical simulation also implies that the fragment mass distribution changes from a power law with a flat tail to a power law with a sudden cutoff, depending on the aspect ratio of the fractured object. copyright 1997 The American Physical Society
Li, Zhigang; Fan, Erica K; Liu, Jinghua; Scott, Melanie J; Li, Yuehua; Li, Song; Xie, Wen; Billiar, Timothy R; Wilson, Mark A; Jiang, Yong; Wang, Ping; Fan, Jie
2017-05-11
Trauma is a major cause of systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Macrophages (Mφ) direct trauma-induced inflammation, and Mφ death critically influences the progression of the inflammatory response. In the current study, we explored an important role of trauma in inducing mitochondrial DNA (mtDNA) damage in Mφ and the subsequent regulation of Mφ death. Using an animal pseudo-fracture trauma model, we demonstrated that tissue damage induced NADPH oxidase activation and increased the release of reactive oxygen species via cold-inducible RNA-binding protein (CIRP)-TLR4-MyD88 signaling. This in turn, activates endonuclease G, which serves as an executor for the fragmentation of mtDNA in Mφ. We further showed that fragmented mtDNA triggered both p62-related autophagy and necroptosis in Mφ. However, autophagy activation also suppressed Mφ necroptosis and pro-inflammatory responses. This study demonstrates a previously unidentified intracellular regulation of Mφ homeostasis in response to trauma.
Gluon fragmentation in T(1S) decays
International Nuclear Information System (INIS)
Bienlein, J.K.
1983-05-01
In T(1S) decays most observables (sphericity, charged multiplicity, photonic energy fraction, inclusive spectra) can be understood assuming that gluons fragment like quarks. New results from LENA use the (axis-independent) Fox-Wolfram moments for the photonic energy deposition. Continuum reactions show 'standard' Field-Feynman fragmentation. T(1S) decays show a significant difference in the photonic energy topology. It is more isotropic than with the Field-Feynman fragmentation scheme. Gluon fragmentation into isoscalar mesons (a la Peterson and Walsh) is excluded. But if one forces the leading particle to be isoscalar, one gets good agreement with the data. (orig.)
Spatial genetic structure in continuous and fragmented populations of Pinus pinaster Aiton.
De-Lucas, A I; González-Martínez, S C; Vendramin, G G; Hidalgo, E; Heuertz, M
2009-11-01
Habitat fragmentation, i.e., the reduction of populations into small isolated remnants, is expected to increase spatial genetic structure (SGS) in plant populations through nonrandom mating, lower population densities and potential aggregation of reproductive individuals. We investigated the effects of population size reduction and genetic isolation on SGS in maritime pine (Pinus pinaster Aiton) using a combined experimental and simulation approach. Maritime pine is a wind-pollinated conifer which has a scattered distribution in the Iberian Peninsula as a result of forest fires and habitat fragmentation. Five highly polymorphic nuclear microsatellites were genotyped in a total of 394 individuals from two population pairs from the Iberian Peninsula, formed by one continuous and one fragmented population each. In agreement with predictions, SGS was significant and stronger in fragments (Sp = 0.020 and Sp = 0.026) than in continuous populations, where significant SGS was detected for one population only (Sp = 0.010). Simulations suggested that under fat-tailed dispersal, small population size is a stronger determinant of SGS than genetic isolation, while under normal dispersal, genetic isolation has a stronger effect. SGS was always stronger in real populations than in simulations, except if unrealistically narrow dispersal and/or high variance of reproductive success were modelled (even when accounting for potential overestimation of SGS in real populations as a result of short-distance sampling). This suggests that factors such as nonrandom mating or selection not considered in the simulations were additionally operating on SGS in Iberian maritime pine populations.
Fragmentation of Relativistic 56Fe Nuclei in Emulsion
International Nuclear Information System (INIS)
Chernov, G.M.; Gulamov, K.G.; Gulyamov, U.G.; Navotny, V.Sh.; Petrov, N.V.; Svechnikova, L.N.; Jakobsson, B.; Oskarsson, A.; Otterlund, I.
1983-03-01
Experimental data on general characteristics of projectile fragments in inelastic interactions of relativistic 56 Fe nuclei in emulsion (multiplicities, transverse momentum distributions, azimuthal correlations) are presented and discussed. A strong dependence on the mass number of the projectile nucleus is observed for the transverse momenta of the emitted projectile fragments. These fragments exhibit an azimuthal asymmetry caused by the transverse motion of the fragmenting residue, but it is shown that this motion can be responsible only for a part of the increase in the average transverse momentum of the fragments with increasing mass of the projectile. (author)
Percutaneous transhepatic fragmentation of gall stones and extraction of fragments
International Nuclear Information System (INIS)
Guenther, R.; Klose, K.; Schmidt, H.D.; Staritz, M.; Mainz Univ.; Mainz Univ.
1983-01-01
Attempts at percutaneous removal have been made in 13 patients with solitary and multiple intra- and extra-hepatic biliary duct stones measuring 5 to 30 mm. The stones were fragmented with a Dormia basket and the fragments removed transhepatically. In ten patients the procedure was successful, including one patient with multiple intra-hepatic stones. The procedure can be recommended for cases of calculous obstruction of biliary anastomoses or of stones which could not be removed by endoscopy, or where there is already biliary drainage being carried out, or in patients with a high opertive risk. In two patients, dilatation of the papilla was also carried out, in four patients a stenosis was dilated and in a further two patients, electro-incision of a stenosis was performed. (orig.) [de
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.
International Nuclear Information System (INIS)
Isoda, Haruo; Masui, Takayuki; Mochizuki, Takao; Ushimi, Takashi; Takahashi, Motoichiro; Kaneko, Masao; Ohta, Atsuko; Shirakawa, Toyomi; Takizawa, Osamu.
1994-01-01
The purpose of this study was to investigate the utility of fat suppression T 1 -weighted MR images using a frequency-selective presaturation pulse when evaluating the pituitary gland and parasellar lesions. Conventional spin echo T 1 weighted images and fat suppression spin echo T 1 -weighted images were obtained in twenty-three patients with clinically suspected pituitary gland diseases or parasellar lesions using a 1.5T superconductive MR imager with a head coil. Both conventional T 1 -weighted images and fat suppression T 1 -weighted images of the pituitary anterior lobe, posterior lobe, pituitary stalk and pituitary tumors were compared by two radiologists. The visibility of the anterior lobe, posterior lobe, pituitary stalk and pituitary tumors on fat suppression T 1 -weighted images was equal to or better than that on conventional T 1 -weighted images. After the intravenous administration of Gd-DTPA, both imaging methods showed little difference in the visibility of the posterior lobe and pituitary stalk. In conclusion, fat suppression T 1 -weighted images using a frequency-selective presaturation pulse can be useful in evaluating the pituitary gland and parasellar lesions. (author)
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)
Off-resonance suppression for multispectral MR imaging near metallic implants.
den Harder, J Chiel; van Yperen, Gert H; Blume, Ulrike A; Bos, Clemens
2015-01-01
Metal artifact reduction in MRI within clinically feasible scan-times without through-plane aliasing. Existing metal artifact reduction techniques include view angle tilting (VAT), which resolves in-plane distortions, and multispectral imaging (MSI) techniques, such as slice encoding for metal artifact correction (SEMAC) and multi-acquisition with variable resonances image combination (MAVRIC), that further reduce image distortions, but significantly increase scan-time. Scan-time depends on anatomy size and anticipated total spectral content of the signal. Signals outside the anticipated spatial region may cause through-plane back-folding. Off-resonance suppression (ORS), using different gradient amplitudes for excitation and refocusing, is proposed to provide well-defined spatial-spectral selectivity in MSI to allow scan-time reduction and flexibility of scan-orientation. Comparisons of MSI techniques with and without ORS were made in phantom and volunteer experiments. Off-resonance suppressed SEMAC (ORS-SEMAC) and outer-region suppressed MAVRIC (ORS-MAVRIC) required limited through-plane phase encoding steps compared with original MSI. Whereas SEMAC (scan time: 5'46") and MAVRIC (4'12") suffered from through-plane aliasing, ORS-SEMAC and ORS-MAVRIC allowed alias-free imaging in the same scan-times. ORS can be used in MSI to limit the selected spatial-spectral region and contribute to metal artifact reduction in clinically feasible scan-times while avoiding slice aliasing. © 2014 Wiley Periodicals, Inc.
Memory effects in nuclear fragmentation?
International Nuclear Information System (INIS)
Colonna, M.; Di Toro, M.; Guarnera, A.
1994-01-01
A general procedure to identify instability regions which lead to multifragmentation events is presented. The dominant mode at the instability point is determined from the knowledge of the mean properties (density and temperature) of the system at that point. For spinodal instabilities the dependence of fragment structures on the dynamical conditions is studied changing the beam energy and the considered equation of state. An important competition between two dynamical effects, expansion of the system and growth of fluctuations, is revealed. It is shown that in heavy-ion central collisions at medium energies memory effects of the configuration formed at the instability time could be observed in the final fragmentation pattern. Some hints towards a fully dynamical picture of fragmentation processes are finally suggested. ((orig.))
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)
Gluon fragmentation into 3 PJ quarkonium
International Nuclear Information System (INIS)
Ma, J.P.
1995-01-01
The functions of the gluon fragmentation into 3 P j quarkonium are calculated to order α 2 s . With the recent progress in analysing quarkonium systems in QCD it is possible show how the so called divergence in the limit of the zero-binding energy, which is related to P-wave quarkonia, is treated correctly in the case of fragmentation functions. The obtained fragmentation functions satisfy explicitly at the order of α 2 s the Altarelli-Parisi equation and when z → 0 they behave as z -1 as expected. 19 refs., 7 figs
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)
Contralateral Suppression of DPOAEs in Mice after Ouabain Treatment
Directory of Open Access Journals (Sweden)
Jieying Li
2018-01-01
Full Text Available Medial olivocochlear (MOC efferent feedback is suggested to protect the ear from acoustic injury and to increase its ability to discriminate sounds against a noisy background. We investigated whether type II spiral ganglion neurons participate in the contralateral suppression of the MOC reflex. The application of ouabain to the round window of the mouse cochlea selectively induced the apoptosis of the type I spiral ganglion neurons, left the peripherin-immunopositive type II spiral ganglion neurons intact, and did not affect outer hairs, as evidenced by the maintenance of the distorted product otoacoustic emissions (DPOAEs. With the ouabain treatment, the threshold of the auditory brainstem response increased significantly and the amplitude of wave I decreased significantly in the ouabain-treated ears, consistent with the loss of type I neurons. Contralateral suppression was measured as reduction in the amplitude of the 2f1−f2 DPOAEs when noise was presented to the opposite ear. Despite the loss of all the type I spiral ganglion neurons, virtually, the amplitude of the contralateral suppression was not significantly different from the control when the suppressor noise was delivered to the treated cochlea. These results are consistent with the type II spiral ganglion neurons providing the sensory input driving contralateral suppression of the MOC reflex.
Neutronics Assessments for a RIA Fragmentation Line Beam Dump Concept
Boles, Jason; Reyes, Susana; Stein, Werner
2005-01-01
Heavy ion and radiation transport calculations are in progress for conceptual beam dump designs for the fragmentation line of the proposed Rare Isotope Accelerator (RIA). Using the computer code PHITS, a preliminary design of a motor-driven rotating wheel beam dump and adjacent downstream multipole has been modeled. Selected results of these calculations are given, including neutron and proton flux in the wheel, absorbed dose and displacements per atom in the hub materials, and heating from prompt radiation and from decay heat in the multipole.
Fuel fragmentation data review and separate effects testing
International Nuclear Information System (INIS)
Yueh, Ken. H.; Snis, N.; Mitchell, D.; Munoz-Reja, C.
2014-01-01
A simple alternative test has been developed to study the fuel fragmentation process at loss of coolant accident (LOCA) temperatures. The new test heats a short section of fuel, approximately two pellets worth of material, in a tube furnace open to air. An axial slit is cut in the test sample cladding to reduce radial restraint and to simulate ballooned condition. The tube furnace allows the fuel fragmentation process be observed during the experiment. The test was developed as a simple alternative so large number of tests could be conducted quickly and efficiently to identify key variables that influence fuel fragmentation and to zeroing on the fuel fragmentation burn-up threshold. Several tests were conducted, using fuel materials from fuel rods that were used in earlier integral tests to benchmark and validate the test technique. High burn-up fuel materials known to be above the fragmentation threshold was used to evaluate the fragmentation process as a function of temperature. Even with an axial slit and both ends open, no significant fuel detachment/release was detected until above 750°C. Additional tests were conducted with fuel materials at burn-ups closer to the fuel fragmentation burn-up threshold. Results from these tests indicate a minor power history effect on the fuel fragmentation burn-up threshold. An evaluation of available literature and data generated from this work suggest a fuel fragmentation burn-up threshold between 70 and 75 GWd/MTU. (author)
Biological effectiveness of high-energy protons - Target fragmentation
International Nuclear Information System (INIS)
Cucinotta, F.A.; Katz, R.; Wilson, J.W.; Townsend, L.W.; Shinn, J.; Hajnal, F.
1991-01-01
High-energy protons traversing tissue produce local sources of high-linear-energy-transfer ions through nuclear fragmentation. The contribution of these target fragments to the biological effectiveness of high-energy protons using the cellular track model is examined. The effects of secondary ions are treated in terms of the production collision density using energy-dependent parameters from a high-energy fragmentation model. Calculations for mammalian cell cultures show that at high dose, at which intertrack effects become important, protons deliver damage similar to that produced by gamma rays, and with fragmentation the relative biological effectiveness (RBE) of protons increases moderately from unity. At low dose, where sublethal damage is unimportant, the contribution from target fragments dominates, causing the proton effectiveness to be very different from that of gamma rays with a strongly fluence-dependent RBE. At high energies, the nuclear fragmentation cross sections become independent of energy. This leads to a plateau in the proton single-particle-action cross section, below 1 keV/micron, since the target fragments dominate. 29 refs
Bootstrap embedding: An internally consistent fragment-based method
Energy Technology Data Exchange (ETDEWEB)
Welborn, Matthew; Tsuchimochi, Takashi; Van Voorhis, Troy [Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139 (United States)
2016-08-21
Strong correlation poses a difficult problem for electronic structure theory, with computational cost scaling quickly with system size. Fragment embedding is an attractive approach to this problem. By dividing a large complicated system into smaller manageable fragments “embedded” in an approximate description of the rest of the system, we can hope to ameliorate the steep cost of correlated calculations. While appealing, these methods often converge slowly with fragment size because of small errors at the boundary between fragment and bath. We describe a new electronic embedding method, dubbed “Bootstrap Embedding,” a self-consistent wavefunction-in-wavefunction embedding theory that uses overlapping fragments to improve the description of fragment edges. We apply this method to the one dimensional Hubbard model and a translationally asymmetric variant, and find that it performs very well for energies and populations. We find Bootstrap Embedding converges rapidly with embedded fragment size, overcoming the surface-area-to-volume-ratio error typical of many embedding methods. We anticipate that this method may lead to a low-scaling, high accuracy treatment of electron correlation in large molecular systems.
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
Quark fragmentation functions in NJL-jet model
Bentz, Wolfgang; Matevosyan, Hrayr; Thomas, Anthony
2014-09-01
We report on our studies of quark fragmentation functions in the Nambu-Jona-Lasinio (NJL) - jet model. The results of Monte-Carlo simulations for the fragmentation functions to mesons and nucleons, as well as to pion and kaon pairs (dihadron fragmentation functions) are presented. The important role of intermediate vector meson resonances for those semi-inclusive deep inelastic production processes is emphasized. Our studies are very relevant for the extraction of transverse momentum dependent quark distribution functions from measured scattering cross sections. We report on our studies of quark fragmentation functions in the Nambu-Jona-Lasinio (NJL) - jet model. The results of Monte-Carlo simulations for the fragmentation functions to mesons and nucleons, as well as to pion and kaon pairs (dihadron fragmentation functions) are presented. The important role of intermediate vector meson resonances for those semi-inclusive deep inelastic production processes is emphasized. Our studies are very relevant for the extraction of transverse momentum dependent quark distribution functions from measured scattering cross sections. Supported by Grant in Aid for Scientific Research, Japanese Ministry of Education, Culture, Sports, Science and Technology, Project No. 20168769.
Alkaline glass as induced fission fragment detectors
International Nuclear Information System (INIS)
Amorim, A.M.M.
1986-01-01
The slide glass, registered trade marks INLAB, INVICT and PERFECTA were compared. For the three kinds of glasses the following studies were done: chemical composition; general dissolution rate for hydrofluoric acid solutions of concentrations between 1 and 10M, at 30 0 C and ultrasound shaking; relative efficiency for recording fission fragment tracks from 252 Cf. The INLAB glass was selected due to the better quality of its surface after chemical etching. The HF concentration 2.5M was determined for chemical etching of INLAB glass, and the optimum etching time was chosen between 8 and 10 minutes. The thermal attenuation of latent tracks in the environmental temperature was observed for intervals uo to 31 days between the detector exposure to the fission fragment source and etching of tracks. Several methods were used for determining the detector parameters, such as: critical angle, angle of the cone and efficiency of etching. The effects of gamma irradiation from 60 Co and reactor neutrons in material properties as track detector were studied. Attenuation of latent tracks and saturation of color centers were observed for doses over 100M Rad. Since this kind of material contains uranium as impurity, uniformely distributed, slide glass were calibrated to be applied as a monitor of thermal neutron flux in nuclear reactor. (Author) [pt
Mass-Selective Laser Photoionization.
Smalley, R. E.
1982-01-01
Discusses the nature and applications of mass-selective laser photoionization. The ionization can be done with a single intense laser pulse lasting a few billionths of a second with no molecular fragmentation. Applications focus on: (1) benzene clusters, excimers, and exciplexes; (2) metal clusters; and (3) triplet formation and decay. (Author/JN)
A suppression hierarchy among competing motor programs drives sequential grooming in Drosophila.
Seeds, Andrew M; Ravbar, Primoz; Chung, Phuong; Hampel, Stefanie; Midgley, Frank M; Mensh, Brett D; Simpson, Julie H
2014-08-19
Motor sequences are formed through the serial execution of different movements, but how nervous systems implement this process remains largely unknown. We determined the organizational principles governing how dirty fruit flies groom their bodies with sequential movements. Using genetically targeted activation of neural subsets, we drove distinct motor programs that clean individual body parts. This enabled competition experiments revealing that the motor programs are organized into a suppression hierarchy; motor programs that occur first suppress those that occur later. Cleaning one body part reduces the sensory drive to its motor program, which relieves suppression of the next movement, allowing the grooming sequence to progress down the hierarchy. A model featuring independently evoked cleaning movements activated in parallel, but selected serially through hierarchical suppression, was successful in reproducing the grooming sequence. This provides the first example of an innate motor sequence implemented by the prevailing model for generating human action sequences. Copyright © 2014, Seeds et al.
Fructans and water suppression on intact and fragmented rhizophores of Vernonia herbacea
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Gláucia M. Dias-Tagliacozzo
2004-07-01
Full Text Available In order to evaluate the involvement of fructans in drought tolerance, experiments were conducted using intact plants and excised rhizophores of Vernonia herbacea. The water content in rhizophores of intact plants was maintained for 30 days when plants were watered every 7 and 15 days, whereas plants remained alive up to 60 days without water. Total fructan, oligo- to polysaccharides ratio and mean molecular mass of polysaccharides increased in these plants indicating depolymerization of median size molecules. In apical fragments of rhizophores kept dry the oligosaccharides increased in relation to polysaccharides one day after excision in treated tissues. This was reflected in the HPLC profile of the oligosaccharides in which the proportion of free fructose and fructans with DP 4-10 increased markedly. Results indicate that fructan metabolism is involved in drought tolerance of V. herbacea.A vegetação herbácea do cerrado brasileiro apresenta sistemas subterrâneos ricos em frutanos e estacionalmente expostos à restrição hídrica. A fim de avaliar o envolvimento dos frutanos na tolerância à dessecação foram conduzidos experimentos utilizando plantas intactas e fragmentos de rizóforos de Vernonia herbacea. O conteúdo de água nos rizóforos de plantas intactas foi mantido por 30 dias, quando as plantas foram molhadas a cada 7 ou 15 dias, sendo que as plantas permaneceram vivas até 60 dias sem água. O conteúdo total de frutanos, a razão oligo/polissacarídeos e a massa molecular média dos polissacarídeos nessas plantas aumentaram, indicando haver ocorrido despolimerização de moléculas com tamanho intermediário das cadeias. Nos fragmentos apicais de rizóforos submetidos à dessecação, os oligossacarídeos aumentaram em relação aos polissacarídeos, um dia após a excisão dos tecidos tratados. Essas alterações foram facilmente detectadas através dos perfis de oligossacarídeos analisados por HPLC, nos quais a propor
Kinematical properties of spectator fragments in heavy-ion collisions at relativistic energies
International Nuclear Information System (INIS)
Bacquias, A.
2008-07-01
Contrary to central collisions experiments, some experiments are designed for the investigation of nuclear-matter properties thanks to spectator matter. These experiments concentrate their selection on events of peripheral and mid-peripheral collisions. Spectator matter is not subject to compression but is highly excited. The observables related to spectator fragments can then be used as probes on nuclear matter at low density in the case of mid-peripheral collisions. Recently, experiments with the Fragment Separator (FRS) at GSI have proven to be suited for yielding valuable complementary information to spectator matter studies. We will first give an overview of the types of reaction relevant for this study and the different features that condition the reaction mechanisms leading to fragmentation. In the second chapter, we will describe the experimental set-up used at the FRS and explain the role of each detector and the method to exploit these data at best. In the third chapter we will concentrate our efforts on kinematics data from a 136 Xe + Pb experiment at the energy of 1 GeV per nucleon. Experimental results come in the fourth chapter and they are interpreted and discussed in chapters 5, 6 and 7. We will first comment the shapes of the velocity spectra and discuss the link between observation and physical processes. The surprising fact that one has means to assess the centrality despite the low acceptance of the experimental set-up will be underlined. This new way of presenting the data will permit a new approach to the nucleon-nucleon cross-section, by making comparison with theoretical models possible. Eventually, we will concentrate on the width of the velocity spectra. After going through previous models and predictions we will present a new description of the reaction mechanisms and their influence on the kinematics of observed fragments, reliable for a very broad range of fragments. (A.C.)
Keystone Species, Forest and Landscape: A Model to Select Protected Areas
Lins, Daniela Barbosa da Silva; Gardon, Fernando Ravanini; Meyer, João Frederico da Costa Azevedo; Santos, Rozely Ferreira dos
2017-06-01
The selection of forest fragments for conservation is usually based on spatial parameters as forest size and canopy integrity. This strategy assumes that chosen fragments present high conservation status, ensuring biodiversity and ecological functions. We argue that a well-preserved forest fragment that remains connected by the landscape structure, does not necessarily hold attributes that ensure the presence of keystone species. We also discuss that the presence of keystone species does not always mean that it has the best conditions for its occurrence and maintenance. We developed a model to select areas in forest landscapes to be prioritized for protection based on suitability curves that unify and compare spatial indicators of three categories: forest fragment quality, landscape quality, and environmental conditions for the occurrence of a keystone species. We use a case study to compare different suitability degrees for Euterpe edulis presence, considered an important functional element in Atlantic Forest (São Paulo, Brazil) landscapes and a forest resource for local people. The results show that the identification of medium or advanced stage fragments as singular indicator of forest quality does not guarantee the existence or maintenance of this keystone species. Even in some well-preserved forest fragments, connected to others and with palm presence, the reverse J-shaped distribution of the population size structure is not sustained and these forests continue to be threatened due to human disturbances.
International Nuclear Information System (INIS)
Hahn, P.J.; Giddings, L.; Lane, M.J.
1989-01-01
Restriction mapping of relatively large genomes (e.g. human) utilizing randomly generated DNA segments requires high mapping redundancy to successfully organize 'contigs' to represent the entire genome. The number of independent DNA segment maps required is dependent on the average size of a mapping segment; the larger the segment, the fewer required. The authors have developed a strategy for subcloning intact multimegabase subchromosomal fragments as double minute chromosomes. Such fragments could serve as primary mapping elements or as adjunct (linking) fragments to rapidly connect already existent contigs generated using yeast artificial chromosomes or cosmids. They present several lines of evidence supporting the viability of this approach. (1) X-ray treated EMT-6 mouse cells (7.5 Gr.) which are selected over several months with increasing levels of methotrexate (MTX) contain highly amplified circular DNA molecules (double minutes) which include the dihydrofolate reductase (DHFR) gene in a size range between 1,000 and 3,500 kilobases as determined by pulsed-field gel electrophoresis and these acentric chromosomal fragments have been stably maintained in culture for at least a year. (2) Preliminary data based on experiments involving fusion of X-irradiated Chinese Hamster Ovary (CH0 DG44) cells containing randomly inserted cotransfected Neomycin resistance and DHFR genes to mouse EMT-6 cells shows that the linked genes can be readily cotransferred as acentric subchromosomal fragment(s) suitable for gene amplification. (3) The studies of CHO cells with cell fusion transferred X-ray induced chromosomal fragments containing the natural CHO DHFR gene suggest that transferred chromosome fragments undergo gene amplification much more readily than nonfragmented endogenous DHFR genes
The VERDI fission fragment spectrometer
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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.
Nanoparticles Containing Curcumin Useful for Suppressing Macrophages In Vivo in Mice.
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Chie Amano
Full Text Available To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice.
Directory of Open Access Journals (Sweden)
Krystal Cole
Full Text Available High throughput screening technologies such as acoustic droplet ejection (ADE greatly increase the rate at which X-ray diffraction data can be acquired from crystals. One promising high throughput screening application of ADE is to rapidly combine protein crystals with fragment libraries. In this approach, each fragment soaks into a protein crystal either directly on data collection media or on a moving conveyor belt which then delivers the crystals to the X-ray beam. By simultaneously handling multiple crystals combined with fragment specimens, these techniques relax the automounter duty-cycle bottleneck that currently prevents optimal exploitation of third generation synchrotrons. Two factors limit the speed and scope of projects that are suitable for fragment screening using techniques such as ADE. Firstly, in applications where the high throughput screening apparatus is located inside the X-ray station (such as the conveyor belt system described above, the speed of data acquisition is limited by the time required for each fragment to soak into its protein crystal. Secondly, in applications where crystals are combined with fragments directly on data acquisition media (including both of the ADE methods described above, the maximum time that fragments have to soak into crystals is limited by evaporative dehydration of the protein crystals during the fragment soak. Here we demonstrate that both of these problems can be minimized by using small crystals, because the soak time required for a fragment hit to attain high occupancy depends approximately linearly on crystal size.
Prakash, Celine; Haeseler, Arndt Von
2017-03-01
RNA sequencing (RNA-seq) has emerged as the method of choice for measuring the expression of RNAs in a given cell population. In most RNA-seq technologies, sequencing the full length of RNA molecules requires fragmentation into smaller pieces. Unfortunately, the issue of nonuniform sequencing coverage across a genomic feature has been a concern in RNA-seq and is attributed to biases for certain fragments in RNA-seq library preparation and sequencing. To investigate the expected coverage obtained from fragmentation, we develop a simple fragmentation model that is independent of bias from the experimental method and is not specific to the transcript sequence. Essentially, we enumerate all configurations for maximal placement of a given fragment length, F, on transcript length, T, to represent every possible fragmentation pattern, from which we compute the expected coverage profile across a transcript. We extend this model to incorporate general empirical attributes such as read length, fragment length distribution, and number of molecules of the transcript. We further introduce the fragment starting-point, fragment coverage, and read coverage profiles. We find that the expected profiles are not uniform and that factors such as fragment length to transcript length ratio, read length to fragment length ratio, fragment length distribution, and number of molecules influence the variability of coverage across a transcript. Finally, we explore a potential application of the model where, with simulations, we show that it is possible to correctly estimate the transcript copy number for any transcript in the RNA-seq experiment.
Dexamethasone suppression test
DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...
Effective Fragmentation and Flyrock Control Strategies at Quarries
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Sedat Esen
2017-01-01
Full Text Available This paper presents the effective fragmentation and flyrock control strategies that could be applied at quarries to improve the productivity and safety. Fragmentation measurement and modelling as well as a comprehensive drill and blast audit are essential for improving the fragmentation. Face profiling and bore tracking are good tools to manage the ―as-designed‖ and ―as-drilled‖ conditions to get reasonable fragmentation from face burden zone and minimise the flyrock risk. In general, a large scatter in fragmentation data was observed at sites and the causes should be analysed by a detailed root-cause analysis technique. Two case studies were presented in this paper showing some of the effective fragmentation strategies. Finally, a flyrock model was shown to determine the safe blast exclusion zone for the mining equipment and personnel. Some key guidelines were suggested to minimise the occurrence of the flyrock.
Release and characteristics of fungal fragments in various conditions
Energy Technology Data Exchange (ETDEWEB)
Mensah-Attipoe, Jacob [Department of Environmental Science, University of Eastern Finland, Yliopistonranta 1D, P. O. Box 1627, FI-70211 Kuopio (Finland); Saari, Sampo [Department of Physics, Tampere University of Technology, Korkeakoulunkatu 3, 33720 Tampere (Finland); Veijalainen, Anna-Maria; Pasanen, Pertti [Department of Environmental Science, University of Eastern Finland, Yliopistonranta 1D, P. O. Box 1627, FI-70211 Kuopio (Finland); Keskinen, Jorma [Department of Physics, Tampere University of Technology, Korkeakoulunkatu 3, 33720 Tampere (Finland); Leskinen, Jari T.T. [SIB Labs, University of Eastern Finland, Yliopistonranta 1E, P. O. Box 1627, FI-70211, Kuopio (Finland); Reponen, Tiina, E-mail: reponeta@ucmail.uc.edu [Department of Environmental Science, University of Eastern Finland, Yliopistonranta 1D, P. O. Box 1627, FI-70211 Kuopio (Finland); Department of Environmental Health, University of Cincinnati, P.O. Box 670056, Cincinnati, OH 45267-0056 (United States)
2016-03-15
Intact spores and submicrometer size fragments are released from moldy building materials during growth and sporulation. It is unclear whether all fragments originate from fungal growth or if small pieces of building materials are also aerosolized as a result of microbial decomposition. In addition, particles may be formed through nucleation from secondary metabolites of fungi, such as microbial volatile organic compounds (MVOCs). In this study, we used the elemental composition of particles to characterize the origin of submicrometer fragments released from materials contaminated by fungi. Particles from three fungal species (Aspergillus versicolor, Cladosporium cladosporioides and Penicillium brevicompactum), grown on agar, wood and gypsum board were aerosolized using the Fungal Spore Source Strength Tester (FSSST) at three air velocities (5, 16 and 27 m/s). Released spores (optical size, d{sub p} ≥ 0.8 μm) and fragments (d{sub p} ≤ 0.8 μm) were counted using direct-reading optical aerosol instruments. Particles were also collected on filters, and their morphology and elemental composition analyzed using scanning electron microscopes (SEMs) coupled with an Energy-Dispersive X-ray spectroscopy (EDX). Among the studied factors, air velocity resulted in the most consistent trends in the release of fungal particles. Total concentrations of both fragments and spores increased with an increase in air velocity for all species whereas fragment–spore (F/S) ratios decreased. EDX analysis showed common elements, such as C, O, Mg and Ca, for blank material samples and fungal growth. However, N and P were exclusive to the fungal growth, and therefore were used to differentiate biological fragments from non-biological ones. Our results indicated that majority of fragments contained N and P. Because we observed increased release of fragments with increased air velocities, nucleation of MVOCs was likely not a relevant process in the formation of fungal fragments. Based
Szpot, Paweł; Buszewicz, Grzegorz; Jurek, Tomasz; Teresiński, Grzegorz
2018-05-15
This paper presents a rapid, sensitive and precise method for the determination of metaldehyde in human blood, using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Separation was performed with a Poroshell 120 EC-C18 column; 2.7 μm atrazine‑d5 (IS) and 200 mg NaCl were added to the blood sample. Proteins in human blood were precipitated using acetonitrile; the supernatant was then analyzed with the UHPLC-Q-TOF-MS or HPLC-QqQ-MS/MS system. The results of selectivity, linearity, accuracy, precision, limits of quantification, recovery, and matrix effects were sufficient to enable the measurement of metaldehyde in human blood samples. In addition, we proposed a fragmentation pathway involving ammonium adduct fragment ions for metaldehyde. Copyright © 2018. Published by Elsevier B.V.
Graph Theory. 1. Fragmentation of Structural Graphs
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Lorentz JÄNTSCHI
2002-12-01
Full Text Available The investigation of structural graphs has many fields of applications in engineering, especially in applied sciences like as applied chemistry and physics, computer sciences and automation, electronics and telecommunication. The main subject of the paper is to express fragmentation criteria in graph using a new method of investigation: terminal paths. Using terminal paths are defined most of the fragmentation criteria that are in use in molecular topology, but the fields of applications are more generally than that, as I mentioned before. Graphical examples of fragmentation are given for every fragmentation criteria. Note that all fragmentation is made with a computer program that implements a routine for every criterion.[1] A web routine for tracing all terminal paths in graph can be found at the address: http://vl.academicdirect.ro/molecular_topology/tpaths/ [1] M. V. Diudea, I. Gutman, L. Jäntschi, Molecular Topology, Nova Science, Commack, New York, 2001, 2002.
Route to three-dimensional fragments using diversity-oriented synthesis.
Hung, Alvin W; Ramek, Alex; Wang, Yikai; Kaya, Taner; Wilson, J Anthony; Clemons, Paul A; Young, Damian W
2011-04-26
Fragment-based drug discovery (FBDD) has proven to be an effective means of producing high-quality chemical ligands as starting points for drug-discovery pursuits. The increasing number of clinical candidate drugs developed using FBDD approaches is a testament of the efficacy of this approach. The success of fragment-based methods is highly dependent on the identity of the fragment library used for screening. The vast majority of FBDD has centered on the use of sp(2)-rich aromatic compounds. An expanded set of fragments that possess more 3D character would provide access to a larger chemical space of fragments than those currently used. Diversity-oriented synthesis (DOS) aims to efficiently generate a set of molecules diverse in skeletal and stereochemical properties. Molecules derived from DOS have also displayed significant success in the modulation of function of various "difficult" targets. Herein, we describe the application of DOS toward the construction of a unique set of fragments containing highly sp(3)-rich skeletons for fragment-based screening. Using cheminformatic analysis, we quantified the shapes and physical properties of the new 3D fragments and compared them with a database containing known fragment-like molecules.
Fragment-based discovery of a potent NAMPT inhibitor.
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.
Light fragment formation at intermediate energies
International Nuclear Information System (INIS)
Boal, D.H.
1982-03-01
This paper concerns itself mainly with the production of energetic protons and light fragments at wide angles. The experiments point to nucleon emission in proton-induced reactions as involving a mechanism in which the observed nucleon is directly knocked out of the nucleus. A similar feature seems to be required to explain (p,F) and (e,F) reactions: an energetic nucleon is produced in one scattering of the projectile, and the struck nucleon subsequently loses some of its energy as it traverses the remaining part of the nucleus, gathering up other nucleons as it goes, to become a fragment. This is what one might call the extreme snowball model, and a more accurate description probably involves multiple scattering of the projectile in addition to the extreme snowball contribution. This will be particularly true for fragments in the mass 6 to 9 region. This scenario also appears to apply to deuteron-induced fragment production. However, for alpha-induced reactions it would appear that the nucleons forming a fragment can originate from collisions involving different incident nucleons in the projectile. For heavy ions, this effect is even stronger, and the snowball contribution is greatly reduced compared to that of the traditional coalescence model
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.
Abbiendi, G.; Akesson, P.F.; Alexander, G.; Allison, John; Amaral, P.; Anagnostou, G.; Anderson, K.J.; Asai, S.; Axen, D.; Azuelos, G.; Bailey, I.; Barberio, E.; Barillari, T.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brigliadori, L.; Brown, Robert M.; Buesser, K.; Burckhart, H.J.; Campana, S.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, D.G.; Ciocca, C.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Feld, L.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Gagnon, P.; Gary, John William; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harel, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hill, J.C.; Hoffman, Kara Dion; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kramer, T.; Krieger, P.; von Krogh, J.; Kruger, K.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Layter, J.G.; Lellouch, D.; Lettso, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, A.; Ludwig, J.; Mader, W.; Marcellini, S.; Martin, A.J.; Masetti, G.; Mashimo, T.; Mattig, Peter; McKenna, J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Meyer, Niels T.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Moed, S.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poli, B.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Roney, J.M.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schorner-Sadenius, T.; Schroder, Matthias; Schumacher, M.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija
Flavour inclusive, udsc and b fragmentation functions in unbiased jets, and flavour inclusive, udsc, b and gluon fragmentation functions in biased jets are measured in e+e- annihilations from data collected at centre-of-mass energies of 91.2, and 183-209 GeV with the OPAL detector at LEP. The unbiased jets are defined by hemispheres of inclusive hadronic events, while the biased jet measurements are based on three-jet events selected with jet algorithms. Several methods are employed to extract the fragmentation functions over a wide range of scales. Possible biases are studied in the results are obtained. The fragmentation functions are compared to results from lower energy e+e- experiments and with earlier LEP measurements and are found to be consistent. Scaling violations are observed and are found to be stronger for the fragmentation functions of gluon jets than for those of quarks. The measured fragmentation functions are compared to three recent theoretical next-to-leading order calculations and to the p...