WorldWideScience

Sample records for current refinements target

  1. Refined Orbital Architecture for Targets of Naval Interest

    Science.gov (United States)

    2015-03-01

    pioneered the Walker delta pattern.29 The technique distributes t total satellites into p orbital planes, evenly spaced with a f relative phasing...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited REFINED ORBITAL ...Thesis 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS REFINED ORBITAL ARCHITECTURE FOR TARGETS OF NAVAL INTEREST 6. AUTHOR(S) Andrew Konowicz 7

  2. Current State and Prospect of China's Refining Sector%Current State and Prospect of China's Refining Sector

    Institute of Scientific and Technical Information of China (English)

    Zhu He

    2012-01-01

    (1) China's refining capacity will reach 650 million tons per year, the cooperation with oil producing countries in refining sector will be strengthened and a diversified competitive framework for the sector will be further pushed forward.

  3. Quiet eye training: the acquisition, refinement and resilient performance of targeting skills.

    Science.gov (United States)

    Vine, Samuel J; Moore, Lee J; Wilson, Mark R

    2014-01-01

    How we learn and refine motor skills in the most effective manner and how we prevent performance breakdown in pressurised or demanding circumstances are among the most important questions within the sport psychology and skill acquisition literature. The quiet eye (QE) has emerged as a characteristic of highly skilled perceptual and motor performance in visually guided motor tasks. Defined as the final fixation that occurs prior to a critical movement, over 70 articles have been published in the last 15 years probing the role that the QE plays in underpinning skilled performance. The aim of this review is to integrate research findings from studies examining the QE as a measure of visuomotor control in the specific domain of targeting skills; motor skills requiring an object to be propelled to a distant target. Previous reviews have focused primarily on the differences in QE between highly skilled performers and their less skilled counterparts. The current review aims to discuss contemporary findings relating to 1. The benefits of QE training for the acquisition and refinement of targeting skills; 2. The effects of anxiety upon the QE and subsequent targeting skill performance and 3. The benefits of QE training in supporting resilient performance under elevated anxiety. Finally, potential processes through which QE training proffers this advantage, including improved attentional control, response programming and external focus, will be discussed and directions for future research proposed.

  4. Flanking region sequence information to refine microRNA target predictions

    Indian Academy of Sciences (India)

    Russiachand Heikham; Ravi Shankar

    2010-03-01

    The non-coding elements of a genome, with many of them considered as junk earlier, have now started gaining long due respectability, with microRNAs as the best current example. MicroRNAs bind preferentially to the 3′ untranslated regions (UTRs) of the target genes and negatively regulate their expression most of the time. Several microRNA:target prediction softwares have been developed based upon various assumptions and the majority of them consider the free energy of binding of a target to its microRNA and seed conservation. However, the average concordance between the predictions made by these softwares is limited and compounded by a large number of false-positive results. In this study, we describe a methodology developed by us to refine microRNA:target prediction by target prediction softwares through observations made from a comprehensive study. We incorporated the information obtained from dinucleotide content variation patterns recorded for flanking regions around the target sites using support vector machines (SVMs) trained over two different major sources of experimental data, besides other sources. We assessed the performance of our methodology with rigorous tests over four different dataset models and also compared it with a recently published refinement tool, MirTif. Our methodology attained a higher average accuracy of 0.88, average sensitivity and specificity of 0.81 and 0.94, respectively, and areas under the curves (AUCs) for all the four models scored above 0.9, suggesting better performance by our methodology and a possible role of flanking regions in microRNA targeting control. We used our methodology over genes of three different pathways – toll-like receptor (TLR), apoptosis and insulin – to finally predict the most probable targets. We also investigated their possible regulatory associations, and identified a hsa-miR-23a regulatory module.

  5. Preparative Separation of Six Rhynchophylla Alkaloids from Uncaria macrophylla Wall by pH-Zone Refining Counter-Current Chromatography

    Directory of Open Access Journals (Sweden)

    Qinghai Zhang

    2013-12-01

    Full Text Available pH-Zone refining counter-current chromatography was successfully applied to the preparative isolation and purification of six alkaloids from the ethanol extracts of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%, w/w in U. macrophylla Wall, the target compounds were enriched by pH-zone refining counter-current chromatography using a two-phase solvent system composed of petroleum ether–ethyl acetate–isopropanol–water (2:6:3:9, v/v, adding 10 mM triethylamine in organic stationary phase and 5 mM hydrochloric acid in aqueous mobile phase. Then pH-zone refining counter-current chromatography using the other two-phase solvent system was used for final purification. Six target compounds were finally isolated and purified by following two-phase solvent system composed of methyl tert-butyl ether (MTBE–acetonitrile–water (4:0.5:5, v/v, adding triethylamine (TEA (10 mM to the organic phase and HCl (5 mM to aqueous mobile phase. The separation of 2.8 g enriched total alkaloids yielded 36 mg hirsutine, 48 mg hirsuteine, 82 mg uncarine C, 73 mg uncarine E, 163 mg rhynchophylline, and 149 mg corynoxeine, all with purities above 96% as verified by HPLC Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS and 1H-NMR spectroscopy.

  6. Microstructural refinement of weld fusion zones in {alpha}-{beta} titanium alloys using pulsed current welding

    Energy Technology Data Exchange (ETDEWEB)

    Sundaresan, S.; Janaki Ram, G.D. [Indian Inst. of Technol., Chennai (India). Dept. of Metallurgical Engineering; Madhusudhan Reddy, G. [Defence Metallurgical Research Lab., Hyderabad (India)

    1999-04-01

    Pulsing of the welding current is one approach for refining the fusion zone grain structure in {alpha}-{beta} titanium alloy welds. This paper reports work in which gas tungsten-arc welds were produced in two {alpha}-{beta} titanium alloys under a variety of conditions including direct current (d.c.) pulsing and alternating current (a.c.) pulsing. The results show that, while d.c. pulsing did also refine the weld metal {beta} grain structure, the effect of a.c. pulsing was much greater. Current pulsing enhances fluid flow, reduces temperature gradients and causes a continual change in the weld pool size and shape. These effects, which are believed to be responsible for refining the solidification structure, are much stronger in a.c. pulsing than in d.c. pulsing. The observed grain refinement was shown to result in an appreciable increase in fusion zone tensile ductility. Post-weld heat treatment improved ductility both in pulsed and unpulsed welds, but pulsed welds showed greater tensile elongation even in the heat treated condition. (orig.) 27 refs.

  7. Protein structure refinement of CASP target proteins using GNEIMO torsional dynamics method.

    Science.gov (United States)

    Larsen, Adrien B; Wagner, Jeffrey R; Jain, Abhinandan; Vaidehi, Nagarajan

    2014-02-24

    A longstanding challenge in using computational methods for protein structure prediction is the refinement of low-resolution structural models derived from comparative modeling methods into highly accurate atomistic models useful for detailed structural studies. Previously, we have developed and demonstrated the utility of the internal coordinate molecular dynamics (MD) technique, generalized Newton-Euler inverse mass operator (GNEIMO), for refinement of small proteins. Using GNEIMO, the high-frequency degrees of freedom are frozen and the protein is modeled as a collection of rigid clusters connected by torsional hinges. This physical model allows larger integration time steps and focuses the conformational search in the low frequency torsional degrees of freedom. Here, we have applied GNEIMO with temperature replica exchange to refine low-resolution protein models of 30 proteins taken from the continuous assessment of structure prediction (CASP) competition. We have shown that GNEIMO torsional MD method leads to refinement of up to 1.3 Å in the root-mean-square deviation in coordinates for 30 CASP target proteins without using any experimental data as restraints in performing the GNEIMO simulations. This is in contrast with the unconstrained all-atom Cartesian MD method performed under the same conditions, where refinement requires the use of restraints during the simulations.

  8. ISAC target operation with high proton currents

    CERN Document Server

    Dombsky, M; Schmor, P; Lane, M

    2003-01-01

    The TRIUMF-ISAC facility target stations were designed for ISOL target irradiations with up to 100 mu A proton beam currents. Since beginning operation in 1998, ISAC irradiation currents have progressively increased from initial values of approx 1 mu A to present levels of up to 40 mu A on refractory metal foil targets. In addition, refractory carbide targets have operated at currents of up to 15 mu A for extended periods. The 1-40 mu A operational regime is achieved by tailoring each target to the thermal requirements dictated by material properties such as beam power deposition, thermal conductivity and maximum operating temperature of the target material. The number of heat shields on each target can be varied in order to match the effective emissivity of the target surface for the required radiative power dissipation. Targets of different thickness, surface area and volume have been investigated to study the effect of diffusion and effusion delays on the yield of radioisotopes. For yields of short-lived p...

  9. An emerging antiarrhythmic target: late sodium current.

    Science.gov (United States)

    Banyasz, T; Szentandrássy, N; Magyar, J; Szabo, Z; Nánási, P P; Chen-Izu, Y; Izu, L T

    2015-01-01

    The cardiac late sodium current (INa,L) has been in the focus of research in the recent decade. The first reports on the sustained component of voltage activated sodium current date back to the seventies, but early studies interpreted this tiny current as a product of a few channels that fail to inactivate, having neither physiologic nor pathologic implications. Recently, the cardiac INa,L has emerged as a potentially major arrhythmogenic mechanism in various heart diseases, attracting the attention of clinicians and researchers. Research activity on INa,L has exponentially increased since Ranolazine, an FDA-approved antianginal drug was shown to successfully suppress cardiac arrhythmias by inhibiting INa,L. This review aims to summarize and discuss a series of papers focusing on the cardiac late sodium current and its regulation under physiological and pathological conditions. We will discuss critical evidences implicating INa,L as a potential target for treating myocardial dysfunction and cardiac arrhythmias.

  10. Numerical Simulation of Current Sheet Formation in a Quasi-Separatrix Layer using Adaptive Mesh Refinement

    CERN Document Server

    Effenberger, Frederic; Arnold, Lukas; Grauer, Rainer; Dreher, Jürgen

    2011-01-01

    The formation of a thin current sheet in a magnetic quasi-separatrix layer (QSL) is investigated by means of numerical simulation using a simplified ideal, low-$\\beta$, MHD model. The initial configuration and driving boundary conditions are relevant to phenomena observed in the solar corona and were studied earlier by Aulanier et al., A&A 444, 961 (2005). In extension to that work, we use the technique of adaptive mesh refinement (AMR) to significantly enhance the local spatial resolution of the current sheet during its formation, which enables us to follow the evolution into a later stage. Our simulations are in good agreement with the results of Aulanier et al. up to the calculated time in that work. In a later phase, we observe a basically unarrested collapse of the sheet to length scales that are more than one order of magnitude smaller than those reported earlier. The current density attains correspondingly larger maximum values within the sheet. During this thinning process, which is finally limite...

  11. Obesity: Current and potential pharmacotherapeutics and targets.

    Science.gov (United States)

    Narayanaswami, Vidya; Dwoskin, Linda P

    2017-02-01

    Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms that regulate hedonic aspects of food intake override the homeostatic regulation of eating. In addition to functional interactions between homeostatic and reward systems in the regulation of food intake, homeostatic signals have the ability to alter vulnerability to drug abuse. Regarding the treatment of obesity, pharmacological monotherapies primarily focus on a single protein target. FDA-approved monotherapy options include phentermine (Adipex-P®), orlistat (Xenical®), lorcaserin (Belviq®) and liraglutide (Saxenda®). However, monotherapies have limited efficacy, in part due to the recruitment of alternate and counter-regulatory pathways. Consequently, a multi-target approach may provide greater benefit. Recently, two combination products have been approved by the FDA to treat obesity, including phentermine/topiramate (Qsymia®) and naltrexone/bupropion (Contrave®). The current review provides an overview of homeostatic and reward mechanisms that regulate energy balance, potential therapeutic targets for obesity and current treatment options, including some candidate therapeutics in clinical development. Finally, challenges in anti-obesity drug development are discussed. Copyright © 2016 Elsevier

  12. Current research progress in grain refinement of cast magnesium alloys: A review article

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Yahia; Qiu, Dong [School of Mechanical and Mining Engineering, University of Queensland, St Lucia, QLD 4072 (Australia); Jiang, Bin; Pan, Fusheng [College of Materials Science and Engineering, Chongqing University, Chongqing 400030 (China); Zhang, Ming-Xing, E-mail: Mingxing.Zhang@uq.edu.au [School of Mechanical and Mining Engineering, University of Queensland, St Lucia, QLD 4072 (Australia)

    2015-01-15

    Grain refinement of cast magnesium alloys, particularly in magnesium–aluminium (Mg–Al) based alloys, has been an active research topic in the past two decades, because it has been considered as one of the most effective approaches to simultaneously increase the strength, ductility and formability. The development of new grain refiners was normally based on the theories/models that were established through comprehensive and considerable studies of grain refinement in cast Al alloys. Generally, grain refinement in cast Al can be achieved through either inoculation treatment, which is a process of adding, or in situ forming, foreign particles to promote heterogeneous nucleation rate, or restricting grain growth by controlling the constitutional supercooling or both. But, the concrete and tangible grain refinement mechanism in cast metals is still not fully understood and there are a number of controversies. Therefore, most of the new developed grain refiners for Mg–Al based alloys are not as efficient as the commercially available ones, such as zirconium in non-Al containing Mg alloys. To facilitate the research in grain refinement of cast magnesium alloys, this review starts with highlighting the theoretical aspects of grain refinement in cast metals, followed by reviewing the latest research progress in grain refinement of magnesium alloys in terms of the solute effect and potent nucleants.

  13. Technical support to the Solvent Refined Coal (SRC) demonstration projects: assessment of current research and development

    Energy Technology Data Exchange (ETDEWEB)

    Edwards, M.S.; Rodgers, B.R.; Brown, C.H.; Carlson, P.K.; Gambill, W.R.; Gilliam, T.M.; Holmes, J.M.; Krishnan, R.P.; Parsly, L.F.

    1980-12-01

    A program to demonstrate Solvent Refined Coal (SRC) technology has been initiated by the US Department of Energy (DOE) in partnership with two industrial groups. Project management responsibility has been assigned to the Oak Ridge Operations Office (ORO) of DOE. ORO requested that the Oak Ridge National Laboratory assess current research and development (R and D) activities and develop recommendations for those activities that might contribute to successful completion of the SRC demonstration plant projects. The objectives of this final report are to discuss in detail the problem areas in SRC; to discuss the current and planned R and D investigations relevant to the problems identified; and to suggest appropriate R and D activities in support of designs for the SRC demonstration plants. Four types of R and D activities are suggested: continuation of present and planned activities; coordination of activities and results, present and proposed; extension/redirection of activities not involving major equipment purchase or modifications; and new activities. Important examples of the first type of activity include continuation of fired heater, slurry rheology, and slurry mixing studies at Ft. Lewis. Among the second type of activity, coordination of data acquisition and interpretation is recommended in the areas of heat transfer, vapor/liquid equilibria, and physical properties. Principal examples of recommendations for extension/redirection include screening studies at laboratory scale on the use of carbonaceous precoat (e.g., anthracite) infiltration, and 15- to 30-day continuous tests of the Texaco gasifier at the Texaco Montebello facility (using SRC residues).

  14. Preparative Isolation of Seven Diterpenoid Alkaloids from Aconitum coreanum by pH-Zone-Refining Counter-Current Chromatography

    Directory of Open Access Journals (Sweden)

    Xueyong Wang

    2014-08-01

    Full Text Available The aim of this paper was to seek an efficient method to preparative separation of alkaloid compounds from Aconitum coreanum (Guanbaifu, a well-known traditional Chinese medicinal plant for heart disease. Seven alkaloid compounds were successfully purified by pH-zone-refining counter-current chromatography with two-phase solvent system of petroleum ether–ethyl acetate–methanol–water (5:5:1:9, v/v/v/v, 10 mM triethylamine in upper phase and 10 mM hydrochloric acid in lower phase. From 3.5 g of crude extract, 356 mg of Guanfu base I, 578 mg of Guanfu base A, 74 mg of atisine, 94 mg of Guanfu base F, 423 mg of Guanfu base G, 67 mg of Guanfu base R and 154 mg of Guanfu base P were obtained with the purity of 96.40%, 97.2%, 97.5%, 98.1%, 98.9%, 98.3% and 98.4%. Their chemical structures were identified by TOF-MS and 1H-NMR. This study indicated that pH-zone-refining counter-current chromatography was an efficient method for separating the kind of alkaloids with low absorbance values.

  15. Targeted transcranial direct current stimulation for rehabilitation after stroke.

    Science.gov (United States)

    Dmochowski, Jacek P; Datta, Abhishek; Huang, Yu; Richardson, Jessica D; Bikson, Marom; Fridriksson, Julius; Parra, Lucas C

    2013-07-15

    Transcranial direct current stimulation (tDCS) is being investigated as an adjunctive technique to behavioral rehabilitation treatment after stroke. The conventional "dosage", consisting of a large (25 cm(2)) anode over the target with the cathode over the contralateral hemisphere, has been previously shown to yield broadly distributed electric fields whose intensities at the target region are less than maximal. Here, we report the results of a systematic targeting procedure with small "high-definition" electrodes that was used in preparation for a pilot study on 8 stroke patients with chronic aphasia. We employ functional and anatomical magnetic resonance imagery (fMRI/MRI) to define a target and optimize (with respect to the electric field magnitude at the target) the electrode configuration, respectively, and demonstrate that electric field strengths in targeted cortex can be substantially increased (63%) over the conventional approach. The optimal montage exhibits significant variation across subjects as well as when perturbing the target location within a subject. However, for each displacement of the target co-ordinates, the algorithm is able to determine a montage which delivers a consistent amount of current to that location. These results demonstrate that MRI-based models of current flow yield maximal stimulation of target structures, and as such, may aid in reliably assessing the efficacy of tDCS in neuro-rehabilitation.

  16. Comparative Study on the Grain Refinement of Al-Si Alloy Solidified under the Impact of Pulsed Electric Current and Travelling Magnetic Field

    Directory of Open Access Journals (Sweden)

    Yunhu Zhang

    2016-07-01

    Full Text Available It is high of commercial importance to generate the grain refinement in alloys during solidification by means of electromagnetic fields. Two typical patterns of electromagnetic fields, pulsed electric currents (ECP and traveling magnetic field (TMF, are frequently employed to produce the finer equiaxed grains in solidifying alloys. Various mechanisms were proposed to understand the grain refinement in alloys caused by ECP and TMF. In this paper, a comparative study is carried out in the same solidification regime to investigate the grain refinement of Al-7 wt. %Si alloy driven by ECP and TMF. Experimental results show that the application of ECP or TMF can cause the same grain refinement occurrence period, during which the refinement of primary Al continuously occurs. In addition, the related grain refinement mechanisms are reviewed and discussed, which shows the most likely one caused by ECP and TMF is the promoted dendrite fragmentation as the result of the ECP-induced or TMF-induced forced flow. It suggests that the same grain refinement process in alloys is provoked when ECP and TMF are applied in the same solidification regime, respectively.

  17. Clinical Challenges to Current Molecularly Targeted Therapies in Lung Cancer.

    Science.gov (United States)

    Chhabra, Gagan; Eggert, Ashley; Puri, Neelu

    Lung cancer is difficult to treat with a poor prognosis and a five year survival of 15%. Current molecularly targeted therapies are initially effective in non-small cell lung cancer (NSCLC) patients; however, they are plagued with difficulties including induced resistance and small therapeutically responsive populations. This mini review describes the mechanism of resistance to several molecularly targeted therapies which are currently being used to treat NSCLC. The major targets discussed are c-Met, EGFR, HER2, ALK, VEGFR, and BRAF. The first generation tyrosine kinase inhibitors (TKIs) resulted in resistance; however, second and third generation TKIs are being developed, which are generally more efficacious and have potential to treat NSCLC patients with resistance to first generation TKIs. Combination therapies could also be effective in preventing TKI resistance in NSCLC patients.

  18. Grain refinement, hardening and metastable phase formation by high current pulsed electron beam (HCPEB) treatment under heating and melting modes

    Energy Technology Data Exchange (ETDEWEB)

    Grosdidier, T., E-mail: Thierry.grosdidier@univ-metz.f [Laboratoire d' Etude des Textures et Applications aux Materiaux (LETAM, CNRS 3143), Universite Paul Verlaine-Metz, Ile du Saulcy, 57045 Metz (France); Lab of Materials Modification by Laser, Ion and Electron Beams and School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024 (China); Zou, J.X. [Laboratoire d' Etude des Textures et Applications aux Materiaux (LETAM, CNRS 3143), Universite Paul Verlaine-Metz, Ile du Saulcy, 57045 Metz (France); Bolle, B. [Laboratoire d' Etude des Textures et Applications aux Materiaux (LETAM, CNRS 3143), ENIM, Ile du Saulcy, 57045 Metz (France); Hao, S.Z.; Dong, C. [Lab of Materials Modification by Laser, Ion and Electron Beams and School of Materials Science and Engineering, Dalian University of Technology, Dalian 116024 (China)

    2010-08-15

    High current pulsed electron beam is a recently developed technique for surface modification. The pulsed electron irradiation introduces concentrated energy depositions in the thin surface layer of the treated materials, giving rise to an extremely fast heating and subsequent rapid cooling of the surface together with the formation of dynamic stress waves. Improved surface properties (hardness, corrosion resistance) can be obtained under the 'melting' mode when the top surface is melted and rapidly solidified (10{sup 7} K/s). In steels, this is essentially the result of nanostructures formed from the highly undercooled melt, melt surface purification, strain hardening induced by the thermal stress waves as well as metastable phase selections in the rapidly solidified melted layers. The use of the 'heating' mode is less conventional, combining effects of the heavy deformation and recrystallization/recovery mechanisms. A detailed analysis of a FeAl alloy demonstrates grain size refinement, hardening, solid-state enhanced diffusion and texture modification without modification of the surface geometry.

  19. Current and novel therapeutic molecules and targets in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ashwini Kumar

    2016-01-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline, i.e., dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals, low levels of acetylcholine, etc. AD is not simple to diagnose since there is no single diagnostic test for it. Pharmacotherapy for AD currently provides only symptomatic relief and mostly targets cognitive revival. Computational biology approaches have proved to be reliable tools for the selection of novel targets and therapeutic ligands. Molecular docking is a key tool in computer-assisted drug design and development. Docking has been utilized to perform virtual screening on large libraries of compounds, and propose structural hypotheses of how the ligands bind with the target with lead optimization. Another potential application of docking is optimization stages of the drug-discovery cycle. This review summarizes the known drug targets of AD, in vivo active agents against AD, state-of-the-art docking studies done in AD, and future prospects of the docking with particular emphasis on AD.

  20. A refined integro-surface energy-based model for vibration of magnetically actuated double-nanowire-systems carrying electric current

    Science.gov (United States)

    Kiani, Keivan

    2017-02-01

    A novel surface energy-based model is developed to examine more precisely vibrations of current-carrying double-nanowire-systems immersed in a longitudinal magnetic field. Using Biot-Savart and Lorentz laws, a more refined version of interwire interactional magnetic forces is presented. By employing Rayleigh beam theory, the equations of motion are derived. In fact, these are coupled integro-differential equations which are more accurate with respect to those of the previously developed models. For simply supported and clamped nanosystems, governing equations are analyzed via assumed mode method. The effects of interwire distance, slenderness ratio, electric current, magnetic field strength, and surface effect on the fundamental frequency are addressed carefully. The obtained results display the importance of exploiting the refined model for vibration analysis of nanosystems with low interwire distance, high electric current, and high magnetic field strength.

  1. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

    NARCIS (Netherlands)

    Stelloo, Ellen; Bosse, Tjalling; Nout, Remi A.; MacKay, Helen J.; Church, David N.; Nijman, Hans W.; Leary, Alexandra; Edmondson, Richard J.; Powell, Melanie E.; Crosbie, Emma J.; Kitchener, Henry C.; Mileshkin, Linda; Pollock, Pamela M.; Smit, Vincent T.; Creutzberg, Carien L.

    2015-01-01

    This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational res

  2. Immunotherapy and lung cancer: current developments and novel targeted therapies.

    Science.gov (United States)

    Domingues, Duarte; Turner, Alice; Silva, Maria Dília; Marques, Dânia Sofia; Mellidez, Juan Carlos; Wannesson, Luciano; Mountzios, Giannis; de Mello, Ramon Andrade

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is a highly prevalent and aggressive disease. In the metastatic setting, major advances include the incorporation of immunotherapy and targeted therapies into the clinician's therapeutic armamentarium. Standard chemotherapeutic regimens have long been reported to interfere with the immune response to the tumor; conversely, antitumor immunity may add to the effects of those therapies. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field. In addition, anti-tumor vaccines, such as MAGE-A3, Tecetomide, TG4010, CIMAvax, ganglioside vaccines, tumor cell vaccines and dendritic cell vaccines, emerged as potent inducers of immune response against the tumor. The current work aims to address the most recent developments regarding these innovative immunotherapies and their implementation in the treatment of metastatic NSCLC.

  3. Current drug treatments targeting dopamine D3 receptor.

    Science.gov (United States)

    Leggio, Gian Marco; Bucolo, Claudio; Platania, Chiara Bianca Maria; Salomone, Salvatore; Drago, Filippo

    2016-09-01

    Dopamine receptors (DR) have been extensively studied, but only in recent years they became object of investigation to elucidate the specific role of different subtypes (D1R, D2R, D3R, D4R, D5R) in neural transmission and circuitry. D1-like receptors (D1R and D5R) and D2-like receptors (D2R, D2R and D4R) differ in signal transduction, binding profile, localization in the central nervous system and physiological effects. D3R is involved in a number of pathological conditions, including schizophrenia, Parkinson's disease, addiction, anxiety, depression and glaucoma. Development of selective D3R ligands has been so far challenging, due to the high sequence identity and homology shared by D2R and D3R. As a consequence, despite a rational design of selective DR ligands has been carried out, none of currently available medicines selectively target a given D2-like receptor subtype. The availability of the D3R ligand [(11)C]-(+)-PHNO for positron emission tomography studies in animal models as well as in humans, allows researchers to estimate the expression of D3R in vivo; displacement of [(11)C]-(+)-PHNO binding by concurrent drug treatments is used to estimate the in vivo occupancy of D3R. Here we provide an overview of studies indicating D3R as a target for pharmacological therapy, and a review of market approved drugs endowed with significant affinity at D3R that are used to treat disorders where D3R plays a relevant role.

  4. Targeted temperature management: Current evidence and practices in critical care

    Directory of Open Access Journals (Sweden)

    Saurabh Saigal

    2015-01-01

    Full Text Available Targeted temperature management (TTM in today′s modern era, especially in intensive care units represents a promising multifaceted therapy for a variety of conditions. Though hypothermia is being used since Hippocratic era, the renewed interest of late has been since early 21 st century. There have been multiple advancements in this field and varieties of cooling devices are available at present. TTM requires careful titration of its depth, duration and rewarming as it is associated with side-effects. The purpose of this review is to find out the best evidence-based clinical practice criteria of therapeutic hypothermia in critical care settings. TTM is an unique therapeutic modality for salvaging neurological tissue viability in critically ill patients viz. Post-cardiac arrest, traumatic brain injury (TBI, meningitis, acute liver failure and stroke. TTM is standard of care in post-cardiac arrest situations; there has been a lot of controversy of late regarding temperature ranges to be used for the same. In patients with TBI, it reduces intracranial pressure, but has not shown any favorable neurologic outcome. Hypothermia is generally accepted treatment for hypoxic ischemic encephalopathy in newborns. The current available technology to induce and maintain hypothermia allows for precise temperature control. Future studies should focus on optimizing hypothermic treatment to full benefit of our patients and its application in other clinical scenarios.

  5. PERSPECTIVES OF INFLATION TARGETING, IN THE CURRENT ECONOMIC CONTEXT

    Directory of Open Access Journals (Sweden)

    COROIU SORINA IOANA

    2015-04-01

    Full Text Available In the context of economic crisis, monetary policy makers are facing a number of challenges, including the selection and implementation of the best monetary policy. In this paper, we want to see if inflation targeting is or is not a solution to exit the economic crisis. If the answer is positive, then what would be the optimal level of inflation? Many central banks target an inflation rate of 2%. In this paper we intend to show that, in certain circumstances, a very low level of inflation can significantly reduce the stabilizing effects of monetary policy. A slightly higher value of inflation targeting would reduce the constraints on monetary policy, caused by the appearance of liquidity trap. The risk for the interest rates of monetary policy to achieve zero level is related to the central banks’ choise of the appropriate inflation target. We believe that an increase in the inflation target of 2% to 4% would ease monetary policy constraints arising from the liquidity trap problem. If inflation targeting is not a solution to exit the crisis, then are there other strategies that would be a better alternative? Following this analysis, no obvious alternatives were identified, so far, there is no clear reason for that to abandon inflation targeting.

  6. The Current State of Targeted Agents in Rectal Cancer

    OpenAIRE

    2012-01-01

    Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes. Rapidly growing insight into the molecular biology of CRC, as well as recent developments in gene sequencing and molecular diagnostics, has led to high expectations for the identification of molecular markers to be used in personalized treatment regimens. The mechanisms of act...

  7. Targeting to the hair follicles: current status and potential.

    Science.gov (United States)

    Wosicka, Hanna; Cal, Krzysztof

    2010-02-01

    The pilosebaceous unit is a complex structure that undergoes a specific growth cycle and comprises a few important drug targeting sites. For example, drugs can be targeted to the bulge region with stem cells or to the sebaceous glands. Interest in pilosebaceous units is directed towards their utilization as reservoirs for localized therapy and also as a transport pathway for systemic drug delivery. Improved investigative methods, such as differential stripping, are being developed in order to determine follicular penetration. This article reviews relevant aspects of effective follicle-targeting formulations and delivery systems as well as the activity status of hair follicles, and variations in follicle size and distribution throughout various body regions. Each of these factors strongly affects follicular permeation. We provide examples of improved penetration of particle-based formulations and of a size-dependent manner of follicular penetration. Contradictions are also discussed, indicating the need for detailed future investigations.

  8. Temperature calculations of heat loads in rotating target wheels exposed to high beam currents.

    Energy Technology Data Exchange (ETDEWEB)

    Greene, J. P.; Gabor, R.; Neubauer, J.

    2000-11-29

    In heavy-ion physics, high beam currents can eventually melt or destroy the target. Tightly focused beams on stationary targets of modest melting point will exhibit short lifetimes. Defocused or wobbled beams are employed to enhance target survival. Rotating targets using large diameter wheels can help overcome target melting and allow for higher beam currents to be used in experiments. The purpose of the calculations in this work is to try and predict the safe maximum beam currents which produce heat loads below the melting point of the target material.

  9. Service refinement

    Institute of Scientific and Technical Information of China (English)

    HE JiFeng

    2008-01-01

    This paper presents a refinement calculus for service components. We model the behaviour of individual service by a guarded design, which enables one to separate the responsibility of clients from the commitment made by the system, and to iden-tify a component by a set of failures and divergences. Protocols are introduced to coordinate the interactions between a component with the external environment. We adopt the notion of process refinement to formalize the substitutivity of components, and provide a complete proof method based on the notion of simulations.

  10. Ligand-targeted particulate nanomedicines undergoing clinical evaluations: current status

    NARCIS (Netherlands)

    Meel, van der Roy; Vehmeijer, Laurens J.C.; Kok, Robbert J.; Storm, Gert; Gaal, van Ethlinn V.B.

    2013-01-01

    Since the introduction of Doxil® on the market nearly 20 years ago, a number of nanomedicines have become part of treatment regimens in the clinic. With the exception of antibody–drug conjugates, these nanomedicines are all devoid of targeting ligands and rely solely on their physicochemical propert

  11. Current and future drug targets in weight management

    NARCIS (Netherlands)

    Witkamp, R.F.

    2011-01-01

    Obesity will continue to be one of the leading causes of chronic disease unless the ongoing rise in the prevalence of this condition is reversed. Accumulating morbidity figures and a shortage of effective drugs have generated substantial research activity with several molecular targets being investi

  12. Current and prospective pharmacological targets in relation to antimigraine action

    NARCIS (Netherlands)

    S. Mehrotra (Suneet); S. Gupta (Sanjay); K.Y. Chan (Kayi); C.M. Villalón (Carlos); D. Centurion (David); P.R. Saxena (Pramod Ranjan); A. Maassen van den Brink (Antoinette)

    2008-01-01

    textabstractMigraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that h

  13. Breast Cancer: Current Molecular Therapeutic Targets and New Players.

    Science.gov (United States)

    Nagini, Siddavaram

    2017-01-01

    Breast cancer is the most common cancer and the most frequent cause of cancer death among women worldwide. Breast cancer is a complex, heterogeneous disease classified into hormone-receptor-positive, human epidermal growth factor receptor-2 overexpressing (HER2+) and triple-negative breast cancer (TNBC) based on histological features. Endocrine therapy, the mainstay of treatment for hormone-responsive breast cancer involves use of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs) and aromatase inhibitors (AIs). Agents that target estrogen receptor (ER) and HER2 such as tamoxifen and trastuzumab have been the most extensively used therapeutics for breast cancer. Crosstalk between ER and other signalling networks as well as epigenetic mechanisms have been envisaged to contribute to endocrine therapy resistance. TNBC, a complex, heterogeneous, aggressive form of breast cancer in which the cells do not express ER, progesterone receptor or HER2 is refractory to therapy. Several molecular targets are being explored to target TNBC including androgen receptor, epidermal growth factor receptor (EGFR), poly(ADP-ribose) polymerase (PARP), and vascular endothelial growth factor (VEGF). Receptors, protein tyrosine kinases, phosphatases, proteases, PI3K/Akt signalling pathway, microRNAs (miRs) and long noncoding RNAs (lncRNAs) are potential therapeutic targets. miR-based therapeutic approaches include inhibition of oncomiRs by antisense oligonucleotides, restoration of tumour suppressors using miR mimics, and chemical modification of miRs. The lnRNAs HOTAIR, SPRY4-IT1, GAS5, and PANDAR, new players in tumour development and prognosis may have theranostic applications in breast cancer. Several novel classes of mechanism-based drugs have been designed and synthesised for treatment of breast cancer. Integration of nucleic acid sequencing studies with mass spectrometry-based peptide sequencing and posttranslational modifications as

  14. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  15. Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Salvatore Giovanni Vitale

    2017-05-01

    Full Text Available Carcinosarcomas (CS in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%. Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2 open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

  16. Managing tuberous sclerosis in the Asia-Pacific region: refining practice and the role of targeted therapy.

    Science.gov (United States)

    Lawson, John A; Chan, Chi-Fung; Chi, Ching-Shiang; Fan, Pi-Chuan; Kim, Heung Dong; Kim, Ki Joong; Likasitwatanakul, Surachai; Ortiz, Marilyn; Riney, Kate; Tay, Stacey Kiat-Hong; Tham, Chee-Kian

    2014-07-01

    Tuberous sclerosis complex (TSC) is a multisystem genetic disorder, with heterogeneous manifestations that pose major diagnostic and management challenges and incur considerable chronic disease burden on patients, their caregivers and healthcare systems. This survey of clinical practice in the Asia-Pacific region highlights priorities for improving TSC management in the region. The prevalence of TSC in non-Caucasians is uncertain and more data are needed to assess its impact and health-economic burden. There are unmet needs for access to genetic testing and earlier diagnosis and intervention. TSC management is multidisciplinary and largely based on experience, backed by international guidelines; however, physicians in the Asia-Pacific region feel isolated and lack local or regional guidance and support structures to implement best-practice. Raising awareness of TSC and increasing trans-regional collaboration are particular priorities. Understanding of TSC pathophysiology has enabled the development of targeted therapies. Encouraging data indicate that mammalian target of rapamycin (mTOR) inhibitors can ameliorate TSC-related lesions and may potentially change the treatment paradigm. Ultimately, improving outcomes for TSC patients in the region requires greater collaboration and a holistic, patient-focused, continuum of care that is maintained through the transition from pediatric to adult care.

  17. Enrichment and separation of antitumor triterpene acids from the epidermis of Poria cocos by pH-zone-refining counter-current chromatography and conventional high-speed counter-current chromatography.

    Science.gov (United States)

    Dong, Hongjing; Wu, Panpan; Yan, Renyi; Xu, Qihua; Li, Hua; Zhang, Fangbo; Li, Jianrong; Yang, Bin

    2015-06-01

    Triterpene acids were extracted from the epidermis of Poria cocos (Schw.) Wolf. These acids were found to inhibit the growth of lung cancer cells in vitro and in vivo. An efficient method for the preparative separation of antitumor triterpene acids was established that involves the combination of pH-zone-refining counter-current chromatography and conventional high-speed counter-current chromatography. We used pH-zone-refining counter-current chromatography to concentrate the triterpene acids using a two-phase solvent system composed of petroleum ether/ethyl acetate/methanol/water (3:7:5:5, v/v/v/v), trifluoroacetic acid (10 mM) was added to the upper phase as a retainer, and ammonia (10 mM) was added to the lower phase as an eluter. As a result, 200 mg concentrate of triterpene acids was obtained from 1.0 g of crude extract. The concentrate was further separated by conventional high-speed counter-current chromatography using a solvent system composed of petroleum ether/ethyl acetate/methanol/water (0.8:1.2:1.2:0.9, v/v), yielding 50 mg of poricoic acid A and 5 mg of poricoic acid B from 120 mg concentrate, respectively. The inhibitory activity of the major compound on lung A549 cells was examined and poricoic acid A was found to significantly inhibit the growth of A 549 cells.

  18. Preparative separation of C{sub 19}-diterpenoid alkaloids from Aconitum carmichaelii Debx by pH zone-refining counter-current chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dahui [Institute of Medicinal Plants, Yunnan Academy of Agricultural Sciences, Kunming (China); Shu, Xikai; Wang, Xiao; Fang, Lei; Huang, Luqi, E-mail: wxjn1998@126.com [Shandong Analysis and Test Center, Shandong Academy of Sciences, Jinan, Shandong (China); Xi, Xingjun; Zheng, Zhenjia [China National institute of Standardization, Beijing (China)

    2013-11-01

    The technique of pH-zone-refining counter-current chromatography was successfully applied to preparatively separate three C{sub 19}-diterpenoid alkaloids from the crude extracts of Aconitum carmichaelii for the first time using a two-phase solvent system of petroleum ether-ethyl acetate-methanol-water (5:5:1:9, v/v/v/v). Mesaconitine (I), hypaconitine (II), and deoxyaconitine (III) were obtained from 2.5 g of the crude alkaloids in a one-step separation; the yields were 4.16%, 16.96%, and 5.05%, respectively. The purities of compounds I, II, and III were 93.0%, 95%, and 96%, respectively, as determined by HPLC. The chemical structures of the three compounds were identified by electrospray ionization mass spectrometry (ESI-MS) and NMR. (author)

  19. Preparative separation of C19-diterpenoid alkaloids from Aconitum carmichaelii Debx by pH‑zone-refining counter-current chromatography

    Directory of Open Access Journals (Sweden)

    Dahui Liu

    2013-01-01

    Full Text Available The technique of pH-zone-refining counter-current chromatography was successfully applied to preparatively separate three C19-diterpenoid alkaloids from the crude extracts of Aconitum carmichaelii for the first time using a two-phase solvent system of petroleum ether-ethyl acetate-methanol-water (5:5:1:9, v/v/v/v. Mesaconitine (I, hypaconitine (II, and deoxyaconitine (III were obtained from 2.5 g of the crude alkaloids in a one-step separation; the yields were 4.16%, 16.96%, and 5.05%, respectively. The purities of compounds I, II, and III were 93.0%, 95%, and 96%, respectively, as determined by HPLC. The chemical structures of the three compounds were identified by electrospray ionization mass spectrometry (ESI-MS and NMR.

  20. Current Trends in Targeted Therapies for Glioblastoma Multiforme

    Directory of Open Access Journals (Sweden)

    Fumiharu Ohka

    2012-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most frequently occurring tumors in the central nervous system and the most malignant tumor among gliomas. Despite aggressive treatment including surgery, adjuvant TMZ-based chemotherapy, and radiotherapy, GBM still has a dismal prognosis: the median survival is 14.6 months from diagnosis. To date, many studies report several determinants of resistance to this aggressive therapy: (1 O6-methylguanine-DNA methyltransferase (MGMT, (2 the complexity of several altered signaling pathways in GBM, (3 the existence of glioma stem-like cells (GSCs, and (4 the blood-brain barrier. Many studies aim to overcome these determinants of resistance to conventional therapy by using various approaches to improve the dismal prognosis of GBM such as modifying TMZ administration and combining TMZ with other agents, developing novel molecular-targeting agents, and novel strategies targeting GSCs. In this paper, we review up-to-date clinical trials of GBM treatments in order to overcome these 4 hurdles and to aim at more therapeutical effect than conventional therapies that are ongoing or are about to launch in clinical settings and discuss future perspectives.

  1. Separation and purification of two new and two known alkaloids from leaves of Nitraria sibirica by pH-zone-refining counter-current chromatography.

    Science.gov (United States)

    Bakri, Mahinur; Chen, Qibin; Ma, Qingling; Yang, Yi; Abdukadir, Abdumijit; Aisa, Haji Akber

    2015-12-01

    The total alkaloids from Nitraria sibirica leaves have been confirmed to exhibit significant protective effects against inflammatory renal injury, hypertension and albuminuria in angiotensin II-salt hypertension. In the present study, a separation method of pH-zone-refining counter-current chromatography was established for separation of the alkaloids from N. sibirica. The separation was performed with a solvent system of MtBE-n-BuOH-H2O (2:2:5, v/v) at a flow rate of 2.0mL/min. And 15mM triethylamine (TEA) was added to the upper organic phase, while 10mM hydrochloric acid was added to the lower aqueous phase. As a result, a new alkaloid, schobemine (5.6mg), and a known alkaloid, nitraramine (5.0mg), together with fractions A and B were obtained from the total alkaloids of N. sibirica. The fractions A and B were further purified by means of pH-zone-refining counter-current chromatography with solvent systems of n-hexane-n-BuOH-H2O (1.5:3.5:5, v/v) and (2:3:5, v/v), respectively. TEA (10mM) was added to the upper phase, and 10mM of HCl was added to the lower phase in above two solvent systems, respectively. As a result, a known alkaloid, schoberidine (5.0mg), and a new alkaloid, schoberimine (3.0mg) were obtained from fractions A and B, respectively. The purities of the compounds were measured by HPLC-ELSD, and their structures were identified by ESI-MS, 1D and 2D NMR.

  2. Preparation of salvianolic acid A by the degradation reaction of salvianolic acid B in subcritical water integrated with pH-zone-refining counter-current chromatography.

    Science.gov (United States)

    Li, Huaizhi; Cheng, Yan; Dong, Hongjing; Wang, Xiao; Li, Jia; Gao, Qianshan

    2016-10-14

    Salvianolic acid A is the major bioactive compound in Danshen, however, due to the chemical instability and low content in Danshen, it is difficult to extract amount of salvianolic acid A. Therefore, this study was to establish an effective strategy for obtaining adequate amount of salvianolic acid A, subcritical water extraction was used to degrade salvianolic acid B and prepare salvianolic acid A. Different reaction conditions including temperature, time, concentration and pH value in subcritical water were investigated. Under 40mg/mL of reactant concentration, 180°C of temperature, 4.0 of pH value and 60min of reaction time, the highest yield rate of salvianolic acid A reached 34.86%. Then, the degradation products were successfully separated by pH-zone-refining counter-current chromatography with the solvent system Pet-EtAc-n-BuOH-H2O (2:3:1:9, v/v), where 10mM TFA was added in stationary phase and 10mM NH3·H2O in mobile phase. As a result, a total of 227.3mg of salvianolic acid A at 98.2% purity, 38.9mg of danshensu at 99.3% purity, 9.5mg of salvianolic acid D at 92.7% purity, and 32.8mg of protocatechuic aldehyde at 93.1% purity were obtained from 1.2g degradation products of salvianolic acid B by one-step purification. The results demonstrated that the combinative application of subcritical water and pH-zone-refining counter-current chromatography is a potential technique for the preparative separation of salvianolic acid A from salvianolic acid B.

  3. Using OpenRefine

    CERN Document Server

    Verborgh, Ruben

    2013-01-01

    The book is styled on a Cookbook, containing recipes - combined with free datasets - which will turn readers into proficient OpenRefine users in the fastest possible way.This book is targeted at anyone who works on or handles a large amount of data. No prior knowledge of OpenRefine is required, as we start from the very beginning and gradually reveal more advanced features. You don't even need your own dataset, as we provide example data to try out the book's recipes.

  4. Passive Target Tracking Based on Current Statistical Model

    Institute of Scientific and Technical Information of China (English)

    DENG Xiao-long; XIE Jian-ying; YANG Yu-pu

    2005-01-01

    Bearing-only passive tracking is regarded as a nonlinear hard tracking problem. There are still no completely good solutions to this problem until now. Based on current statistical model, the novel solution to this problem utilizing particle filter (PF) and the unscented Kalman filter (UKF) is proposed. The new solution adopts data fusion from two observers to increase the observability of passive tracking. It applies the residual resampling step to reduce the degeneracy of PF and it introduces the Markov Chain Monte Carlo methods (MCMC) to reduce the effect of the "sample impoverish". Based on current statistical model, the EKF, the UKF and particle filter with various proposal distributions are compared in the passive tracking experiments with two observers. The simulation results demonstrate the good performance of the proposed new filtering methods with the novel techniques.

  5. Point Cloud Refinement with a Target-Free Intrinsic Calibration of a Mobile Multi-Beam LIDAR System

    Science.gov (United States)

    Nouiraa, H.; Deschaud, J. E.; Goulettea, F.

    2016-06-01

    LIDAR sensors are widely used in mobile mapping systems. The mobile mapping platforms allow to have fast acquisition in cities for example, which would take much longer with static mapping systems. The LIDAR sensors provide reliable and precise 3D information, which can be used in various applications: mapping of the environment; localization of objects; detection of changes. Also, with the recent developments, multi-beam LIDAR sensors have appeared, and are able to provide a high amount of data with a high level of detail. A mono-beam LIDAR sensor mounted on a mobile platform will have an extrinsic calibration to be done, so the data acquired and registered in the sensor reference frame can be represented in the body reference frame, modeling the mobile system. For a multibeam LIDAR sensor, we can separate its calibration into two distinct parts: on one hand, we have an extrinsic calibration, in common with mono-beam LIDAR sensors, which gives the transformation between the sensor cartesian reference frame and the body reference frame. On the other hand, there is an intrinsic calibration, which gives the relations between the beams of the multi-beam sensor. This calibration depends on a model given by the constructor, but the model can be non optimal, which would bring errors and noise into the acquired point clouds. In the litterature, some optimizations of the calibration parameters are proposed, but need a specific routine or environment, which can be constraining and time-consuming. In this article, we present an automatic method for improving the intrinsic calibration of a multi-beam LIDAR sensor, the Velodyne HDL-32E. The proposed approach does not need any calibration target, and only uses information from the acquired point clouds, which makes it simple and fast to use. Also, a corrected model for the Velodyne sensor is proposed. An energy function which penalizes points far from local planar surfaces is used to optimize the different proposed parameters

  6. Targets for Current Pharmacological Therapy in Cholesterol Gallstone Disease

    Science.gov (United States)

    Di Ciaula, Agostino; Wang, David Q.-H.; Wang, Helen H.; Bonfrate, Leonilde; Portincasa, Piero

    2010-01-01

    Summary Gallstone disease is a frequent condition throughout the world and cholesterol stones are the most frequent form in western countries. Current standard treatment of symptomatic gallstone subjects remains laparoscopic cholecystectomy. The selection of patients amenable for non-surgical, medical therapy is of key importance: a careful analysis should consider the natural history of the disease and the overall costs of therapy. Only patients with mild symptoms and small, uncalcified cholesterol gallstones in a functioning gallbladder with a patent cystic duct will be considered for oral litholysis by the hydrophilic ursodeoxycholic acid (UDCA) hopefully leading to cholesterol desaturation of bile and progressive stone dissolution. Recent studies have raised the possibility that cholesterol-lowering agents which inhibit hepatic cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe), or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis may offer, alone or in combination, additional medical therapeutic tools for treating cholesterol gallstones. Recent perspectives on medical treatment of cholesterol gallstone disease will be discussed in this chapter. PMID:20478485

  7. A Method to Increase Current Density in a Mono Element Internal Tin Processed Superconductor Utilizing Zr Oxide to Refine Grain Size

    Energy Technology Data Exchange (ETDEWEB)

    Bruce A. Zeitlin, Eric Gregory

    2008-04-07

    The effect of Oxygen on (Nb1Zr)3Sn multifilament conductors manufactured by the Mono Element Internal Tin (MEIT) process was explored to improve the current density by refining the grain size. This followed work first done by General Electric on the Nb3Sn tape process. Techniques to fabricate the more difficult Nb1Zr composites are described and allowed fabrication of long lengths of .254 mm diameter wire from an 88.9 mm diameter billet. Oxygen was incorporated through the use of SnO2 mixed with tin powder and incorporated into the core. These were compared to samples with Ti+Sn and Cu+Sn cores. Heat treatments covered the range of 700 C to 1000 C. Current density vs. H, grain size, and reaction percentages are provided for the materials tested. The Oxygen gave superior results in the temperature range of 815-1000 C. It also stabilized the filament geometry of the array in comparison to the other additions at the higher temperatures. At 815 C a peak in layer Jc yielded values of 2537 A/mm2 at 12 T and 1353 A/mm2 at 15T, 8-22% and 30-73% greater respectively than 700 C values. Results with Oxygen at high temperature show the possibility of high speed continuous reaction of the composite versus the current batch or react in place methods. In general the Ti additions gave superior results at the lower reaction temperature. Future work is suggested to determine if the 815 C reaction temperature can lead to higher current density in high tin (Nb1Zr+Ox)3Sn conductors. A second technique incorporated oxygen directly into the Nb1Zr rods through heat treatment with Nb2O5 at 1100 C for 100 hours in vacuum prior to extrusion. The majority of the filaments reduced properly in the composite but some local variations in hardness led to breakage at smaller diameters.

  8. Central nervous system myeloid cells as drug targets: current status and translational challenges.

    Science.gov (United States)

    Biber, Knut; Möller, Thomas; Boddeke, Erik; Prinz, Marco

    2016-02-01

    Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic.

  9. Review of Current Aided/Automatic Target Acquisition Technology for Military Target Acquisition Tasks

    Science.gov (United States)

    2011-07-01

    new advancements in military-relevant performance. C©2011 Society of Photo -Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3601879] Subject...indication (MTI) become first- step candidate approaches. Change detection can be a major tool in improvised explosive detection (IED) detection. Dis- turbed...Wilson, “A time-critical targeting roadmap,” Air Command and Staff Collage , Maxwell AFB, AL, Source Code 405502 ADA420658 (April 2002). 8. J. R. Rufa

  10. A new tropane alkaloid from the leaves of Erythroxylum subsessile isolated by pH-zone-refining counter-current chromatography.

    Science.gov (United States)

    Cruz, Rodrigo Alves Soares; Almeida, Henrique; Fernandes, Caio Pinho; Joseph-Nathan, Pedro; Rocha, Leandro; Leitão, Gilda Guimarães

    2016-04-01

    Tropane alkaloids are bioactive metabolites with great importance in the pharmaceutical industry and the most important class of natural products found in the Erythroxylum genus. However, these compounds are usually separated by traditional chromatographic techniques, in which the sample is progressively purified in multiple chromatographic steps, resulting in a time- and solvent-consuming procedure. In this work we present the isolation of a novel alkaloid, 6β,7β-dibenzoyloxytropan-3α-ol, together with the two known 3α-benzoyloxynortropan-6β-ol and 3α,6β-dibenzoyloxytropane alkaloids, directly from the crude alkaloid fraction from the leaves of Erythroxylum subsessile, by using a single run pH-zone-refining counter-current chromatography method. The ethyl acetate/water (1:1, v/v) biphasic solvent system with triethylamine and HCl as retention and eluter agents, respectively, was used to isolate tropane alkaloids for the first time. The structures of the isolated alkaloids were elucidated by spectroscopic methods.

  11. Targeting breast cancer through its microenvironment: current status of preclinical and clinical research in finding relevant targets.

    Science.gov (United States)

    Nienhuis, H H; Gaykema, S B M; Timmer-Bosscha, H; Jalving, M; Brouwers, A H; Lub-de Hooge, M N; van der Vegt, B; Overmoyer, B; de Vries, E G E; Schröder, C P

    2015-03-01

    It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, are already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment upcoming fields of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. FDTD Simulation of Transfer Impedance of Calibration Current Target for ESD Testing

    Science.gov (United States)

    Gotoh, Tsuyoshi; Taka, Yoshinori; Mori, Ikuko; Fujiwara, Osamu; Ishigami, Shinobu; Yamanaka, Yukio

    Transient electromagnetic fields caused by electrostatic discharges (ESDs) are known to cause a serious failure in high-tech information devices. From this perspective, an international standard for ESD testing or IEC 61000-4-2 has been specified, in which a detailed waveform of the discharge current to be injected onto equipment under test (EUT) by an ESD-gun is prescribed, and is also required for contact discharges onto a calibration current target called Pellegrini target, which is specially designed so that the waveform of an injected current and its observed voltage coincides. However, the coincidence relationship should not hold at high frequencies due to parasitic components which the target has. In this study, we constructed an FDTD model of the Pellegrini target, and calculated its transfer impedance by simulating the injected current onto the target and the corresponding output voltage in combination with an FDTD model being previously developed for an ESD-gun. As a result, we found that the target has a transfer impedance of almost 1-j0 Ω at less than a few hundred MHz, though it has resonance phenomena around 2-3 GHz, which was validated by measuring scattering parameters of the target through a transmission line with a network analyzer. Using the FDTD-calculated transfer impedance, we reconstructed injected current waveforms for contact and air discharges of an ESD-gun from their observed voltages to reveal that the injected current waveform is almost identical to the observed voltage waveform for the contact discharge, while the injected currents for the air discharges have smaller peaks and longer rise times than the observed voltages do due to the presence of resonance properties of the transfer impedance.

  13. Current Status of Targets and Assays for Anti-HIV Drug Screening

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent, treat and to better understand the disease, it is one of the main causes of morbidity and mortality worldwide. Currently, there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects, price and drug resistance, it is essential to discover new targets, to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.

  14. Flat Currents and Solutions of Sigma Model on Supercoset Targets with Z2m Grading

    Institute of Scientific and Technical Information of China (English)

    KE san-Min; SHI Kang-Jie; WANG Chun; WU Sheng

    2007-01-01

    We find one parameter flat currents of the sigma model on supercoset targets with Z2m grading given by Young satisfaction equations of motion and the Virasoro constraint.This meads that one can generate a series of classical solutions from the original one.For these new solutions one can also construct flat currents and conserved charges,which form the same set with the original one.

  15. Therapeutic targeting of microRNAs: current status and future challenges.

    Science.gov (United States)

    Li, Zhonghan; Rana, Tariq M

    2014-08-01

    MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that have crucial roles in regulating gene expression. Increasing evidence supports a role for miRNAs in many human diseases, including cancer and autoimmune disorders. The function of miRNAs can be efficiently and specifically inhibited by chemically modified antisense oligonucleotides, supporting their potential as targets for the development of novel therapies for several diseases. In this Review we summarize our current knowledge of the design and performance of chemically modified miRNA-targeting antisense oligonucleotides, discuss various in vivo delivery strategies and analyse ongoing challenges to ensure the specificity and efficacy of therapeutic oligonucleotides in vivo. Finally, we review current progress on the clinical development of miRNA-targeting therapeutics.

  16. Refining Inductive Types

    CERN Document Server

    Atkey, Robert; Ghani, Neil

    2012-01-01

    Dependently typed programming languages allow sophisticated properties of data to be expressed within the type system. Of particular use in dependently typed programming are indexed types that refine data by computationally useful information. For example, the N-indexed type of vectors refines lists by their lengths. Other data types may be refined in similar ways, but programmers must produce purpose-specific refinements on an ad hoc basis, developers must anticipate which refinements to include in libraries, and implementations must often store redundant information about data and their refinements. In this paper we show how to generically derive inductive characterisations of refinements of inductive types, and argue that these characterisations can alleviate some of the aforementioned difficulties associated with ad hoc refinements. Our characterisations also ensure that standard techniques for programming with and reasoning about inductive types are applicable to refinements, and that refinements can the...

  17. Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

    CERN Document Server

    Abbiendi, G; Abramowicz, H; Acosta, D; Adamczyk, L; Adamus, M; Ahn, S H; Amelung, C; An Shiz Hong; Anselmo, F; Antonioli, P; Arneodo, M; Bacon, Trevor C; Badgett, W F; Bailey, D C; Bailey, D S; Bamberger, A; Barbagli, G; Bari, G; Barreiro, F; Barret, O; Bashindzhagian, G L; Bashkirov, V; Basile, M; Bauerdick, L A T; Bednarek, B; Behrens, U; Bellagamba, L; Bertolin, A; Bhadra, S; Bienlein, J K; Blaikley, H E; Bohnet, I; Bokel, C; Boogert, S; Bornheim, A; Borzemski, P; Boscherini, D; Botje, M; Breitweg, J; Brock, I; Brook, N H; Brugnera, R; Bruni, A; Bruni, G; Brümmer, N; Burgard, C; Burow, B D; Bussey, P J; Butterworth, J M; Bylsma, B; Caldwell, A; Capua, M; Cara Romeo, G; Carlin, R; Cartiglia, N; Cashmore, R J; Castellini, G; Catterall, C D; Chapin, D; Chekanov, S; Chwastowski, J; Ciborowski, J; Cifarelli, Luisa; Cindolo, F; Cirio, R; Cloth, P; Coboken, K; Coldewey, C; Cole, J E; Contin, A; Cooper-Sarkar, A M; Coppola, N; Cor, M; Cormack, C; Corriveau, F; Costa, M; Cottingham, W N; Crittenden, J; Cross, R; D'Agostini, G; Dagan, S; Dal Corso, F; Dardo, M; De Pasquale, S; De Wolf, E; Deffner, R; Del Peso, J; Deppe, O; Derrick, M; Deshpande, Abhay A; Desler, K; Devenish, R C E; Dhawan, S; Dolgoshein, B A; Dondana, S; Dosselli, U; Doyle, A T; Drews, G; Dulinski, Z; Durkin, L S; Dusini, S; Eckert, M; Edmonds, J K; Eisenberg, Y; Eisenhardt, S; Engelen, J; Epperson, D E; Ermolov, P F; Eskreys, Andrzej; Fagerstroem, C P; Fernández, J P; Ferrero, M I; Figiel, J; Filges, D; Foster, B; Foudas, C; Fox-Murphy, A; Fricke, U; Frisken, W R; Fusayasu, T; Gadaj, T; Galea, R; Gallo, E; García, G; Garfagnini, A; Gendner, N; Gialas, I; Gilmore, J; Ginsburg, C M; Giusti, P; Gladilin, L K; Glasman, C; Göbel, F; Golubkov, Yu A; Grabosch, H J; Graciani, R; Grosse-Knetter, J; Grzelak, G; Göttlicher, P; Haas, T; Hain, W; Hall-Wilton, R; Hamatsu, R; Hanna, D S; Harnew, N; Hart, H; Hart, J C; Hartmann, J; Hartner, G F; Hasell, D; Hayes, M E; Heaphy, E A; Heath, G P; Heath, H F; Hebbel, K; Heinloth, K; Heinz, L; Hernández, J M; Heusch, C A; Hilger, E; Hirose, T; Hochman, D; Holm, U; Homma, K; Hong, S J; Howell, G; Hughes, V W; Iacobucci, G; Iannotti, L; Iga, Y; Inuzuka, M; Ishii, T; Jakob, H P; Jelen, K; Jeoung, H Y; Jing, Z; Johnson, K F; Jones, T W; Kananov, S; Kappes, A; Karshon, U; Kasemann, M; Katz, U F; Kcira, D; Kerger, R; Khakzad, M; Khein, L A; Kim, C L; Kim, J Y; Kisielewska, D; Kitamura, S; Klanner, Robert; Klimek, K; Ko, I A; Koch, W; Koffeman, E; Kooijman, P; Koop, T; Korotkova, N A; Kotanski, A; Kowal, A M; Kowalski, H; Kowalski, T; Krakauer, D; Kreisel, A; Kuze, M; Kuzmin, V A; Kötz, U; Labarga, L; Lamberti, L; Lane, J B; Laurenti, G; Lee, J H; Lee, S B; Lee, S W; Levi, G; Levman, G M; Levy, A; Lim, H; Lim, I T; Limentani, S; Lindemann, L; Ling, T Y; Liu, W; Lohrmann, E; Long, K R; Lopez-Duran Viani, A; Lukina, O Yu; Löhr, B; Ma, K J; MacDonald, N; Maccarrone, G; Magill, S; Mallik, U; Margotti, A; Marini, G; Markun, P; Martin, J F; Martínez, M; Maselli, S; Massam, Thomas; Mastroberardino, A; Matsushita, T; Mattingly, M C K; Mattingly, S E K; McCance, G J; McCubbin, N A; McFall, J D; Mellado, B; Menary, S R; Meyer, A; Meyer-Larsen, A; Milewski, J; Milite, M; Miller, D B; Monaco, V; Monteiro, T; Morandin, M; Moritz, M; Murray, W N; Musgrave, B; Mönig, K; Nagano, K; Nam, S W; Nania, R; Nigro, A; Nishimura, T; Notz, D; Nowak, R J; Noyes, V A; Nylander, P; Ochs, A; Oh, B Y; Okrasinski, J R; Olkiewicz, K; Orr, R S; Pac, M Y; Padhi, S; Palmonari, F; Park, I H; Park, S K; Parsons, J A; Paul, E; Pavel, N; Pawlak, J M; Pawlak, R; Pelfer, Pier Giovanni; Pellegrino, A; Pelucchi, F; Peroni, C; Pesci, A; Petrucci, M C; Pfeiffer, M; Pic, D; Piotrzkowski, K; Poelz, G; Polenz, S; Polini, A; Posocco, M; Prinias, A; Proskuryakov, A S; Przybycien, M B; Puga, J; Quadt, A; Raach, H; Raso, M; Rautenberg, J; Re, J; Redondo, I; Reeder, D D; Ritz, S; Riveline, M; Rohde, M; Rulikowska-Zarebska, E; Ruske, O; Ruspa, M; Sabetfakhri, A; Sacchi, R; Sadrozinski, H F W; Saint-Laurent, M; Salehi, H; Samp, S; Sartorelli, G; Saull, P R B; Savin, A A; Saxon, D H; Schechter, A; Schioppa, M; Schlenstedt, S; Schmidke, W B; Schneekloth, U; Schnurbusch, H; Schwarzer, O; Sciulli, F; Scott, J; Sedgbeer, J K; Seiden, A; Selonke, F; Shah, T P; Shcheglova, L M; Sideris, D; Sievers, M; Simmons, D; Sinclair, L E; Skillicorn, I O; Smalska, B; Smith, W H; Solano, A; Solomin, A N; Son, D; Staiano, A; Stairs, D G; Stanco, L; Stanek, R; Stifutkin, A; Stonjek, S; Straub, P B; Strickland, E; Stroili, R; Susinno, G; Suszycki, L; Sutton, M R; Suzuki, I; Tandler, J; Tapper, A D; Tapper, R J; Tassi, E; Terron, J; Tiecke, H G; Tokushuku, K; Toothacker, W S; Tsurugai, T; Tuning, N; Tymieniecka, T; Umemori, K; Vaiciulis, A W; Van Sighem, A; Velthuis, J J; Verkerke, W; Voci, C; Vossebeld, Joost Herman; Votano, L; Walczak, R; Walker, R; Wang, S M; Waters, D S; Waugh, R; Weber, A; Whitmore, J J; Wichmann, R; Wick, K; Wieber, H; Wiggers, L; Wildschek, T; Williams, D C; Wing, M; Wodarczyk, M; Wolf, G; Wollmer, U; Wróblewski, A K; Wölfle, S; Yamada, S; Yamashita, T; Yamauchi, K; Yamazaki, Y; Yoshida, R; Youngman, C; Zajac, J; Zakrzewski, J A; Zamora Garcia, Y; Zawiejski, L; Zetsche, F; Zeuner, W; Zhu, Q; Zichichi, Antonino; Zotkin, S A

    2000-01-01

    Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.

  18. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

    Science.gov (United States)

    Distler, Oliver; Cozzio, Antonio

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

  19. The Effect of Ion Current Density on Target Etching in Radio Frequency-Magnetron Sputtering Process

    Institute of Scientific and Technical Information of China (English)

    王庆; 王永富; 巴德纯; 岳向吉

    2012-01-01

    The effect of ion current density of argon plasma on target sputtering in magnetron sputtering process was investigated. Using home-made ion probe with computer-based data acquisition system, the ion current density as functions of discharge power, gas pressure and positions was measured. A double-hump shape was found in ion current density curve after the analysis of the effects of power and pressure. The data demonstrate that ion current density increases with the increase in gas pressure in spite of slightly at the double-hump site, sharply at wave-trough and side positions. Simultaneously, the ion current density increases upon increase in power. Es- pecially, the ion current density steeply increases at the double-hump site. The highest energy of the secondary electrons arising from Larmor precession was found at the double-hump position, which results in high ion density. The target was etched seriously at the double-hump position due to the high ion density there. The data indicates that the increase in power can lead to a high sputtering speed rate.

  20. Targeted therapy for advanced gastric cancer: A review of current status and future prospects

    Institute of Scientific and Technical Information of China (English)

    Ozkan; Kanat; Bert; O’Neil; Safi; Shahda

    2015-01-01

    In the West in particular, the vast majority of gastric cancer(GC) patients present with advanced-stage disease. Although combination chemotherapy is stillthe most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted therapeutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC.

  1. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application.

    Science.gov (United States)

    Maione, Paolo; Sacco, Paola Claudia; Sgambato, Assunta; Casaluce, Francesca; Rossi, Antonio; Gridelli, Cesare

    2015-09-01

    The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC.

  2. Visual information about past, current and future properties of irregular target paths in isometric force tracking.

    Science.gov (United States)

    Mazich, Molly M; Studenka, Breanna E; Newell, Karl M

    2015-01-01

    In visual-motor tracking, information about past, current, and future properties of a target path can be available but, because they are typically manipulated independently, the relative contribution of these information categories to tracking performance is not well understood. The aim of the current study was to investigate the role of visual information pertaining to past, current, and future states of the target path in guiding isometric tracking performance as a function of the irregularity of the target path (sine wave, brown/pink noise, white noise). The findings from local and global properties of the force output showed that the role of visual information about the past, current, and future states of target paths is dependent on the regularity of the signal to be tracked. The brown/pink noise pathway condition was most strongly influenced by future and past-future visual information for both local error properties (lead/lag, root mean square error (RMSE)) and global properties of the force output (ApEn, cross correlation). The highly irregular white noise pathway did not benefit from past or future information and the highly regular sine wave was only influenced for the local error properties of RMSE and lead/lag. It appears that visual information about past and future tracking states is more effective with a pathway that is middling with respect to regularity/irregularity. This is consistent with the role of visual information in tracking to be dependent on the potential adaptability for change in the dimension of the motor output.

  3. On the refinement calculus

    CERN Document Server

    Vickers, Trevor

    1992-01-01

    On the Refinement Calculus gives one view of the development of the refinement calculus and its attempt to bring together - among other things - Z specifications and Dijkstra's programming language. It is an excellent source of reference material for all those seeking the background and mathematical underpinnings of the refinement calculus.

  4. First Measurement of the Neutral Current Excitation of the Delta Resonance on a Proton Target

    CERN Document Server

    Androic, D; Arvieux, J; Bailey, S L; Beck, D H; Beise, E J; Benesch, J; Benmokhtar, F; Bimbot, L; Birchall, J; Bosted, P; Breuer, H; Capuano, C L; Chao, Y -C; Coppens, A; Davis, C A; Ellis, C; Flores, G; Franklin, G; Furget, C; Gaskell, D; Grames, J; Gericke, M T W; Guillard, G; Hansknecht, J; Horn, T; Jones, M K; King, P M; Korsch, W; Kox, S; Lee, L; Liu, J; Lung, A; Mammei, J; Martin, J W; McKeown, R D; Micherdzinska, A; Mihovilovic, M; Mkrtchyan, H; Muether, M; Page, S A; Papavassiliou, V; Pate, S F; Phillips, S K; Pillot, P; Pitt, M L; Poelker, M; Quinn, B; Ramsay, W D; Real, J -S; Roche, J; Roos, P; Schaub, J; Seva, T; Simicevic, N; Smith, G R; Spayde, D T; Stutzman, M; Suleiman, R; Tadevosyan, V; van Oers, W T H; Versteegen, M; Voutier, E; Vulcan, W; Wells, S P; Williamson, S E; Wood, S A

    2012-01-01

    The parity-violating asymmetry arising from inelastic electron-nucleon scattering at backward angle (~95 degrees) near the Delta(1232) resonance has been measured using a hydrogen target. From this asymmetry, we extracted the axial transition form factor G^A_{N\\Delta}, a function of the axial Adler form factors C^A_i. Though G^A_{N\\Delta} has been previously studied using charged current reactions, this is the first measurement of the weak neutral current excitation of the Delta using a proton target. For Q^2 = 0.34 (GeV/c)^2 and W = 1.18 GeV, the asymmetry was measured to be -33.4 \\pm (5.3)_{stat} \\pm (5.1)_{sys} ppm. The value of G^A_{N\\Delta} determined from the hydrogen asymmetry was -0.05 \\pm (0.35)_{stat} \\pm (0.34)_{sys} \\pm (0.06)_{theory}. These findings agree within errors with theoretical predictions for both the total asymmetry and the form factor. In addition to the hydrogen measurement, the asymmetry was measured at the same kinematics using a deuterium target. The asymmetry for deuterium was de...

  5. OPTIMIZING EUCALYPTUS PULP REFINING

    Institute of Scientific and Technical Information of China (English)

    Vail Manfredi

    2004-01-01

    This paper discusses the refining of bleached eucalyptus kraft pulp (BEKP).Pilot plant tests were carried out in to optimize the refining process and to identify the effects of refining variables on final paper quality and process costs.The following parameters are discussed: pulp consistency, disk pattern design, refiner speed,energy input, refiner configuration (parallel or serial)and refining intensity.The effects of refining on pulp fibers were evaluated against the pulp quality properties, such as physical strengths, bulk, opacity and porosity, as well as the interactions with papermaking process, such as paper machine runnability, paper breaks and refining control.The results showed that process optimization,considering pulp quality and refining costs, were obtained when eucalyptus pulp is refined under the lowest intensity and the highest pulp consistency possible. Changes on the operational refining conditions will have the highest impact on total energy requirements (costs) without any significant effect on final paper properties.It was also observed that classical ways to control the industrial operation, such as those based on drainage measurements, do not represent the best alternative to maximize the final paper properties neither the paper machine runability.

  6. Refines Efficiency Improvement

    Energy Technology Data Exchange (ETDEWEB)

    WRI

    2002-05-15

    Refinery processes that convert heavy oils to lighter distillate fuels require heating for distillation, hydrogen addition or carbon rejection (coking). Efficiency is limited by the formation of insoluble carbon-rich coke deposits. Heat exchangers and other refinery units must be shut down for mechanical coke removal, resulting in a significant loss of output and revenue. When a residuum is heated above the temperature at which pyrolysis occurs (340 C, 650 F), there is typically an induction period before coke formation begins (Magaril and Aksenova 1968, Wiehe 1993). To avoid fouling, refiners often stop heating a residuum before coke formation begins, using arbitrary criteria. In many cases, this heating is stopped sooner than need be, resulting in less than maximum product yield. Western Research Institute (WRI) has developed innovative Coking Index concepts (patent pending) which can be used for process control by refiners to heat residua to the threshold, but not beyond the point at which coke formation begins when petroleum residua materials are heated at pyrolysis temperatures (Schabron et al. 2001). The development of this universal predictor solves a long standing problem in petroleum refining. These Coking Indexes have great potential value in improving the efficiency of distillation processes. The Coking Indexes were found to apply to residua in a universal manner, and the theoretical basis for the indexes has been established (Schabron et al. 2001a, 2001b, 2001c). For the first time, a few simple measurements indicates how close undesired coke formation is on the coke formation induction time line. The Coking Indexes can lead to new process controls that can improve refinery distillation efficiency by several percentage points. Petroleum residua consist of an ordered continuum of solvated polar materials usually referred to as asphaltenes dispersed in a lower polarity solvent phase held together by intermediate polarity materials usually referred to as

  7. Risk-Targeted versus Current Seismic Design Maps for the Conterminous United States

    Science.gov (United States)

    Luco, Nicolas; Ellingwood, Bruce R.; Hamburger, Ronald O.; Hooper, John D.; Kimball, Jeffrey K.; Kircher, Charles A.

    2007-01-01

    The probabilistic portions of the seismic design maps in the NEHRP Provisions (FEMA, 2003/2000/1997), and in the International Building Code (ICC, 2006/2003/2000) and ASCE Standard 7-05 (ASCE, 2005a), provide ground motion values from the USGS that have a 2% probability of being exceeded in 50 years. Under the assumption that the capacity against collapse of structures designed for these "uniformhazard" ground motions is equal to, without uncertainty, the corresponding mapped value at the location of the structure, the probability of its collapse in 50 years is also uniform. This is not the case however, when it is recognized that there is, in fact, uncertainty in the structural capacity. In that case, siteto-site variability in the shape of ground motion hazard curves results in a lack of uniformity. This paper explains the basis for proposed adjustments to the uniform-hazard portions of the seismic design maps currently in the NEHRP Provisions that result in uniform estimated collapse probability. For seismic design of nuclear facilities, analogous but specialized adjustments have recently been defined in ASCE Standard 43-05 (ASCE, 2005b). In support of the 2009 update of the NEHRP Provisions currently being conducted by the Building Seismic Safety Council (BSSC), herein we provide examples of the adjusted ground motions for a selected target collapse probability (or target risk). Relative to the probabilistic MCE ground motions currently in the NEHRP Provisions, the risk-targeted ground motions for design are smaller (by as much as about 30%) in the New Madrid Seismic Zone, near Charleston, South Carolina, and in the coastal region of Oregon, with relatively little (<15%) change almost everywhere else in the conterminous U.S.

  8. Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau

    Directory of Open Access Journals (Sweden)

    Hong-Qi Yang

    2012-10-01

    Full Text Available Abstract Alzheimer’s disease (AD is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly. Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD. Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear, the current treatments are those drugs that can alleviate the symptoms of AD patients. Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation. Thus the pharmacological mechanism of these drugs may be too simply-evaluated. This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.

  9. Refinement Checking on Parametric Modal Transition Systems

    DEFF Research Database (Denmark)

    Benes, Nikola; Kretínsky, Jan; Larsen, Kim Guldstrand

    2015-01-01

    Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refin...

  10. Refinement Checking on Parametric Modal Transition Systems

    DEFF Research Database (Denmark)

    Benes, Nikola; Kretínsky, Jan; Larsen, Kim Guldstrand

    2015-01-01

    Modal transition systems (MTS) is a well-studied specification formalism of reactive systems supporting a step-wise refinement methodology. Despite its many advantages, the formalism as well as its currently known extensions are incapable of expressing some practically needed aspects in the refin...

  11. Targeting the androgen receptor in triple-negative breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Mina A

    2017-09-01

    Full Text Available Alain Mina,1 Rachel Yoder,2 Priyanka Sharma1 1Division of Medical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, 2University of Kansas Cancer Center, Kansas City, KS, USA Abstract: Triple-negative breast cancer (TNBC is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition. Keywords: triple-negative breast cancer, androgen signaling, targeted therapy, biomarkers, prognosis 

  12. A Refined Self-Tuning Filter-Based Instantaneous Power Theory Algorithm for Indirect Current Controlled Three-Level Inverter-Based Shunt Active Power Filters under Non-sinusoidal Source Voltage Conditions

    Directory of Open Access Journals (Sweden)

    Yap Hoon

    2017-02-01

    Full Text Available In this paper, a refined reference current generation algorithm based on instantaneous power (pq theory is proposed, for operation of an indirect current controlled (ICC three-level neutral-point diode clamped (NPC inverter-based shunt active power filter (SAPF under non-sinusoidal source voltage conditions. SAPF is recognized as one of the most effective solutions to current harmonics due to its flexibility in dealing with various power system conditions. As for its controller, pq theory has widely been applied to generate the desired reference current due to its simple implementation features. However, the conventional dependency on self-tuning filter (STF in generating reference current has significantly limited mitigation performance of SAPF. Besides, the conventional STF-based pq theory algorithm is still considered to possess needless features which increase computational complexity. Furthermore, the conventional algorithm is mostly designed to suit operation of direct current controlled (DCC SAPF which is incapable of handling switching ripples problems, thereby leading to inefficient mitigation performance. Therefore, three main improvements are performed which include replacement of STF with mathematical-based fundamental real power identifier, removal of redundant features, and generation of sinusoidal reference current. To validate effectiveness and feasibility of the proposed algorithm, simulation work in MATLAB-Simulink and laboratory test utilizing a TMS320F28335 digital signal processor (DSP are performed. Both simulation and experimental findings demonstrate superiority of the proposed algorithm over the conventional algorithm.

  13. Potential chemotherapeutic targets for Japanese encephalitis: current status of antiviral drug development and future challenges.

    Science.gov (United States)

    Ishikawa, Tomohiro; Konishi, Eiji

    2015-01-01

    Japanese encephalitis (JE) remains a public health threat in Asia. Although several vaccines have been licensed, ∼ 67,900 cases of the disease are estimated to occur annually, probably because the vaccine coverage is low. Therefore, effective antiviral drugs are required to control JE. However, no licensed anti-JE drugs are available, despite extensive efforts to develop them. We provide a general overview of JE and JE virus, including its transmission cycle, distribution, structure, replication machinery, immune evasion mechanisms and vaccines. The current situation in antiviral drug development is then reviewed and future perspectives are discussed. Although the development of effective anti-JE drugs is an urgent issue, only supportive care is currently available. Recent progress in our understanding of the viral replication machinery and immune evasion strategies has identified new targets for anti-JE drug development. To date, most candidate drugs have only been evaluated in single-drug formulations, and efficient drug delivery to the CNS has virtually not been considered. However, an effective anti-JE treatment is expected to be achieved with multiple-drug formulations and a targeted drug delivery system in the near future.

  14. Current Status of Targeted Therapy for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2014-12-01

    Full Text Available The rate of the anaplastic lymphoma kinase (ALK gene rearrangements in non-small cell lung cancer (NSCLC tissues is 3%-5%. The first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. A randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients demonstrated durable responses and well tolerance in the majority of ALK-positive NSCLC patients treated with crizotinib. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802, and AP26113, and new agents shock protein 90 inhibitors. This review aims to present the current knowledge on this fusion gene, the treatment advances, and novel drug clinical trials in ALK rearranged NSCLC.

  15. EGFR Targeting in Hormone-Refractory Prostate Cancer: Current Appraisal and Prospects for Treatment

    Directory of Open Access Journals (Sweden)

    Gerard Milano

    2010-07-01

    Full Text Available The incidence of prostate cancer increases with age and because of its high prevalence this disease has become a major public health concern. Despite advances in our understanding of the biological mechanisms responsible for the development of this cancer, the transition to the hormone refractory stage (HRPC and metastatic progression pose real problems of clinical management. Currently, docetaxel chemotherapy has been shown to have a slight but significant impact on survival, though the gain in median survival is still less than three months. Research is therefore continuing to improve treatment outcomes. The progression of prostate cancer is accompanied by the overexpression of EGFR (epidermal growth factor receptor in a very large majority of cases, suggesting that this may play a mechanistic role. Unfortunately, although preclinical findings seem to be promising for therapies targeting the EGFR in HRPC, current clinical results are disappointing. These results should however encourage us to look for different ways of using anti-EGFR agents or combining them with other targeted therapies.

  16. FEA Analysis of AP-0 Target Hall Collection Lens (Current Design)

    Energy Technology Data Exchange (ETDEWEB)

    Hurh, P.G.; Tang, Z.

    2001-06-22

    The AP-0 Target Hall Collection Lens is a pulsed device which focuses anti-protons just downstream of the Target. Since the angles at which the anti-protons depart the Target can be quite large, a very high focusing strength is required to maximize anti-proton capture into the downstream Debuncher Ring. The current design of the Collection Lens was designed to operate with a focusing gradient of 1,000 T/m. However, multiple failures of early devices resulted in lowering the normal operating gradient to about 750 T/m. At this gradient, the Lens design fares much better, lasting several million pulses, but ultimately still fails. A Finite Element Analysis (FEA) has been performed on this Collection Lens design to help determine the cause and/or nature of the failures. The Collection Lens magnetic field is created by passing high current through a central conductor cylinder. A uniform current distribution through the cylinder will create a tangential or azimuthal magnetic field that varies linearly from zero at the center of the cylinder to a maximum at the outer surface of the cylinder. Anti-proton particles passing through this cylinder (along the longitudinal direction) will see an inward focusing kick back toward the center of the cylinder proportional to the magnetic field strength. For the current Lens design a gradient of 1,000 T/m requires a current of about 580,000 amps. Since the DC power and cooling requirements would be prohibitive, the Lens is operated in a pulsed mode. Each pulse is half sine wave in shape with a pulse duration of about 350 microseconds. Because of the skin effect, the most uniform current density actually occurs about two-thirds of the way through the pulse. This means that the maximum current of the pulse is actually higher than that required in the DC case (about 670,000 amps). Since the beam must pass through the central conductor cylinder it must be made of a conducting material that is also very 'transparent' to the beam

  17. Inflammation: A novel target of current therapies for hepatic encephalopathy in liver cirrhosis.

    Science.gov (United States)

    Luo, Ming; Guo, Jian-Yang; Cao, Wu-Kui

    2015-11-07

    Hepatic encephalopathy (HE) is a severe neuropsychiatric syndrome that most commonly occurs in decompensated liver cirrhosis and incorporates a spectrum of manifestations that ranges from mild cognitive impairment to coma. Although the etiology of HE is not completely understood, it is believed that multiple underlying mechanisms are involved in the pathogenesis of HE, and one of the main factors is thought to be ammonia; however, the ammonia hypothesis in the pathogenesis of HE is incomplete. Recently, it has been increasingly demonstrated that inflammation, including systemic inflammation, neuroinflammation and endotoxemia, acts in concert with ammonia in the pathogenesis of HE in cirrhotic patients. Meanwhile, a good number of studies have found that current therapies for HE, such as lactulose, rifaximin, probiotics and the molecular adsorbent recirculating system, could inhibit different types of inflammation, thereby improving the neuropsychiatric manifestations and preventing the progression of HE in cirrhotic patients. The anti-inflammatory effects of these current therapies provide a novel therapeutic approach for cirrhotic patients with HE. The purpose of this review is to describe the inflammatory mechanisms behind the etiology of HE in cirrhosis and discuss the current therapies that target the inflammatory pathogenesis of HE.

  18. Transcranial direct current stimulation of the prefrontal cortex increases attention to visual target stimuli.

    Science.gov (United States)

    Vierheilig, Nina; Mühlberger, Andreas; Polak, Thomas; Herrmann, Martin J

    2016-10-01

    Both functional imaging or EEG studies and studies including neurological patients found the dorsolateral prefrontal cortex (dLPFC) to be an important brain area for the processing of emotion and attention. The aim of the present study was to investigate whether emotion and attention can be modulated through bilateral transcranial direct current stimulation (tDCS) of the dLPFC. Therefore, we measured electroencephalographic occipital (early posterior negativity, EPN) and parietal ERPs (late positive potential, LPP) during an emotional picture viewing paradigm with an additional attentional instruction while applying bilateral anodal and cathodal tDC-stimulation to the left and right dLPFC. Beyond the well-known emotion and attention effects for both EPN and LPP, we found that left cathodal/right anodal tDCS leads to increased LPP amplitudes to target stimuli. In contrast to our hypothesis bilateral tDCS over the dLPFC did not influence emotional processing.

  19. How to target inter-regional phase synchronization with dual-site Transcranial Alternating Current Stimulation

    DEFF Research Database (Denmark)

    Saturnino, Guilherme Bicalho; Madsen, Kristoffer Hougaard; Siebner, Hartwig Roman

    2017-01-01

    Large-scale synchronization of neural oscillations is a key mechanism for functional information exchange among brain areas. Dual-site Transcranial Alternating Current Stimulation (ds-TACS) has been recently introduced as non-invasive technique to manipulate the temporal phase relationship of local...... oscillations in two connected cortical areas. While the frequency of ds-TACS is matched, the phase of stimulation is either identical (in-phase stimulation) or opposite (anti-phase stimulation) in the two cortical target areas. In-phase stimulation is thought to synchronize the endogenous oscillations...... and hereby to improve behavioral performance. Conversely, anti-phase stimulation is thought to desynchronize neural oscillations in the two areas, which is expected to decrease performance. Critically, in- and anti-phase ds-TACS should only differ with respect to temporal phase, while all other stimulation...

  20. Targeting the neurophysiology of cognitive systems with transcranial alternating current stimulation.

    Science.gov (United States)

    Fröhlich, Flavio; Sellers, Kristin K; Cordle, Asa L

    2015-02-01

    Cognitive impairment represents one of the most debilitating and most difficult symptom to treat of many psychiatric illnesses. Human neurophysiology studies have suggested that specific pathologies of cortical network activity correlate with cognitive impairment. However, we lack demonstration of causal relationships between specific network activity patterns and cognitive capabilities and treatment modalities that directly target impaired network dynamics of cognition. Transcranial alternating current stimulation (tACS), a novel non-invasive brain stimulation approach, may provide a crucial tool to tackle these challenges. Here, we propose that tACS can be used to elucidate the causal role of cortical synchronization in cognition and, eventually, to enhance pathologically weakened synchrony that may underlie cognitive deficits. To accelerate such development of tACS as a treatment for cognitive deficits, we discuss studies on tACS and cognition performed in healthy participants, according to the Research Domain Criteria of the National Institute of Mental Health.

  1. Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets.

    Science.gov (United States)

    Dos Santos Fernandes, Guilherme Felipe; Jornada, Daniela Hartmann; de Souza, Paula Carolina; Chin, Chung Man; Pavan, Fernando Rogerio; Dos Santos, Jean Leandro

    2015-01-01

    Tuberculosis (TB) is an infectious disease caused by bacterium of the Mycobacterium genus, mainly by Mycobacterium tuberculosis (MTB). The World Health Organization aims to substantially reduce the number of cases in the coming years; however, the increased number of multidrug-resistant (MDR) and extremely drug-resistant (XDR) forms of the bacterium and the lack of treatment for latent tuberculosis are challenges to be overcome. In this review, we have identified the most potent compounds described in the literature during recent years with MIC values < 7 µM, low toxicity and a high selective index. In addition, emerging targets in MTB are presented to provide new perspectives for the discovery of new antitubercular drugs. This review aims to summarize the current advances in and promote insights into antitubercular drug discovery.

  2. Targeted therapies with companion diagnostics in the management of breast cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    Myers MB

    2016-01-01

    Full Text Available Meagan B Myers Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, USA Abstract: Breast cancer is a multifaceted disease exhibiting both intertumoral and intratumoral heterogeneity as well as variable disease course. Over 2 decades of research has advanced the understanding of the molecular substructure of breast cancer, directing the development of new therapeutic strategies against these actionable targets. In vitro diagnostics, and specifically companion diagnostics, have been integral in the successful development and implementation of these targeted therapies, such as those directed against the human epidermal growth factor receptor 2. Lately, there has been a surge in the development, commercialization, and marketing of diagnostic assays to assist in breast cancer patient care. More recently, multigene signature assays, such as Oncotype DX, MammaPrint, and Prosigna, have been integrated in the clinical setting in order to tailor decisions on adjuvant endocrine and chemotherapy treatment. This review provides an overview of the current state of breast cancer management and the use of companion diagnostics to direct personalized approaches in the treatment of breast cancer. Keywords: HER2, precision medicine, in vitro diagnostics, estrogen receptor, multigene assay

  3. Analysis of current antifungal agents and their targets within the Pneumocystis carinii genome.

    Science.gov (United States)

    Porollo, Aleksey; Meller, Jaroslaw; Joshi, Yogesh; Jaiswal, Vikash; Smulian, A George; Cushion, Melanie T

    2012-11-01

    Pneumocystis pneumonia (PCP) remains a leading opportunistic infection in patients with weakened immune systems. The fungus causing the infection belongs to the genus, Pneumocystis, and its members are found in a large variety of mammals. Adaptation to the lung environment of a host with an intact immune system has been a key to its successful survival. Unfortunately, the metabolic strategies used by these fungi to grow and survive in this context are largely unknown. There were considerable impediments to standard approaches for investigation of this unique pathogen, the most problematic being the lack of a long term in vitro culture system. The absence of an ex vivo cultivation method remains today, and many fundamental scientific questions about the basic biology, metabolism, and life cycle of Pneumocystis are unanswered. Recent progress in sequencing of the Pneumocystis carinii genome, a species infecting rats, permitted a more informative search for genes and biological pathways within this pathogen that are known to be targets for existing antifungal agents. In this work, we review the classes of antifungal drugs with respect to their potential applicability to the treatment of PCP. Classes covered in the review are the azoles, polyenes, allylamines, and echinocandins. Factors limiting the use of standard antifungal treatments and the currently available alternatives (trimethoprim-sulfamethoxazole, atovaquone, and pentamidine) are discussed. A summary of genomic sequences within Pneumocystis carinii associated with the corresponding targeted biological pathways is provided. All sequences are available via the Pneumocystis Genome Project at http://pgp.cchmc.org/.

  4. PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes

    Institute of Scientific and Technical Information of China (English)

    Ipsita PAL; Mahitosh MANDAL

    2012-01-01

    The PI3K-Akt pathway is a vital regulator of cell proliferation and survival.Alterations in the PIK3CA gene that lead to enhanced PI3K kinase activity have been reported in many human cancer types,including cancers of the colon,breast,brain,liver,stomach and lung.Deregulation of PI3K causes aberrant Akt activity.Therefore targeting this pathway could have implications for cancer treatment.The first generation PI3K-Akt inhibitors were proven to be highly effective with a low IC50,but later,they were shown to have toxic side effects and poor pharmacological properties and selectivity.Thus,these inhibitors were only effective in preclinical models.However,derivatives of these first generation inhibitors are much more selective and are quite effective in targeting the PI3K-Akt pathway,either alone or in combination.These second-generation inhibitors are essentially a specific chemical moiety that helps to form a strong hydrogen bond interaction with the PI3K/Akt molecule.The goal of this review is to delineate the current efforts that have been undertaken to inhibit the various components of the PI3K and Akt pathway in different types of cancer both in vitro and in vivo.Our focus here is on these novel therapies and their inhibitory effects that depend upon their chemical nature,as well as their development towards clinical trials.

  5. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects.

    Science.gov (United States)

    Banerjee, Shubhasree; Biehl, Ann; Gadina, Massimo; Hasni, Sarfaraz; Schwartz, Daniella M

    2017-04-01

    The Janus kinase/signal transduction and activator of transcription (JAK-STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK-STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK-STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK-STAT signaling blockade.

  6. Leishmaniasis:Current status of available drugs and new potential drug targets

    Institute of Scientific and Technical Information of China (English)

    Nisha Singh; Manish Kumar; Rakesh Kumar Singh

    2012-01-01

    The control ofLeishmania infection relies primarily on chemotherapy till date. Resistance to pentavalent antimonials, which have been the recommended drugs to treat cutaneous and visceral leishmaniasis, is now widespread in Indian subcontinents. New drug formulations like amphotericinB, its lipid formulations, and miltefosine have shown great efficacy to treat leishmaniasis but their high cost and therapeutic complications limit their usefulness. In addition, irregular and inappropriate uses of these second line drugs in endemic regions like state of Bihar, India threaten resistance development in the parasite. In context to the limited drug options and unavailability of either preventive or prophylactic candidates, there is a pressing need to develop true antileishmanial drugs to reduce the disease burden of this debilitating endemic disease. Notwithstanding significant progress of leishmanial research during last few decades, identification and characterization of novel drugs and drug targets are far from satisfactory. This review will initially describe current drug regimens and later will provide an overview on few important biochemical and enzymatic machineries that could be utilized as putative drug targets for generation of true antileishmanial drugs.

  7. Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis.

    Science.gov (United States)

    Guptill, Jeffrey T; Soni, Madhu; Meriggioli, Matthew N

    2016-01-01

    Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

  8. Targeting Bone Metabolism in Patients with Advanced Prostate Cancer: Current Options and Controversies

    Directory of Open Access Journals (Sweden)

    Tilman Todenhöfer

    2015-01-01

    Full Text Available Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL, antiresorptive agents have been shown to improve bone mineral density (BMD and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy.

  9. Late sodium current is a new therapeutic target to improve contractility and rhythm in failing heart.

    Science.gov (United States)

    Undrovinas, Albertas; Maltsev, Victor A

    2008-10-01

    Most cardiac Na+ channels open transiently within milliseconds upon membrane depolarization and are responsible for the excitation propagation. However, some channels remain active during hundreds of milliseconds, carrying the so-called persistent or late Na+ current (I(NaL)) throughout the action potential plateau. I(NaL) is produced by special gating modes of the cardiac-specific Na+ channel isoform. Experimental data accumulated over the past decade show the emerging importance of this late current component for the function of both normal and especially failing myocardium, where I(NaL) is reportedly increased. Na+ channels represent a multi-protein complex and its activity is determined not only by the pore-forming alpha subunit but also by its auxiliary beta subunits, cytoskeleton, and by Ca2+ signaling and trafficking proteins. Remodeling of this protein complex and intracellular signaling pathways may lead to alterations of I(NaL) in pathological conditions. Increased I(NaL) and the corresponding Na+ influx in failing myocardium contribute to abnormal repolarization and an increased cell Ca2+ load. Interventions designed to correct I(NaL) rescue normal repolarization and improve Ca2+ handling and contractility of the failing cardiomyocytes. New therapeutic strategies to target both arrhythmias and deficient contractility in HF may not be limited to the selective inhibition of I(NaL) but also include multiple indirect, modulatory (e.g. Ca(2+)- or cytoskeleton- dependent) mechanisms of I(NaL) function.

  10. Enhanced Late Na and Ca Currents as Effective Antiarrhythmic Drug Targets

    Science.gov (United States)

    Karagueuzian, Hrayr S.; Pezhouman, Arash; Angelini, Marina; Olcese, Riccardo

    2017-01-01

    While recent advances clarified the molecular and cellular modes of action of antiarrhythmic drugs (AADs), their link to suppression of dynamical arrhythmia mechanisms remains only partially understood. The current classifications of AADs (Classes I, III, and IV) rely on blocking peak Na, K and L-type calcium currents (ICa,L), with Class II with dominant beta receptor blocking activity and Class V including drugs with diverse classes of actions. The discovery that the calcium and redox sensor, cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) enhances both the late Na (INa-L) and the late ICa,L in patients at high risk of VT/VF provided a new and a rational AAD target. Pathological rise of either or both of INa-L and late ICa,L are demonstrated to promote cellular early afterdepolarizations (EADs) and EAD-mediated triggered activity that can initiate VT/VF in remodeled hearts. Selective inhibition of the INa-L without affecting their peak transients with the highly specific prototype drug, GS-967 suppresses these EAD-mediated VT/VFs. As in the case of INa-L, selective inhibition of the late ICa,L without affecting its peak with the prototype drug, roscovitine suppressed oxidative EAD-mediated VT/VF. These findings indicate that specific blockers of the late inward currents without affecting their peaks (gating modifiers), offer a new and effective AAD class action i.e., “Class VI.” The development of safe drugs with selective Class VI actions provides a rational and effective approach to treat VT/VF particularly in cardiac conditions associated with enhanced CaMKII activity such as heart failure. PMID:28220073

  11. OPTIMIZING EUCALYPTUS PULP REFINING

    Institute of Scientific and Technical Information of China (English)

    VailManfredi

    2004-01-01

    This paper discusses the refining of bleachedeucalyptus kraft pulp (BEKP).Pilot plant tests were carded out in to optimize therefining process and to identify the effects of refiningvariables on final paper quality and process costs.The following parameters are discussed: pulpconsistency, disk pattern design, refiner speed,energy input, refiner configuration (parallel or serial)and refining intensity.The effects of refining on pulp fibers were evaluatedagainst the pulp quality properties, such as physicalstrengths, bulk, opacity and porosity, as well as theinteractions with papermaking process, such as papermachine runnability, paper breaks and refiningcontrol.The results showed that process optimization,considering pulp quality and refining costs, wereobtained when eucalyptus pulp is refined under thelowest intensity and the highest pulp consistencypossible. Changes on the operational refiningconditions will have the highest impact on totalenergy requirements (costs) without any significanteffect on final paper properties.It was also observed that classical ways to control theindustrial operation, such as those based on drainagemeasurements, do not represent the best alternative tomaximize the final paper properties neither the papermachine runability.

  12. A strategy for producing refined currents in the Equatorial Atlantic in the context of the search of the AF447 wreckage

    Science.gov (United States)

    Drévillon, Marie; Greiner, Eric; Paradis, Denis; Payan, Christophe; Lellouche, Jean-Michel; Reffray, Guillaume; Durand, Edmée; Law-Chune, Stéphane; Cailleau, Sylvain

    2013-01-01

    On the night of 1st June 2009, a Rio-Paris Air France flight (AF447) disappeared in a highly variable and poorly observed part of the western tropical Atlantic Ocean. The first debris was located 5 days after the accident. Several reverse drift computations were conducted in order to define the likely position of the wreckage. Unfortunately, the performance of the operational ocean analyses available in the region of interest ranges from 80 to 100 km of positioning error after 5 days of inverse drift computation. In preparation of the third phase of research of the wreckage at sea, a series of numerical experiments was performed at Météo-France and Mercator Océan in an attempt to better compute the surface currents in the region and for the period of the accident of the AF447 (May and June 2009). Tailored high-resolution atmosphere and ocean reanalyses were first produced respectively at Météo-France and Mercator Océan. Several nested experiments were then performed with a small and flexible ocean model limited to the region of interest. The date of the initial conditions and the type of atmospheric forcing fields were varied in order to produce a small ensemble from which information on the sensitivity to these changes could be derived. Probabilistic and statistical combinations between model and observations were tested and a solution was finally selected by means of a comparison of drift computations with independent surface drift observations.

  13. Antiviral therapies targeting host ER alpha-glucosidases: current status and future directions.

    Science.gov (United States)

    Chang, Jinhong; Block, Timothy M; Guo, Ju-Tao

    2013-09-01

    Endoplasmic reticulum (ER)-resident α-glucosidases I and II sequentially trim the three terminal glucose moieties on N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because most viral envelope glycoproteins contain N-linked glycans, inhibition of ER α-glucosidases with derivatives of 1-deoxynojirimycin (DNJ) or castanospermine (CAST), two well-studied pharmacophores of α-glucosidase inhibitors, efficiently disrupts the morphogenesis of a broad spectrum of enveloped viruses. Moreover, both DNJ and CAST derivatives have been demonstrated to prevent the death of mice infected with several distinct flaviviruses and filoviruses and suppress the multiplication of several other species of viruses in infected animals. N-Butyl derivative of DNJ (NB-DNJ) and 6 O-bytanoyl prodrug of CAST (Bu-CAST) have been evaluated in human clinical trials for their antiviral activities against human immunodeficiency virus and hepatitis C virus, and there is an ongoing trial of treating dengue patients with Bu-CAST. This article summarizes the current status of ER α-glucosidase-targeted antiviral therapy and proposes strategies for development of more efficacious and specific ER α-glucosidase inhibitors as broad-spectrum, drug resistance-refractory antiviral therapeutics. These host function-targeted, broad-spectrum antiviral agents do not rely on time-consuming etiologic diagnosis, and should therefore be particularly promising in the management of viral hemorrhagic fever and respiratory tract viral infections, medical conditions that can be caused by many different enveloped RNA viruses, with a short window for medical intervention.

  14. Current advances in biomarkers for targeted therapy in triple-negative breast cancer

    Directory of Open Access Journals (Sweden)

    Fleisher B

    2016-10-01

    Full Text Available Brett Fleisher,1 Charlotte Clarke,2 Sihem Ait-Oudhia1 1Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, FL, 2Department of Translational Research, UT MD Anderson Cancer Center, Houston, TX, USA Abstract: Triple-negative breast cancer (TNBC is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-­8; cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the glucocorticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC. Keywords: anti-cancer directed pharmacotherapy, difficult

  15. Refined Semilattices of Semigroups

    Institute of Scientific and Technical Information of China (English)

    Liang Zhang; K.P. Shum; Ronghua Zhang

    2001-01-01

    In this paper, we introduce the concept of refined semilattices of semigroups. This is a modified concept of the generally strong semilattice of semigroups initiated by Zhang and Huang. By using the concept of generally strong semilattice, Zhang and Huang showed that a regular band can be expressed by a generally strong semilattice of rectangular bands. However, the proof of the associativity for the multiplication is not complete and there exist some gaps in their construction of regular bands. We now revise the generally strong semilattices and call them refined semilattices. In this way, we are able to remove the gaps,and the associative law of the multiplication can be verified. As an application, we prove that a band is regular if and only if it is a refined semilattice of rectangular bands. In fact, refined semilattices provide a new device in the construction of new semigroups from the old ones.

  16. Emergence of liposome as targeted magic bullet for inflammatory disorders: current state of the art.

    Science.gov (United States)

    Rahman, Mahfoozur; Kumar, Vikas; Beg, Sarwar; Sharma, Gajanand; Katare, Om Prakash; Anwar, Firoz

    2016-11-01

    Inflammatory diseases are considered to be highly dreadful ones responsible for higher mortality in the developed countries. This includes cancer, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. The tremendous strides in the area of drug development to find newer molecules like non-steroidal and steroidal agents and immunosuppressant agents delivered by conventional formulation. These therapy have enhances the life expectancy of patient, but it provide the therapeutic benefits only to a limited extent. Recent advancement in liposomes based nanomedicines has led to the possibility of improves the efficacy and safety of the pharmacotherapy of inflammatory disorders. Of late, liposomes have been highly explored as one of the promising systems for delivering numerous anti-inflammatory drugs for attaining enhanced therapeutic outcomes. Over the conventional carriers, liposomal systems have numerous drug delivery merits including advantages in both passive and active targeting of drug molecules to the inflammatory lesions. The current review article, therefore, endeavors to provide a bird's eye view account on the success of liposome-based therapeutic systems in the management of dreadful inflammatory disorders along with updated knowledge to pharmaceutical scientists in the field.

  17. Targeting breast cancer through its microenvironment : Current status of preclinical and clinical research in finding relevant targets

    NARCIS (Netherlands)

    Nienhuis, H. H.; Gaykema, S. B. M.; Timmer-Bosscha, H.; Jalving, M.; Brouwers, A. H.; Lub-de Hooge, M. N.; van der Vegt, B.; Overmoyer, B.; de Vries, E. G. E.; Schroder, C. P.

    2015-01-01

    It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the mi

  18. Refinement by interface instantiation

    DEFF Research Database (Denmark)

    Hallerstede, Stefan; Hoang, Thai Son

    2012-01-01

    be easily refined. Our first contribution hence is a proposal for a new construct called interface that encapsulates the external variables, along with a mechanism for interface instantiation. Using the new construct and mechanism, external variables can be refined consistently. Our second contribution...... is an approach for verifying the correctness of Event-B extensions using the supporting Rodin tool. We illustrate our approach by proving the correctness of interface instantiation....

  19. NAFTA opportunities: Petroleum refining

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-01

    The North American Free Trade Agreement (NAFTA) creates a more transparent environment for the sale of refined petroleum products to Mexico, and locks in access to Canada's relatively open market for these products. Canada and Mexico are sizable United States export markets for refined petroleum products, with exports of $556 million and $864 million, respectively, in 1992. These markets represent approximately 24 percent of total U.S. exports of these goods.

  20. Refinement Modal Logic

    CERN Document Server

    Bozzelli, Laura; French, Tim; Hales, James; Pinchinat, Sophie

    2012-01-01

    In this paper we present refinement modal logic. A refinement is like a bisimulation, except that from the three relational requirements only 'atoms' and 'back' need to be satisfied. Our logic contains a new operator 'forall' in additional to the standard modalities 'Box' for each agent. The operator 'forall' acts as a quantifier over the set of all refinements of a given model. We call it the refinement operator. As a variation on a bisimulation quantifier, it can be seen as a refinement quantifier over a variable not occurring in the formula bound by the operator. The logic combines the simplicity of multi-agent modal logic with some powers of monadic second order quantification. We present a sound and complete axiomatization of multiagent refinement modal logic. We also present an extension of the logic to the modal mu-calculus, and an axiomatization for the single-agent version of this logic. Examples and applications are also discussed: to software verification and design (the set of agents can also be s...

  1. Targeted contrast agents--an adjunct to whole-body imaging: current concepts.

    Science.gov (United States)

    Foran, Paul; Bolster, Ferdia; Crosbie, Ian; MacMahon, Peter; O'Kennedy, Richard; Eustace, Stephen J

    2010-03-01

    This article reviews the potential use of a combination of whole-body imaging and targeted contrast agents in improving diagnostics, with a particular focus on oncology imaging. It looks at the rationale for nanoparticles and their development as targeted contrast agents. It subsequently describes many of the advances made thus far in developing tissue-specific contrast agents capable of targeting tumors that combined with whole-body imaging may enable superior cancer detection and characterization.

  2. Promising targets and current clinical trials in metastatic non-squamous NSCLC

    Directory of Open Access Journals (Sweden)

    Alona eZer

    2014-11-01

    Full Text Available Lung adenocarcinoma is the most rapidly increasing subtype of lung cancer today. With the discovery of EGFR mutations and ALK rearrangements and targeted therapy, personalized medicine has become a reality for patients with lung adenocarcinoma. Here we review potential additional targets and novel therapies of interest in lung adenocarcinoma including targets within the cell surface (receptor tyrosine kinases EGFR, HER2, RET, ROS1, MET, TRK, targets in intracellular pathways (ALK, RAS-RAF-MEK, PI3K-AKT-PTEN, WNT, nuclear targets such as PARP, HSP90 and histone deacetylase, and selected pathways in the tumour environment. With the evolving ability to identify specific molecular aberrations in patient tumours in routine practice, our ability to further personalize therapy in lung adenocarcinoma is rapidly expanding.

  3. Refining and petrochemicals

    Energy Technology Data Exchange (ETDEWEB)

    Constancio, Silva

    2006-07-01

    In 2004, refining margins showed a clear improvement that persisted throughout the first three quarters of 2005. This enabled oil companies to post significantly higher earnings for their refining activity in 2004 compared to 2003, with the results of the first half of 2005 confirming this trend. As for petrochemicals, despite a steady rise in the naphtha price, higher cash margins enabled a turnaround in 2004 as well as a clear improvement in oil company financial performance that should continue in 2005, judging by the net income figures reported for the first half-year. Despite this favorable business environment, capital expenditure in refining and petrochemicals remained at a low level, especially investment in new capacity, but a number of projects are being planned for the next five years. (author)

  4. [Current strategies in the treatment of renal-cell cancer: targeted therapies].

    Science.gov (United States)

    Trigo, José Manuel; Bellmunt, Joaquim

    2008-03-22

    Renal-cell carcinoma represents 95% of all renal tumours. The Von Hippel-Lindau (VHL) tumor-suppressor gene is mutated or silenced in most clear cell renal carcinomas. pVHL loss results in the stabilization of the heterodimeric transcription factor hypoxia-inducible factor (HIF) and enhanced transactivation of HIF target genes. HIF itself has been difficult to inhibit with drug-like molecules although a number of agents that indirectly inhibit HIF, including mTOR (mammalian target of rapamycin) inhibitors, have been identified. Moreover, a number of drugs have been developed that target HIF-responsive gene products, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), implicated in tumor angiogenesis. Many of these targeted therapies, especially sunitinib, have demonstrated significant activity in kidney cancer clinical trials and represent a substantive advance in the treatment of this disease.

  5. Small targeted cytotoxics: current state and promises from DNA-encoded chemical libraries.

    Science.gov (United States)

    Krall, Nikolaus; Scheuermann, Jörg; Neri, Dario

    2013-01-28

    The targeted delivery of potent cytotoxic agents has emerged as a promising strategy for the treatment of cancer and other serious conditions. Traditionally, antibodies against markers of disease have been used as drug-delivery vehicles. More recently, lower molecular weight ligands have been proposed for the generation of a novel class of targeted cytotoxics with improved properties. Advances in this field crucially rely on efficient methods for the identification and optimization of organic molecules capable of high-affinity binding and selective recognition of target proteins. The advent of DNA-encoded chemical libraries allows the construction and screening of compound collections of unprecedented size. In this Review, we survey developments in the field of small ligand-based targeted cytotoxics and show how innovative library technologies will help develop the drugs of the future.

  6. Targeted Therapy for Older Patients with Uncontrolled Severe Asthma: Current and Future Prospects.

    Science.gov (United States)

    de Roos, E W; In 't Veen, J C C M; Braunstahl, G-J; Lahousse, L; Brusselle, G G O

    2016-09-01

    Severe asthma in the elderly places a high burden on affected individuals and society. Emerging therapies target specific phenotypes of the asthma disease spectrum, and can be beneficial for older asthmatics, albeit their response might be altered due to age-related characteristics. Paradoxically, these characteristics are often ground for exclusion from clinical trials. The question thus arises how the senior asthmatic population can successfully enter the era of targeted therapy. Therefore, we highlight characteristics of this population relevant to effective treatment, and review the evidence for targeted therapy in elderly patients. For targeted therapy it is important to account for aging, as this affects the distribution of phenotypes (e.g. late-onset asthma, non-eosinophilic asthma) and may alter biomarkers and drug metabolism. Elderly asthmatics suffer from age-related comorbidities and subsequent polypharmacy. A systematic search into targeted asthma therapy yielded no randomized clinical trials dedicated to older asthmatics. Post hoc analyses of the anti-immunoglobulin E agent omalizumab indicate similar efficacy in both younger and older adults. Conference abstracts on anti-interleukin-5 and anti-interleukin-13 therapy suggest even more pronounced effects of targeted treatments in late-onset disease and in asthmatic patients 65 years or older, but full reports are lacking. For non-eosinophilic asthma in the elderly, there is not yet high-level evidence for targeted therapy, but macrolides may offer a viable option. In conclusion, there is a gap in knowledge regarding the effect of older age on the safety and efficacy of targeted asthma therapy. Further investigations in the elderly are needed, with special emphasis on both late-onset asthma and therapeutics for non-eosinophilic asthma.

  7. Incremental Bisimulation Abstraction Refinement

    DEFF Research Database (Denmark)

    Godskesen, Jens Christian; Song, Lei; Zhang, Lijun

    2013-01-01

    an abstraction refinement approach for the probabilistic computation tree logic (PCTL), which is based on incrementally computing a sequence of may- and must-quotient automata. These are induced by depth-bounded bisimulation equivalences of increasing depth. The approach is both sound and complete, since...

  8. Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

    Science.gov (United States)

    Siafaka, Panoraia I.; Üstündağ Okur, Neslihan; Karavas, Evangelos; Bikiaris, Dimitrios N.

    2016-01-01

    Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined. PMID:27589733

  9. TARGET:?

    National Research Council Canada - National Science Library

    James M Acton

    2014-01-01

      By 2003. as military planners had become worried that the country's long-range conventional weapons, such as cruise missiles, might be too slow to reach hypothetical distant targets that needed to be struck urgently...

  10. Ion current extracted from a self ignition plasma around the target immersed in a pulsed rf ICP methane plasma

    Science.gov (United States)

    Tanaka, Takeshi; Watanabe, Satoshi; Mizuno, Giichiro; Takagi, Toshinori; Yoshida, Mitsuhiro; Horibe, Hiroshi; Yukimura, Ken

    2003-05-01

    When a pulsed voltage is applied to a target immersed in plasma, the surrounding medium of the target is self-ignited under an appropriate discharge condition. For a three-dimensional substrate, ion implantation and deposition of the plasma species are promising to be uniformly attained by the self-ignition plasma. A retained dose of conformal ion implantation may increase with the self-ignition plasma generated in the target-immersed plasma. Ion are extracted from both the target-immersed plasma and the self-ignition plasma. In this research, a stainless steel target with a diameter of 140 mm and a thickness of 18 mm was immersed in a pulsed inductively coupled methane plasma to which a pulse voltage of -400 V to -10 kV with a width of 12 μs was repeatedly applied. The self-ignition plasma was generated at the voltage higher than about -1.2 kV. It was found that the shape of the current waveform changes by varying the applied voltage due to the change of the current from the self-ignition plasma.

  11. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions.

    Science.gov (United States)

    Lee, Dae-Won; Lee, Kyung-Hun; Kim, Jin Wook; Keam, Bhumsuk

    2016-07-05

    Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.

  12. Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions

    Directory of Open Access Journals (Sweden)

    Dae-Won Lee

    2016-07-01

    Full Text Available Leptomeningeal carcinomatosis (LMC is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR-targeted therapy or an anaplastic lymphoma kinase (ALK inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma. Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC.

  13. ORAL COLON TARGETED DRUG DELIVERY SYSTEM: A REVIEW ON CURRENT AND NOVEL PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    Asija Rajesh

    2012-10-01

    Full Text Available Small intestine is mostly the site for drug absorption but in some cases the drug needs to be targeted to colon due to some factors like local colonic disease, degradation related conditions, delayed release of drugs, systemic delivery of protein and peptide drugs etc. Colon targeted drug delivery is important and relatively new concept for the absorption of drugs because it offers almost neutral pH and long residence time, thereby increasing the drug absorption. Colon has proved to be a site for the absorption of poorly soluble drugs. For the successful targeting of drugs to colon the dosage form should be designed such that it prevents the drug release in upper GIT and releasing it in the colonic region. This review article discusses in brief about introduction of colon along with the novel and emerging technologies for colon targeting of drug molecule. Treatment of these diseases with colon-specific drug delivery system provides an interesting alternative over systemic drug administration because of lower dosing and fewer systemic side effects.

  14. Targeting Oral and Cultural Proficiency for Medical Personnel: An Examination of Current Medical Spanish Textbooks

    Science.gov (United States)

    Hardin, Karol

    2012-01-01

    Demand for medical Spanish courses has grown with the rising needs of Spanish-speaking patients in the United States, but while there is no shortage of beginning medical Spanish textbooks, very few target the intermediate level. This article examines eighteen medical Spanish texts published in the last twenty years with respect to seven factors:…

  15. Policy Dialogue and Target Setting: Do Current Indicators of Education for All Signify Progress?

    Science.gov (United States)

    Lewin, Keith M.

    2011-01-01

    Governments and development agencies met at Jomtien in 1990 and Dakar in 2000 and committed themselves to achieve "Education for All" (EFA). Most aid to education is now the umbrella of EFA and its associated goals, targets and indicators. This paper selects some of the indicators used for EFA and analyses their strengths and weaknesses. Gross and…

  16. Perspicuity and Granularity in Refinement

    CERN Document Server

    Boiten, Eerke

    2011-01-01

    This paper reconsiders refinements which introduce actions on the concrete level which were not present at the abstract level. It draws a distinction between concrete actions which are "perspicuous" at the abstract level, and changes of granularity of actions between different levels of abstraction. The main contribution of this paper is in exploring the relation between these different methods of "action refinement", and the basic refinement relation that is used. In particular, it shows how the "refining skip" method is incompatible with failures-based refinement relations, and consequently some decisions in designing Event-B refinement are entangled.

  17. Current idea of an algorithm for drug treatment and optimal succession of using targeted drugs

    Directory of Open Access Journals (Sweden)

    D. A. Nosov

    2014-11-01

    Full Text Available The application of targeted and pathogenetically sound medicational approaches could considerably improve the results of therapy in patients with metastatic renal-cell carcinoma (mRCC. To date, VEGF/VEGFR inhibitors continue to remain a basic and most effective drug treatment in patients with mRCC and the choice of a drug for first-line therapy is based on the following factors: disease prognosis, a patient’s general somatic state, and the understanding of immediate therapy goals, anticipated toxicity and tolerability.Most patients develop resistance to VEGFR inhibitors within 6–11 months after treatment initiation. The basis for resistance development may be the following mechanisms: activation of alternative proangiogenic signaling pathways, that of angiogenesis-independent progression pathways, a microenvironment-induced phenotypic change of tumor cells to form their resistance to targeted drugs, and pharmacokinetic and pharmacodynamic changes in the drug itself during therapy. To overcome resistance to VEGFR inhibitors, there are 2 possible options: 1 switching to a drug having another mechanism of action (the mTOR inhibitor everolimus; 2 that to a more selective and potent tyrosine kinase inhibitor (axitinib that selectively affects and suppresses the activityof the same targets – VEGFR (Vascular Endothelial Growth Factor Receptor 1–3. As before, there is scanty convincing evidence for unique benefits in a particular succession of targeted drugs: a VEGFR inhibitor – a VEGFR inhibitor or a VEGFR inhibitor – an mТOR inhibitor. In a number of cases, the succession of prescribing of targeted drugs may be practically determined by clinical criteria, specifically by the possibility of controlling toxic complications that may be typical for VEFGR inhibitors and may accumulate in case of their successive use. It must be also remembered that VEGFR inhibitors may be successfully reused in patients who have received second- or

  18. Current idea of an algorithm for drug treatment and optimal succession of using targeted drugs

    Directory of Open Access Journals (Sweden)

    D. A. Nosov

    2014-01-01

    Full Text Available The application of targeted and pathogenetically sound medicational approaches could considerably improve the results of therapy in patients with metastatic renal-cell carcinoma (mRCC. To date, VEGF/VEGFR inhibitors continue to remain a basic and most effective drug treatment in patients with mRCC and the choice of a drug for first-line therapy is based on the following factors: disease prognosis, a patient’s general somatic state, and the understanding of immediate therapy goals, anticipated toxicity and tolerability.Most patients develop resistance to VEGFR inhibitors within 6–11 months after treatment initiation. The basis for resistance development may be the following mechanisms: activation of alternative proangiogenic signaling pathways, that of angiogenesis-independent progression pathways, a microenvironment-induced phenotypic change of tumor cells to form their resistance to targeted drugs, and pharmacokinetic and pharmacodynamic changes in the drug itself during therapy. To overcome resistance to VEGFR inhibitors, there are 2 possible options: 1 switching to a drug having another mechanism of action (the mTOR inhibitor everolimus; 2 that to a more selective and potent tyrosine kinase inhibitor (axitinib that selectively affects and suppresses the activityof the same targets – VEGFR (Vascular Endothelial Growth Factor Receptor 1–3. As before, there is scanty convincing evidence for unique benefits in a particular succession of targeted drugs: a VEGFR inhibitor – a VEGFR inhibitor or a VEGFR inhibitor – an mТOR inhibitor. In a number of cases, the succession of prescribing of targeted drugs may be practically determined by clinical criteria, specifically by the possibility of controlling toxic complications that may be typical for VEFGR inhibitors and may accumulate in case of their successive use. It must be also remembered that VEGFR inhibitors may be successfully reused in patients who have received second- or

  19. Refinement for Administrative Policies

    OpenAIRE

    Dekker, MAC; Etalle, S Sandro

    2007-01-01

    Flexibility of management is an important requisite for access control systems as it allows users to adapt the access control system in accordance with practical requirements. This paper builds on earlier work where we defined administrative policies for a general class of RBAC models. We present a formal definition of administrative refinnement and we show that there is an ordering for administrative privileges which yields administrative refinements of policies. We argue (by giving an examp...

  20. Current status and future perspectives of PSMA-targeted therapy in Europe: opportunity knocks

    Energy Technology Data Exchange (ETDEWEB)

    Pfestroff, A.; Luster, M. [University Hospital Marburg, Department of Nuclear Medicine, Marburg (Germany); Jilg, C.A. [University Hospital Freiburg, Department of Urology, Freiburg (Germany); Olbert, P.J. [University Hospital Marburg, Department of Urology, Marburg (Germany); Ohlmann, C.H. [Saarland University Hospital, Department of Urology, Homburg/Saar (Germany); Lassmann, M. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maecke, H.R. [University Hospital Freiburg, Department of Nuclear Medicine and Radiopharmacy, Freiburg (Germany); Ezziddin, S. [Saarland University Hospital, Department of Nuclear Medicine, Homburg/Saar (Germany); Bodei, L. [European Institute of Oncology, Department of Nuclear Medicine, Milan (Italy); Collaboration: on behalf of the Radionuclide Therapy Committee of the European Association of Nuclear Medicine

    2015-12-15

    {sup 177}Lu-based PSMA-targeted therapy appears to be a promising treatment for advanced PCA. However, lessons should be learned from PRRT of neuroendocrine tumours, which was referred to as a ''promising'' tool for 15 years before the advent of evidence-based comparative studies. This experience strongly suggests that the communities involved with PSMA-targeted therapy, namely nuclear medicine, urology, radiochemistry, and medical physics, should capitalize without delay on the great opportunity to conduct well-designed prospective studies. Doing so should advance this modality from the proof-of principle stage to the potential standard-of-Care-stage. From our perspective, crucial components of this process are: - Harmonization of therapy protocols - Implementation of a patient selection algorithm into clinical routine - Standardization of toxicity assessment - Establishment of standardized dosimetry protocols to assess safety and efficacy - Transfer of expertise in PSMA therapy throughout Europe - Regulatory approval of {sup 177}Lu-PSMA-targeted compounds.

  1. Targeted Therapy of FLT3 in Treatment of AML—Current Status and Future Directions

    Directory of Open Access Journals (Sweden)

    Caroline Benedicte Nitter Engen

    2014-12-01

    Full Text Available Internal tandem duplications (ITDs of the gene encoding the Fms-Like Tyrosine kinase-3 (FLT3 receptor are present in approximately 25% of patients with acute myeloid leukemia (AML. The mutation is associated with poor prognosis, and the aberrant protein product has been hypothesized as an attractive therapeutic target. Various tyrosine kinase inhibitors (TKIs have been developed targeting FLT3, but in spite of initial optimism the first generation TKIs tested in clinical studies generally induce only partial and transient hematological responses. The limited treatment efficacy generally observed may be explained by numerous factors; extensively pretreated and high risk cohorts, suboptimal pharmacodynamic and pharmacokinetic properties of the compounds, acquired TKI resistance, or the possible fact that inhibition of mutated FLT3 alone is not sufficient to avoid disease progression. The second-generation agent quizartinb is showing promising outcomes and seems better tolerated and with less toxic effects than traditional chemotherapeutic agents. Therefore, new generations of TKIs might be feasible for use in combination therapy or in a salvage setting in selected patients. Here, we sum up experiences so far, and we discuss the future outlook of targeting dysregulated FLT3 signaling in the treatment of AML.

  2. Current Status of Studies on Targeted Therapy for Renal Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shaoqi Wang; Shaoxiang Wang; Juan Wang

    2008-01-01

    Renal cell carcinoma (RCC) is regarded as one of the most refractory malignancies. A further study of the molecular mechanism of RCC formation has led to a series of successful examples for treatment of patients with advanced RCC. Over the past 20 years, a nonspecific immunotherapy, with cytokines, has been employed as the gold standard for therapy of metastatic RCC. However, with scientific development and clinical testing of new drugs, targeted molecular cancer therapy has become a focus of interest. At the same time, with a better understanding of RCC,the treatment method has converged on anti-vascular endothelial growth factor (VEGF) and related molecular-targeted pathways.A large amount of research and numerous clinical trials have demonstrated the clinical efficacy of the targeted molecular therapies in patients with metastatic RCC. For example sorafenib and sunitinib were approved, in 2005 and 2006 respectively, by the U.S. FDA for treating advanced RCC. In this report, issues such as the importance of VEGF in RCC and the studies of bevacizumab,sunitinib and sorafenib in treating metastatic RCC etc., are reviewed.

  3. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    Institute of Scientific and Technical Information of China (English)

    Anil; Suri; Nirmala; Jagadish; Shikha; Saini; Namita; Gupta

    2015-01-01

    Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

  4. Current therapeutic leads for the treatment of melanoma: targeted immunotherapy in the post-genomic era.

    Science.gov (United States)

    Papanastasiou, Anastasios D; Sirinian, Chaido; Kalofonos, Haralabos P; Repanti, Maria

    2014-01-01

    Metastatic melanoma has a poor prognosis and until today most therapeutic approaches are ineffective. Advances in molecular pathology and genome analysis technologies have led to the identification of genetic events and immune regulatory checkpoints that provide novel targets for pharmaceutical intervention in melanoma. Development of selective mitogen-activated kinase (MAPK) pathway inhibitors was the first major achievement coming from genetic studies that identified a constitutively active MAP kinase pathway and BRAF activating mutations in melanoma. At the same time, the manipulation of immune system checkpoints through monoclonal antibodies changed clinical practice and led to further improvement of patient outcomes. In an effort to further develop melanoma targeted therapies that depend on the genetic profile of a given patient, high-throughput genome wide approaches (next-generation sequencing [NGS], gene arrays, etc) have been employed for the characterization of genetic alterations in the patient's tumor. In the near future, the combined information from the genetic and immune background of an individual will provide the basis for a personalized, highly targeted approach in the treatment of melanoma.

  5. Grain Refinement of Deoxidized Copper

    Science.gov (United States)

    Balart, María José; Patel, Jayesh B.; Gao, Feng; Fan, Zhongyun

    2016-10-01

    This study reports the current status of grain refinement of copper accompanied in particular by a critical appraisal of grain refinement of phosphorus-deoxidized, high residual P (DHP) copper microalloyed with 150 ppm Ag. Some deviations exist in terms of the growth restriction factor ( Q) framework, on the basis of empirical evidence reported in the literature for grain size measurements of copper with individual additions of 0.05, 0.1, and 0.5 wt pct of Mo, In, Sn, Bi, Sb, Pb, and Se, cast under a protective atmosphere of pure Ar and water quenching. The columnar-to-equiaxed transition (CET) has been observed in copper, with an individual addition of 0.4B and with combined additions of 0.4Zr-0.04P and 0.4Zr-0.04P-0.015Ag and, in a previous study, with combined additions of 0.1Ag-0.069P (in wt pct). CETs in these B- and Zr-treated casts have been ascribed to changes in the morphology and chemistry of particles, concurrently in association with free solute type and availability. No further grain-refining action was observed due to microalloying additions of B, Mg, Ca, Zr, Ti, Mn, In, Fe, and Zn (~0.1 wt pct) with respect to DHP-Cu microalloyed with Ag, and therefore are no longer relevant for the casting conditions studied. The critical microalloying element for grain size control in deoxidized copper and in particular DHP-Cu is Ag.

  6. Synergistic effect of bias and target currents for magnetron sputtered MoS{sub 2}-Ti composite films

    Energy Technology Data Exchange (ETDEWEB)

    Buelbuel, Ferhat; Efeoglu, Ihsan [Ataturk Univ., Erzurum (Turkey). Dept. of Mechanical Engineering

    2016-07-01

    In terms of modification of the properties of MoS{sub 2}-Ti composite films, especially tribological properties, significant advances have recently been recorded. However, the commercially production of MoS{sub 2}-Ti composite films is still limited, because the production of desirable MoS{sub 2}-Ti composite coating is only possible by using closed field unbalanced magnetron systems and by the selection of convenient deposition parameters. This requirement has focused the researchers' attention on optimization of deposition parameters. This study is concentrating on the effect of the bias voltage and the target currents for MoS{sub 2}-Ti composite films deposited by pulsed magnetron sputtering (PMS). It is found that the bias and the target currents clearly affect the mechanical, structural and tribological properties of MoS{sub 2}-Ti films.

  7. 国外成品油管道运输发展现状与启示%The Current Situation of Pipeline Transportation of Overseas Refined Oil and Its Implications

    Institute of Scientific and Technical Information of China (English)

    张兆吉; 欧毅; 李应晓

    2012-01-01

    The pipeline transportation of the refined oil has many advantages.At the present stage,although the pipeline transportation network of the refined oil is gradually matured,there still exist aspects to be improved.Based on the research of the distribution of the overseas pipeline transportation of the refined oil,the paper puts forward a scientific and reasonable suggestion to map out the construction of the pipeline transportation of the refined oil in the future,which can better improves the productive and marketing efficiency of our refined oil.The study is of profound significance.%成品油管道运输有诸多明显优势,现阶段我国成品油运输管网正逐步走向成熟,但仍有部分不完善之处。本文通过对国外成品油管道运输分布情况的研究,提出科学合理规划我国未来成品油管网建设的建议,可更好地提高我国成品油的生产、销售等环节效率,研究内容具有重要而长远的意义。

  8. Current understanding of BRAF alterations in diagnosis, prognosis and therapeutic targeting in paediatric low grade gliomas

    Directory of Open Access Journals (Sweden)

    Catherine Louise Penman

    2015-03-01

    Full Text Available The mitogen-activated protein kinase (MAPK pathway is known to play a key role in the initiation and maintenance of many tumours as well as normal development. This often occurs through mutation of the genes encoding RAS and RAF proteins which are involved in signal transduction in this pathway. BRAF is one of three RAF kinases which act as downstream effectors of growth factor signalling leading to cell cycle progression, proliferation and survival. Initially reported as a point mutation (V600E in the majority of metastatic melanomas, other alterations in the BRAF gene have now been reported in a variety of human cancers including papillary thyroid cancer, colon carcinomas, hairy cell leukaemia and more recently in gliomas. The identification of oncogenic mutations in the BRAF gene have led to a revolution in the treatment of metastatic melanoma using targeted molecular therapies that affect the MAPK pathway either directly through BRAF inhibition or downstream through inhibition of MEK. This review describes the molecular biology of BRAF in the context of paediatric low grade gliomas, the role of BRAF as a diagnostic marker, the prognostic implications of BRAF and evidence for therapeutic targeting of BRAF.

  9. Past and current perspective on new therapeutic targets for Type-II diabetes.

    Science.gov (United States)

    Patil, Pradip D; Mahajan, Umesh B; Patil, Kalpesh R; Chaudhari, Sandip; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

    2017-01-01

    Loss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Recently, United Kingdom Prospective Diabetes Study reported that Type-II DM is a progressive disorder. Although, DM can be treated initially by monotherapy with oral agent; eventually, it may require multiple drugs. Additionally, insulin therapy is needed in many patients to achieve glycemic control. Pharmacological approaches are unsatisfactory in improving the consequences of insulin resistance. Single therapeutic approach in the treatment of Type-II DM is unsuccessful and usually a combination therapy is adopted. Increased understanding of biochemical, cellular and pathological alterations in Type-II DM has provided new insight in the management of Type-II DM. Knowledge of underlying mechanisms of Type-II DM development is essential for the exploration of novel therapeutic targets. Present review provides an insight into therapeutic targets of Type-II DM and their role in the development of insulin resistance. An overview of important signaling pathways and mechanisms in Type-II DM is provided for the better understanding of disease pathology. This review includes case studies of drugs that are withdrawn from the market. The experience gathered from previous studies and knowledge of Type-II DM pathways can guide the anti-diabetic drug development toward the discovery of clinically viable drugs that are useful in Type-II DM.

  10. Lowering serum lipids via PCSK9-targeting drugs: current advances and future perspectives

    Science.gov (United States)

    He, Ni-ya; Li, Qing; Wu, Chun-yan; Ren, Zhong; Gao, Ya; Pan, Li-hong; Wang, Mei-mei; Wen, Hong-yan; Jiang, Zhi-sheng; Tang, Zhi-han; Liu, Lu-shan

    2017-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9), also known as neural apoptosis regulated convertase (NARC1), is a key modulator of cholesterol metabolism. PCSK9 increases the serum concentration of low-density lipoprotein cholesterol by escorting low-density lipoprotein receptors (LDLRs) from the membrane of hepatic cells into lysosomes, where the LDLRs are degraded. Owing to the importance of PCSK9 in lipid metabolism, considerable effort has been made over the past decade in developing drugs targeting PCSK9 to lower serum lipid levels. Nevertheless, some problems and challenges remain. In this review we first describes the structure and function of PCSK9 and its gene polymorphisms. We then discuss the various designs of pharmacological targets of PCSK9, including those that block the binding of PCSK9 to hepatic LDLRs (mimetic peptides, adnectins, and monoclonal antibodies), inhibit PCSK9 expression (the clustered regularly interspaced short palindromic repeats/Cas9 platform, small molecules, antisense oligonucleotides, and small interfering RNAs), and interfere with PCSK9 secretion. Finally, this review highlights future challenges in this field, including safety concerns associated with PCSK9 monoclonal antibodies, the limited utility of PCSK9 inhibitors in the central nervous system, and the cost-effectiveness of PCSK9 inhibitors. PMID:28112180

  11. The targeted heating and current drive applications for the ITER electron cyclotron system

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, M.; Darbos, C.; Gandini, F.; Gassmann, T.; Loarte, A.; Omori, T.; Purohit, D. [ITER Organization, Route de Vinon-sur-Verdon, CS 90 046, 13067 St. Paul Lez Durance Cedex (France); Saibene, G.; Gagliardi, M. [Fusion for Energy, Josep Pla 2, Barcelona 08019 (Spain); Farina, D.; Figini, L. [Istituto di Fisica del Plasma CNR, 20125 Milano (Italy); Hanson, G. [US ITER Project Office, ORNL, 1055 Commerce Park, PO Box 2008, Oak Ridge, Tennessee 37831 (United States); Poli, E. [Max-Planck-Institut für Plasmaphysik, D-85748 Garching (Germany); Takahashi, K. [Japan Atomic Energy Agency (JAEA), Naka, Ibaraki 311-0193 (Japan)

    2015-02-15

    A 24 MW Electron Cyclotron (EC) system operating at 170 GHz and 3600 s pulse length is to be installed on ITER. The EC plant shall deliver 20 MW of this power to the plasma for Heating and Current Drive (H and CD) applications. The EC system is designed for plasma initiation, central heating, current drive, current profile tailoring, and Magneto-hydrodynamic control (in particular, sawteeth and Neo-classical Tearing Mode) in the flat-top phase of the plasma. A preliminary design review was performed in 2012, which identified a need for extended application of the EC system to the plasma ramp-up, flattop, and ramp down phases of ITER plasma pulse. The various functionalities are prioritized based on those applications, which can be uniquely addressed with the EC system in contrast to other H and CD systems. An initial attempt has been developed at prioritizing the allocated H and CD applications for the three scenarios envisioned: ELMy H-mode (15 MA), Hybrid (∼12 MA), and Advanced (∼9 MA) scenarios. This leads to the finalization of the design requirements for the EC sub-systems.

  12. Hirshfeld atom refinement.

    Science.gov (United States)

    Capelli, Silvia C; Bürgi, Hans-Beat; Dittrich, Birger; Grabowsky, Simon; Jayatilaka, Dylan

    2014-09-01

    Hirshfeld atom refinement (HAR) is a method which determines structural parameters from single-crystal X-ray diffraction data by using an aspherical atom partitioning of tailor-made ab initio quantum mechanical molecular electron densities without any further approximation. Here the original HAR method is extended by implementing an iterative procedure of successive cycles of electron density calculations, Hirshfeld atom scattering factor calculations and structural least-squares refinements, repeated until convergence. The importance of this iterative procedure is illustrated via the example of crystalline ammonia. The new HAR method is then applied to X-ray diffraction data of the dipeptide Gly-l-Ala measured at 12, 50, 100, 150, 220 and 295 K, using Hartree-Fock and BLYP density functional theory electron densities and three different basis sets. All positions and anisotropic displacement parameters (ADPs) are freely refined without constraints or restraints - even those for hydrogen atoms. The results are systematically compared with those from neutron diffraction experiments at the temperatures 12, 50, 150 and 295 K. Although non-hydrogen-atom ADPs differ by up to three combined standard uncertainties (csu's), all other structural parameters agree within less than 2 csu's. Using our best calculations (BLYP/cc-pVTZ, recommended for organic molecules), the accuracy of determining bond lengths involving hydrogen atoms from HAR is better than 0.009 Å for temperatures of 150 K or below; for hydrogen-atom ADPs it is better than 0.006 Å(2) as judged from the mean absolute X-ray minus neutron differences. These results are among the best ever obtained. Remarkably, the precision of determining bond lengths and ADPs for the hydrogen atoms from the HAR procedure is comparable with that from the neutron measurements - an outcome which is obtained with a routinely achievable resolution of the X-ray data of 0.65 Å.

  13. SGLT 2 Inhibitors: A New Therapeutic Target And Its Role In Current Clinical Practice

    Directory of Open Access Journals (Sweden)

    PV Shiji

    2015-10-01

    Full Text Available Diabetes, one of the major life style diseases, is associated with high morbidity and mortality owing to its microvascular and macrovascular complications. The chance of development of various complications can be effectively prevented by tight glycemic control. We have various groups of drugs like Biguanides, Sulfonyl ureas, Glitazones, Alpha-glucosidase inhibitors, Incretin based therapy, Insulin and Insulin analogues in the armamentarium to treat diabetes. But still, the number of patients attaining glycemic targets are relatively low and various adverse effect limit the use of some of these drugs, especially in special groups. Hence there is ongoing research to develop newer and newer drugs which provide sustained blood glucose reduction with minimal adverse effects. SGLT-2 inhibitors are a new group of drugs recently approved by FDA to treat Diabetes. In this review we discuss about mechanism of action, various adverse effects and the clinical role of various SGLT-2 Inhibitors.

  14. Targeting heart failure with preserved ejection fraction: current status and future prospects

    Directory of Open Access Journals (Sweden)

    Kanwar M

    2016-04-01

    Full Text Available Manreet Kanwar, Claire Walter, Megan Clarke, Maria Patarroyo-Aponte Department of Cardiology, Allegheny General Hospital, Pittsburgh, PA, USA Abstract: Heart failure with preserved ejection fraction (HFpEF portrays a significant burden in terms of prevalence, morbidity, mortality, and health care costs. There is a lack of consensus on the basic pathophysiology, definition, and therapeutic targets for therapy for this syndrome. To date, there are no approved therapies available for reducing mortality or hospitalization for these patients. Several clinical trials have recently started to try and bridge this major gap. There is an urgent need to focus on drug and device development for HFpEF as well as to understand HFpEF pathophysiology. Keywords: HFpEF therapies, diastolic dysfunction

  15. Refining and petrochemicals

    Energy Technology Data Exchange (ETDEWEB)

    Benazzi, E.; Alario, F

    2004-07-01

    In 2003, refining margins showed a clear improvement that continued throughout the first three quarters of 2004. Oil companies posted significantly higher earnings in 2003 compared to 2002, with the results of first quarter 2004 confirming this trend. Due to higher feedstock prices, the implementation of new capacity and more intense competition, the petrochemicals industry was not able to boost margins in 2003. In such difficult business conditions, aggravated by soaring crude prices, the petrochemicals industry is not likely to see any improvement in profitability before the second half of 2004. (author)

  16. Refining and petrochemicals

    Energy Technology Data Exchange (ETDEWEB)

    Benazzi, E

    2003-07-01

    Down sharply in 2002, refining margins showed a clear improvement in the first half-year of 2003. As a result, the earnings reported by oil companies for financial year 2002 were significantly lower than in 2001, but the prospects are brighter for 2003. In the petrochemicals sector, slow demand and higher feedstock prices eroded margins in 2002, especially in Europe and the United States. The financial results for the first part of 2003 seem to indicate that sector profitability will not improve before 2004. (author)

  17. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management.

    Science.gov (United States)

    Woodruff, Prescott G; Agusti, Alvar; Roche, Nicolas; Singh, Dave; Martinez, Fernando J

    2015-05-02

    Chronic obstructive pulmonary disease (COPD) is a common, complex, and heterogeneous disorder that is responsible for substantial and growing morbidity, mortality, and health-care expense worldwide. Of imperative importance to decipher the complexity of COPD is to identify groups of patients with similar clinical characteristics, prognosis, or therapeutic needs, the so-called clinical phenotypes. This strategy is logical for research but might be of little clinical value because clinical phenotypes can overlap in the same patient and the same clinical phenotype could result from different biological mechanisms. With the goal to match assessment with treatment choices, the latest iteration of guidelines from the Global Initiative for Chronic Obstructive Lung Disease reorganised treatment objectives into two categories: to improve symptoms (ie, dyspnoea and health status) and to decrease future risk (as predicted by forced expiratory volume in 1 s level and exacerbations history). This change thus moves treatment closer to individualised medicine with available bronchodilators and anti-inflammatory drugs. Yet, future treatment options are likely to include targeting endotypes that represent subtypes of patients defined by a distinct pathophysiological mechanism. Specific biomarkers of these endotypes would be particularly useful in clinical practice, especially in patients in which clinical phenotype alone is insufficient to identify the underlying endotype. A few series of potential COPD endotypes and biomarkers have been suggested. Empirical knowledge will be gained from proof-of-concept trials in COPD with emerging drugs that target specific inflammatory pathways. In every instance, specific endotype and biomarker efforts will probably be needed for the success of these trials, because the pathways are likely to be operative in only a subset of patients. Network analysis of human diseases offers the possibility to improve understanding of disease pathobiological

  18. Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

    Science.gov (United States)

    Ruffini, Giulio; Fox, Michael D; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

    2014-04-01

    Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general

  19. Adaptive mesh refinement for storm surge

    KAUST Repository

    Mandli, Kyle T.

    2014-03-01

    An approach to utilizing adaptive mesh refinement algorithms for storm surge modeling is proposed. Currently numerical models exist that can resolve the details of coastal regions but are often too costly to be run in an ensemble forecasting framework without significant computing resources. The application of adaptive mesh refinement algorithms substantially lowers the computational cost of a storm surge model run while retaining much of the desired coastal resolution. The approach presented is implemented in the GeoClaw framework and compared to ADCIRC for Hurricane Ike along with observed tide gauge data and the computational cost of each model run. © 2014 Elsevier Ltd.

  20. Adaptive Mesh Refinement for Storm Surge

    CERN Document Server

    Mandli, Kyle T

    2014-01-01

    An approach to utilizing adaptive mesh refinement algorithms for storm surge modeling is proposed. Currently numerical models exist that can resolve the details of coastal regions but are often too costly to be run in an ensemble forecasting framework without significant computing resources. The application of adaptive mesh refinement algorithms substantially lowers the computational cost of a storm surge model run while retaining much of the desired coastal resolution. The approach presented is implemented in the \\geoclaw framework and compared to \\adcirc for Hurricane Ike along with observed tide gauge data and the computational cost of each model run.

  1. IDH1 and IDH2 mutations as novel therapeutic targets: current perspectives

    Directory of Open Access Journals (Sweden)

    Mondesir J

    2016-09-01

    Full Text Available Johanna Mondesir1,2 Christophe Willekens3–5 Mehdi Touat6,7 Stéphane de Botton3–5 1Service d’Immunopathologie Clinique, Hôpital Saint Louis, 2CNRS UMR8104, INSERM U1016, Institut Cochin, Université Paris Descartes, Paris, 3Gustave Roussy, Université Paris-Saclay, Service d’Hématologie Clinique, 4INSERM U1170, Gustave Roussy, Université Paris-Saclay, Villejuif, 5Faculté de médecine Paris-Sud, Kremlin-Bicêtre, 6AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière – Charles Foix, Service de Neurologie 2-Mazarin, Paris, 7Gustave Roussy, Université Paris‑Saclay, Département d’Innovation Thérapeutique et d’Essais Précoces, Villejuif, France Abstract: Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2 are key metabolic enzymes that convert isocitrate to α-ketoglutarate. IDH1/2 mutations define distinct subsets of cancers, including low-grade gliomas and secondary glioblastomas, chondrosarcomas, intrahepatic cholangiocarcinomas, and hematologic malignancies. Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in the accumulation and secretion in vast excess of an oncometabolite, the D-2-hydroxyglutarate (D-2HG. Overproduction of D-2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis. Indeed, high levels of D-2HG inhibit α-ketoglutarate-dependent dioxygenases, including histone and DNA demethylases, leading to histone and DNA hypermethylation and finally a block in cell differentiation. Furthermore, D-2HG is a biomarker suitable for the detection of IDH1/2 mutations at diagnosis and predictive of the clinical response. Finally, mutant-IDH1/2 enzymes inhibitors have entered clinical trials for patients with IDH1/2 mutations and represent a novel drug class for targeted therapy. Keywords: tumor metabolism, epigenetic, oncogene, IDH1, IDH2, glioma, acute myeloid leukemia, 2-HG, targeted therapies

  2. Current Challenges in Prostate Cancer Management and the Rationale behind Targeted Focal Therapy

    Directory of Open Access Journals (Sweden)

    Al B. Barqawi

    2012-01-01

    Full Text Available Among men, prostate cancer has a high prevalence, with relatively lower cancer-specific mortality risk compared to lung and colon cancer. Prostate-specific antigen (PSA screening has increased prostate cancer awareness since its implementation as a screening tool almost 25 years ago, but, due to the largely indolent course of this disease and the unspecific nature of the PSA test, increased incidence has largely been associated with cancers that would not go on to cause death (clinically insignificant, leading to an overdiagnosis challenge and an ensuing overtreatment consequences. The overtreatment problem is exacerbated by the high risk of side effects that current treatment techniques have, putting patients’ quality of life at risk with little or no survival benefit. The goals of this paper are to evaluate the rise, prevalence, and impact of the overdiagnosis and ensuing overtreatment problems, as well as highlight potential solutions. In this effort, a review of major epidemiological and screening studies, cancer statistics from the advent of prostate-specific antigen screening to the present, and reports on patient concerns and treatment outcomes was conducted to present the dominant factors that underlie current challenges in prostate cancer treatment and illuminate potential solutions.

  3. Macromolecular crystallographic estructure refinement

    Directory of Open Access Journals (Sweden)

    Afonine, Pavel V.

    2015-04-01

    Full Text Available Model refinement is a key step in crystallographic structure determination that ensures final atomic structure of macromolecule represents measured diffraction data as good as possible. Several decades have been put into developing methods and computational tools to streamline this step. In this manuscript we provide a brief overview of major milestones of crystallographic computing and methods development pertinent to structure refinement.El refinamiento es un paso clave en el proceso de determinación de una estructura cristalográfica al garantizar que la estructura atómica de la macromolécula final represente de la mejor manera posible los datos de difracción. Han hecho falta varias décadas para poder desarrollar nuevos métodos y herramientas computacionales dirigidas a dinamizar esta etapa. En este artículo ofrecemos un breve resumen de los principales hitos en la computación cristalográfica y de los nuevos métodos relevantes para el refinamiento de estructuras.

  4. Single photon production induced by (anti)neutrino neutral current scattering on nucleons and nuclear targets

    Energy Technology Data Exchange (ETDEWEB)

    Alvarez-Ruso, L.; Nieves, J. [Instituto de Física Corpuscular (IFIC), Centro Mixto CSIC-Universidad de Valencia, Institutos de Investigación de Paterna, E-46071 Valencia (Spain); Wang, E. [Instituto de Física Corpuscular (IFIC), Centro Mixto CSIC-Universidad de Valencia, Institutos de Investigación de Paterna, E-46071 Valencia (Spain); Department of Physics, Zhengzhou University, Zhengzhou, Henan 450001 (China)

    2015-10-15

    We review our theoretical approach to neutral current photon emission on nucleons and nuclei in the few-GeV energy region, relevant for neutrino oscillation experiments. These reactions are dominated by the weak excitation of the Δ(1232) resonance but there are also important non-resonant contributions. We have also included terms mediated by nucleon excitations from the second resonance region. On nuclei, Pauli blocking, Fermi motion and the in-medium Δ resonance broadening have been taken into account for both incoherent and coherent reaction channels. With this model, the number and distributions of photon events at the MiniBooNE and T2K experiments have been obtained. We have also compared to the NOMAD upper limit at higher energies. The implications of our findings and future perspectives are discussed.

  5. Single photon production induced by (anti)neutrino neutral current scattering on nucleons and nuclear targets

    CERN Document Server

    Alvarez-Ruso, L; Wang, E

    2015-01-01

    We review our theoretical approach to neutral current photon emission on nucleons and nuclei in the few-GeV energy region, relevant for neutrino oscillation experiments. These reactions are dominated by the weak excitation of the $\\Delta(1232)$ resonance but there are also important non-resonant contributions. We have also included terms mediated by nucleon excitations from the second resonance region. On nuclei, Pauli blocking, Fermi motion and the in-medium $\\Delta$ resonance broadening have been taken into account for both incoherent and coherent reaction channels. With this model, the number and distributions of photon events at the MiniBooNE and T2K experiments have been obtained. We have also compared to the NOMAD upper limit at higher energies. The implications of our findings and future perspectives are discussed.

  6. Hirshfeld atom refinement

    Directory of Open Access Journals (Sweden)

    Silvia C. Capelli

    2014-09-01

    Full Text Available Hirshfeld atom refinement (HAR is a method which determines structural parameters from single-crystal X-ray diffraction data by using an aspherical atom partitioning of tailor-made ab initio quantum mechanical molecular electron densities without any further approximation. Here the original HAR method is extended by implementing an iterative procedure of successive cycles of electron density calculations, Hirshfeld atom scattering factor calculations and structural least-squares refinements, repeated until convergence. The importance of this iterative procedure is illustrated via the example of crystalline ammonia. The new HAR method is then applied to X-ray diffraction data of the dipeptide Gly–l-Ala measured at 12, 50, 100, 150, 220 and 295 K, using Hartree–Fock and BLYP density functional theory electron densities and three different basis sets. All positions and anisotropic displacement parameters (ADPs are freely refined without constraints or restraints – even those for hydrogen atoms. The results are systematically compared with those from neutron diffraction experiments at the temperatures 12, 50, 150 and 295 K. Although non-hydrogen-atom ADPs differ by up to three combined standard uncertainties (csu's, all other structural parameters agree within less than 2 csu's. Using our best calculations (BLYP/cc-pVTZ, recommended for organic molecules, the accuracy of determining bond lengths involving hydrogen atoms from HAR is better than 0.009 Å for temperatures of 150 K or below; for hydrogen-atom ADPs it is better than 0.006 Å2 as judged from the mean absolute X-ray minus neutron differences. These results are among the best ever obtained. Remarkably, the precision of determining bond lengths and ADPs for the hydrogen atoms from the HAR procedure is comparable with that from the neutron measurements – an outcome which is obtained with a routinely achievable resolution of the X-ray data of 0.65 Å.

  7. Targeting the Glutamatergic System to Treat Pathological Gambling: Current Evidence and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Mauro Pettorruso

    2014-01-01

    Full Text Available Pathological gambling or gambling disorder has been defined by the DSM-5 as a behavioral addiction. To date, its pathophysiology is not completely understood and there is no FDA-approved treatment for gambling disorders. Glutamate is the principal excitatory neurotransmitter in the nervous system and it has been recently involved in the pathophysiology of addictive behaviors. In this paper, we review the current literature on a class of drugs that act as modulating glutamate system in PG. A total of 19 studies have been included, according to inclusion and exclusion criteria. Clinical trial and case series using glutamatergic drugs (N-acetylcysteine, memantine, amantadine, topiramate, acamprosate, baclofen, gabapentin, pregabalin, and modafinil will be presented to elucidate the effectiveness on gambling behaviors and on the related clinical dimensions (craving, withdrawal, and cognitive symptoms in PG patients. The results have been discussed to gain more insight in the pathophysiology and treatment of PG. In conclusion, manipulation of glutamatergic neurotransmission appears to be promising in developing improved therapeutic agents for the treatment of gambling disorders. Further studies are required. Finally, we propose future directions and challenges in this research area.

  8. [School shootings in Germany: current trends in the prevention of severe, targeted violence in German schools].

    Science.gov (United States)

    Bondü, Rebecca; Scheithauer, Herbert

    2009-01-01

    In March and September 2009 the school shootings in Winnenden and Ansbach once again demonstrated the need for preventive approaches in order to prevent further offences in Germany. Due to the low frequency of such offences and the low specificity of relevant risk factors known so far, prediction and prevention seems difficult though. None the less, several preventive approaches are currently discussed. The present article highlights these approaches and their specific advantages and disadvantages. As school shootings are multicausally determined, approaches focussing only on single aspects (i.e. prohibiting violent computer games or further strengthening gun laws) do not meet requirements. Other measures such as installing technical safety devices or optimizing actions of police and school attendants are supposed to reduce harm in case of emergency. Instead, scientifically founded and promising preventive approaches focus on secondary prevention and for this purpose employ the threat assessment approach, which is widespread within the USA. In this framework, responsible occupational groups such as teachers, school psychologists and police officers are to be trained in identifying students' warning signs, judging danger of these students for self and others in a systematic process and initiating suitable interventions.

  9. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives

    Directory of Open Access Journals (Sweden)

    Ozaki E

    2015-01-01

    Full Text Available Ema Ozaki,1 Matthew Campbell,1 Sarah L Doyle2,3 1Department of Genetics, 2Department of Clinical Medicine, School of Medicine, Trinity College Dublin, 3National Children's Research Centre, Our Lady's Children's Hospital Crumlin, Dublin, Ireland Abstract: The inflammasome is a molecular platform formed by activation of an innate immune pattern recognition receptor seed, such as NLRP3. Once activated, NLRP3 recruits the adapter ASC (apoptosis-related speck-like protein containing a caspase recruitment domain, which in turn recruits procaspase-1. Procaspase-1 autocatalyzes its cleavage and activation, resulting in maturation of the precursor forms of interleukin (IL-1β and IL-18 into active proinflammatory cytokines and initiation of pyroptotic cell death. The NLRP3 inflammasome has been implicated in the pathogenesis of a wide variety of diseases, including genetically inherited autoinflammatory conditions as well as chronic diseases in which NLRP3 is abnormally activated. The NLRP3 inflammasome has been linked to diseases such as Alzheimer's disease, atherosclerosis, metabolic syndrome, and age-related macular degeneration. In this review, we describe the NLRP3 inflammasome complex and its activation in disease, and detail the current therapies that modulate either the NLRP3 inflammasome complex itself or the two cytokines it is responsible for activating, ie, IL-1β and IL-18. Keywords: NLRP3, interleukin-1, interleukin-18, caspase-1, therapeutics, inflammasome

  10. Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

    Directory of Open Access Journals (Sweden)

    Hohenforst-Schmidt W

    2013-07-01

    through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR negative stage IIIa–IV International Union Against Cancer 7 (UICC-7, and with Eastern Cooperative Oncology Group (ECOG 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of

  11. Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer.

    Science.gov (United States)

    Haque, Absarul; Alam, Qamre; Alam, Mohammad Zubair; Azhar, Esam I; Sait, Khalid Hussain Wali; Anfinan, Nisrin; Mushtaq, Gohar; Kamal, Mohammad Amjad; Rasool, Mahmood

    2016-01-01

    Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors.

  12. Targeting PD-1/PD-L1 in lung cancer: current perspectives

    Directory of Open Access Journals (Sweden)

    González-Cao M

    2015-07-01

    Full Text Available María González-Cao,1 Niki Karachaliou,1 Santiago Viteri,1 Daniela Morales-Espinosa,1 Cristina Teixidó,2 Jesús Sánchez Ruiz,3 Miquel Ángel Molina-Vila,2 Mariacarmela Santarpia,4 Rafael Rosell1,2,5,61Translational Cancer Research Unit, Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain; 2Pangaea Biotech SL, Barcelona, Spain; 3Centro Nacional de Investigación Oncología (CNIO, Madrid, Spain; 4Medical Oncology Unit, Human Pathology Department, University of Messina, Messina, Italy; 5Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Campus Can Ruti, Badalona, Barcelona, Spain; 6Fundación Molecular Oncology Research, Barcelona, SpainAbstract: Increased understanding of tumor immunology has led to the development of effective immunotherapy treatments. One of the most important advances in this field has been due to pharmacological design of antibodies against immune checkpoint inhibitors. Anti-PD-1/PD-L1 antibodies are currently in advanced phases of clinical development for several tumors, including lung cancer. Results from Phase I–III trials with anti-PD-1/PD-L1 antibodies in non-small-cell lung cancer have demonstrated response rates of around 20% (range, 16%–50%. More importantly, responses are long-lasting (median duration of response, 18 months and fast (50% of responses are detected at time of first tumor evaluation with very low grade 3–4 toxicity (less than 5%. Recently, the anti-PD-1 antibody pembrolizumab received US Food and Drug Administration (FDA breakthrough therapy designation for treatment of non-small-cell lung cancer, supported by data from a Phase Ib trial. Another anti-PD-1 antibody, nivolumab, has also been approved for lung cancer based on survival advantage demonstrated in recently released data from a Phase III trial in squamous cell lung cancer.Keywords: immunotherapy, immunoncology

  13. C-Met as a potential target for the treatment of gastrointestinal cancer: Current status and future perspectives.

    Science.gov (United States)

    Bahrami, Afsane; Shahidsales, Soodabeh; Khazaei, Majid; Ghayour-Mobarhan, Majid; Maftouh, Mina; Hassanian, Seyed Mahdi; Avan, Amir

    2017-10-01

    Aberrant activation of the HGF/c-Met signalling pathways is shown to be related with cell proliferation, progression, metastasis, and worse prognosis in several tumor types, including gastrointestinal cancers, suggesting its value as a stimulating-target for cancer-therapy. Several approaches have been developed for targeting HGF and/or c-Met, and one of them, crizotinib (dual c-Met/ALK inhibitor), is recently been approved by FDA for lung-cancers with ALK-rearrangement. The main aim of current review is to give an overview on the role of c-Met/HGF pathway in gastrointestinal cancer, in preclinical and clinical trials. Although several important matters is still remained to be elucidated on the molecular pathways underlying the antitumor effects of this therapy in gastrointestinal-cancers. Further investigations are warranted to recognize the main determinants of the activity of c-Met inhibitors, for parallel targeting signalling pathway associated/activated via MET/HGF pathway or in response to the cell resistance to anti-c-Met agents. Additionally, identification of patients that might benefit from therapy could help to increase the selectivity and efficacy of the therapy. © 2017 Wiley Periodicals, Inc.

  14. Structure refinement of astrophyllite

    Institute of Scientific and Technical Information of China (English)

    MA; Zhesheng

    2001-01-01

    [1]Abdel-Fattah M. Abdel-Rahman., Mineral chemistry and paragenesis of astrophyllite from Egypt, Mineralogical Magazine, 1992, 56: 17-26.[2]Liu Yan, Ma Zhesheng, Han Xiuling et al, Astrophyllite from the Namjabarwa Area, Eastern Tibet, Acta Petrologica et Mineralogica, 1997,16(4): 338-340.[3]Peng Zhizhong, Ma Zhesheng, The crystal structure of astrophyllite (in Russian), Scientia Sinica, 1963, 12(2): 272-276.[4]Pen Zhizhong, Ma Zhesheng, The crystal structure of Tricinic Mangano-astrophyllite (in Russian), Scientia Sinica (Scien-ce in China), 1964, 13(7): 1180-1183.[5]Shi Nicheng, Ma Zhesheng, Li Guowu et al., Stucyure Refinement of Monoclinic astrophyllite, Acta Crystallographica, Section B, 1998, B54: 109-114.[6]Woodrow, P. J., The Crystal structure of astrophyllite, Acta Crystallographica, 1967, 22: 673-678.[7]СеменовЕ. И., Куплетскит-Новый Минерал Группы Астрофиллита, ДАН, 1956, 108(5), 933-936.[8]Nickel, E. H., Rowland, J. E., Charette, D. J., Niobophyllite the niobium analogue of astrophyllite: A new mineral from Sead Laxe Labrador, Canad. Mine., 1964, 8(1): 40.[9]X-Ray Laboratory of Hubei Geologic College, The crystal chemistry of astrophyllite group minerals (in Chinese), Scientia Geologica Sinica, 1974, (1): 18-30.[10]Sheldrick, G. M., Program for the solution of crystal structures, SHELX86, University of G?ttingen, 1985, Germany.[11]Sheldrick, G. M., Program for the refinement of crystal structures, SHELXL93, University of G?ttingen, 1993, Germany.[12]Liebau, F., Structural Chemistry of Silicates Structure, Bonding, and Classification, Heidelberg: Springer-Verlag QD181, S6L614, 1985.[13]Ferraris, G., Ivaldi, G., Khomyakov, A. P. et al., Nafertisite, a layer titanosilicate member of a polysomatic series including mica, Eur. J. Mineral.,1996, 8: 241-249.[14]Ferraris, G., Polysomatism as a tool for correlating properties and structure, in EMU Notes in

  15. Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

    Directory of Open Access Journals (Sweden)

    Simone Mocellin

    Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

  16. Targeted Therapy Database (TTD): A Model to Match Patient's Molecular Profile with Current Knowledge on Cancer Biology

    Science.gov (United States)

    Mocellin, Simone; Shrager, Jeff; Scolyer, Richard; Pasquali, Sandro; Verdi, Daunia; Marincola, Francesco M.; Briarava, Marta; Gobbel, Randy; Rossi, Carlo; Nitti, Donato

    2010-01-01

    Background The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. Objective To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. Methods To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. Results and Conclusions We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit

  17. INTERACTION OF RADIATION WITH MATTER. LASER PLASMA: Increase in the amplitude of hf currents during exposure of a neutral target to microsecond CO2 laser pulses

    Science.gov (United States)

    Antipov, A. A.; Losev, Leonid L.; Meshalkin, E. A.

    1988-09-01

    High-frequency electric currents were generated by irradiation of a metal target with CO2 laser pulses. It was found that the region where the ambient gas was photoionized had a decisive influence on the hf current amplitude. A method for increasing the amplitude of the current by creating an auxiliary laser jet on the target was proposed and used. An hf current of up to 1 A amplitude was observed at a frequency of 75 MHz and this current lasted for 1.5 μs.

  18. Protein structure refinement by optimization.

    Science.gov (United States)

    Carlsen, Martin; Røgen, Peter

    2015-09-01

    Knowledge-based protein potentials are simplified potentials designed to improve the quality of protein models, which is important as more accurate models are more useful for biological and pharmaceutical studies. Consequently, knowledge-based potentials often are designed to be efficient in ordering a given set of deformed structures denoted decoys according to how close they are to the relevant native protein structure. This, however, does not necessarily imply that energy minimization of this potential will bring the decoys closer to the native structure. In this study, we introduce an iterative strategy to improve the convergence of decoy structures. It works by adding energy optimized decoys to the pool of decoys used to construct the next and improved knowledge-based potential. We demonstrate that this strategy results in significantly improved decoy convergence on Titan high resolution decoys and refinement targets from Critical Assessment of protein Structure Prediction competitions. Our potential is formulated in Cartesian coordinates and has a fixed backbone potential to restricts motions to be close to those of a dihedral model, a fixed hydrogen-bonding potential and a variable coarse grained carbon alpha potential consisting of a pair potential and a novel solvent potential that are b-spline based as we use explicit gradient and Hessian for efficient energy optimization.

  19. Integrating Climate Change Resilience Features into the Incremental Refinement of an Existing Marine Park

    Science.gov (United States)

    Beckley, Lynnath E.; Kobryn, Halina T.; Lombard, Amanda T.; Radford, Ben; Heyward, Andrew

    2016-01-01

    Marine protected area (MPA) designs are likely to require iterative refinement as new knowledge is gained. In particular, there is an increasing need to consider the effects of climate change, especially the ability of ecosystems to resist and/or recover from climate-related disturbances, within the MPA planning process. However, there has been limited research addressing the incorporation of climate change resilience into MPA design. This study used Marxan conservation planning software with fine-scale shallow water (<20 m) bathymetry and habitat maps, models of major benthic communities for deeper water, and comprehensive human use information from Ningaloo Marine Park in Western Australia to identify climate change resilience features to integrate into the incremental refinement of the marine park. The study assessed the representation of benthic habitats within the current marine park zones, identified priority areas of high resilience for inclusion within no-take zones and examined if any iterative refinements to the current no-take zones are necessary. Of the 65 habitat classes, 16 did not meet representation targets within the current no-take zones, most of which were in deeper offshore waters. These deeper areas also demonstrated the highest resilience values and, as such, Marxan outputs suggested minor increases to the current no-take zones in the deeper offshore areas. This work demonstrates that inclusion of fine-scale climate change resilience features within the design process for MPAs is feasible, and can be applied to future marine spatial planning practices globally. PMID:27529820

  20. Crystal structure refinement with SHELXL

    Energy Technology Data Exchange (ETDEWEB)

    Sheldrick, George M., E-mail: gsheldr@shelx.uni-ac.gwdg.de [Department of Structural Chemistry, Georg-August Universität Göttingen, Tammannstraße 4, Göttingen 37077 (Germany)

    2015-01-01

    New features added to the refinement program SHELXL since 2008 are described and explained. The improvements in the crystal structure refinement program SHELXL have been closely coupled with the development and increasing importance of the CIF (Crystallographic Information Framework) format for validating and archiving crystal structures. An important simplification is that now only one file in CIF format (for convenience, referred to simply as ‘a CIF’) containing embedded reflection data and SHELXL instructions is needed for a complete structure archive; the program SHREDCIF can be used to extract the .hkl and .ins files required for further refinement with SHELXL. Recent developments in SHELXL facilitate refinement against neutron diffraction data, the treatment of H atoms, the determination of absolute structure, the input of partial structure factors and the refinement of twinned and disordered structures. SHELXL is available free to academics for the Windows, Linux and Mac OS X operating systems, and is particularly suitable for multiple-core processors.

  1. Parallel Adaptive Mesh Refinement

    Energy Technology Data Exchange (ETDEWEB)

    Diachin, L; Hornung, R; Plassmann, P; WIssink, A

    2005-03-04

    As large-scale, parallel computers have become more widely available and numerical models and algorithms have advanced, the range of physical phenomena that can be simulated has expanded dramatically. Many important science and engineering problems exhibit solutions with localized behavior where highly-detailed salient features or large gradients appear in certain regions which are separated by much larger regions where the solution is smooth. Examples include chemically-reacting flows with radiative heat transfer, high Reynolds number flows interacting with solid objects, and combustion problems where the flame front is essentially a two-dimensional sheet occupying a small part of a three-dimensional domain. Modeling such problems numerically requires approximating the governing partial differential equations on a discrete domain, or grid. Grid spacing is an important factor in determining the accuracy and cost of a computation. A fine grid may be needed to resolve key local features while a much coarser grid may suffice elsewhere. Employing a fine grid everywhere may be inefficient at best and, at worst, may make an adequately resolved simulation impractical. Moreover, the location and resolution of fine grid required for an accurate solution is a dynamic property of a problem's transient features and may not be known a priori. Adaptive mesh refinement (AMR) is a technique that can be used with both structured and unstructured meshes to adjust local grid spacing dynamically to capture solution features with an appropriate degree of resolution. Thus, computational resources can be focused where and when they are needed most to efficiently achieve an accurate solution without incurring the cost of a globally-fine grid. Figure 1.1 shows two example computations using AMR; on the left is a structured mesh calculation of a impulsively-sheared contact surface and on the right is the fuselage and volume discretization of an RAH-66 Comanche helicopter [35]. Note the

  2. Amyloid Beta and Tau Proteins as Therapeutic Targets for Alzheimer’s Disease Treatment: Rethinking the Current Strategy

    Directory of Open Access Journals (Sweden)

    Siddhartha Mondragón-Rodríguez

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is defined by the concurrence of accumulation of abnormal aggregates composed of two proteins: Amyloid beta (Aβ and tau, and of cellular changes including neurite degeneration and loss of neurons and cognitive functions. Based on their strong association with disease, genetically and pathologically, it is not surprising that there has been a focus towards developing therapies against the aggregated structures. Unfortunately, current therapies have but mild benefit. With this in mind we will focus on the relationship of synaptic plasticity with Aβ and tau protein and their role as potential targets for the development of therapeutic drugs. Finally, we will provide perspectives in developing a multifactorial strategy for AD treatment.

  3. Adjoint Methods for Guiding Adaptive Mesh Refinement in Tsunami Modeling

    Science.gov (United States)

    Davis, B. N.; LeVeque, R. J.

    2016-12-01

    One difficulty in developing numerical methods for tsunami modeling is the fact that solutions contain time-varying regions where much higher resolution is required than elsewhere in the domain, particularly when tracking a tsunami propagating across the ocean. The open source GeoClaw software deals with this issue by using block-structured adaptive mesh refinement to selectively refine around propagating waves. For problems where only a target area of the total solution is of interest (e.g., one coastal community), a method that allows identifying and refining the grid only in regions that influence this target area would significantly reduce the computational cost of finding a solution. In this work, we show that solving the time-dependent adjoint equation and using a suitable inner product with the forward solution allows more precise refinement of the relevant waves. We present the adjoint methodology first in one space dimension for illustration and in a broad context since it could also be used in other adaptive software, and potentially for other tsunami applications beyond adaptive refinement. We then show how this adjoint method has been integrated into the adaptive mesh refinement strategy of the open source GeoClaw software and present tsunami modeling results showing that the accuracy of the solution is maintained and the computational time required is significantly reduced through the integration of the adjoint method into adaptive mesh refinement.

  4. Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

    Science.gov (United States)

    Mahan, Charles E

    2015-04-01

    Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

  5. Device Architecture and Materials for Organic Light-Emitting Devices Targeting High Current Densities and Control of the Triplet Concentration

    CERN Document Server

    Schols, Sarah

    2011-01-01

    Device Architecture and Materials for Organic Light-Emitting Devices focuses on the design of new device and material concepts for organic light-emitting devices, thereby targeting high current densities and an improved control of the triplet concentration. A new light-emitting device architecture, the OLED with field-effect electron transport, is demonstrated. This device is a hybrid between a diode and a field-effect transistor. Compared to conventional OLEDs, the metallic cathode is displaced by one to several micrometers from the light-emitting zone, reducing optical absorption losses. The electrons injected by the cathode accumulate at an organic heterojunction and are transported to the light-emission zone by field-effect. High mobilities for charge carriers are achieved in this way, enabling a high current density and a reduced number of charge carriers in the device. Pulsed excitation experiments show that pulses down to 1 µs can be applied to this structure without affecting the light intensity, sug...

  6. Computer technology in oil refining: cost or benefit

    Energy Technology Data Exchange (ETDEWEB)

    Payne, B. (KBC Process Technology (GB))

    1990-04-01

    There is undoubtedly a commitment in the oil refining industry to computerise wherever possible, and to develop advanced mathematical modelling techniques to improved profitability. However, many oil refiners are now asking themselves whether computer solutions are a cost, or are truly a benefit to their organisation. Problems have been caused by distributed computing running out of control in many organisations. This has been partly brought to reign recently, by advanced networking of PCs along with mainframe facilities, and development of management information systems with common data bases for all users to build their applications on. Implementation of information technology strategies helped many refiners to plan the way ahead for the future. The use of computers across the refining sector in the current marketplace is reviewed. The conclusion drawn is that although computer technology is a cost it can also be ranked as a significant benefit and success in the refining industry at present. (author).

  7. Crystal structure refinement with SHELXL.

    Science.gov (United States)

    Sheldrick, George M

    2015-01-01

    The improvements in the crystal structure refinement program SHELXL have been closely coupled with the development and increasing importance of the CIF (Crystallographic Information Framework) format for validating and archiving crystal structures. An important simplification is that now only one file in CIF format (for convenience, referred to simply as `a CIF') containing embedded reflection data and SHELXL instructions is needed for a complete structure archive; the program SHREDCIF can be used to extract the .hkl and .ins files required for further refinement with SHELXL. Recent developments in SHELXL facilitate refinement against neutron diffraction data, the treatment of H atoms, the determination of absolute structure, the input of partial structure factors and the refinement of twinned and disordered structures. SHELXL is available free to academics for the Windows, Linux and Mac OS X operating systems, and is particularly suitable for multiple-core processors.

  8. On Modal Refinement and Consistency

    DEFF Research Database (Denmark)

    Nyman, Ulrik; Larsen, Kim Guldstrand; Wasowski, Andrzej

    2007-01-01

    Almost 20 years after the original conception, we revisit several fundamental question about modal transition systems. First, we demonstrate the incompleteness of the standard modal refinement using a counterexample due to Hüttel. Deciding any refinement, complete with respect to the standard...... notions of implementation, is shown to be computationally hard (co-NP hard). Second, we consider four forms of consistency (existence of implementations) for modal specifications. We characterize each operationally, giving algorithms for deciding, and for synthesizing implementations, together...

  9. Current data of targeted therapies for the treatment of triple-negative advanced breast cancer: empiricism or evidence-based?

    Science.gov (United States)

    Petrelli, Fausto; Cabiddu, Mary; Ghilardi, Mara; Barni, Sandro

    2009-10-01

    Approximately 10 - 15% of breast carcinomas (BCs) are known to be 'triple-negative (TN) receptor' (i.e., not expressing ER or PR and not exhibiting overexpression and/or gene amplification of HER2-neu). Triple-negative BCs comprise approximately 85% of all basal-type tumours. Classically, basal-like BCs have been characterised by low expression of ER, PR, and HER2 neu and high expression of CK5, CK14, caveolin-1, CAIX, p63, and EGFR (HER1), which reflects the mammary gland basal/myoepithelial cell component. Although there is no standard first-line chemotherapy regimen for metastatic TN BCs, anthracycline- and taxane-containing regimens are acceptable treatments. A large number of agents, including DNA-damaging agents, EGFR inhibitors, antiangiogenic agents and novel taxane formulations are currently being tested in clinical trials for first-line and pretreated patients. Limited experiences with platinum salts, poly(ADP-ribose) polymerase (PARP) inhibitors, cetuximab, bevacizumab and ixabepilone have been published in recent years and will be reported. Novel immunohistochemistry analysis for identification of basal like/TN phenotype are awaited to correctly select this population. The clinical trials investigating new agents have to be designed for a specific (and possibly large) subset of patients with BC. In the future, a gene array platform with greater sensitivity for distinguishing the various BC subtypes, as well as having the power to predict the molecular biology of the disease, will be an indispensible tool for treatment selection. Currently, treatment of TN BC is more empirical than evidence-based. The cornerstone of treatment is chemotherapy, but in the near future, novel target agents will emerge as possible partners.

  10. Measurement of multiplicity and momentum spectra in the current and target regions of the Breit frame in Deep Inelastic Scattering at HERA

    CERN Document Server

    Abbiendi, G; Abramowicz, H; Acosta, D; Adamczyk, L; Adamus, M; Ahn, S H; Amelung, C; An Shiz Hong; Anselmo, F; Antonioli, P; Arneodo, M; Bacon, Trevor C; Badgett, W F; Bailey, D C; Bailey, D S; Bamberger, A; Barbagli, G; Bari, G; Barreiro, F; Barret, O; Bashindzhagian, G L; Bashkirov, V; Basile, M; Bauerdick, L A T; Bednarek, B; Behrens, U; Beier, H; Bellagamba, L; Bertolin, A; Bhadra, S; Bienlein, J K; Blaikley, H E; Bohnet, I; Bokel, C; Bornheim, A; Borzemski, P; Boscherini, D; Botje, M; Breitweg, J; Brock, I; Bromley, J T; Brook, N H; Brugnera, R; Brümmer, N; Bruni, A; Bruni, G; Burgard, C; Burow, B D; Bussey, P J; Butterworth, J M; Bylsma, B; Caldwell, A; Capua, M; Cara Romeo, G; Carlin, R; Cartiglia, N; Cashmore, R J; Castellini, G; Catterall, C D; Chapin, D; Chekanov, S; Chwastowski, J; Ciborowski, J; Cifarelli, Luisa; Cindolo, F; Cirio, R; Cloth, P; Coboken, K; Coldewey, C; Cole, J E; Contin, A; Cooper-Sarkar, A M; Coppola, N; Cormack, C; Corradi, M; Corriveau, F; Costa, M; Cottingham, W N; Crittenden, J; Cross, R; D'Agostini, G; Dagan, S; Dal Corso, F; Dardo, M; De Pasquale, S; Deffner, R; Deppe, O; Derrick, M; Deshpande, Abhay A; Desler, K; Devenish, R C E; Dhawan, S; Dolgoshein, B A; Dosselli, U; Doyle, A T; Drews, G; Dulinski, Z; Durkin, L S; Dusini, S; Eckert, M; Edmonds, J K; Eisenberg, Y; Eisenhardt, S; Engelen, J; Epperson, D E; Ermolov, P F; Eskreys, Andrzej; Fagerstroem, C P; Fernández, J P; Ferrero, M I; Figiel, J; Filges, D; Foster, B; Foudas, C; Fox-Murphy, A; Fricke, U; Frisken, W R; Fusayasu, T; Gadaj, T; Galea, R; Gallo, E; García, G; Garfagnini, A; Gendner, N; Gialas, I; Gilmore, J; Ginsburg, C M; Giusti, P; Gladilin, L K; Glasman, C; Göbel, F; Golubkov, Yu A; Göttlicher, P; Grabosch, H J; Graciani, R; Grosse-Knetter, J; Grzelak, G; Haas, T; Hain, W; Hall-Wilton, R; Hamatsu, R; Hanna, D S; Harnew, N; Hart, J C; Hartmann, H; Hartmann, J; Hartner, G F; Hasell, D; Hayes, M E; Heaphy, E A; Heath, G P; Heath, H F; Hebbel, K; Heinloth, K; Heinz, L; Hernández, J M; Heusch, C A; Hilger, E; Hirose, T; Hochman, D; Holm, U; Homma, K; Hong, S J; Howell, G; Hughes, V W; Iacobucci, G; Iannotti, L; Iga, Y; Inuzuka, M; Ishii, T; Jakob, H P; Jelen, K; Jeoung, H Y; Jing, Z; Johnson, K F; Jones, T W; Kananov, S; Kappes, A; Karshon, U; Kasemann, M; Katz, U F; Kcira, D; Kerger, R; Khakzad, M; Khein, L A; Kim, C L; Kim, J Y; Kisielewska, D; Kitamura, S; Klanner, Robert; Klimek, K; Koch, W; Koffeman, E; Kooijman, P; Koop, T; Korotkova, N A; Korzhavina, I A; Kotanski, A; Kötz, U; Kowal, A M; Kowalski, H; Kowalski, T; Krakauer, D; Kreisel, A; Kuze, M; Kuzmin, V A; Labarga, L; Lamberti, L; Lane, J B; Laurenti, G; Lee, J H; Lee, S B; Lee, S W; Levi, G; Levman, G M; Levy, A; Lim, H; Lim, I T; Limentani, S; Lindemann, L; Ling, T Y; Liu, W; Löhr, B; Lohrmann, E; Long, K R; Lopez-Duran Viani, A; Lukina, O Yu; Ma, K J; Maccarrone, G; MacDonald, N; Magill, S; Mallik, U; Margotti, A; Marini, G; Markun, P; Martin, J F; Martínez, M; Maselli, S; Massam, Thomas; Mastroberardino, A; Matsushita, T; Mattingly, M C K; Mattingly, S E K; McCance, G J; McCubbin, N A; McFall, J D; Mellado, B; Menary, S; Meyer, A; Meyer-Larsen, A; Milewski, J; Milite, M; Miller, D B; Monaco, V; Mönig, K; Monteiro, T; Morandin, M; Moritz, M; Murray, W N; Musgrave, B; Nagano, K; Nam, S W; Nania, R; Nigro, A; Nishimura, T; Notz, D; Nowak, R J; Noyes, V A; Nylander, P; Ochs, A; Oh, B Y; Okrasinski, J R; Olkiewicz, K; Orr, R S; Pac, M Y; Padhi, S; Palmonari, F; Park, I H; Park, S K; Parsons, J A; Paul, E; Pavel, N; Pawlak, J M; Pawlak, R; Pelfer, Pier Giovanni; Pellegrino, A; Pelucchi, F; Peroni, C; Pesci, A; Petrucci, M C; Pfeiffer, M; Piccioni, D; Piotrzkowski, K; Poelz, G; Polenz, S; Polini, A; Posocco, M; Prinias, A; Proskuryakov, A S; Przybycien, M B; Puga, J; Quadt, A; Raach, H; Raso, M; Rautenberg, J; Redondo, I; Reeder, D D; Repond, J; Ritz, S; Riveline, M; Rohde, M; Rulikowska-Zarebska, E; Ruske, O; Ruspa, M; Sabetfakhri, A; Sacchi, R; Sadrozinski, H F W; Salehi, H; Sampson, S; Sartorelli, G; Saull, P R B; Savin, A A; Saxon, D H; Schechter, A; Schioppa, M; Schlenstedt, S; Schmidke, W B; Schneekloth, U; Schnurbusch, H; Schwarzer, O; Sciulli, F; Scott, J; Sedgbeer, J K; Seiden, A; Selonke, F; Shah, T P; Shcheglova, L M; Sideris, D; Sievers, M; Simmons, D; Sinclair, L E; Skillicorn, I O; Smalska, B; Smith, W H; Solano, A; Solomin, A N; Son, D; Saint-Laurent, M G; Staiano, A; Stairs, D G; Stanco, L; Stanek, R; Stifutkin, A; Stonjek, S; Straub, P B; Strickland, E; Stroili, R; Susinno, G; Suszycki, L; Sutton, M R; Suzuki, I; Tandler, J; Tapper, A D; Tapper, R J; Tassi, E; Terron, J; Tiecke, H G; Tokushuku, K; Toothacker, W S; Tsurugai, T; Tuning, N; Tymieniecka, T; Umemori, K; Vaiciulis, A W; Velthuis, J J; Verkerke, W; Voci, C; Vossebeld, Joost Herman; Votano, L; Walczak, R; Walker, R; Wang, S M; Waters, D S; Waugh, R; Weber, A; Westphal, D; Whitmore, J J; Wichmann, R; Wick, K; Wieber, H; Wiggers, L; Wildschek, T; Williams, D C; Wills, H H; Wing, M; Wodarczyk, M; Wolf, G; Wölfle, S; Wollmer, U; Wróblewski, A K; Yamada, S; Yamashita, T; Yamauchi, K; Yamazaki, Y; Yoshida, R; Youngman, C; Zajac, J; Zakrzewski, J A; Zamora Garcia, Y; Zawiejski, L; Zetsche, F; Zeuner, W; Zhu, Q; Zichichi, Antonino; Zotkin, S A; De Wolf, E; Del Peso, J; Van Sighem, A

    1999-01-01

    Charged particle production in neutral current deep inelastic scattering (DIS) has been studied using the ZEUS detector.The evolution of the mean multiplicities, scaled momenta and transverse momenta in Q^2 and x for $10 6\\times 10^{-4}$ has been investigated in the current and target fragmentation regions of the Breit frame. Distributions in the target region, using HERA data for the first time, are compared to distributions in the current region. Predictions based on MLLA and LPHD are inconsistent with the data.

  11. Zone refining of plutonium metal

    Energy Technology Data Exchange (ETDEWEB)

    Blau, Michael S. [Univ. of Idaho, Moscow, ID (United States)

    1994-08-01

    The zone refining process was applied to Pu metal containing known amounts of impurities. Rod specimens of plutonium metal were melted into and contained in tantalum boats, each of which was passed horizontally through a three-turn, high-frequency coil in such a manner as to cause a narrow molten zone to pass through the Pu metal rod 10 times. The impurity elements Co, Cr, Fe, Ni, Np, U were found to move in the same direction as the molten zone as predicted by binary phase diagrams. The elements Al, Am, and Ga moved in the opposite direction of the molten zone as predicted by binary phase diagrams. As the impurity alloy was zone refined, {delta}-phase plutonium metal crystals were produced. The first few zone refining passes were more effective than each later pass because an oxide layer formed on the rod surface. There was no clear evidence of better impurity movement at the slower zone refining speed. Also, constant or variable coil power appeared to have no effect on impurity movement during a single run (10 passes). This experiment was the first step to developing a zone refining process for plutonium metal.

  12. Monte-Carlo model development for evaluation of current clinical target volume definition for heterogeneous and hypoxic glioblastoma.

    Science.gov (United States)

    Moghaddasi, L; Bezak, E; Harriss-Phillips, W

    2016-05-07

    Clinical target volume (CTV) determination may be complex and subjective. In this work a microscopic-scale tumour model was developed to evaluate current CTV practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a Geant4 cell-based dosimetry model was developed to calculate the dose deposited in individual GBM cells. Microscopic extension probability (MEP) models were then developed using Matlab-2012a. The results of the cell-based dosimetry model and MEP models were combined to calculate survival fractions (SF) for CTV margins of 2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous radiosensitivity profiles were incorporated into the GBM model. The genetic heterogeneity was modelled using a range of α/β values (linear-quadratic model parameters) associated with different GBM cell lines. These values were distributed among the cells randomly, taken from a Gaussian-weighted sample of α/β values. Cellular oxygen pressure was distributed randomly taken from a sample weighted to profiles obtained from literature. Three types of GBM models were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous-hypoxic. The SF in different regions of the tumour model and the effect of the CTV margin extension from 2.0-2.5 cm on SFs were investigated for three MEP models. The SF within the beam was increased by up to three and two orders of magnitude following incorporation of heterogeneous radiosensitivities and hypoxia, respectively, in the GBM model. However, the total SF was shown to be overdominated by the presence of tumour cells in the penumbra region and to a lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm reduced the SF by a maximum of 78.6  ±  3.3%, 78.5  ±  3.3%, and 77.7  ±  3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs, respectively. Monte-Carlo model was developed to quantitatively evaluate SF for genetically

  13. Monte-Carlo model development for evaluation of current clinical target volume definition for heterogeneous and hypoxic glioblastoma

    Science.gov (United States)

    Moghaddasi, L.; Bezak, E.; Harriss-Phillips, W.

    2016-05-01

    Clinical target volume (CTV) determination may be complex and subjective. In this work a microscopic-scale tumour model was developed to evaluate current CTV practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a Geant4 cell-based dosimetry model was developed to calculate the dose deposited in individual GBM cells. Microscopic extension probability (MEP) models were then developed using Matlab-2012a. The results of the cell-based dosimetry model and MEP models were combined to calculate survival fractions (SF) for CTV margins of 2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous radiosensitivity profiles were incorporated into the GBM model. The genetic heterogeneity was modelled using a range of α/β values (linear-quadratic model parameters) associated with different GBM cell lines. These values were distributed among the cells randomly, taken from a Gaussian-weighted sample of α/β values. Cellular oxygen pressure was distributed randomly taken from a sample weighted to profiles obtained from literature. Three types of GBM models were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous-hypoxic. The SF in different regions of the tumour model and the effect of the CTV margin extension from 2.0-2.5 cm on SFs were investigated for three MEP models. The SF within the beam was increased by up to three and two orders of magnitude following incorporation of heterogeneous radiosensitivities and hypoxia, respectively, in the GBM model. However, the total SF was shown to be overdominated by the presence of tumour cells in the penumbra region and to a lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm reduced the SF by a maximum of 78.6  ±  3.3%, 78.5  ±  3.3%, and 77.7  ±  3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs, respectively. Monte-Carlo model was developed to quantitatively evaluate SF for genetically

  14. Bauxite Mining and Alumina Refining

    Science.gov (United States)

    Frisch, Neale; Olney, David

    2014-01-01

    Objective: To describe bauxite mining and alumina refining processes and to outline the relevant physical, chemical, biological, ergonomic, and psychosocial health risks. Methods: Review article. Results: The most important risks relate to noise, ergonomics, trauma, and caustic soda splashes of the skin/eyes. Other risks of note relate to fatigue, heat, and solar ultraviolet and for some operations tropical diseases, venomous/dangerous animals, and remote locations. Exposures to bauxite dust, alumina dust, and caustic mist in contemporary best-practice bauxite mining and alumina refining operations have not been demonstrated to be associated with clinically significant decrements in lung function. Exposures to bauxite dust and alumina dust at such operations are also not associated with the incidence of cancer. Conclusions: A range of occupational health risks in bauxite mining and alumina refining require the maintenance of effective control measures. PMID:24806720

  15. Data refinement for true concurrency

    Directory of Open Access Journals (Sweden)

    Brijesh Dongol

    2013-05-01

    Full Text Available The majority of modern systems exhibit sophisticated concurrent behaviour, where several system components modify and observe the system state with fine-grained atomicity. Many systems (e.g., multi-core processors, real-time controllers also exhibit truly concurrent behaviour, where multiple events can occur simultaneously. This paper presents data refinement defined in terms of an interval-based framework, which includes high-level operators that capture non-deterministic expression evaluation. By modifying the type of an interval, our theory may be specialised to cover data refinement of both discrete and continuous systems. We present an interval-based encoding of forward simulation, then prove that our forward simulation rule is sound with respect to our data refinement definition. A number of rules for decomposing forward simulation proofs over both sequential and parallel composition are developed.

  16. Pointing Refinement of SIRTF Images

    CERN Document Server

    Masci, F; Moshir, M; Shupe, D; Fowler, J W; Fowler, John W.

    2002-01-01

    The soon-to-be-launched Space Infrared Telescope Facility (SIRTF) shall produce image data with an a-posteriori pointing knowledge of 1.4 arcsec (1 sigma radial) with a goal of 1.2 arcsec in the International Celestial Reference System (ICRS). To perform robust image coaddition, mosaic generation, extraction and position determination of faint sources, the pointing will need to be refined to better than a few-tenths of an arcsecond. We use a linear-sparse matrix solver to find a "global-minimization" of all relative image offsets in a mosaic from which refined pointings and orientations can be computed. This paper summarizes the pointing-refinement algorithm and presents the results of testing on simulated data.

  17. DSm Vector Spaces of Refined Labels

    CERN Document Server

    Kandasamy, W B Vasantha

    2011-01-01

    In this book the authors introduce the notion of DSm vector spaces of refined labels. They also realize the refined labels as a plane and a n-dimensional space. Further, using these refined labels, several algebraic structures are defined. Finally DSm semivector space or refined labels is described. Authors also propose some research problems.

  18. Refining Nodes and Edges of State Machines

    DEFF Research Database (Denmark)

    Hallerstede, Stefan; Snook, Colin

    2011-01-01

    State machines are hierarchical automata that are widely used to structure complex behavioural specifications. We develop two notions of refinement of state machines, node refinement and edge refinement. We compare the two notions by means of examples and argue that, by adopting simple convention...... refinement theory and UML-B state machine refinement influences the style of node refinement. Hence we propose a method with direct proof of state machine refinement avoiding the detour via Event-B that is needed by UML-B....

  19. Conformal refinement of unstructured quadrilateral meshes

    Energy Technology Data Exchange (ETDEWEB)

    Garmella, Rao [Los Alamos National Laboratory

    2009-01-01

    We present a multilevel adaptive refinement technique for unstructured quadrilateral meshes in which the mesh is kept conformal at all times. This means that the refined mesh, like the original, is formed of only quadrilateral elements that intersect strictly along edges or at vertices, i.e., vertices of one quadrilateral element do not lie in an edge of another quadrilateral. Elements are refined using templates based on 1:3 refinement of edges. We demonstrate that by careful design of the refinement and coarsening strategy, we can maintain high quality elements in the refined mesh. We demonstrate the method on a number of examples with dynamically changing refinement regions.

  20. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    Directory of Open Access Journals (Sweden)

    Kaichun Li

    2016-01-01

    Full Text Available Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2, can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab, VEGF targeting monoclonal antibodies (bevacizumab, mTOR inhibitor (everolimus, or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer.

  1. Refining analgesia strategies using lasers.

    Science.gov (United States)

    Hampshire, Victoria

    2015-08-01

    Sound programs for the humane care and use of animals within research facilities incorporate experimental refinements such as multimodal approaches for pain management. These approaches can include non-traditional strategies along with more established ones. The use of lasers for pain relief is growing in popularity among companion animal veterinary practitioners and technologists. Therefore, its application in the research sector warrants closer consideration.

  2. On Interaction Refinement in Middleware

    DEFF Research Database (Denmark)

    Truyen, Eddy; Jørgensen, Bo Nørregaard; Joosen, Wouter;

    2000-01-01

    components together. We have examined a reflective technique that improve the dynamics of this gluing process such that interaction between components can be refined at run-time. In this paper, we show how we have used this reflective technique to dynamically integrate into the architecture of middleware...

  3. A measurement of the muon neutrino charged current quasielastic-like cross section on a hydrocarbon target and final state interaction effects

    Energy Technology Data Exchange (ETDEWEB)

    Walton, Tammy [Hampton Univ., Hampton, VA (United States)

    2014-01-01

    Presented is the analysis of the μ charged-current quasielastic-like interaction with a polystyrene (CH or hydrocarbon) target in the MINER A experiment, which was exposed to a neutrino beam that peaked at 3.5 GeV.

  4. On Refined Mining%论精细采矿

    Institute of Scientific and Technical Information of China (English)

    曲胜利; 孙豁然; 李少辉

    2011-01-01

    随着一些废弃矿山的重新恢复生产,在开采残留矿脉的过程中,传统的粗放型采矿模式遇到了诸多问题,解决这些问题的途径是采用新的矿产资源开采模式--精细采矿模式.介绍了精细生产的基本含义和原理,提出了精细采矿的概念及其廊用范围.精细采矿的主要内容包括开采对象的描述精细化、回采方案精细化、矿山施工精细化、矿山信息精细化、安全保障精细化以及管理精细化等诸多方面.精细采矿综合采用各方面的先进技术,配合精细生产管理,以获得最好的矿山开采经济效益、环境效益与社会效益.%With the production of some abandoned mines restarting, there are many problems in the traditional mode of extensive mining during the exploration of residual ore. The way to solve these problems is to undertake the new model for exploring mineral resources - the mode of refined mining. The basic meanings and principle of refined mining are introduced,and its definition and application field are proposed. The refined mining mainly include refining the description of production target, refining the stoping scheme, refining the mining construction, refining the mining information, refining the safety control,refining the management of mining and so on. The refined mining comprehensively adopts advanced technologies in many respects, so as to acquire greatest economic benefits, environmental benefits and social benefits with the addition of refined management.

  5. Refining Visually Detected Object poses

    DEFF Research Database (Denmark)

    Holm, Preben; Petersen, Henrik Gordon

    2010-01-01

    Automated industrial assembly today require that the 3D position and orientation (hereafter ''pose`) of the objects to be assembled are known precisely. Today this precision is mostly established by a dedicated mechanical object alignment system. However, such systems are often dedicated...... that enables direct assembly. Conventional vision systems and laser triangulation systems can locate randomly placed known objects (with 3D CAD models available) with some accuracy, but not necessarily a good enough accuracy. In this paper, we present a novel method for refining the pose accuracy of an object...... that has been located based on the appearance as detected by a monocular camera. We illustrate the quality of our refinement method experimentally....

  6. Ultrasonic sensor to characterize wood pulp during refining.

    Science.gov (United States)

    Greenwood, M S; Panetta, P D; Bond, L J; McCaw, M W

    2006-12-22

    A novel sensor concept has been developed for measuring the degree of refining, the water retention value (WRV), and the weight percentage of wood pulp during the refining process. The measurement time is less than 5 min and the sensor can operate in a slip-stream of the process line or as an at-line instrument. The degree of refining and the WRV are determined from settling measurements. The settling of a pulp suspension (with a weight percentage less than 0.5 wt%) is observed, after the mixer, which keeps the pulp uniformly distributed, is turned off. The attenuation of ultrasound as a function of time is recorded and these data show a peak at a time designated as the "peak time." The peak time T increases with the degree of refining, as demonstrated by measuring pulp samples with known degrees of refining. The WRV can be determined using the relative peak time, defined as the ratio T(2)/T(1), where T(1) is an initial peak time and T(2) is the value after additional refining. This method offers an alternative WRV test for the industry to the current time-consuming method.

  7. Iterative Goal Refinement for Robotics

    Science.gov (United States)

    2014-06-01

    Iterative Goal Refinement for Robotics Mark Roberts1, Swaroop Vattam1, Ronald Alford2, Bryan Auslander3, Justin Karneeb3, Matthew Molineaux3... robotics researchers and practitioners. We present a goal lifecycle and define a formal model for GR that (1) relates distinct disciplines concerning...researchers to collaborate in exploring this exciting frontier. 1. Introduction Robotic systems often act using incomplete models in environments

  8. Conserved sequences in the current strains of HIV-1 subtype A in Russia are effectively targeted by artificial RNAi in vitro.

    Science.gov (United States)

    Tchurikov, Nickolai A; Fedoseeva, Daria M; Gashnikova, Natalya M; Sosin, Dmitri V; Gorbacheva, Maria A; Alembekov, Ildar R; Chechetkin, Vladimir R; Kravatsky, Yuri V; Kretova, Olga V

    2016-05-25

    Highly active antiretroviral therapy has greatly reduced the morbidity and mortality of AIDS. However, many of the antiretroviral drugs are toxic with long-term use, and all currently used anti-HIV agents generate drug-resistant mutants. Therefore, there is a great need for new approaches to AIDS therapy. RNAi is a powerful means of inhibiting HIV-1 production in human cells. We propose to use RNAi for gene therapy of HIV/AIDS. Previously we identified a number of new biologically active siRNAs targeting several moderately conserved regions in HIV-1 transcripts. Here we analyze the heterogeneity of nucleotide sequences in three RNAi targets in sequences encoding the reverse transcriptase and integrase domains of current isolates of HIV-1 subtype A in Russia. These data were used to generate genetic constructs expressing short hairpin RNAs 28-30-bp in length that could be processed in cells into siRNAs. After transfection of the constructs we observed siRNAs that efficiently attacked the selected targets. We expect that targeting several viral genes important for HIV-1 reproduction will help overcome the problem of viral adaptation and will prevent the appearance of RNAi escape mutants in current virus strains, an important feature of gene therapy of HIV/AIDS.

  9. Semi-inclusive DIS Experiments Using Transversely Polarized Targets in Hall-A: Current Results and Future Plans

    Directory of Open Access Journals (Sweden)

    Allada Kalyan

    2012-12-01

    Full Text Available Measurement of single (SSA and double spin asymmetries (DSA in semiinclusive DIS reactions using polarized targets provide a powerful method to probe transverse momentum dependent parton distribution functions (TMDs. In particular, the experimentally measured SSA on nucleon targets can help in extracting the transversity and Sivers distribution functions of u and d-quarks. Similarly, the measured DSA are sensitive to the quark spin-orbital correlations, and provide an access to the TMD parton distribution function (g1T. A recent experiment conducted in Hall-A Jefferson Lab using transversely polarized 3He provide first such measurements on “effective” neutron target. The measurement was performed using 5.9 GeV beam from CEBAF and measured the target SSA/DSA in the SIDIS reaction 3He↑(e, e′π±X. The kinematical range, x = 0.19 ~ 0.34, at Q2 = 1.77 ~ 2.73 (GeV/c2, was focused on the valence quark region. The results from this measurement along with our plans for future high precision measurements in Hall-A are presented.

  10. Model-based drug administration : current status of target-controlled infusion and closed-loop control

    NARCIS (Netherlands)

    Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.

    2016-01-01

    Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the

  11. Construction and Application of a Refined Hospital Management Chain.

    Science.gov (United States)

    Lihua, Yi

    2016-01-01

    Large scale development was quite common in the later period of hospital industrialization in China. Today, Chinese hospital management faces such problems as service inefficiency, high human resources cost, and low rate of capital use. This study analyzes the refined management chain of Wuxi No.2 People's Hospital. This consists of six gears namely, "organizational structure, clinical practice, outpatient service, medical technology, and nursing care and logistics." The gears are based on "flat management system targets, chief of medical staff, centralized outpatient service, intensified medical examinations, vertical nursing management and socialized logistics." The core concepts of refined hospital management are optimizing flow process, reducing waste, improving efficiency, saving costs, and taking good care of patients as most important. Keywords: Hospital, Refined, Management chain

  12. Persistent sodium current is a target for cAMP-induced neuronal plasticity in a state-setting modulatory interneuron.

    Science.gov (United States)

    Nikitin, E S; Kiss, T; Staras, K; O'shea, M; Benjamin, P R; Kemenes, G

    2006-01-01

    We have identified a TTX-resistant low-threshold persistent inward sodium current in the cerebral giant cells (CGCs) of Lymnaea, an important state-setting modulatory cell type of molluscan feeding networks. This current has slow voltage-dependent activation and de-activation kinetics, ultra-slow inactivation kinetics and fast de-inactivation kinetics. It activates at approximately -90 mV, peaks at approximately -30 mV, reverses at approximately +35 mV and does not show full voltage-dependent inactivation even at positive voltage steps. Lithium-sodium replacement experiments indicate that the persistent sodium current makes a significant contribution to the CGC membrane potential. Injection of cyclic adenosine monophosphate (cAMP) into the CGC cell body produces a large increase in the persistent sodium current that lasts for several hours. cAMP injection also leads to increased bursting, a significant decrease in the resistance and a significant depolarization of the soma membrane, indicating that cAMP-dependent mechanisms induce prolonged neuronal plasticity in the CGCs. Our observations provide the first link between cAMP-mediated modulation of a TTX-resistant persistent sodium current and prolonged neuronal plasticity in an identified modulatory cell type that plays an important role in behavioral state setting.

  13. The Refined Function-Behaviour-Structure Framework

    NARCIS (Netherlands)

    Diertens, B.

    2013-01-01

    We refine the function-behaviour-structure framework for design introduced by John Gero in order to deal with complexity. We do this by connecting the frameworks for the desing of two models, one the refinement of the other. The result is a refined framework for the design of an object on two levels

  14. Refining United States Policy on Offensive Cyber Operations

    Science.gov (United States)

    2014-11-01

    address state- sponsored cyber threats with a very different set of tools ranging from diplomacy to kinetic strikes. Categorizing attacks by actor will...AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY REFINING UNITED STATES POLICY ON OFFENSIVE CYBER OPERATIONS by Max...to offensive cyber warfare, specifically cyber exploitation and cyber attack. Current domestic and international policies lack mechanisms to

  15. Inflation in a refined racetrack

    CERN Document Server

    Wen, Wen-Yu

    2007-01-01

    In this note, we refine the racetrack inflation model constructed in arXiv:hep-th/0406230 by including the open string modulus. This modulus encodes the embedding of our braneworld inside some Calabi-Yau throat. We argue that in generic this open string modulus dynamically runs with the inflaton field thanks to its nonlinear coupling. A full analysis becomes difficult because the scalar potential changes progressively during the inflation epoch. Nevertheless, by explicit construction we are still able to build a realistic model through appropriate choices of the initial conditions.

  16. A randomised clinical trial of subgrouping and targeted treatment for low back pain compared with best current care. The STarT Back Trial Study Protocol

    Directory of Open Access Journals (Sweden)

    Vohora Kanchan

    2008-04-01

    Full Text Available Abstract Background Back pain is a major health problem and many sufferers develop persistent symptoms. Detecting relevant subgroups of patients with non-specific low back pain has been highlighted as a priority area for research, as this could enable better secondary prevention through the targeting of prognostic indicators for persistent, disabling symptoms. We plan to conduct a randomised controlled trial to establish whether subgrouping using a novel tool, combined with targeted treatment, is better than best current care at reducing long-term disability from low back pain. Methods/Design We will recruit 800 participants aged 18 years and over with non-specific low back pain from 8–10 GP practices within two Primary Care Trusts in Staffordshire, England. Our primary outcome measures are low back pain disability and catastrophising. Secondary outcomes include back pain intensity, global change, leg pain, fear avoidance, anxiety, depression, illness perceptions, patient satisfaction, overall health status and cost-effectiveness. Data will be collected before randomisation, and 4 and 12 months later. Participants are randomised to receive either newly developed interventions, delivered by trained physiotherapists and targeted according to subgroups defined by tool scores, or best current care. Discussion This paper presents detail on the rationale, design, methods and operational aspects of the trial. Trial registration Current Controlled Trials ISRCTN37113406.

  17. 78 FR 68849 - Draft Current Intelligence Bulletin “Update of NIOSH Carcinogen Classification and Target Risk...

    Science.gov (United States)

    2013-11-15

    ... consistent with the current scientific knowledge of toxicology, risk assessment, industrial hygiene, and... there additional scientific information related to the issues of the proposed NIOSH carcinogen policies...) where clarification is needed. (7) An analytical feasibility (AF) notation will be used to identify...

  18. Current strategies for targeted delivery of bio-active drug molecules in the treatment of brain tumor.

    Science.gov (United States)

    Garg, Tarun; Bhandari, Saurav; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Brain tumor is one of the most challenging diseases to treat. The major obstacle in the specific drug delivery to brain is blood-brain barrier (BBB). Mostly available anti-cancer drugs are large hydrophobic molecules which have limited permeability via BBB. Therefore, it is clear that the protective barriers confining the passage of the foreign particles into the brain are the main impediment for the brain drug delivery. Hence, the major challenge in drug development and delivery for the neurological diseases is to design non-invasive nanocarrier systems that can assist controlled and targeted drug delivery to the specific regions of the brain. In this review article, our major focus to treat brain tumor by study numerous strategies includes intracerebral implants, BBB disruption, intraventricular infusion, convection-enhanced delivery, intra-arterial drug delivery, intrathecal drug delivery, injection, catheters, pumps, microdialysis, RNA interference, antisense therapy, gene therapy, monoclonal/cationic antibodies conjugate, endogenous transporters, lipophilic analogues, prodrugs, efflux transporters, direct conjugation of antitumor drugs, direct targeting of liposomes, nanoparticles, solid-lipid nanoparticles, polymeric micelles, dendrimers and albumin-based drug carriers.

  19. Targeting cellular and molecular drivers of head and neck squamous cell carcinoma: current options and emerging perspectives.

    Science.gov (United States)

    Ausoni, Simonetta; Boscolo-Rizzo, Paolo; Singh, Bhuvanesh; Da Mosto, Maria Cristina; Spinato, Giacomo; Tirelli, Giancarlo; Spinato, Roberto; Azzarello, Giuseppe

    2016-09-01

    Despite improvements in functional outcomes attributable to advances in radiotherapy, chemotherapy, surgical techniques, and imaging techniques, survival in head and neck squamous cell carcinoma (HNSCC) patients has improved only marginally during the last couple of decades, and optimal therapy has yet to be devised. Genomic complexity and intratumoral genetic heterogeneity may contribute to treatment resistance and the propensity for locoregional recurrence. Countering this, it demands a significant effort from both basic and clinical scientists in the search for more effective targeted therapies. Recent genomewide studies have provided valuable insights into the genetic basis of HNSCC, uncovering potential new therapeutic opportunities. In addition, several studies have elucidated how inflammatory, immune, and stromal cells contribute to the particular properties of these neoplasms. In the present review, we introduce recent findings on genomic aberrations resulting from whole-genome sequencing of HNSCC, we discuss how the particular microenvironment affects the pathogenesis of this disease, and we describe clinical trials exploring new perspectives on the use of combined genetic and cellular targeted therapies.

  20. 高光谱图像目标检测算法分析%A summary on the development of current target detection algorithms for hyperspectral imagery

    Institute of Scientific and Technical Information of China (English)

    孙林; 鲍金河; 刘一超

    2012-01-01

    Target detection for hyperspectral imagery is an important part in the application oi hyperspectral imagery, and the research on target detection will be helpful to the deep use of hyperspectral imagery. This paper divided target detection algorithms for hyperspectral imagery into three categories, which are spectral anomaly detection, spectral matching detection and target detection making use of both hyperspectral and high spatial resolution imagery. Then, the development of current algorithms was summarized. This paper also analyzed the theories, application characteristics and limitations of these three algorithms. In the end, the direction of future target detection algorithms was discussed.%本文将国内外的高光谱图像目标检测算法分为光谱异常检测、光谱匹配检测和高光谱与高空间分辨率结合目标检测三种检测算法,分析了三种检测算法的原理、应用特点和局限性,并探讨了目标检测算法的发展的可能性.

  1. Rotary impeller refinement of 7075Al alloy

    Institute of Scientific and Technical Information of China (English)

    WANG Liping; GUO Erjun; HUANG Yongchang; LU Bin

    2009-01-01

    The effects of four parameters, gas flow, rotational speed, refining time, and stewing time, on the rotary impeller refinement of 7075 Al were studied. The effects of C2Cl6refining, rotary impeller refuting, and composite refining of 7075 AI alloy were compared with each other. The results showed that the greatest impact parameter of rotary impeller refinement was rotational speed, followed by gas flow, refining time, and stewing time. The optimum purification parameters obtained by orthogonal analysis were as follows: rotor speed of 400 r/min, inert gas flow of 0.4 mL/h, refining time of 15 min, and stewing time of 6 min. The best degassing effect can be obtained by the composite refuting of C2Cl6 and rotary impeller. The degassing rate of C2Cl6 rotary impeller, and composite refining was 34.5%, 69.2%, and 78%, respectively. The mechanical properties of the specimen refined by rotary impeller were higher than those by C2C16 refining, but lower than those by composite refining.

  2. Zone refining of plutonium metal

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-05-01

    The purpose of this study was to investigate zone refining techniques for the purification of plutonium metal. The redistribution of 10 impurity elements from zone melting was examined. Four tantalum boats were loaded with plutonium impurity alloy, placed in a vacuum furnace, heated to 700{degrees}C, and held at temperature for one hour. Ten passes were made with each boat. Metallographic and chemical analyses performed on the plutonium rods showed that, after 10 passes, moderate movement of certain elements were achieved. Molten zone speeds of 1 or 2 inches per hour had no effect on impurity element movement. Likewise, the application of constant or variable power had no effect on impurity movement. The study implies that development of a zone refining process to purify plutonium is feasible. Development of a process will be hampered by two factors: (1) the effect on impurity element redistribution of the oxide layer formed on the exposed surface of the material is not understood, and (2) the tantalum container material is not inert in the presence of plutonium. Cold boat studies are planned, with higher temperature and vacuum levels, to determine the effect on these factors. 5 refs., 1 tab., 5 figs.

  3. The current status of fluoride salt cooled high temperature reactor (FHR) technology and its overlap with HIF target chamber concepts

    Science.gov (United States)

    Scarlat, Raluca O.; Peterson, Per F.

    2014-01-01

    The fluoride salt cooled high temperature reactor (FHR) is a class of fission reactor designs that use liquid fluoride salt coolant, TRISO coated particle fuel, and graphite moderator. Heavy ion fusion (HIF) can likewise make use of liquid fluoride salts, to create thick or thin liquid layers to protect structures in the target chamber from ablation by target X-rays and damage from fusion neutron irradiation. This presentation summarizes ongoing work in support of design development and safety analysis of FHR systems. Development work for fluoride salt systems with application to both FHR and HIF includes thermal-hydraulic modeling and experimentation, salt chemistry control, tritium management, salt corrosion of metallic alloys, and development of major components (e.g., pumps, heat exchangers) and gas-Brayton cycle power conversion systems. In support of FHR development, a thermal-hydraulic experimental test bay for separate effects (SETs) and integral effect tests (IETs) was built at UC Berkeley, and a second IET facility is under design. The experiments investigate heat transfer and fluid dynamics and they make use of oils as simulant fluids at reduced scale, temperature, and power of the prototypical salt-cooled system. With direct application to HIF, vortex tube flow was investigated in scaled experiments with mineral oil. Liquid jets response to impulse loading was likewise studied using water as a simulant fluid. A set of four workshops engaging industry and national laboratory experts were completed in 2012, with the goal of developing a technology pathway to the design and licensing of a commercial FHR. The pathway will include experimental and modeling efforts at universities and national laboratories, requirements for a component test facility for reliability testing of fluoride salt equipment at prototypical conditions, requirements for an FHR test reactor, and development of a pre-conceptual design for a commercial reactor.

  4. A novel 9 × 9 map-based solvent selection strategy for targeted counter-current chromatography isolation of natural products.

    Science.gov (United States)

    Liang, Junling; Meng, Jie; Wu, Dingfang; Guo, Mengzhe; Wu, Shihua

    2015-06-26

    Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography technique for separation and purification of complex mixtures like natural products extracts and synthetic chemicals. However, CCC is still a challenging process requiring some special technical knowledge especially in the selection of appropriated solvent systems. In this work, we introduced a new 9 × 9 map-based solvent selection strategy for CCC isolation of targets, which permit more than 60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start candidates for the selection of solvent systems. Among these solvent systems, there are clear linear correlations between partition coefficient (K) and the system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K = 1) may be hit by measurement of k values of the target only in two random solvent systems. Besides this, surprisingly, we found that through two sweet spots, we could get a line ("Sweet line") where there are infinite sweet solvent systems being suitable for CCC separation. In these sweet solvent systems, the target has the same partition coefficient (K) but different solubilities. Thus, the better sweet solvent system with higher sample solubility can be obtained for high capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet zone") where all solvent systems have their own sweet partition coefficients values for the target in range of 0.4 natural products as standards and further confirmed by isolation of several targets including honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to get a suitable solvent system only by making a simple screening two to four HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without special knowledge or comprehensive standards as references. This is an important advancement for solvent system selection

  5. Automated Assume-Guarantee Reasoning by Abstraction Refinement

    Science.gov (United States)

    Pasareanu, Corina S.; Giannakopoulous, Dimitra; Glannakopoulou, Dimitra

    2008-01-01

    Current automated approaches for compositional model checking in the assume-guarantee style are based on learning of assumptions as deterministic automata. We propose an alternative approach based on abstraction refinement. Our new method computes the assumptions for the assume-guarantee rules as conservative and not necessarily deterministic abstractions of some of the components, and refines those abstractions using counter-examples obtained from model checking them together with the other components. Our approach also exploits the alphabets of the interfaces between components and performs iterative refinement of those alphabets as well as of the abstractions. We show experimentally that our preliminary implementation of the proposed alternative achieves similar or better performance than a previous learning-based implementation.

  6. Measurement of the Charged-Current Quasi-Elastic Cross-Section for Electron Neutrinos on a Hydrocarbon Target

    Energy Technology Data Exchange (ETDEWEB)

    Wolcott, Jeremy [Univ. of Rochester, NY (United States)

    2016-01-01

    Appearance-type neutrino oscillation experiments, which observe the transition from muon neutrinos to electron neutrinos, promise to help answer some of the fundamental questions surrounding physics in the post-Standard-Model era. Because they wish to observe the interactions of electron neutrinos in their detectors, and because the power of current results is typically limited by their systematic uncertainties, these experiments require precise estimates of the cross-section for electron neutrino interactions. Of particular interest is the charged-current quasi-elastic (CCQE) process, which gures signi cantly in the composition of the reactions observed at the far detector. However, no experimental measurements of this crosssection currently exist for electron neutrinos; instead, current experiments typically work from the abundance of muon neutrino CCQE cross-section data and apply corrections from theoretical arguments to obtain a prediction for electron neutrinos. Veri cation of these predictions is challenging due to the di culty of constructing an electron neutrino beam, but the advent of modern high-intensity muon neutrino beams|together with the percent-level electron neutrino impurity inherent in these beams| nally presents the opportunity to make such a measurement. We report herein the rst-ever measurement of a cross-section for an exclusive state in electron neutrino scattering, which was made using the MINER A detector in the NuMI neutrino beam at Fermilab. We present the electron neutrino CCQE di erential cross-sections, which are averaged over neutrinos of energies 1-10 GeV (with mean energy of about 3 GeV), in terms of various kinematic variables: nal-state electron angle, nal-state electron energy, and the square of the fourmomentum transferred to the nucleus by the neutrino , Q2. We also provide a total cross-section vs. neutrino energy. While our measurement of this process is found to be in agreement with the predictions of the GENIE

  7. CaMKII inhibition targeted to the sarcoplasmic reticulum inhibits frequency dependent acceleration of relaxation and Ca2+ current facilitation

    OpenAIRE

    Picht, Eckard; DeSantiago, Jaime; Huke, Sabine; Kaetzel, Marcia A.; Dedman, John R.; Bers, Donald M.

    2006-01-01

    Cardiac Ca2+/calmodulin-dependent protein kinase II (CaMKII) in heart has been implicated in Ca2+ current (ICa) facilitation, enhanced sarcoplasmic reticulum (SR) Ca2+ release and frequency dependent acceleration of relaxation (FDAR) via enhanced SR Ca2+ uptake. However, questions remain about how CaMKII may work in these three processes. Here we tested the role of CaM-KII in these processes using transgenic mice (SR-AIP) that express four concatenated repeats of the CaMKII inhibitory peptide...

  8. Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

    Directory of Open Access Journals (Sweden)

    Ming Hong

    2015-12-01

    Full Text Available Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

  9. Fluorine-doped tin oxide films grown by pulsed direct current magnetron sputtering with an Sn target.

    Science.gov (United States)

    Liao, Bo-Huei; Kuo, Chien-Cheng; Chen, Pin-Jen; Lee, Cheng-Chung

    2011-03-20

    Fluorine-doped tin oxide (FTO) films have been deposited by pulsed DC magnetron sputtering with an Sn target. Various ratios of CF4/O2 gas were injected to enhance the optical and electrical properties of the films. The extinction coefficient was lower than 1.5×10(-3) in the range from 400 to 800 nm when the CF4O2 ratio was 0.375. The resistivity of fluorine-doped SnO2 films (1.63×10(-3) Ω cm) deposited at 300 °C was 27.9 times smaller than that of undoped SnO2 (4.55×10(-2) Ω cm). Finally, an FTO film was consecutively deposited for protecting the oxidation of indium tin oxide films. The resistivity of the double-layered film was 2.68×10(-4) Ω cm, which increased by less than 39% at a 450 °C annealing temperature for 1 h in air.

  10. Current and future perspectives on the TARGET system: the registration system for Glivec established by the JSH.

    Science.gov (United States)

    Kizaki, Masahiro; Okamoto, Shinichiro; Tauchi, Tetsuzo; Tanaka, Hideo; Tanimoto, Mitsune; Inokuchi, Koiti; Murayama, Tohru; Saburi, Yoshio; Hino, Masayuki; Tsudo, Mitsuru; Shimomura, Taizo; Isobe, Yasushi

    2008-11-01

    Since hematology is a highly specialized field, an individual physician may not have much direct treatment experience with a given disease. Therefore, the Japanese Society of Hematology (JSH) has discussed establishing a registry of hematologic disorders, in order to contribute to improving the quality of treatments and clinical outcomes in this field. As a first step, the Timely and Appropriate Registration System for GLIVEC Therapy (TARGET), a registration system for chronic myeloid leukemia (CML) patients treated with imatinib, was established in October 2003. We present the preliminary results of the first 4 years' experience with this system. CML patients treated with imatinib in Japan were registered through the website and the patient's clinical course, including parameters and events like imatinib dose, blood counts, adverse events, and efficacy were recorded in months 1, 3, 6, 9, and 12 and then every 6 months thereafter. By September 2007, 862 patients from 176 hospitals were registered. Follow-up period was 0-54 months, and 127 patients were followed-up for more than 36 months. Based on these cumulative data, present imatinib treatment trends were analyzed and safety and efficacy were compared with international trial data.

  11. Novel Therapeutic Targets for Phosphodiesterase 5 Inhibitors: current state-of-the-art on systemic arterial hypertension and atherosclerosis.

    Science.gov (United States)

    Vasquez, Elisardo C; Gava, Agata L; Graceli, Jones B; Balarini, Camille M; Campagnaro, Bianca P; Pereira, Thiago Melo C; Meyrelles, Silvana S

    2016-01-01

    The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature. An important effect of sildenafil is reduction of hypertension and improvement of endothelial function in experimental models of hypertension and hypertensive subjects. Interestingly, in angiotensin-dependent hypertension, its beneficial effects on endothelial and kidney dysfunctions seem to at least in part be caused by its ability to decrease the levels of angiotensin II and increase angiotensin 1-7, in addition to improving nitric oxide bioavailability and diminishing reactive oxygen species. Another remarkable finding on the effects of sildenafil comes from studies in apolipoprotein E knockout mice, a model of atherosclerosis that closely resembles human atherosclerotic disease. In this review, we focus on the promising beneficial effects of sildenafil for treating systemic high blood pressure, especially resistant hypertension, and the endothelial dysfunction that is present in hypertension and atherosclerosis.

  12. Adaptive mesh refinement in titanium

    Energy Technology Data Exchange (ETDEWEB)

    Colella, Phillip; Wen, Tong

    2005-01-21

    In this paper, we evaluate Titanium's usability as a high-level parallel programming language through a case study, where we implement a subset of Chombo's functionality in Titanium. Chombo is a software package applying the Adaptive Mesh Refinement methodology to numerical Partial Differential Equations at the production level. In Chombo, the library approach is used to parallel programming (C++ and Fortran, with MPI), whereas Titanium is a Java dialect designed for high-performance scientific computing. The performance of our implementation is studied and compared with that of Chombo in solving Poisson's equation based on two grid configurations from a real application. Also provided are the counts of lines of code from both sides.

  13. Algorithm refinement for fluctuating hydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Sarah A.; Bell, John B.; Garcia, Alejandro L.

    2007-07-03

    This paper introduces an adaptive mesh and algorithmrefinement method for fluctuating hydrodynamics. This particle-continuumhybrid simulates the dynamics of a compressible fluid with thermalfluctuations. The particle algorithm is direct simulation Monte Carlo(DSMC), a molecular-level scheme based on the Boltzmann equation. Thecontinuum algorithm is based on the Landau-Lifshitz Navier-Stokes (LLNS)equations, which incorporate thermal fluctuations into macroscopichydrodynamics by using stochastic fluxes. It uses a recently-developedsolver for LLNS, based on third-order Runge-Kutta. We present numericaltests of systems in and out of equilibrium, including time-dependentsystems, and demonstrate dynamic adaptive refinement by the computationof a moving shock wave. Mean system behavior and second moment statisticsof our simulations match theoretical values and benchmarks well. We findthat particular attention should be paid to the spectrum of the flux atthe interface between the particle and continuum methods, specificallyfor the non-hydrodynamic (kinetic) time scales.

  14. SILICON REFINING BY VACUUM TREATMENT

    Directory of Open Access Journals (Sweden)

    André Alexandrino Lotto

    2014-12-01

    Full Text Available This work aims to investigate the phosphorus removal by vacuum from metallurgical grade silicon (MGSi (98.5% to 99% Si. Melting experiments were carried out in a vacuum induction furnace, varying parameters such as temperature, time and relation area exposed to the vacuum / volume of molten silicon. The results of chemical analysis were obtained by inductively coupled plasma (ICP, and evaluated based on thermodynamic and kinetic aspects of the reaction of vaporization of the phosphorus in the silicon. The phosphorus was decreased from 33 to approximately 1.5 ppm after three hours of vacuum treatment, concluding that the evaporation step is the controlling step of the process for parameters of temperature, pressure and agitation used and refining by this process is technically feasible.

  15. Improved successive refinement for wavelet-based embedded image compression

    Science.gov (United States)

    Creusere, Charles D.

    1999-10-01

    In this paper we consider a new form of successive coefficient refinement which can be used in conjunction with embedded compression algorithms like Shapiro's EZW (Embedded Zerotree Wavelet) and Said & Pearlman's SPIHT (Set Partitioning in Hierarchical Trees). Using the conventional refinement process, the approximation of a coefficient that was earlier determined to be significantly is refined by transmitting one of two symbols--an `up' symbol if the actual coefficient value is in the top half of the current uncertainty interval or a `down' symbol if it is the bottom half. In the modified scheme developed here, we transmit one of 3 symbols instead--`up', `down', or `exact'. The new `exact' symbol tells the decoder that its current approximation of a wavelet coefficient is `exact' to the level of precision desired. By applying this scheme in earlier work to lossless embedded compression (also called lossy/lossless compression), we achieved significant reductions in encoder and decoder execution times with no adverse impact on compression efficiency. These excellent results for lossless systems have inspired us to adapt this refinement approach to lossy embedded compression. Unfortunately, the results we have achieved thus far for lossy compression are not as good.

  16. Zone refining of cadmium and related characterization

    Indian Academy of Sciences (India)

    N R Munirathnam; D S Prasad; Ch Sudheer; J V Rao; T L Prakash

    2005-06-01

    We present the zone refining results of cadmium using horizontal resistive zone refiner under constant flow of moisture free hydrogen gas. The boron impurity in cadmium can be avoided using quartz (GE 214 grade) boat in lieu of high pure graphite boat. The analytical results using inductively coupled plasma optical emission spectrometry (ICPOES) show that majority of the impurities are less than the detection limits. Comparatively, zinc is the most difficult impurity element to remove in cadmium matrix by zone refining.

  17. Refined curve counting on complex surfaces

    OpenAIRE

    Göttsche, Lothar; Shende, Vivek

    2012-01-01

    We define refined invariants which "count" nodal curves in sufficiently ample linear systems on surfaces, conjecture that their generating function is multiplicative, and conjecture explicit formulas in the case of K3 and abelian surfaces. We also give a refinement of the Caporaso-Harris recursion, and conjecture that it produces the same invariants in the sufficiently ample setting. The refined recursion specializes at y = -1 to the Itenberg-Kharlamov-Shustin recursion for Welschinger invari...

  18. New method of a "point-like" neutron source creation based on sharp focusing of high-current deuteron beam onto deuterium-saturated target for neutron tomography

    Science.gov (United States)

    Golubev, S.; Skalyga, V.; Izotov, I.; Sidorov, A.

    2017-02-01

    A possibility of a compact powerful point-like neutron source creation is discussed. Neutron yield of the source based on deuterium-deuterium (D-D) reaction is estimated at the level of 1011 s‑1 (1013 s‑1 for deuterium-tritium reaction). The fusion takes place due to bombardment of deuterium- (or tritium) loaded target by high-current focused deuterium ion beam with energy of 100 keV. The ion beam is formed by means of high-current quasi-gasdynamic ion source of a new generation based on an electron cyclotron resonance (ECR) discharge in an open magnetic trap sustained by powerful microwave radiation. The prospects of proposed generator for neutron tomography are discussed. Suggested method is compared to the point-like neutron sources based on a spark produced by powerful femtosecond laser pulses.

  19. Optimization of Melt Treatment for Austenitic Steel Grain Refinement

    Science.gov (United States)

    Lekakh, Simon N.; Ge, Jun; Richards, Von; O'Malley, Ron; TerBush, Jessica R.

    2017-02-01

    Refinement of the as-cast grain structure of austenitic steels requires the presence of active solid nuclei during solidification. These nuclei can be formed in situ in the liquid alloy by promoting reactions between transition metals (Ti, Zr, Nb, and Hf) and metalloid elements (C, S, O, and N) dissolved in the melt. Using thermodynamic simulations, experiments were designed to evaluate the effectiveness of a predicted sequence of reactions targeted to form precipitates that could act as active nuclei for grain refinement in austenitic steel castings. Melt additions performed to promote the sequential precipitation of titanium nitride (TiN) onto previously formed spinel (Al2MgO4) inclusions in the melt resulted in a significant refinement of the as-cast grain structure in heavy section Cr-Ni-Mo stainless steel castings. A refined as-cast structure consisting of an inner fine-equiaxed grain structure and outer columnar dendrite zone structure of limited length was achieved in experimental castings. The sequential of precipitation of TiN onto Al2MgO4 was confirmed using automated SEM/EDX and TEM analyses.

  20. Model Checking Linearizability via Refinement

    Science.gov (United States)

    Liu, Yang; Chen, Wei; Liu, Yanhong A.; Sun, Jun

    Linearizability is an important correctness criterion for implementations of concurrent objects. Automatic checking of linearizability is challenging because it requires checking that 1) all executions of concurrent operations be serializable, and 2) the serialized executions be correct with respect to the sequential semantics. This paper describes a new method to automatically check linearizability based on refinement relations from abstract specifications to concrete implementations. Our method avoids the often difficult task of determining linearization points in implementations, but can also take advantage of linearization points if they are given. The method exploits model checking of finite state systems specified as concurrent processes with shared variables. Partial order reduction is used to effectively reduce the search space. The approach is built into a toolset that supports a rich set of concurrent operators. The tool has been used to automatically check a variety of implementations of concurrent objects, including the first algorithms for the mailbox problem and scalable NonZero indicators. Our system was able to find all known and injected bugs in these implementations.

  1. Refined large N duality for torus knots

    DEFF Research Database (Denmark)

    Nawata, Satoshi; Kameyama, Masaya

    We formulate large N duality of U(N) refined Chern-Simons theory with a torus knot/link in S³. By studying refined BPS states in M-theory, we provide the explicit form of low-energy effective actions of Type IIA string theory with D4-branes on the Ω-background. This form enables us to relate...

  2. Refined Black Hole Ensembles and Topological Strings

    CERN Document Server

    Aganagic, Mina

    2012-01-01

    We formulate a refined version of the Ooguri-Strominger-Vafa (OSV) conjecture. The OSV conjecture that Z_{BH} = |Z_{top}|^2 relates the BPS black hole partition function to the topological string partition function Z_{top}. In the refined conjecture, Z_{BH} is the partition function of BPS black holes counted with spin, or more precisely the protected spin character. Z_{top} becomes the partition function of the refined topological string, which is itself an index. Both the original and the refined conjecture are examples of large N duality in the 't Hooft sense. The refined conjecture applies to non-compact Calabi-Yau manifolds only, so the black holes are really BPS particles with large entropy, of order N^2. The refined OSV conjecture states that the refined BPS partition function has a large N dual which is captured by the refined topological string. We provide evidence that the conjecture holds by studying local Calabi-Yau threefolds consisting of line bundles over a genus g Riemann surface. We show that...

  3. Refined large N duality for torus knots

    DEFF Research Database (Denmark)

    Nawata, Satoshi; Kameyama, Masaya

    We formulate large N duality of U(N) refined Chern-Simons theory with a torus knot/link in S³. By studying refined BPS states in M-theory, we provide the explicit form of low-energy effective actions of Type IIA string theory with D4-branes on the Ω-background. This form enables us to relate...

  4. Region-of-interest volumetric visual hull refinement

    KAUST Repository

    Knoblauch, Daniel

    2010-01-01

    This paper introduces a region-of-interest visual hull refinement technique, based on flexible voxel grids for volumetric visual hull reconstructions. Region-of-interest refinement is based on a multipass process, beginning with a focussed visual hull reconstruction, resulting in a first 3D approximation of the target, followed by a region-of-interest estimation, tasked with identifying features of interest, which in turn are used to locally refine the voxel grid and extract a higher-resolution surface representation for those regions. This approach is illustrated for the reconstruction of avatars for use in tele-immersion environments, where head and hand regions are of higher interest. To allow reproducability and direct comparison a publicly available data set for human visual hull reconstruction is used. This paper shows that region-of-interest reconstruction of the target is faster and visually comparable to higher resolution focused visual hull reconstructions. This approach reduces the amount of data generated through the reconstruction, allowing faster post processing, as rendering or networking of the surface voxels. Reconstruction speeds support smooth interactions between the avatar and the virtual environment, while the improved resolution of its facial region and hands creates a higher-degree of immersion and potentially impacts the perception of body language, facial expressions and eye-to-eye contact. Copyright © 2010 by the Association for Computing Machinery, Inc.

  5. China Becomes Globe's Second Largest Oil Refiner

    Institute of Scientific and Technical Information of China (English)

    Zhang Weijun

    2010-01-01

    @@ China's refining capacity of crude oil reached 477 million tons by the end of last year,ranking the second in the world.CNPC and Sinopec now own 27 percent of the country's oil refineries with a combined refining capacity amounting to 76 percent of the country's total.As the country's biggest oil refiner,Sinopec's refining ability has increased 72.8 percent in the past ten years with a growth rate of 6.3 percent per year,ranking the third in the world,according to statistics released by Sinopec.Meanwhile,China's local oil refining enterprises' total capacity has reached 88 million tons per year.According to Sinopec,China has built 17 ten-million-ton-oil refineries which amount to half of the country's total capacity.

  6. North Dakota Refining Capacity Study

    Energy Technology Data Exchange (ETDEWEB)

    Dennis Hill; Kurt Swenson; Carl Tuura; Jim Simon; Robert Vermette; Gilberto Marcha; Steve Kelly; David Wells; Ed Palmer; Kuo Yu; Tram Nguyen; Juliam Migliavacca

    2011-01-05

    According to a 2008 report issued by the United States Geological Survey, North Dakota and Montana have an estimated 3.0 to 4.3 billion barrels of undiscovered, technically recoverable oil in an area known as the Bakken Formation. With the size and remoteness of the discovery, the question became 'can a business case be made for increasing refining capacity in North Dakota?' And, if so what is the impact to existing players in the region. To answer the question, a study committee comprised of leaders in the region's petroleum industry were brought together to define the scope of the study, hire a consulting firm and oversee the study. The study committee met frequently to provide input on the findings and modify the course of the study, as needed. The study concluded that the Petroleum Area Defense District II (PADD II) has an oversupply of gasoline. With that in mind, a niche market, naphtha, was identified. Naphtha is used as a diluent used for pipelining the bitumen (heavy crude) from Canada to crude markets. The study predicted there will continue to be an increase in the demand for naphtha through 2030. The study estimated the optimal configuration for the refinery at 34,000 barrels per day (BPD) producing 15,000 BPD of naphtha and a 52 percent refinery charge for jet and diesel yield. The financial modeling assumed the sponsor of a refinery would invest its own capital to pay for construction costs. With this assumption, the internal rate of return is 9.2 percent which is not sufficient to attract traditional investment given the risk factor of the project. With that in mind, those interested in pursuing this niche market will need to identify incentives to improve the rate of return.

  7. Selective refinement and selection of near-native models in protein structure prediction.

    Science.gov (United States)

    Zhang, Jiong; Barz, Bogdan; Zhang, Jingfen; Xu, Dong; Kosztin, Ioan

    2015-10-01

    In recent years in silico protein structure prediction reached a level where fully automated servers can generate large pools of near-native structures. However, the identification and further refinement of the best structures from the pool of models remain problematic. To address these issues, we have developed (i) a target-specific selective refinement (SR) protocol; and (ii) molecular dynamics (MD) simulation based ranking (SMDR) method. In SR the all-atom refinement of structures is accomplished via the Rosetta Relax protocol, subject to specific constraints determined by the size and complexity of the target. The best-refined models are selected with SMDR by testing their relative stability against gradual heating through all-atom MD simulations. Through extensive testing we have found that Mufold-MD, our fully automated protein structure prediction server updated with the SR and SMDR modules consistently outperformed its previous versions.

  8. Boxlib with tiling: an adaptive mesh refinement software framework

    OpenAIRE

    Unat, Didem; Zhang, W.; Almgren, A.; Day, M.; Nguyen, T.; Shalf, J.

    2016-01-01

    In this paper we introduce a block-structured adaptive mesh refinement software framework that incorporates tiling, a well-known loop transformation. Because the multiscale, multiphysics codes built in boxlib are designed to solve complex systems at high resolution, performance on current and next generation architectures is essential. With the expectation of many more cores per node on next generation architectures, the ability to effectively utilize threads within a node is essential, and t...

  9. A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis.

    Science.gov (United States)

    Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E

    2015-01-01

    The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host-parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major-C57BL/6 mice (or-vervet monkey, or-rhesus monkeys), L. tropica-CsS-16 mice, L. amazonensis-CBA mice, L. braziliensis-golden hamster (or-rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations.

  10. Biological targets in the treatment of rheumatoid arthritis: a comprehensive review of current and in-development biological disease modifying anti-rheumatic drugs

    Directory of Open Access Journals (Sweden)

    Manil Kukar

    2009-09-01

    Full Text Available Manil Kukar1, Olga Petryna1, Petros Efthimiou21Rheumatology Division, Lincoln Medical and Mental Health Center, New York, NY, USA; 2Lincoln Medical and Mental Health Center, Weill Cornell Medical College, New York, NY, USAAbstract: Enhanced understanding of the rheumatoid arthritis (RA pathophysiology and the role of cytokines has enabled the development of innovative biological agents in the last 10 years that target specific parts of the immune response. Failure to achieve adequate response with traditional disease modifying anti-rheumatic drugs (DMARDs and increasing evidence of ongoing radiographic deterioration of the affected joints despite seemingly clinical response were essential stimuli for the development of biologics. The current and upcoming biological agents are primarily aimed at neutralizing circulating and cell-bound pro-inflammatory cytokines, interfering in the interaction of antigen-presenting and T-lymphocytes, eliminating circulating B-lymphocytes or by interfering with the intracellular signaling mechanisms of immuno-competent cells that lead to inflammation. These agents have improved the currently available treatments due to greater efficacy, fast action and greater tolerability. However, use of these agents has also been associated with significant, although rare, adverse events and considerable cost. Therefore, these agents should be used with caution by experienced clinicians. The present work aims to provide a global and updated review of the current and in-development biological DMARDs for the treatment of RA.Keywords: biological agents, rheumatoid arthritis, immunomodulators, treatment, cytokines

  11. A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Emily Rose Mears

    Full Text Available The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i host-parasite interactions, (ii pathogenesis, (iii biochemical changes/pathways, (iv in vivo maintenance of parasites, and (v clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major-C57BL/6 mice (or-vervet monkey, or-rhesus monkeys, L. tropica-CsS-16 mice, L. amazonensis-CBA mice, L. braziliensis-golden hamster (or-rhesus monkey. We also provide in-depth guidance for which models are not suitable for these investigations.

  12. Refined Modeling of Water Temperature and Salinity in Coastal Areas

    Institute of Scientific and Technical Information of China (English)

    SHEN Yongming; ZHENG Yonghong; QIU Dahong

    2000-01-01

    The prediction of water temperature and salinity in coastal areas is one of the essential tasks in water quality control and management. This paper takes a refined forecasting model of water temperature and salinity in coastal areas as a basic target. Based on the Navier-Stokes equation and k- turbulence model, taking the characteristics of coastal areas into account, a refined model for water temperatureand salinity in coastal areas has been developed to simulate the seasonal variations of water temperatureand salinity fields in the Hakata Bay, Japan. The model takes into account the effects of a variety ofhydrodynamic and meteorological factors on water temperature and salinity. It predicts daily fluctuations in water temperature and salinity at different depths throughout the year. The model has been calibrated well against the data set of historical water temperature and salinity observations in the Hakata Bay,Japan.

  13. Grain refinement of AZ31 magnesium alloy by electromagnetic stirring under effect of grain-refiner

    Indian Academy of Sciences (India)

    S Y Gao; Q C Le; Z Q Zhang; J Z Cui

    2012-08-01

    The effects of electromagnetic stirring and Al4C3 grain refiner on the grain refinement of semicontinuously cast AZ31 magnesium alloy were discussed in this investigation. The results indicate that electromagnetic stirring has an effective refining effect on the grain size of AZ31 magnesium alloy under the effect of Al4C3 grain refiner. Electromagnetic stirring can `activate’ the Al4C3 particles, resulting in more heterogeneous nucleation sites for the primary -Mg grains. But, longer holding time can `deactivate’ the Al4C3 particles and poison the grain refining effect.

  14. Linear Prediction Using Refined Autocorrelation Function

    Directory of Open Access Journals (Sweden)

    M. Shahidur Rahman

    2007-07-01

    Full Text Available This paper proposes a new technique for improving the performance of linear prediction analysis by utilizing a refined version of the autocorrelation function. Problems in analyzing voiced speech using linear prediction occur often due to the harmonic structure of the excitation source, which causes the autocorrelation function to be an aliased version of that of the vocal tract impulse response. To estimate the vocal tract characteristics accurately, however, the effect of aliasing must be eliminated. In this paper, we employ homomorphic deconvolution technique in the autocorrelation domain to eliminate the aliasing effect occurred due to periodicity. The resulted autocorrelation function of the vocal tract impulse response is found to produce significant improvement in estimating formant frequencies. The accuracy of formant estimation is verified on synthetic vowels for a wide range of pitch frequencies typical for male and female speakers. The validity of the proposed method is also illustrated by inspecting the spectral envelopes of natural speech spoken by high-pitched female speaker. The synthesis filter obtained by the current method is guaranteed to be stable, which makes the method superior to many of its alternatives.

  15. Refinement for Probabilistic Systems with Nondeterminism

    Directory of Open Access Journals (Sweden)

    David Streader

    2011-06-01

    Full Text Available Before we combine actions and probabilities two very obvious questions should be asked. Firstly, what does "the probability of an action" mean? Secondly, how does probability interact with nondeterminism? Neither question has a single universally agreed upon answer but by considering these questions at the outset we build a novel and hopefully intuitive probabilistic event-based formalism. In previous work we have characterised refinement via the notion of testing. Basically, if one system passes all the tests that another system passes (and maybe more we say the first system is a refinement of the second. This is, in our view, an important way of characterising refinement, via the question "what sort of refinement should I be using?" We use testing in this paper as the basis for our refinement. We develop tests for probabilistic systems by analogy with the tests developed for non-probabilistic systems. We make sure that our probabilistic tests, when performed on non-probabilistic automata, give us refinement relations which agree with for those non-probabilistic automata. We formalise this property as a vertical refinement.

  16. Protein NMR structures refined without NOE data.

    Science.gov (United States)

    Ryu, Hyojung; Kim, Tae-Rae; Ahn, SeonJoo; Ji, Sunyoung; Lee, Jinhyuk

    2014-01-01

    The refinement of low-quality structures is an important challenge in protein structure prediction. Many studies have been conducted on protein structure refinement; the refinement of structures derived from NMR spectroscopy has been especially intensively studied. In this study, we generated flat-bottom distance potential instead of NOE data because NOE data have ambiguity and uncertainty. The potential was derived from distance information from given structures and prevented structural dislocation during the refinement process. A simulated annealing protocol was used to minimize the potential energy of the structure. The protocol was tested on 134 NMR structures in the Protein Data Bank (PDB) that also have X-ray structures. Among them, 50 structures were used as a training set to find the optimal "width" parameter in the flat-bottom distance potential functions. In the validation set (the other 84 structures), most of the 12 quality assessment scores of the refined structures were significantly improved (total score increased from 1.215 to 2.044). Moreover, the secondary structure similarity of the refined structure was improved over that of the original structure. Finally, we demonstrate that the combination of two energy potentials, statistical torsion angle potential (STAP) and the flat-bottom distance potential, can drive the refinement of NMR structures.

  17. New drugs targeting the cardiac ultra-rapid delayed-rectifier current (I Kur): rationale, pharmacology and evidence for potential therapeutic value.

    Science.gov (United States)

    Ford, John W; Milnes, James T

    2008-08-01

    There is a clear unmet medical need for new pharmacologic therapies for the treatment of atrial fibrillation (AF) with improved efficacy and safety. This article reviews the development of new and novel Kv1.5/ultra-rapid delayed-rectifier current (I Kur) inhibitors and presents evidence that Kv1.5 modulation provides an atrial-selective mechanism for treating AF. Academia and industry have invested heavily in Kv1.5 (>500 scientific publications and >50 patents published since 1993); however, to realize the full value of this therapeutic drug target, clinical efficacy and safety data are required for a selective Kv1.5 modulator. The reward for demonstrating clinical efficacy and safety in a pivotal Phase 3 trial, on regulatory approval, is "first in class" status.

  18. Measurements of the Total Charge-Changing Cross Sections for Collisions of Fast Ions with Target Gas Using High Current Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Covo, Michel Kireeff; Molvik, Arthur W.; Kaganovich, Igor D.; Shnidman, Ariel; Vujic, Jasmina L.

    2009-04-13

    The sum of ionization and charge-exchange cross sections of several gas targets (H2, N2, He, Ne, Kr, Xe, Ar, and water vapor) impacted by 1MeV K+ beam are measured. In a high current ion beam, the self-electric field of the beam is high enough that ions produced from the gas ionization or charge exchange by the ion beam are quickly swept to the sides of accelerator. The flux of the expelled ions is measured by a retarding field analyzer. This allows accurate measuring of the total charge-changing cross sections (ionization plus charge exchange) of the beam interaction with gas. Cross sections for H2, He, and N2 are simulated using classical trajectory Monte Carlo (CTMC) method and compared with the experimental results, showing good agreement.

  19. Editorial: Current status and perspective on drug targets in tubercle bacilli and drug design of antituberculous agents based on structure-activity relationship.

    Science.gov (United States)

    Tomioka, Haruaki

    2014-01-01

    Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. However, the development of new drugs for the treatment and prophylaxis of TB, particularly those truly active against dormant and persistent types of tubercle bacilli, has been slow, although some promising drugs, such as diarylquinoline TMC207, nitroimidazopyran PA-824, nitroimidazo-oxazole Delamanid (OPC-67683), oxazolidinone PNU-100480, ethylene diamine SQ-109, and pyrrole derivative LL3858, are currently under phase 1 to 3 clinical trials. Therefore, novel types of antituberculous drug, which act on unique drug targets in Mycobacterium tuberculosis (MTB) pathogens, particularly drug targets related to the establishment of mycobacterial dormancy in the host's macrophages, are urgently needed. In this context, it should be noted that current anti-TB drugs mostly target the metabolic reactions and proteins which are essential for the growth of MTB in extracellular milieus. It may also be promising to develop another type of drug that exerts an inhibitory action against bacterial virulence factors which cross-talk and interfere with signaling pathways of MTB-infected immunocompetent host cells, such as lymphocytes, macrophages, and NK cells, thereby changing the intracellular milieus that are favorable to intramacrophage survival and the growth of infected bacilli. This special issue contains ten review articles, dealing with recent approaches to identify and establish novel drug targets in MTB for the development of new and unique antitubercular drugs, including those related to mycobacterial dormancy and crosstalk with cellular signaling pathways. In addition, this special issue contains some review papers with special reference to the drug design based on quantitative structure-activity relationship (QSAR) analysis, especially three-dimensional (3D)-QSAR. New, critical information on the entire genome of MTB and mycobacterial virulence genes is

  20. Structure prediction for CASP8 with all-atom refinement using Rosetta

    Science.gov (United States)

    Raman, Srivatsan; Vernon, Robert; Thompson, James; Tyka, Michael; Sadreyev, Ruslan; Pei, Jimin; Kim, David; Kellogg, Elizabeth; DiMaio, Frank; Lange, Oliver; Kinch, Lisa; Sheffler, Will; Kim, Bong-Hyun; Das, Rhiju; Grishin, Nick V.; Baker, David

    2012-01-01

    We describe predictions made using the Rosetta structure prediction methodology for the Eighth Critical Assessment of Techniques for Protein Structure Prediction. Aggressive sampling and all-atom refinement were carried out for nearly all targets. A combination of alignment methodologies was used to generate starting models from a range of templates, and the models were then subjected to Rosetta all atom refinement. For 50 targets with readily identified templates, the best submitted model was better than the best alignment to the best template in the Protein Data Bank for 24 domains, and improved over the best starting model for 43 domains. For 13 targets where only very distant sequence relationships to proteins of known structure were detected, models were generated using the Rosetta de novo structure prediction methodology followed by all-atom refinement; in several cases the submitted models were better than those based on the available templates. Of the 12 refinement challenges, the best submitted model improved on the starting model in 7 cases. These improvements over the starting template-based models and refinement tests demonstrate the power of Rosetta structure refinement in improving model accuracy. PMID:19701941

  1. EGFR-targeted drugs for colorectal cancer: current status and future challenges%EGFR靶向药物在结直肠癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    王丽; 余英豪

    2011-01-01

    Colorectal cancer is a common gastrointestinal malignancy. The effects of traditional chemotherapy and radiation therapy against colorectal cancer are not satisfactory. The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in tumor proliferation, angiogenesis, invasion, and metastasis in colorectal cancer. EGFR-targeted drugs have been developed and applied to the treatment of colorectal cancer. This paper provides a literature review on the current status and future challenges of EGFR-targeted therapy of colorectal cancer.%结直肠癌是常见的消化系恶性肿瘤,传统的化疗和放疗效果均不甚理想.表皮生长因子受体(EGFR)q%号转导通路在结直肠癌细胞的增殖、血管生成、侵袭、转移等方面有重要作用.因此,针对EGFR的靶向药物已陆续开发,并应用于结直肠癌治疗的临床实践.本文就EGFR靶向药物在结直肠癌中的研究现状及其相关问题进行综述.

  2. Lossless, Near-Lossless, and Refinement Coding of Bi-level Images

    DEFF Research Database (Denmark)

    Martins, Bo; Forchhammer, Søren Otto

    1997-01-01

    We present general and unified algorithms for lossy/lossless codingof bi-level images. The compression is realized by applying arithmetic coding to conditional probabilities. As in the current JBIG standard the conditioning may be specified by a template.For better compression, the more general...... to the specialized soft pattern matching techniques which work better for text. Template based refinement coding is applied for lossy-to-lossless refinement.We demonstrate that both single pass refinement coding and multiple pass refinement coding yielding progressive build-up may be carried out very efficiently....... Introducing only a small amount of loss in halftoned test images, compression is increased by up to a factor of four compared with JBIG. Lossy, lossless, and refinement decoding speed and lossless encoding speed are less than a factor of two slower than JBIG. The (de)coding method is proposed as part of JBIG...

  3. Spectral-element adaptive refinement magnetohydrodynamic simulations of the island coalescence instability

    Science.gov (United States)

    Rosenberg, D.; Pouquet, A.; Germaschewski, K.; Ng, C. S.; Bhattacharjee, A.

    2006-10-01

    A recently developed spectral-element adaptive refinement incompressible magnetohydrodynamic (MHD) code is applied to simulate the problem of island coalescence instability (ICI) in 2D. The MHD solver is explicit, and uses the Elsasser formulation on high-order elements. It automatically takes advantage of the adaptive grid mechanics that have been described in [Rosenberg, Fournier, Fischer, Pouquet, J. Comp. Phys., 215, 59-80 (2006)], allowing both statically refined and dynamically refined grids. ICI is a MHD process that can produce strong current sheets and subsequent reconnection and heating in a high-Lundquist number plasma such as the solar corona [cf., Ng and Bhattacharjee, Phys. Plasmas, 5, 4028 (1998)]. Thus, it is desirable to use adaptive refinement grids to increase resolution, and to maintain accuracy at the same time. Results are compared with simulations using finite difference method with the same refinement grid, as well as pesudo-spectral simulations using uniform grid.

  4. A Matricial Algorithm for Polynomial Refinement

    CERN Document Server

    King, Emily J

    2011-01-01

    In order to have a multiresolution analysis, the scaling function must be refinable. That is, it must be the linear combination of 2-dilation, $\\mathbb{Z}$-translates of itself. Refinable functions used in connection with wavelets are typically compactly supported. In 2002, David Larson posed the question, "Are all polynomials (of a single variable) finitely refinable?" That summer the author proved that the answer indeed was true using basic linear algebra. The result was presented in a number of talks but had not been typed up until now. The purpose of this short note is to record that particular proof.

  5. Bipolar Neutrosophic Refined Sets and Their Applications in Medical Diagnosis

    OpenAIRE

    Deli, Irfan; Yusuf, Şubaş

    2016-01-01

    This paper proposes concept of bipolar neutrosophic refined set and its some operations. Firstly, a score certainty and accuracy function to compare the bipolar neutrosophic refined information is defined. Secondly, to aggregate the bipolar neutrosophic refined information, a bipolar neutrosophic refined weighted average operator and a bipolar neutrosophic refined weighted geometric operator is developed.

  6. Bipolar Neutrosophic Refined Sets and Their Applications in Medical Diagnosis

    OpenAIRE

    Deli, Irfan; Yusuf, Şubaş

    2016-01-01

    This paper proposes concept of bipolar neutrosophic refined set and its some operations. Firstly, a score certainty and accuracy function to compare the bipolar neutrosophic refined information is defined. Secondly, to aggregate the bipolar neutrosophic refined information, a bipolar neutrosophic refined weighted average operator and a bipolar neutrosophic refined weighted geometric operator is developed.

  7. NASA's Advanced Exploration Systems Mars Transit Habitat Refinement Point of Departure Design

    Science.gov (United States)

    Simon, Matthew; Latorella, Kara; Martin, John; Cerro, Jeff; Lepsch, Roger; Jefferies, Sharon; Goodliff, Kandyce; McCleskey, Carey; Smitherman, David; Stromgren, Chel

    2017-01-01

    This paper describes the recently developed point of departure design for a long duration, reusable Mars Transit Habitat, which was established during a 2016 NASA habitat design refinement activity supporting the definition of NASA's Evolvable Mars Campaign. As part of its development of sustainable human Mars mission concepts achievable in the 2030s, the Evolvable Mars Campaign has identified desired durations and mass/dimensional limits for long duration Mars habitat designs to enable the currently assumed solar electric and chemical transportation architectures. The Advanced Exploration Systems Mars Transit Habitat Refinement Activity brought together habitat subsystem design expertise from across NASA to develop an increased fidelity, consensus design for a transit habitat within these constraints. The resulting design and data (including a mass equipment list) contained in this paper are intended to help teams across the agency and potential commercial, academic, or international partners understand: 1) the current architecture/habitat guidelines and assumptions, 2) performance targets of such a habitat (particularly in mass, volume, and power), 3) the driving technology/capability developments and architectural solutions which are necessary for achieving these targets, and 4) mass reduction opportunities and research/design needs to inform the development of future research and proposals. Data presented includes: an overview of the habitat refinement activity including motivation and process when informative; full documentation of the baseline design guidelines and assumptions; detailed mass and volume breakdowns; a moderately detailed concept of operations; a preliminary interior layout design with rationale; a list of the required capabilities necessary to enable the desired mass; and identification of any worthwhile trades/analyses which could inform future habitat design efforts. As a whole, the data in the paper show that a transit habitat meeting the 43

  8. Current and emerging treatment options for ANCA-associated vasculitis: potential role of belimumab and other BAFF/APRIL targeting agents

    Directory of Open Access Journals (Sweden)

    Lenert A

    2015-01-01

    Full Text Available Aleksander Lenert,1 Petar Lenert21Division of Rheumatology, University of Kentucky, Kentucky Clinic, Lexington, KY, USA; 2Division of Immunology, Department of Internal Medicine, The University of Iowa, Iowa City, IA, USAAbstract: Antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission induction, and rituximab appeared even more beneficial in patients with relapsing disease. This raised hopes that other B-cell-targeted therapies directed either against CD19, CD20, CD22, or B-cell survival factors, B-cell activating factor of the tumor necrosis factor family (BAFF and a proliferation-inducing ligand could also be beneficial for the management of AAV. BAFF neutralization with the fully humanized monoclonal antibody belimumab has already shown success in human systemic lupus erythematosus and, along with another anti-BAFF reagent blisibimod, is currently undergoing Phase II and III clinical trials in AAV. Local production of BAFF in granulomatous lesions and elevated levels of serum BAFF in AAV provide a rationale for BAFF-targeted therapies not only in AAV but also in other forms of vasculitis such as Behcet’s disease, large-vessel vasculitis, or cryoglobulinemic vasculitis secondary to chronic hepatitis C infection. BAFF-targeted

  9. Multivariate refinement equation with nonnegative masks

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper is concerned with multivariate refinement equations of the type ψ = ∑α∈Zs a(α)ψ(Mx - α),where ψ is the unknown function defined on the s-dimensional Euclidean space Rs, a is a finitely supported nonnegative sequence on Zs, and M is an s × s dilation matrix with m := |detM|. We characterize the existence of L2-solution of refinement equation in terms of spectral radius of a certain finite matrix or transition operator associated with refinement mask a and dilation matrix M. For s = 1 and M = 2, the sufficient and necessary conditions are obtained to characterize the existence of continuous solution of this refinement equation.

  10. Refining the theory of basic individual values.

    Science.gov (United States)

    Schwartz, Shalom H; Cieciuch, Jan; Vecchione, Michele; Davidov, Eldad; Fischer, Ronald; Beierlein, Constanze; Ramos, Alice; Verkasalo, Markku; Lönnqvist, Jan-Erik; Demirutku, Kursad; Dirilen-Gumus, Ozlem; Konty, Mark

    2012-10-01

    We propose a refined theory of basic individual values intended to provide greater heuristic and explanatory power than the original theory of 10 values (Schwartz, 1992). The refined theory more accurately expresses the central assumption of the original theory that research has largely ignored: Values form a circular motivational continuum. The theory defines and orders 19 values on the continuum based on their compatible and conflicting motivations, expression of self-protection versus growth, and personal versus social focus. We assess the theory with a new instrument in 15 samples from 10 countries (N = 6,059). Confirmatory factor and multidimensional scaling analyses support discrimination of the 19 values, confirming the refined theory. Multidimensional scaling analyses largely support the predicted motivational order of the values. Analyses of predictive validity demonstrate that the refined values theory provides greater and more precise insight into the value underpinnings of beliefs. Each value correlates uniquely with external variables.

  11. Progressive refinement for robust image registration

    Institute of Scientific and Technical Information of China (English)

    Li Song; Yuanhua Zhou; Jun Zhou

    2005-01-01

    @@ A new image registration algorithm with robust cost function and progressive refinement estimation is developed on the basis of direct method (DM). The robustness lies in M-estimation to avert larger local noise and outliers.

  12. Oil Refining Giants to Cut Output

    Institute of Scientific and Technical Information of China (English)

    Zhang Dingmin

    2002-01-01

    @@ China's refined oil product output rose slightly in the first five months of this year on strong demand,but the two biggest domestic producers plan to cut production rates in an attempt to bolster the sluggish price.

  13. Role of functional imaging in the development and refinement of invasive neuromodulation for psychiatric disorders

    Institute of Scientific and Technical Information of China (English)

    Nolan; R; Williams; Joseph; J; Taylor; Kayla; Lamb; Colleen; A; Hanlon; E; Baron; Short; Mark; S; George

    2014-01-01

    Deep brain stimulation(DBS) is emerging as a pow-erful tool for the alleviation of targeted symptoms in treatment-resistant neuropsychiatric disorders. Despite the expanding use of neuropsychiatric DBS, the mecha-nisms responsible for its effects are only starting to be elucidated. Several modalities such as quantitative elec-troencephalography as well a intraoperative recordings have been utilized to attempt to understand the under-pinnings of this new treatment modality, but functional imaging appears to offer several unique advantages. Functional imaging techniques like positron emission tomography, single photon emission computed tomog-raphy and functional magnetic resonance imaging have been used to examine the effects of focal DBS on activ-ity in a distributed neural network. These investigations are critical for advancing the field of invasive neuro-modulation in a safe and effective manner, particularly in terms of defining the neuroanatomical targets and refining the stimulation protocols. The purpose of this review is to summarize the current functional neuroim-aging findings from neuropsychiatric DBS implantation for three disorders: treatment-resistant depression, obsessive-compulsive disorder, and Tourette syndrome. All of the major targets will be discussed(Nucleus ac-cumbens, anterior limb of internal capsule, subcallosal cingulate, Subthalamic nucleus, Centromedial nucleus of the thalamus-Parafasicular complex, frontal pole, and dorsolateral prefrontal cortex). We will also address some apparent inconsistencies within this literature, and suggest potential future directions for this promis-ing area.

  14. Multidataset Refinement Resonant Diffraction, and Magnetic Structures

    OpenAIRE

    Attfield, J. Paul

    2004-01-01

    The scope of Rietveld and other powder diffraction refinements continues to expand, driven by improvements in instrumentation, methodology and software. This will be illustrated by examples from our research in recent years. Multidataset refinement is now commonplace; the datasets may be from different detectors, e.g., in a time-of-flight experiment, or from separate experiments, such as at several x-ray energies giving resonant information. The complementary use of x rays and neutrons is exe...

  15. Corrosion problems and solutions in oil refining and petrochemical industry

    CERN Document Server

    Groysman, Alec

    2017-01-01

    This book addresses corrosion problems and their solutions at facilities in the oil refining and petrochemical industry, including cooling water and boiler feed water units. Further, it describes and analyzes corrosion control actions, corrosion monitoring, and corrosion management. Corrosion problems are a perennial issue in the oil refining and petrochemical industry, as they lead to a deterioration of the functional properties of metallic equipment and harm the environment – both of which need to be protected for the sake of current and future generations. Accordingly, this book examines and analyzes typical and atypical corrosion failure cases and their prevention at refineries and petrochemical facilities, including problems with: pipelines, tanks, furnaces, distillation columns, absorbers, heat exchangers, and pumps. In addition, it describes naphthenic acid corrosion, stress corrosion cracking, hydrogen damages, sulfidic corrosion, microbiologically induced corrosion, erosion-corrosion, and corrosion...

  16. Refined empirical line method to calibrate IKONOS imagery

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To extract quantitative biophysical parameters such as leaf biomass and leaf chlorophyll concentration from the remotely sensed imagery, the effect of atmospheric attenuation must be removed. The refined empirical line (REL) method was used to calibrate the IKONOS multispectral imagery. The IKONOS digital numbers (DN) were converted to the at-satellite retargets are unavailable or measurement of dark target is inconvenient, the REL method was most crucial for retrieving surface spectral reflectance. The REL offers a simple approach for quantitative retrieval of biophysical parameters from IKONOS imagery.

  17. Mechanism of pulse magneto-oscillation grain refinement on pure Al

    Directory of Open Access Journals (Sweden)

    Pei Ning

    2011-02-01

    Full Text Available Pulse magneto-oscillation (PMO was developed as a novel technique to refine the solidification structure of pure aluminium. Its grain refining mechanism was proposed. The PMO refinement mechanism is that the nucleus falls off from the mould wall and drifts into the melt under the action of PMO. The solidification structure of Al melt depends on the linear electric current density, and also the discharge and oscillation frequencies. The radial pressure of PMO sound wave is the major factor that contributes to the migration of nucleus into the melt.

  18. Fatigue strength of MAR-M509 alloy with structure refined by rapid crystallization

    Directory of Open Access Journals (Sweden)

    M. Mróz

    2010-07-01

    Full Text Available This study presents test results of high-cycle (N>2⋅107 fatigue bending strength of MAR-M-509 cobalt alloy samples, as cast and aftersurface refining with a concentrated stream of heat. Tests were conducted on samples of MAR-M59 alloy casts, obtained using the lostwax method. Cast structure refining was performed with the GTAW method in argon atmosphere, using the current I = 200 A andelectrical arc scanning velocity vs = 250 mm/min. The effect of rapid crystallization occurring after the fusion process is refinement of the MAR-M509 alloy cast microstructure and significant improvement in bending fatigue strength.

  19. Some Strategies for the Refinement of Disordered Structures with the SHELXL-97 Refinement Program

    Institute of Scientific and Technical Information of China (English)

    Ng Seik Weng

    2005-01-01

    Examples of the refinement of disordered structures taken from work published in Acta Crystallographica are presented together with explanations on how the disordered structures are dealt with. The constraint and restraint commands in the SHELXL-97 refinement program that are specific to the particular type of disorder are described. Some ways to divine the hydrogen atoms on water are given in detail. The refinements of the Flack parameters and twinned structures are briefly discussed.

  20. A unified framework for mesh refinement in random and physical space

    Science.gov (United States)

    Li, Jing; Stinis, Panos

    2016-10-01

    In recent work we have shown how an accurate reduced model can be utilized to perform mesh refinement in random space. That work relied on the explicit knowledge of an accurate reduced model which is used to monitor the transfer of activity from the large to the small scales of the solution. Since this is not always available, we present in the current work a framework which shares the merits and basic idea of the previous approach but does not require an explicit knowledge of a reduced model. Moreover, the current framework can be applied for refinement in both random and physical space. In this manuscript we focus on the application to random space mesh refinement. We study examples of increasing difficulty (from ordinary to partial differential equations) which demonstrate the efficiency and versatility of our approach. We also provide some results from the application of the new framework to physical space mesh refinement.

  1. Game Refinement Relations and Metrics

    CERN Document Server

    de Alfaro, Luca; Raman, Vishwanath; Stoelinga, Mariëlle

    2008-01-01

    We consider two-player games played over finite state spaces for an infinite number of rounds. At each state, the players simultaneously choose moves; the moves determine a successor state. It is often advantageous for players to choose probability distributions over moves, rather than single moves. Given a goal, for example, reach a target state, the question of winning is thus a probabilistic one: what is the maximal probability of winning from a given state? On these game structures, two fundamental notions are those of equivalences and metrics. Given a set of winning conditions, two states are equivalent if the players can win the same games with the same probability from both states. Metrics provide a bound on the difference in the probabilities of winning across states, capturing a quantitative notion of state similarity. We introduce equivalences and metrics for two-player game structures, and we show that they characterize the difference in probability of winning games whose goals are expressed in the...

  2. Refining search terms for nanotechnology

    Science.gov (United States)

    Porter, Alan L.; Youtie, Jan; Shapira, Philip; Schoeneck, David J.

    2008-05-01

    The ability to delineate the boundaries of an emerging technology is central to obtaining an understanding of the technology's research paths and commercialization prospects. Nowhere is this more relevant than in the case of nanotechnology (hereafter identified as "nano") given its current rapid growth and multidisciplinary nature. (Under the rubric of nanotechnology, we also include nanoscience and nanoengineering.) Past efforts have utilized several strategies, including simple term search for the prefix nano, complex lexical and citation-based approaches, and bootstrapping techniques. This research introduces a modularized Boolean approach to defining nanotechnology which has been applied to several research and patenting databases. We explain our approach to downloading and cleaning data, and report initial results. Comparisons of this approach with other nanotechnology search formulations are presented. Implications for search strategy development and profiling of the nanotechnology field are discussed.

  3. Refining search terms for nanotechnology

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Alan L. [Georgia Institute of Technology (United States); Youtie, Jan [Georgia Institute of Technology, Enterprise Innovation Institute (United States)], E-mail: jan.youtie@innovate.gatech.edu; Shapira, Philip [Georgia Institute of Technology (United States); Schoeneck, David J. [Search Technology, Inc. (United States)

    2008-05-15

    The ability to delineate the boundaries of an emerging technology is central to obtaining an understanding of the technology's research paths and commercialization prospects. Nowhere is this more relevant than in the case of nanotechnology (hereafter identified as 'nano') given its current rapid growth and multidisciplinary nature. (Under the rubric of nanotechnology, we also include nanoscience and nanoengineering.) Past efforts have utilized several strategies, including simple term search for the prefix nano, complex lexical and citation-based approaches, and bootstrapping techniques. This research introduces a modularized Boolean approach to defining nanotechnology which has been applied to several research and patenting databases. We explain our approach to downloading and cleaning data, and report initial results. Comparisons of this approach with other nanotechnology search formulations are presented. Implications for search strategy development and profiling of the nanotechnology field are discussed.

  4. Multidataset Refinement Resonant Diffraction, and Magnetic Structures.

    Science.gov (United States)

    Attfield, J Paul

    2004-01-01

    The scope of Rietveld and other powder diffraction refinements continues to expand, driven by improvements in instrumentation, methodology and software. This will be illustrated by examples from our research in recent years. Multidataset refinement is now commonplace; the datasets may be from different detectors, e.g., in a time-of-flight experiment, or from separate experiments, such as at several x-ray energies giving resonant information. The complementary use of x rays and neutrons is exemplified by a recent combined refinement of the monoclinic superstructure of magnetite, Fe3O4, below the 122 K Verwey transition, which reveals evidence for Fe(2+)/Fe(3+) charge ordering. Powder neutron diffraction data continue to be used for the solution and Rietveld refinement of magnetic structures. Time-of-flight instruments on cold neutron sources can produce data that have a high intensity and good resolution at high d-spacings. Such profiles have been used to study incommensurate magnetic structures such as FeAsO4 and β-CrPO4. A multiphase, multidataset refinement of the phase-separated perovskite (Pr0.35Y0.07Th0.04Ca0.04Sr0.5)MnO3 has been used to fit three components with different crystal and magnetic structures at low temperatures.

  5. The evolution of oil refining in Europe

    Energy Technology Data Exchange (ETDEWEB)

    Reid, A. [CONCAWE, Brussels (Belgium)

    2013-04-01

    Back in 1963 when CONCAWE was founded, the world looked very different from what it is today, and so did the global and European refining industry. Oil product markets were expanding fast and new refineries were being built at a steady rate. The oil crisis of the 1970s brought an abrupt end to this, heralding a long era of consolidation and stepwise adaptation. At the same time the nature of the global oil business shifted from fully integrated companies producing, transporting and refining their own oil to a much more diversified situation where oil production ('upstream') and refining/distribution ('downstream') gradually became two essentially separate businesses. From being purely a 'cost centre' in an integrated chain, refining has become a separate activity in its own right, operating as a 'profit centre' between two global markets - crude oil and products - which, although not entirely independent, have their own dynamics and influences. In addition demand gradually shifted towards lighter products while the quality requirements on all products were considerably tightened. This article explores the new challenges that these changes have imposed on EU refiners, and describes CONCAWE's contributions to understanding their impact on refinery production and investments.

  6. Nose tip refinement using interdomal suture in caucasian nose

    Directory of Open Access Journals (Sweden)

    Pasinato, Rogério

    2012-01-01

    Full Text Available Introduction: Refinement of the nose tip can be accomplished by a variety of techniques, but currently, the use of sutures in the nasal tip with conservative resection of the alar cartilage is the most frequently recommended approach. Objective: To classify the nasal tip and to demonstrate the interdomal suture applied to nasal tip refinement in the Caucasian nose, as well as to provide a simple and practical presentation of the surgical steps. Method: Development of surgical algorithm for nasal tip surgery: 1. Interdomal suture (double binding suture, 2. Interdomal suture with alar cartilage weakening (cross-hatching, 3. Interdomal suture with cephalic removal of the alar cartilage (McIndoe technique based on the nasal tip type classification. This classification assesses the interdomal distance (angle of domal divergence and intercrural distance, domal arch width, cartilage consistency, and skin type. Interdomal suture is performed through endonasal rhinoplasty by basic technique without delivery (Converse-Diamond technique under local anesthesia Conclusion: This classification is simple and facilitates the approach of surgical treatment of the nasal tip through interdomal suture, systematizing and standardizing surgical maneuvers for better refinement of the Caucasian nose.

  7. The role of optimization in structural model refinement

    Science.gov (United States)

    Lehman, L. L.

    1984-01-01

    To evaluate the role that optimization can play in structural model refinement, it is necessary to examine the existing environment for the structural design/structural modification process. The traditional approach to design, analysis, and modification is illustrated. Typically, a cyclical path is followed in evaluating and refining a structural system, with parallel paths existing between the real system and the analytical model of the system. The major failing of the existing approach is the rather weak link of communication between the cycle for the real system and the cycle for the analytical model. Only at the expense of much human effort can data sharing and comparative evaluation be enhanced for the two parallel cycles. Much of the difficulty can be traced to the lack of a user-friendly, rapidly reconfigurable engineering software environment for facilitating data and information exchange. Until this type of software environment becomes readily available to the majority of the engineering community, the role of optimization will not be able to reach its full potential and engineering productivity will continue to suffer. A key issue in current engineering design, analysis, and test is the definition and development of an integrated engineering software support capability. The data and solution flow for this type of integrated engineering analysis/refinement system is shown.

  8. A new refinement indicator for adaptive parameterization: Application to the estimation of the diffusion coefficient in an elliptic problem

    Science.gov (United States)

    Hayek, Mohamed; Ackerer, Philippe; Sonnendrücker, Éric

    2009-02-01

    We propose a new refinement indicator (NRI) for adaptive parameterization to determine the diffusion coefficient in an elliptic equation in two-dimensional space. The diffusion coefficient is assumed to be a piecewise constant space function. The unknowns are both the parameter values and the zonation. Refinement indicators are used to localize parameter discontinuities in order to construct iteratively the zonation (parameterization). The refinement indicator is obtained usually by using the first-order effect on the objective function of removing degrees of freedom for a current set of parameters. In this work, in order to reduce the computation costs, we propose a new refinement indicator based on the second-order effect on the objective function. This new refinement indicator depends on the objective function, and its first and second derivatives with respect to the parameter constraints. Numerical experiments show the high efficiency of the new refinement indicator compared to the standard one.

  9. Refined exposure assessment for Brilliant Black BN (E 151

    Directory of Open Access Journals (Sweden)

    European Food Safety Authority

    2015-01-01

    Full Text Available The European Food Safety Authority (EFSA carried out an exposure assessment of Brilliant Black BN (E 151, taking into account new information on its use as a food additive in foods. In 2010, the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS adopted a scientific opinion on the re-evaluation of Brilliant Black BN and concluded that dietary exposure in 1- to 10-year-old children at the high level may exceed the Acceptable Daily Intake (ADI for Brilliant Black BN of 5 mg/kg body weight (bw/day at the upper end of the range. Following this conclusion, the European Commission requested that EFSA performs a refined exposure assessment for this food colour. Data on the presence of Brilliant Black BN in foods were requested from relevant stakeholders through a call for usage and concentration data. Usage levels were provided to EFSA for 11 out of 37 food categories in which Brilliant Black is authorised. In addition, 4 337 analytical results were also reported to EFSA, with the majority of values being below the limit of detection (LOD or limit of quantification (LOQ. Exposure assessment was performed using the EFSA Comprehensive Food Consumption Database. Three scenarios were considered: (1 exposure estimates based on Maximum Permitted Levels (MPLs, (2 a refined brand-loyal exposure scenario, and (3 a refined non-brand-loyal exposure scenario. Considering the first scenario, high exposure levels (95th percentile exceeded the ADI for toddlers and children in four dietary surveys. In comparison with the previous assessment, for both children and adults, the current mean exposure estimates are of the same order of magnitude, whereas the 95th percentile exposure is lower, particularly in adults. The mean and high-level exposure estimates of Brilliant Black BN are below the ADI for all population groups when considering the refined scenarios (brand-loyal and non-brand-loyal.

  10. Refining Animal Models to Enhance Animal Welfare

    Institute of Scientific and Technical Information of China (English)

    Patricia V.Turner

    2012-01-01

    The use of animals in research will be necessary for scientific advances in the basic and biomedical sciences for the foreseeable future.As we learn more about the ability of animals to experience pain,suffering,and distress,and particularly for mammals,it becomes the responsibility of scientists,institutions,animal caregivers,and veterinarians to seek ways to improve the lives of research animals and refine their care and use.Refinement is one of the three R's emphasized by Russell and Burch,and refers to modification of procedures to minimise the potential for pain,suffering and distress. It may also refer to procedures used to enhance animal comfort. This paper summarizes considerations for refinements in research animal.

  11. FEM electrode refinement for electrical impedance tomography.

    Science.gov (United States)

    Grychtol, Bartlomiej; Adler, Andy

    2013-01-01

    Electrical Impedance Tomography (EIT) reconstructs images of electrical tissue properties within a body from electrical transfer impedance measurements at surface electrodes. Reconstruction of EIT images requires the solution of an inverse problem in soft field tomography, where a sensitivity matrix, J, of the relationship between internal changes and measurements is calculated, and then a pseudo-inverse of J is used to update the image estimate. It is therefore clear that a precise calculation of J is required for solution accuracy. Since it is generally not possible to use analytic solutions, the finite element method (FEM) is typically used. It has generally been recommended in the EIT literature that FEMs be refined near electrodes, since the electric field and sensitivity is largest there. In this paper we analyze the accuracy requirement for FEM refinement near electrodes in EIT and describe a technique to refine arbitrary FEMs.

  12. Model refinement for offshore platforms: Experimental study

    Science.gov (United States)

    Zhang, Min; Chen, Zongli; Wu, Yanjian

    2017-08-01

    Offshore jacket platforms are widely used in offshore oil and gas exploitation. Finite element models of such structures need to have many degrees of freedom (DOFs) to represent the geometrical detail of complex structures, thereby leading to incompatibility in the number of DOFs of experimental models. To bring them both to the same order while ensuring that the essential eigen- properties of the refined model match those of experimental models, an extended model refinement procedure is presented in this paper. Vibration testing of an offshore jacket platform model is performed to validate the applicability of the proposed approach. A full-order finite element model of the platform is established and then tuned to meet the measured modal properties identified from the acceleration signals. Both model reduction and modal expansion methods are investigated, as well as various scenarios of sensor arrangements. Upon completion of the refinement, the updated jacket platform model matches the natural frequencies of the measured model well.

  13. Refining Linear Fuzzy Rules by Reinforcement Learning

    Science.gov (United States)

    Berenji, Hamid R.; Khedkar, Pratap S.; Malkani, Anil

    1996-01-01

    Linear fuzzy rules are increasingly being used in the development of fuzzy logic systems. Radial basis functions have also been used in the antecedents of the rules for clustering in product space which can automatically generate a set of linear fuzzy rules from an input/output data set. Manual methods are usually used in refining these rules. This paper presents a method for refining the parameters of these rules using reinforcement learning which can be applied in domains where supervised input-output data is not available and reinforcements are received only after a long sequence of actions. This is shown for a generalization of radial basis functions. The formation of fuzzy rules from data and their automatic refinement is an important step in closing the gap between the application of reinforcement learning methods in the domains where only some limited input-output data is available.

  14. The Influence of Grain Refiners on the Efficiency of Ceramic Foam Filters

    Science.gov (United States)

    Towsey, Nicholas; Schneider, Wolfgang; Krug, Hans-Peter; Hardman, Angela; Keegan, Neil J.

    An extensive program of work has been carried out to evaluate the efficiency of ceramic foam filters under carefully controlled conditions. Work reported at previous TMS meetings showed that in the absence of grain refiners, ceramic foam filters have the capacity for high filtration efficiency and consistent, reliable performance. The current phase of the investigation focuses on the impact grain refiner additions have on filter performance. The high filtration efficiencies obtained using 50 or 80ppi CFF's in the absence of grain refiners diminish when Al-3%Ti-1%B grain refiners are added. This, together with the impact of incoming inclusion loading on filter performance and the level of grain refiner addition are considered in detail. The new generation Al-3%Ti-0.15%C grain refiner has also been included. At typical addition levels (1kg/tonne) the effect on filter efficiency is similar to that for TiB2based grain refiners. The work was again conducted on a production scale using AA1050 alloy. Metal quality was determined using LiMCA and PoDFA. Spent filters were also analysed.

  15. Grid refinement for entropic lattice Boltzmann models.

    Science.gov (United States)

    Dorschner, B; Frapolli, N; Chikatamarla, S S; Karlin, I V

    2016-11-01

    We propose a multidomain grid refinement technique with extensions to entropic incompressible, thermal, and compressible lattice Boltzmann models. Its validity and accuracy are assessed by comparison to available direct numerical simulation and experiment for the simulation of isothermal, thermal, and viscous supersonic flow. In particular, we investigate the advantages of grid refinement for the setups of turbulent channel flow, flow past a sphere, Rayleigh-Bénard convection, as well as the supersonic flow around an airfoil. Special attention is paid to analyzing the adaptive features of entropic lattice Boltzmann models for multigrid simulations.

  16. Grid refinement for entropic lattice Boltzmann models

    CERN Document Server

    Dorschner, B; Chikatamarla, S S; Karlin, I V

    2016-01-01

    We propose a novel multi-domain grid refinement technique with extensions to entropic incompressible, thermal and compressible lattice Boltzmann models. Its validity and accuracy are accessed by comparison to available direct numerical simulation and experiment for the simulation of isothermal, thermal and viscous supersonic flow. In particular, we investigate the advantages of grid refinement for the set-ups of turbulent channel flow, flow past a sphere, Rayleigh-Benard convection as well as the supersonic flow around an airfoil. Special attention is payed to analyzing the adaptive features of entropic lattice Boltzmann models for multi-grid simulations.

  17. Contextual Distance Refining for Image Retrieval

    KAUST Repository

    Islam, Almasri

    2014-09-16

    Recently, a number of methods have been proposed to improve image retrieval accuracy by capturing context information. These methods try to compensate for the fact that a visually less similar image might be more relevant because it depicts the same object. We propose a new quick method for refining any pairwise distance metric, it works by iteratively discovering the object in the image from the most similar images, and then refine the distance metric accordingly. Test show that our technique improves over the state of art in terms of accuracy over the MPEG7 dataset.

  18. Concrete Cutting Refinement for Crater Repair

    Science.gov (United States)

    2015-08-01

    ER D C/ G SL T R- 15 -2 9 Concrete Cutting Refinement for Crater Repair G eo te ch ni ca l a nd S tr uc tu re s La bo ra to ry...by ERDC, visit the ERDC online library at http://acwc.sdp.sirsi.net/client/default. ERDC/GSL TR-15-29 August 2015 Concrete Cutting Refinement...equipment in both soft and hard aggregate-mixed concrete . The investigated equipment included the Vermeer RW1236W and CC1531, Caterpillar SW45 and

  19. Using supercritical fluids to refine hydrocarbons

    Science.gov (United States)

    Yarbro, Stephen Lee

    2015-06-09

    A system and method for reactively refining hydrocarbons, such as heavy oils with API gravities of less than 20 degrees and bitumen-like hydrocarbons with viscosities greater than 1000 cp at standard temperature and pressure, using a selected fluid at supercritical conditions. A reaction portion of the system and method delivers lightweight, volatile hydrocarbons to an associated contacting unit which operates in mixed subcritical/supercritical or supercritical modes. Using thermal diffusion, multiphase contact, or a momentum generating pressure gradient, the contacting unit separates the reaction products into portions that are viable for use or sale without further conventional refining and hydro-processing techniques.

  20. Relativistic MHD with Adaptive Mesh Refinement

    CERN Document Server

    Anderson, M; Liebling, S L; Neilsen, D; Anderson, Matthew; Hirschmann, Eric; Liebling, Steven L.; Neilsen, David

    2006-01-01

    We solve the relativistic magnetohydrodynamics (MHD) equations using a finite difference Convex ENO method (CENO) in 3+1 dimensions within a distributed parallel adaptive mesh refinement (AMR) infrastructure. In flat space we examine a Balsara blast wave problem along with a spherical blast wave and a relativistic rotor test both with unigrid and AMR simulations. The AMR simulations substantially improve performance while reproducing the resolution equivalent unigrid simulation results. We also investigate the impact of hyperbolic divergence cleaning for the spherical blast wave and relativistic rotor. We include unigrid and mesh refinement parallel performance measurements for the spherical blast wave.

  1. Refining - Panorama 2008; Raffinage - Panorama 2008

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    Investment rallied in 2007, and many distillation and conversion projects likely to reach the industrial stage were announced. With economic growth sustained in 2006 and still pronounced in 2007, oil demand remained strong - especially in emerging countries - and refining margins stayed high. Despite these favorable business conditions, tensions persisted in the refining sector, which has fallen far behind in terms of investing in refinery capacity. It will take renewed efforts over a long period to catch up. Looking at recent events that have affected the economy in many countries (e.g. the sub-prime crisis), prudence remains advisable.

  2. Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats.

    Science.gov (United States)

    Chi, Liguo; Belardinelli, Luiz; Zeng, Aliya; Hirakawa, Ryoko; Rajamani, Sridharan; Ling, Haiyun; Dhalla, Arvinder K

    2016-05-15

    Late Na(+) current (INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high-salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 ± 96 vs. 891 ± 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 ± 0.5 vs. 18.9 ± 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 ± 1.9 vs. 14.9 ± 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 ± 0.02 from 0.14 ± 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 ± 12 from 68 ± 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 ± 8 vs. 212 ± 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 ± 0.01 and 0.17 ± 0.02 pA/pF, respectively, vs. 0.41 ± 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg·kg(-1)·day(-1) dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure. Copyright © 2016 the American Physiological Society.

  3. Mesh Generation via Local Bisection Refinement of Triangulated Grids

    Science.gov (United States)

    2015-06-01

    tb [Maubach 1995, Theorem 5.1]. This is exploited in the recursive algorithm RefineTriangle (Algorithm 2) to com- patibly refine a given triangle; the... recursion depth of RefineTriangle is bounded by the maximum level of refinement in T [Maubach 1995]. RefineTriangle calls itself repeatedly on a... sequence of triangles until a compatibly divisible triangle is found. This sequence of triangles is then bisected in reverse order to preserve

  4. POLY-SCALE REFINABLE FUNCTION AND THEIR PROPERTIES

    Institute of Scientific and Technical Information of China (English)

    YANG Shou-zhi

    2006-01-01

    Poly-scale refinable function with dilation factor a is introduced. The existence of solution of poly-scale refinable equation is investigated. Specially, necessary and sufficient conditions for the orthonormality of solution function φ of poly-scale refinable equation with integer dilation factor a are established. Some properties of poly-scale refinable function are discussed. Several examples illustrating how to use the method to construct poly-scale refinable function are given.

  5. Anomalies in the refinement of isoleucine

    NARCIS (Netherlands)

    Berntsen, K.R.M.; Vriend, G.

    2014-01-01

    A study of isoleucines in protein structures solved using X-ray crystallography revealed a series of systematic trends for the two side-chain torsion angles chi1 and chi2 dependent on the resolution, secondary structure and refinement software used. The average torsion angles for the nine rotamers w

  6. Structural refinement and coarsening in deformed metals

    DEFF Research Database (Denmark)

    Hansen, N.; Huang, X.; Xing, Q.

    2005-01-01

    The microstructural refinement by plastic deformation is analysed in terms of key parameters, the spacing between and the misorientation angle across the boundaries subdividing the structure. Coarsening of such structures by annealing is also characterised. For both deformed and annealed structur...

  7. Energy Bandwidth for Petroleum Refining Processes

    Energy Technology Data Exchange (ETDEWEB)

    none,

    2006-10-01

    The petroleum refining energy bandwidth report analyzes the most energy-intensive unit operations used in U.S. refineries: crude oil distillation, fluid catalytic cracking, catalytic hydrotreating, catalytic reforming, and alkylation. The "bandwidth" provides a snapshot of the energy losses that can potentially be recovered through best practices and technology R&D.

  8. SOME REFINEMENTS OF ENESTROM-KAKEYA THEOREM

    Institute of Scientific and Technical Information of China (English)

    A.Aziz; B.A.Zargar

    2007-01-01

    In this paper we present certain interesting refinements of a well-known Enestrom-Kakeya theorem in the theory of distribution of zeros of polynomials which among other things also improve upon some results of Aziz and Mohammad, Govil and Rehman and others.

  9. Refinement from a control problem to program

    DEFF Research Database (Denmark)

    Schenke, Michael; Ravn, Anders P.

    1996-01-01

    for a control task, exemplified by a steam boiler.The same formalism is used to refine requirements to a functional design.Through a suitable transformation this is taken to an event andaction based formalism. Finally components in this design for a distributedarchitecture are transformed to occam-like programs....

  10. Satellite SAR geocoding with refined RPC model

    Science.gov (United States)

    Zhang, Lu; Balz, Timo; Liao, Mingsheng

    2012-04-01

    Recent studies have proved that the Rational Polynomial Camera (RPC) model is able to act as a reliable replacement of the rigorous Range-Doppler (RD) model for the geometric processing of satellite SAR datasets. But its capability in absolute geolocation of SAR images has not been evaluated quantitatively. Therefore, in this article the problems of error analysis and refinement of SAR RPC model are primarily investigated to improve the absolute accuracy of SAR geolocation. Range propagation delay and azimuth timing error are identified as two major error sources for SAR geolocation. An approach based on SAR image simulation and real-to-simulated image matching is developed to estimate and correct these two errors. Afterwards a refined RPC model can be built from the error-corrected RD model and then used in satellite SAR geocoding. Three experiments with different settings are designed and conducted to comprehensively evaluate the accuracies of SAR geolocation with both ordinary and refined RPC models. All the experimental results demonstrate that with RPC model refinement the absolute location accuracies of geocoded SAR images can be improved significantly, particularly in Easting direction. In another experiment the computation efficiencies of SAR geocoding with both RD and RPC models are compared quantitatively. The results show that by using the RPC model such efficiency can be remarkably improved by at least 16 times. In addition the problem of DEM data selection for SAR image simulation in RPC model refinement is studied by a comparative experiment. The results reveal that the best choice should be using the proper DEM datasets of spatial resolution comparable to that of the SAR images.

  11. A refined Frequency Domain Decomposition tool for structural modal monitoring in earthquake engineering

    Science.gov (United States)

    Pioldi, Fabio; Rizzi, Egidio

    2017-07-01

    Output-only structural identification is developed by a refined Frequency Domain Decomposition ( rFDD) approach, towards assessing current modal properties of heavy-damped buildings (in terms of identification challenge), under strong ground motions. Structural responses from earthquake excitations are taken as input signals for the identification algorithm. A new dedicated computational procedure, based on coupled Chebyshev Type II bandpass filters, is outlined for the effective estimation of natural frequencies, mode shapes and modal damping ratios. The identification technique is also coupled with a Gabor Wavelet Transform, resulting in an effective and self-contained time-frequency analysis framework. Simulated response signals generated by shear-type frames (with variable structural features) are used as a necessary validation condition. In this context use is made of a complete set of seismic records taken from the FEMA P695 database, i.e. all 44 "Far-Field" (22 NS, 22 WE) earthquake signals. The modal estimates are statistically compared to their target values, proving the accuracy of the developed algorithm in providing prompt and accurate estimates of all current strong ground motion modal parameters. At this stage, such analysis tool may be employed for convenient application in the realm of Earthquake Engineering, towards potential Structural Health Monitoring and damage detection purposes.

  12. Refinement of humoral immune monitoring in kidney transplantation: the role of "hidden" alloreactive memory B cells.

    Science.gov (United States)

    Luque, Sergi; Lúcia, Marc; Bestard, Oriol

    2017-10-01

    The advent of novel sensitive assays assessing circulating anti-human leukocyte antigen (HLA) antibodies has allowed recognizing humoral alloimmunity as the main immune-mediated mechanism responsible for allograft rejection and graft loss in kidney transplantation. However, current immune-monitoring techniques, exclusively focusing on circulating anti-HLA antibodies, may underestimate the magnitude of humoral immune response as they exclude the memory B-cell (mBC) pool. Different biological compartments are involved in the intricate mechanisms triggering humoral alloimmune responses even in absence of detectable circulating alloantibodies. Recent studies in animal models as well as in clinical kidney transplantation have shown the key role of this B-cell subset triggering allograft rejection, thus emphasizing the value of recognizing antidonor mBC both as a biomarker of allosensitization and as therapeutic targets. Therefore, considerable efforts are being made among the transplant research community to better understand the role, hierarchy, and impact of mBC in the context of organ transplantation. In this review article, we provide a deep insight into the biology of mBC as well as main evidence of their role orchestrating allograft rejection. Also, we provide a thorough description of main immune-monitoring tools aiming at tracking mBC and a rational for their potential use to refine current humoral immune-risk assessment in kidney transplantation. © 2017 Steunstichting ESOT.

  13. Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I.

    Science.gov (United States)

    Geromichalos, George D; Alifieris, Constantinos E; Geromichalou, Elena G; Trafalis, Dimitrios T

    2016-01-01

    Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anti- cancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. Increasing insight into the genetics and molecular biology of cancer has resulted in the identification of an increasing number of potential molecular targets, for anticancer drug discovery and development. These targets can be approached through exploitation of emerging structural biology, "rational" drug design, screening of chemical libraries, or a combination of these methods. The result is the rapid discovery of new anticancer drugs. In this article we discuss the application of molecular modeling, molecular docking and virtual high-throughput screening to multi-targeted anticancer drug discovery. Efforts have been made to employ in silico methods for facilitating the search and design of selective multi-target agents. These computer aided molecular design methods have shown promising potential in facilitating drug discovery directed at selective multiple targets and is expected to contribute to intelligent lead anticancer drugs.

  14. Parabolic refined invariants and Macdonald polynomials

    CERN Document Server

    Chuang, Wu-yen; Donagi, Ron; Pantev, Tony

    2013-01-01

    A string theoretic derivation is given for the conjecture of Hausel, Letellier, and Rodriguez-Villegas on the cohomology of character varieties with marked points. Their formula is identified with a refined BPS expansion in the stable pair theory of a local root stack, generalizing previous work of the first two authors in collaboration with G. Pan. Haiman's geometric construction for Macdonald polynomials is shown to emerge naturally in this context via geometric engineering. In particular this yields a new conjectural relation between Macdonald polynomials and refined local orbifold curve counting invariants. The string theoretic approach also leads to a new spectral cover construction for parabolic Higgs bundles in terms of holomorphic symplectic orbifolds.

  15. Adaptive Mesh Refinement for Characteristic Grids

    CERN Document Server

    Thornburg, Jonathan

    2009-01-01

    I consider techniques for Berger-Oliger adaptive mesh refinement (AMR) when numerically solving partial differential equations with wave-like solutions, using characteristic (double-null) grids. Such AMR algorithms are naturally recursive, and the best-known past Berger-Oliger characteristic AMR algorithm, that of Pretorius & Lehner (J. Comp. Phys. 198 (2004), 10), recurses on individual "diamond" characteristic grid cells. This leads to the use of fine-grained memory management, with individual grid cells kept in 2-dimensional linked lists at each refinement level. This complicates the implementation and adds overhead in both space and time. Here I describe a Berger-Oliger characteristic AMR algorithm which instead recurses on null \\emph{slices}. This algorithm is very similar to the usual Cauchy Berger-Oliger algorithm, and uses relatively coarse-grained memory management, allowing entire null slices to be stored stored in contiguous arrays in memory. The algorithm is very efficient in both space and ti...

  16. Crystallization in lactose refining-a review.

    Science.gov (United States)

    Wong, Shin Yee; Hartel, Richard W

    2014-03-01

    In the dairy industry, crystallization is an important separation process used in the refining of lactose from whey solutions. In the refining operation, lactose crystals are separated from the whey solution through nucleation, growth, and/or aggregation. The rate of crystallization is determined by the combined effect of crystallizer design, processing parameters, and impurities on the kinetics of the process. This review summarizes studies on lactose crystallization, including the mechanism, theory of crystallization, and the impact of various factors affecting the crystallization kinetics. In addition, an overview of the industrial crystallization operation highlights the problems faced by the lactose manufacturer. The approaches that are beneficial to the lactose manufacturer for process optimization or improvement are summarized in this review. Over the years, much knowledge has been acquired through extensive research. However, the industrial crystallization process is still far from optimized. Therefore, future effort should focus on transferring the new knowledge and technology to the dairy industry.

  17. Cleaning Data with OpenRefine

    Directory of Open Access Journals (Sweden)

    Seth van Hooland

    2013-08-01

    Full Text Available Duplicate records, empty values and inconsistent formats are phenomena we should be prepared to deal with when using historical data sets. This lesson will teach you how to discover inconsistencies in data contained within a spreadsheet or a database. As we increasingly share, aggregate and reuse data on the web, historians will need to respond to data quality issues which inevitably pop up. Using a program called OpenRefine, you will be able to easily identify systematic errors such as blank cells, duplicates, spelling inconsistencies, etc. OpenRefine not only allows you to quickly diagnose the accuracy of your data, but also to act upon certain errors in an automated manner.

  18. Using supercritical fluids to refine hydrocarbons

    Science.gov (United States)

    Yarbro, Stephen Lee

    2014-11-25

    This is a method to reactively refine hydrocarbons, such as heavy oils with API gravities of less than 20.degree. and bitumen-like hydrocarbons with viscosities greater than 1000 cp at standard temperature and pressure using a selected fluid at supercritical conditions. The reaction portion of the method delivers lighter weight, more volatile hydrocarbons to an attached contacting device that operates in mixed subcritical or supercritical modes. This separates the reaction products into portions that are viable for use or sale without further conventional refining and hydro-processing techniques. This method produces valuable products with fewer processing steps, lower costs, increased worker safety due to less processing and handling, allow greater opportunity for new oil field development and subsequent positive economic impact, reduce related carbon dioxide, and wastes typical with conventional refineries.

  19. European refiners re-adjust margins strategy

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, R.G. [ed.

    1996-05-01

    Refiners in Europe are adjusting operating strategies to reflect the volatilities of tight operating margins. From the unexpected availability of quality crudes (e.g., Brent, 0.3% sulfur), to the role of government in refinery planning, the European refining industry is positioning itself to reverse the past few years of steadily declining profitability. Unlike expected increases in US gasoline demand, European gasoline consumption is not expected to increase, and heavy fuel oil consumption is also declining. However, diesel fuel consumption is expected to increase, even though diesel processing capacity has recently decreased (i.e., more imports). Some of the possible strategies that Europeans may adapt to improve margins and reduce volatility include: Increase conversion capacity to supply growing demand for middle distillates and LPG; alleviate refinery cash flow problems with alliances; and direct discretionary investment toward retail merchandising (unless there is a clear trend toward a widening of the sweet-sour crude price differential).

  20. Security Policy Enforcement Through Refinement Process

    CERN Document Server

    Stouls, Nicolas

    2010-01-01

    In the area of networks, a common method to enforce a security policy expressed in a high-level language is based on an ad-hoc and manual rewriting process. We argue that it is possible to build a formal link between concrete and abstract terms, which can be dynamically computed from the environment data. In order to progressively introduce configuration data and then simplify the proof obligations, we use the B refinement process. We present a case study modeling a network monitor. This program, described by refinement following the layers of the TCP/IP suite protocol, has to warn for all observed events which do not respect the security policy. To design this model, we use the event-B method because it is suitable for modeling network concepts. This work has been done within the framework of the POTESTAT project, based on the research of network testing methods from a high-level security policy.

  1. Solidification Based Grain Refinement in Steels

    Science.gov (United States)

    2009-07-24

    and a coarser microstructure forms (See Figure 17). ROLE OF COBALT ALUMINATE CoAI204 produced very different results in the 1010 and 1030 TA...determine what role CoAl204 played in both steels. Other researchers have observed refinement with cobalt aluminate .2"󈧙 Their work has been using...produced in this work. The one unexplained result for CoAl204 is the different undercooling behavior found. Cobalt aluminate reduced undercooling in the

  2. Mesh refinement strategy for optimal control problems

    OpenAIRE

    Paiva, Luis Tiago; Fontes, Fernando,

    2013-01-01

    International audience; Direct methods are becoming the most used technique to solve nonlinear optimal control problems. Regular time meshes having equidistant spacing are frequently used. However, in some cases these meshes cannot cope accurately with nonlinear behavior. One way to improve the solution is to select a new mesh with a greater number of nodes. Another way, involves adaptive mesh refinement. In this case, the mesh nodes have non equidistant spacing which allow a non uniform node...

  3. Understanding Solidification Based Grain Refinement in Steels

    Science.gov (United States)

    2014-12-18

    interatomic spacing along [uvw]s, and 0 = the angle between the [uvwjjand [uvw]n.^’ Work on the grain refinement of aluminum and magnesium alloys has found...chemistry ternary plot from ASPEX system. The author found some evidence of reactions occurring with some rare earth oxide or sulfide inclusions and... sulfide .^^"^^ Another approach would be to react a sample of misch metal or rare earth silicide at elevated temperatures to form the desired oxide or

  4. REFINEMENTS OF THE FAN-TODD'S INEQUALITIES

    Institute of Scientific and Technical Information of China (English)

    庄国基

    2002-01-01

    Refinements to inequalities oninner product spaces are presented. In this respect, inequalities dealt with in this paper are: Cauchy's inequality, Bessel's inequality, Fan-Todd's inequality and Fan-Todd's determinantal inequality. In each case, a strictly increasing function is put forward, which lies between the smaller and the larger quantities of each inequality. As a result,an improved condition for equality of the Fan-Todd's determinantal inequality is deduced.

  5. Crystal Structure Refinement of Synthetic Pure Gyrolite

    Directory of Open Access Journals (Sweden)

    Arūnas Baltušnikas

    2015-03-01

    Full Text Available Pure calcium silicate hydrate – gyrolite was prepared under the saturated steam pressure at 473 K temperature in rotating autoclave. The crystal structure of synthetic gyrolite was investigated by X-ray diffraction and refined using Le Bail, Rietveld and crystal structure modelling methods. Background, peak shape parameters and verification of the space group were performed by the Le Bail full pattern decomposition. Peculiarities of interlayer sheet X of gyrolite unit cell were highlighted by Rietveld refinement. Possible atomic arrangement in interlayer sheet X was solved by global optimization method. Most likelihood crystal structure model of gyrolite was calculated by final Rietveld refinement. It was crystallographically showed, that cell parameters are: a = 0.9713(2 nm, b = 0.9715(2 nm, c = 2.2442(3 nm and alfa = 95.48(2 º, beta = 91.45(2 °, gamma = l20.05(3 °.DOI: http://dx.doi.org/10.5755/j01.ms.21.1.5460

  6. Mesh refinement strategy for optimal control problems

    Science.gov (United States)

    Paiva, L. T.; Fontes, F. A. C. C.

    2013-10-01

    Direct methods are becoming the most used technique to solve nonlinear optimal control problems. Regular time meshes having equidistant spacing are frequently used. However, in some cases these meshes cannot cope accurately with nonlinear behavior. One way to improve the solution is to select a new mesh with a greater number of nodes. Another way, involves adaptive mesh refinement. In this case, the mesh nodes have non equidistant spacing which allow a non uniform nodes collocation. In the method presented in this paper, a time mesh refinement strategy based on the local error is developed. After computing a solution in a coarse mesh, the local error is evaluated, which gives information about the subintervals of time domain where refinement is needed. This procedure is repeated until the local error reaches a user-specified threshold. The technique is applied to solve the car-like vehicle problem aiming minimum consumption. The approach developed in this paper leads to results with greater accuracy and yet with lower overall computational time as compared to using a time meshes having equidistant spacing.

  7. Refining of biodiesel by ceramic membrane separation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yong; Ou, Shiyi; Tan, Yanlai; Tang, Shuze [Department of Food Science and Engineering, Jinan University, Guangzhou 510632 (China); Wang, Xingguo; Liu, Yuanfa [School of Food Science and Technology, Jiangnan University, Wuxi 214112 (China)

    2009-03-15

    A ceramic membrane separation process for biodiesel refining was developed to reduce the considerable usage of water needed in the conventional water washing process. Crude biodiesel produced by refined palm oil was micro-filtered by ceramic membranes of the pore size of 0.6, 0.2 and 0.1 {mu}m to remove the residual soap and free glycerol, at the transmembrane pressure of 0.15 MPa and temperature of 60 C. The flux through membrane maintained at 300 L m{sup -} {sup 2} h{sup -} {sup 1} when the volumetric concentrated ratio reached 4. The content of potassium, sodium, calcium and magnesium in the whole permeate was 1.40, 1.78, 0.81 and 0.20 mg/kg respectively, as determined by inductively coupled plasma-atomic emission spectroscopy. These values are lower than the EN 14538 specifications. The residual free glycerol in the permeate was estimated by water extraction, its value was 0.0108 wt.%. This ceramic membrane technology was a potential environmental process for the refining of biodiesel. (author)

  8. Using Induction to Refine Information Retrieval Strategies

    Science.gov (United States)

    Baudin, Catherine; Pell, Barney; Kedar, Smadar

    1994-01-01

    Conceptual information retrieval systems use structured document indices, domain knowledge and a set of heuristic retrieval strategies to match user queries with a set of indices describing the document's content. Such retrieval strategies increase the set of relevant documents retrieved (increase recall), but at the expense of returning additional irrelevant documents (decrease precision). Usually in conceptual information retrieval systems this tradeoff is managed by hand and with difficulty. This paper discusses ways of managing this tradeoff by the application of standard induction algorithms to refine the retrieval strategies in an engineering design domain. We gathered examples of query/retrieval pairs during the system's operation using feedback from a user on the retrieved information. We then fed these examples to the induction algorithm and generated decision trees that refine the existing set of retrieval strategies. We found that (1) induction improved the precision on a set of queries generated by another user, without a significant loss in recall, and (2) in an interactive mode, the decision trees pointed out flaws in the retrieval and indexing knowledge and suggested ways to refine the retrieval strategies.

  9. Parallel object-oriented adaptive mesh refinement

    Energy Technology Data Exchange (ETDEWEB)

    Balsara, D.; Quinlan, D.J.

    1997-04-01

    In this paper we study adaptive mesh refinement (AMR) for elliptic and hyperbolic systems. We use the Asynchronous Fast Adaptive Composite Grid Method (AFACX), a parallel algorithm based upon the of Fast Adaptive Composite Grid Method (FAC) as a test case of an adaptive elliptic solver. For our hyperbolic system example we use TVD and ENO schemes for solving the Euler and MHD equations. We use the structured grid load balancer MLB as a tool for obtaining a load balanced distribution in a parallel environment. Parallel adaptive mesh refinement poses difficulties in expressing both the basic single grid solver, whether elliptic or hyperbolic, in a fashion that parallelizes seamlessly. It also requires that these basic solvers work together within the adaptive mesh refinement algorithm which uses the single grid solvers as one part of its adaptive solution process. We show that use of AMR++, an object-oriented library within the OVERTURE Framework, simplifies the development of AMR applications. Parallel support is provided and abstracted through the use of the P++ parallel array class.

  10. Formal refinement of extended state machines

    Directory of Open Access Journals (Sweden)

    Thomas Fayolle

    2016-06-01

    Full Text Available In a traditional formal development process, e.g. using the B method, the informal user requirements are (manually translated into a global abstract formal specification. This translation is especially difficult to achieve. The Event-B method was developed to incrementally and formally construct such a specification using stepwise refinement. Each increment takes into account new properties and system aspects. In this paper, we propose to couple a graphical notation called Algebraic State-Transition Diagrams (ASTD with an Event-B specification in order to provide a better understanding of the software behaviour. The dynamic behaviour is captured by the ASTD, which is based on automata and process algebra operators, while the data model is described by means of an Event-B specification. We propose a methodology to incrementally refine such specification couplings, taking into account new refinement relations and consistency conditions between the control specification and the data specification. We compare the specifications obtained using each approach for readability and proof complexity. The advantages and drawbacks of the traditional approach and of our methodology are discussed. The whole process is illustrated by a railway CBTC-like case study. Our approach is supported by tools for translating ASTD's into B and Event-B into B.

  11. A Formal Software Development Approach Using Refinement Calculus

    Institute of Scientific and Technical Information of China (English)

    王云峰; 庞军; 等

    2001-01-01

    The advantage of COOZ(Complete Object-Oriented Z) is to specify large scale software,but it does not support refinement calculus.Thus its application is comfined for software development.Including refinement calculus into COOZ overcomes its disadvantage during design and implementation.The separation between the design and implementation for structure and notation is removed as well .Then the software can be developed smoothly in the same frame.The combination of COOZ and refinement calculus can build object-oriented frame,in which the specification in COOZ is refined stepwise to code by calculus.In this paper,the development model is established.which is based on COOZ and refinement calculus.Data refinement is harder to deal with in a refinement tool than ordinary algorithmic refinement,since data refinement usually has to be done on a large program component at once.As to the implementation technology of refinement calculus,the data refinement calculator is constructed and an approach for data refinement which is based on data refinement calculus and program window inference is offered.

  12. A Formal Software Development Approach Using Refinement Calculus

    Institute of Scientific and Technical Information of China (English)

    WANG Yunfeng; PANG Jun; ZHA Ming; YANG Zhaohui; ZHENG Guoliang

    2001-01-01

    The advantage of COOZ (Complete Object-Oriented Z) is to specify large scale software, but it does not support refinement calculus. Thus its applica tion is confined for software development. Including refinement calculus into COOZ overcomes its disadvantage during design and implementation. The separation be tween the design and implementation for structure and notation is removed as well. Then the software can be developed smoothly in the same frame. The combina tion of COOZ and refinement calculus can build object-oriented frame, in which the specification in COOZ is refined stepwise to code by calculus. In this paper, the development model is established, which is based on COOZ and refinement calculus. Data refinement is harder to deal with in a refinement tool than ordinary algorithmic refinement, since data refinement usually has to be done on a large program compo nent at once. As to the implementation technology of refinement calculus, the data refinement calculator is constructed and an approach for data refinement which is based on data refinement calculus and program window inference is offered.

  13. Level 5: user refinement to aid the fusion process

    Science.gov (United States)

    Blasch, Erik P.; Plano, Susan

    2003-04-01

    The revised JDL Fusion model Level 4 process refinement covers a broad spectrum of actions such as sensor management and control. A limitation of Level 4 is the purpose of control - whether it be for user needs or system operation. Level 5, User Refinement, is a modification to the Revised JDL model that distinguishes between machine process refinement and user refinement. User refinement can either be human control actions or refinement of the user's cognitive model. In many cases, fusion research concentrates on the machine and does not take full advantage of the human as not only a qualified expert to refine the fusion process, but also as customer for whom the fusion system is designed. Without user refinement, sensor fusion is incomplete, inadequate, and the user neglects its worthiness. To capture user capabilities, we explore the concept of user refinement through decision and action based on situational leadership models. We develop a Fuse-Act Situational User Refinement (FASUR) model that details four refinement behaviors: Neglect, Consult, Rely, and Interact and five refinement functions: Planning, Organizing, Coordinating, Directing, and Controlling. Process refinement varies for different systems and different user information needs. By designing a fusion system with a specific user in mind, vis Level 5, a fusion architecture can meet user's information needs for varying situations, extend user sensing capabilities for action, and increase the human-machine interaction.

  14. Grain Refinement of Permanent Mold Cast Copper Base Alloys

    Energy Technology Data Exchange (ETDEWEB)

    M.Sadayappan; J.P.Thomson; M.Elboujdaini; G.Ping Gu; M. Sahoo

    2005-04-01

    Grain refinement is a well established process for many cast and wrought alloys. The mechanical properties of various alloys could be enhanced by reducing the grain size. Refinement is also known to improve casting characteristics such as fluidity and hot tearing. Grain refinement of copper-base alloys is not widely used, especially in sand casting process. However, in permanent mold casting of copper alloys it is now common to use grain refinement to counteract the problem of severe hot tearing which also improves the pressure tightness of plumbing components. The mechanism of grain refinement in copper-base alloys is not well understood. The issues to be studied include the effect of minor alloy additions on the microstructure, their interaction with the grain refiner, effect of cooling rate, and loss of grain refinement (fading). In this investigation, efforts were made to explore and understand grain refinement of copper alloys, especially in permanent mold casting conditions.

  15. The Analysis of the Refined Financial Management of Modern Enterprises

    OpenAIRE

    Li Ran

    2016-01-01

    This paper briefly introduces the concept of the refined financial management, elaborates on its characteristics and puts forward some main points about it. It also comes up with some personal suggestions for reference on effective ways of refining financial management.

  16. Proof of concept test and evaluation (pilot/mill testing) of Lasentec refining sensor. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, J.E.

    1994-06-03

    On-line measurement of refining development is of vital concern to the papermaker since its control directly affects the uniformity of the product, drainage, drying and energy consumption. The current methods of monitoring fiber development during refining rely on secondary measures such as: Drainage rate, either measured off-line as Canadian standard freeness, or on-line with a number of commercial sample and test devices; energy consumption at the refiner; or changes in vacuum on the paper machine. To overcome these limitations of the existing technology, this project was designed to evaluate the use of a new type of sensor to monitor fiber development during refining. This sensor, a Lasentec Scanning Laser Microscope (SLM), is currently used as a particle size analyzer for slurries. The sensor will be described in more detail later. The use of this sensor had been successful in the laboratory. This project, was to establish this instrument as an in-line means to directly monitor refining.

  17. Introducing BioSARN - an ecological niche model refinement tool.

    Science.gov (United States)

    Heap, Marshall J

    2016-08-01

    Environmental niche modeling outputs a biological species' potential distribution. Further work is needed to arrive at a species' realized distribution. The Biological Species Approximate Realized Niche (BioSARN) application provides the ecological modeler with a toolset to refine Environmental niche models (ENMs). These tools include soil and land class filtering, niche area quantification and novelties like enhanced temporal corridor definition, and output to a high spatial resolution land class model. BioSARN is exemplified with a study on Fraser fir, a tree species with strong land class and edaphic correlations. Soil and land class filtering caused the potential distribution area to decline 17%. Enhanced temporal corridor definition permitted distinction of current, continuing, and future niches, and thus niche change and movement. Tile quantification analysis provided further corroboration of these trends. BioSARN does not substitute other established ENM methods. Rather, it allows the experimenter to work with their preferred ENM, refining it using their knowledge and experience. Output from lower spatial resolution ENMs to a high spatial resolution land class model is a pseudo high-resolution result. Still, it maybe the best that can be achieved until wide range high spatial resolution environmental data and accurate high precision species occurrence data become generally available.

  18. REFINEMENT OF PRODUCER GAS GENERATED FROM BIOMASS GASIFIER

    Directory of Open Access Journals (Sweden)

    L. KUMARARAJA

    2016-01-01

    Full Text Available Producer gas (PG generated from biomass by thermo-chemical gasification process has been proved to be a reliable and renewable substitute for petroleum fuels to drive internal combustion engines. The gasification technology has been developed well and also commercialised. However, more technological advancements must happen in the refining of PG. Generally, the refinement is confined to the removal of tar and particulates from PG before supplying it to the engines. This paper proposes to remove additionally carbon dioxide and water vapour from PG so that its heating value can be increased and faster combustion can be attained in the engine cylinder. In this direction, the various CO2 removal technologies which are currently employed for combustion flue gas, natural gas and biogas have been first studied in detail. They are: physical absorption in solvents, chemical absorption by reagents, adsorption, membrane separation and refrigeration. In the present research, a batch of experiments has been conducted by washing PG with water to absorb CO2 physically and in a separate batch of experiments PG has been treated with aqueous ammonia to absorb CO2 chemically. For both experiments, the PG was generated by a downdraft biomass gasifier fed with wood pieces. The CO2 reduction obtained was 10.9% in physical absorption by water and 95% in chemical absorption by aqueous ammonia. Along with the reduction of CO2 and H2O from PG, the tar and particulates content of PG could also be reduced by absorption method.

  19. Coloured Petri Net Refinement Specification and Correctness Proof with Coq

    Science.gov (United States)

    Choppy, Christine; Mayero, Micaela; Petrucci, Laure

    2009-01-01

    In this work, we address the formalisation of symmetric nets, a subclass of coloured Petri nets, refinement in COQ. We first provide a formalisation of the net models, and of their type refinement in COQ. Then the COQ proof assistant is used to prove the refinement correctness lemma. An example adapted from a protocol example illustrates our work.

  20. Fatty acid esters of monochloropropanediol (MCPD) and glycidol in refined edible oils.

    Science.gov (United States)

    Craft, B D; Chiodini, A; Garst, J; Granvogl, M

    2013-01-01

    Recently, fatty acid esters of monochloropropanediol (MCPD) and that of glycidol have been reported in refined edible oils. Since then a wealth of research has been published on the factors influencing the formation of these contaminants in foods. It can be noted that the predominant precursors in a given matrix will not necessarily be the same as in other matrices. Further, proven relationships in the past between precursors responsible for free MCPD or free glycidol formation will not necessarily be valid for their fatty acid-esterified counterparts. This review attempts to summarise the current status of the literature as it pertains to the reasons surrounding the manifestation of MCPD esters and glycidyl esters in oils and fats. Recent efforts to mitigate the levels of these contaminants were highlighted and put into the context of their respective reaction matrices. As more accurate occurrence data for MCPD esters and glycidyl esters in other foods are collected, more targeted mitigation experiments can be formulated with respect to the reaction matrices under investigation.

  1. Quantum Geometry of Refined Topological Strings

    CERN Document Server

    Aganagic, Mina; Dijkgraaf, Robbert; Krefl, Daniel; Vafa, Cumrun

    2011-01-01

    We consider branes in refined topological strings. We argue that their wave-functions satisfy a Schr\\"odinger equation depending on multiple times and prove this in the case where the topological string has a dual matrix model description. Furthermore, in the limit where one of the equivariant rotations approaches zero, the brane partition function satisfies a time-independent Schroedinger equation. We use this observation, as well as the back reaction of the brane on the closed string geometry, to offer an explanation of the connection between integrable systems and N=2 gauge systems in four dimensions observed by Nekrasov and Shatashvili.

  2. Quantum geometry of refined topological strings

    Science.gov (United States)

    Aganagic, Mina; Cheng, Miranda C. N.; Dijkgraaf, Robbert; Krefl, Daniel; Vafa, Cumrun

    2012-11-01

    We consider branes in refined topological strings. We argue that their wavefunctions satisfy a Schrödinger equation depending on multiple times and prove this in the case where the topological string has a dual matrix model description. Furthermore, in the limit where one of the equivariant rotations approaches zero, the brane partition function satisfies a time-independent Schrödinger equation. We use this observation, as well as the back reaction of the brane on the closed string geometry, to offer an explanation of the connection between integrable systems and {N}=2 gauge systems in four dimensions observed by Nekrasov and Shatashvili.

  3. A refinement driven component-based design

    DEFF Research Database (Denmark)

    Chen, Zhenbang; Liu, Zhiming; Ravn, Anders Peter;

    2007-01-01

    to integrate sophisticated checkers, generators and transformations. A feasible approach to ensuring high quality of such add-ins is to base them on sound formal foundations. This paper summarizes our research on the Refinement of Component and Object Systems (rCOS) and illustrates it with experiences from...... the work on the Common Component Modelling Example (CoCoME). This gives evidence that the formal techniques developed in rCOS can be integrated into a model-driven development process and shows where it may be integrated in computer-aided software engineering (CASE) tools for adding formally supported...

  4. Liquid rheology study on refined rapeseed oil

    Institute of Scientific and Technical Information of China (English)

    刘其梅; 罗迎社; 殷水平; 陈胜铭; 张党权; 彭万喜

    2008-01-01

    The rapeseed oil extracted from the mature seeds was purified by refining processing,and the rheological characteristic analysis of the viscosity and dynamic shear rate at gradient temperatures was made.The result shows that at 20,40,60 and 80 ℃ respectively,when the shear rate gradually rises,the torque increases accordingly but its viscosity does not vary distinctly.The result suggests that when rapeseed oil is used as the raw of edible oils and industries,the working procedures at high temperature will not influence its rheological characteristic distinctly.

  5. Retrenchment. An engineering variation on refinement

    Energy Technology Data Exchange (ETDEWEB)

    Banach, R.; Poppleton, M

    1999-07-01

    It is argued that refinement, in which I/O signatures stay the same, preconditions are weakened and postconditions strengthened, is too restrictive to describe all but a fraction of many realistic developments. An alternative notion is proposed called retrenchment, which allows information to migrate between I/O and state aspects of operations at different levels of abstraction, and which allows only a fraction of the high level behaviour to be captured at the low level. This permits more of the informal aspects of design to be formally captured and checked. The details are worked out for the B-Method. (author)

  6. Surface biotechnology for refining cochlear implants.

    Science.gov (United States)

    Tan, Fei; Walshe, Peter; Viani, Laura; Al-Rubeai, Mohamed

    2013-12-01

    The advent of the cochlear implant is phenomenal because it is the first surgical prosthesis that is capable of restoring one of the senses. The subsequent rapid evolution of cochlear implants through increasing complexity and functionality has been synchronized with the recent advancements in biotechnology. Surface biotechnology has refined cochlear implants by directly influencing the implant–tissue interface. Emerging surface biotechnology strategies are exemplified by nanofibrous polymeric materials, topographical surface modification, conducting polymer coatings, and neurotrophin-eluting implants. Although these novel developments have received individual attention in the recent literature, the time has come to investigate their collective applications to cochlear implants to restore lost hearing.

  7. Adaptive refinement tools for tetrahedral unstructured grids

    Science.gov (United States)

    Pao, S. Paul (Inventor); Abdol-Hamid, Khaled S. (Inventor)

    2011-01-01

    An exemplary embodiment providing one or more improvements includes software which is robust, efficient, and has a very fast run time for user directed grid enrichment and flow solution adaptive grid refinement. All user selectable options (e.g., the choice of functions, the choice of thresholds, etc.), other than a pre-marked cell list, can be entered on the command line. The ease of application is an asset for flow physics research and preliminary design CFD analysis where fast grid modification is often needed to deal with unanticipated development of flow details.

  8. Computing Refined Buneman Trees in Cubic Time

    DEFF Research Database (Denmark)

    Brodal, G.S.; Fagerberg, R.; Östlin, A.

    2003-01-01

    Reconstructing the evolutionary tree for a set of n species based on pairwise distances between the species is a fundamental problem in bioinformatics. Neighbor joining is a popular distance based tree reconstruction method. It always proposes fully resolved binary trees despite missing evidence...... in the underlying distance data. Distance based methods based on the theory of Buneman trees and refined Buneman trees avoid this problem by only proposing evolutionary trees whose edges satisfy a number of constraints. These trees might not be fully resolved but there is strong combinatorial evidence for each...

  9. Acoustic Logging Modeling by Refined Biot's Equations

    Science.gov (United States)

    Plyushchenkov, Boris D.; Turchaninov, Victor I.

    An explicit uniform completely conservative finite difference scheme for the refined Biot's equations is proposed. This system is modified according to the modern theory of dynamic permeability and tortuosity in a fluid-saturated elastic porous media. The approximate local boundary transparency conditions are constructed. The acoustic logging device is simulated by the choice of appropriate boundary conditions on its external surface. This scheme and these conditions are satisfactory for exploring borehole acoustic problems in permeable formations in a real axial-symmetrical situation. The developed approach can be adapted for a nonsymmetric case also.

  10. Refining thick brane models via electroweak data

    CERN Document Server

    Chumbes, A E R; Hott, M B

    2015-01-01

    After discussing the localization of Abelian and non-Abelian gauge fields and Higgs fields on a thick brane, we introduce a procedure of dimensional reduction and its consequences to the rescaled parameters of the boson sector of the Standard Model. The parameters encodes some power dependence on the extra dimension, usually narrow, warp factor and hence it also depend on the position related with the extra dimension inside the thick brane. In this vein, the observable parameters may be used to refine the braneworld models via the brane thickness.

  11. Formal language theory: refining the Chomsky hierarchy.

    Science.gov (United States)

    Jäger, Gerhard; Rogers, James

    2012-07-19

    The first part of this article gives a brief overview of the four levels of the Chomsky hierarchy, with a special emphasis on context-free and regular languages. It then recapitulates the arguments why neither regular nor context-free grammar is sufficiently expressive to capture all phenomena in the natural language syntax. In the second part, two refinements of the Chomsky hierarchy are reviewed, which are both relevant to the extant research in cognitive science: the mildly context-sensitive languages (which are located between context-free and context-sensitive languages), and the sub-regular hierarchy (which distinguishes several levels of complexity within the class of regular languages).

  12. A Technical Refinement of the Vernier Optometer.

    Science.gov (United States)

    1988-07-01

    Naa Aeropc Meia Reeac - -.- .r* ES * A TECHNICAL REFINEMENT OF THE VERNIER OPTOMETER William B. Cushman and Leonard A. Temme N DTIC fELECTE NOVI 6 W8...Vernier Optometer 12 PERSONAL AUTHOR(S) William B. Cushman* and Leonard A. Temme 14._ DATE_ OF_ REPORT_(YearMonth, _Day)_15_______COUN 13a14. DATE OF...Fellow 17 COSATI CODES 18 SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP Vernier optometer , laser

  13. Refining the asteroid taxonomy by polarimetric observations

    Science.gov (United States)

    Belskaya, I. N.; Fornasier, S.; Tozzi, G. P.; Gil-Hutton, R.; Cellino, A.; Antonyuk, K.; Krugly, Yu. N.; Dovgopol, A. N.; Faggi, S.

    2017-03-01

    We present new results of polarimetric observations of 15 main belt asteroids of different composition. By merging new and published data we determined polarimetric parameters characterizing individual asteroids and mean values of the same parameters characterizing different taxonomic classes. The majority of asteroids show polarimetric phase curves close to the average curve of the corresponding class. We show that using polarimetric data it is possible to refine asteroid taxonomy and derive a polarimetric classification for 283 main belt asteroids. Polarimetric observations of asteroid (21) Lutetia are found to exhibit possible variations of the position angle of the polarization plane over the surface.

  14. Relativistic MHD with adaptive mesh refinement

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Matthew [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803-4001 (United States); Hirschmann, Eric W [Department of Physics and Astronomy, Brigham Young University, Provo, UT 84602 (United States); Liebling, Steven L [Department of Physics, Long Island University-C W Post Campus, Brookville, NY 11548 (United States); Neilsen, David [Department of Physics and Astronomy, Brigham Young University, Provo, UT 84602 (United States)

    2006-11-22

    This paper presents a new computer code to solve the general relativistic magnetohydrodynamics (GRMHD) equations using distributed parallel adaptive mesh refinement (AMR). The fluid equations are solved using a finite difference convex ENO method (CENO) in 3 + 1 dimensions, and the AMR is Berger-Oliger. Hyperbolic divergence cleaning is used to control the {nabla} . B = 0 constraint. We present results from three flat space tests, and examine the accretion of a fluid onto a Schwarzschild black hole, reproducing the Michel solution. The AMR simulations substantially improve performance while reproducing the resolution equivalent unigrid simulation results. Finally, we discuss strong scaling results for parallel unigrid and AMR runs.

  15. Unitary appreciative inquiry: evolution and refinement.

    Science.gov (United States)

    Cowling, W Richard; Repede, Elizabeth

    2010-01-01

    Unitary appreciative inquiry (UAI), developed over the past 20 years, provides an orientation and process for uncovering human wholeness and discovering life patterning in individuals and groups. Refinements and a description of studies using UAI are presented. Assumptions and conceptual underpinnings of the method distinguishing its contributions from other methods are reported. Data generation strategies that capture human wholeness and elucidate life patterning are proposed. Data synopsis as an alternative to analysis is clarified and explicated. Standards that suggest enhancing the legitimacy of knowledge and credibility of research are specified. Potential expansions of UAI offer possibilities for extending epistemologies, aesthetic integration, and theory development.

  16. 靶向抗肿瘤药物个体化用药的研究现状%Research current situation and prospect on personalized medicine by targeted anticancer drugs

    Institute of Scientific and Technical Information of China (English)

    丁征; 宋洪涛

    2012-01-01

    随着靶向抗肿瘤药物在肿瘤治疗中地位日益提高,越来越多作用于不同靶点的药物在临床上应用;通过对药物生物标志物的研究来预测疗效和预后,对患者进行个体化治疗.本文对靶向抗肿瘤药物在个体化用药的现状和应用前景作一综述.%As the growing importance of targeted anticancer drugs in the tumor treatment, more and more drugs working through different targets are widely available in clinic. The study of biomarkers makes it possible for predicting efficacy and prognosis and personalized medicine. The research progress on current situation and prospect on personalized medicine by targeted anticancer drugs was summarized in this paper.

  17. Conditions for preparation of ultrapure beryllium by electrolytic refining in molten alkali-metal chlorides

    Energy Technology Data Exchange (ETDEWEB)

    Wohlfarth, Hagen

    1982-02-01

    Electrolytic refining is regarded as the most suitable process for the production of beryllium with impurity contents below 1 at.-ppM. Several parameters are important for electrolytic refining of beryllium in a BeCl/sub 2/-containing LiCl-KCl melt: current density, BeCl/sub 2/ content, electrolyte temperature, composition of the unpurified beryllium and impurity-ion concentrations in the melt, as well as apparatus characteristics such as rotation speed of the cathode and condition of the crucible material. These factors were studied and optimized such that extensive removal of the maximum number of accompanying and alloying elements was achieved.

  18. Refined localization of the Prieto-syndrome locus

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, F.; Prieto, F. [Unidad de Genetica, Valencia (Spain); Gal, A. [Universitaets-Krankenhaus Eppendorf, Hamburg (Germany)

    1996-07-12

    PRS designates the locus for a syndromal form of X-linked mental retardation (Prieto syndrome) characterized by minor facial anomalies, ear malformation, abnormal growth of teeth, clinodactyly, sacral dimple, patellar luxation, malformation of lower limbs, abnormalities of the fundus of the eye, and subcortical cerebral atrophy. Linkage analysis localized the disease locus between DXS84 (Xp21.1) and DXS255. Here we present additional linkage data that provide further support and refinement of this localization. Individual III-18 gave birth to a male, currently aged 2 7/12 years, who clearly shows delayed psychomotor development. He began to walk at 23 months and his speech is delayed. In addition, he shows the characteristic facial anomalies, {open_quotes}dysplastic{close_quotes} ears, sacral dimple, and clinodactyly, as do all other affected males in this family. 7 refs., 1 tab.

  19. Proposals for refinements in international nuclear knowledge management activities

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Bum Jin; Kang, Doo Hyuk; Ko, Sang Hyuk; Kim, Hyung Seok [Cheju National University, Cheju (Korea, Republic of)

    2004-07-01

    Concerns are raised world-wide on the sustainability of nuclear society due to the aging of nuclear manpower, coming massive retirements of senior workers within the next several years, declination of nuclear education and training, as well as the shortage of nuclear manpower supply. These concerns were reflected in the international activities such as the OECD/NEA report on the nuclear education and training and the IAEA conference on Nuclear Knowledge Management. Many more follow-up activities are currently being formulated and implemented. This paper discusses the nature of the issue, proposes a Four-Season Model of nuclear industry and manpower demand and supply, and raises an issue regarding the possibility of manpower shortage propagation from the advanced countries to the developing countries. The international activities are also reviewed and proposals for further refinements of the nuclear knowledge management activities are made.

  20. A precise measurement of the muon neutrino-nucleon inclusive charged current cross section off an isoscalar target in the energy range 2.5

    Science.gov (United States)

    Wu, Q.; Mishra, S. R.; Godley, A.; Petti, R.; Alekhin, S.; Astier, P.; Autiero, D.; Baldisseri, A.; Baldo-Ceolin, M.; Banner, M.; Bassompierre, G.; Benslama, K.; Besson, N.; Bird, I.; Blumenfeld, B.; Bobisut, F.; Bouchez, J.; Boyd, S.; Bueno, A.; Bunyatov, S.; Camilleri, L.; Cardini, A.; Cattaneo, P. W.; Cavasinni, V.; Cervera-Villanueva, A.; Challis, R.; Chukanov, A.; Collazuol, G.; Conforto, G.; Conta, C.; Contalbrigo, M.; Cousins, R.; Degaudenzi, H.; Del Prete, T.; de Santo, A.; di Lella, L.; Do Couto E Silva, E.; Dumarchez, J.; Ellis, M.; Feldman, G. J.; Ferrari, R.; Ferrère, D.; Flaminio, V.; Fraternali, M.; Gaillard, J.-M.; Gangler, E.; Geiser, A.; Geppert, D.; Gibin, D.; Gninenko, S.; Gomez-Cadenas, J.-J.; Gosset, J.; Gößling, C.; Gouanère, M.; Grant, A.; Graziani, G.; Guglielmi, A.; Hagner, C.; Hernando, J.; Hurst, P.; Hyett, N.; Iacopini, E.; Joseph, C.; Juget, F.; Kent, N.; Kim, J. J.; Kirsanov, M.; Klimov, O.; Kokkonen, J.; Kovzelev, A.; Krasnoperov, A.; Kulagin, S.; Lacaprara, S.; Lachaud, C.; Lakić, B.; Lanza, A.; La Rotonda, L.; Laveder, M.; Letessier-Selvon, A.; Levy, J.-M.; Ling, J.; Linssen, L.; Ljubič, A.; Long, J.; Lupi, A.; Lyubushkin, V.; Marchionni, A.; Martelli, F.; Méchain, X.; Mendiburu, J.-P.; Meyer, J.-P.; Mezzetto, M.; Moorhead, G. F.; Naumov, D.; Nédélec, P.; Nefedov, Yu.; Nguyen-Mau, C.; Orestano, D.; Pastore, F.; Peak, L. S.; Pennacchio, E.; Pessard, H.; Placci, A.; Polesello, G.; Pollmann, D.; Polyarush, A.; Poulsen, C.; Popov, B.; Rebuffi, L.; Rico, J.; Riemann, P.; Roda, C.; Rubbia, A.; Salvatore, F.; Samoylov, O.; Schahmaneche, K.; Schmidt, B.; Schmidt, T.; Sconza, A.; Seaton, M.; Sevior, M.; Sillou, D.; Soler, F. J. P.; Sozzi, G.; Steele, D.; Stiegler, U.; Stipčević, M.; Stolarczyk, Th.; Tareb-Reyes, M.; Taylor, G. N.; Tereshchenko, V.; Toropin, A.; Touchard, A.-M.; Tovey, S. N.; Tran, M.-T.; Tsesmelis, E.; Ulrichs, J.; Vacavant, L.; Valdata-Nappi, M.; Valuev, V.; Vannucci, F.; Varvell, K. E.; Veltri, M.; Vercesi, V.; Vidal-Sitjes, G.; Vieira, J.-M.; Vinogradova, T.; Weber, F. V.; Weisse, T.; Wilson, F. F.; Winton, L. J.; Yabsley, B. D.; Zaccone, H.; Zuber, K.; Zuccon, P.; NOMAD Collaboration

    2008-02-01

    We present a measurement of the muon neutrino-nucleon inclusive charged current cross section, off an isoscalar target, in the neutrino energy range 2.5 ⩽Eν ⩽ 40 GeV. The significance of this measurement is its precision, ±4% in 2.5 ⩽Eν ⩽ 10 GeV, and ±2.6% in 10 ⩽Eν ⩽ 40 GeV regions, where significant uncertainties in previous experiments still exist, and its importance to the current and proposed long baseline neutrino oscillation experiments.

  1. A precise measurement of the muon neutrino nucleon inclusive charged current cross section off an isoscalar target in the energy range 2.5

    Science.gov (United States)

    NOMAD Collaboration; Wu, Q.; Mishra, S. R.; Godley, A.; Petti, R.; Alekhin, S.; Astier, P.; Autiero, D.; Baldisseri, A.; Baldo-Ceolin, M.; Banner, M.; Bassompierre, G.; Benslama, K.; Besson, N.; Bird, I.; Blumenfeld, B.; Bobisut, F.; Bouchez, J.; Boyd, S.; Bueno, A.; Bunyatov, S.; Camilleri, L.; Cardini, A.; Cattaneo, P. W.; Cavasinni, V.; Cervera-Villanueva, A.; Challis, R.; Chukanov, A.; Collazuol, G.; Conforto, G.; Conta, C.; Contalbrigo, M.; Cousins, R.; Degaudenzi, H.; Del Prete, T.; de Santo, A.; di Lella, L.; Do Couto E Silva, E.; Dumarchez, J.; Ellis, M.; Feldman, G. J.; Ferrari, R.; Ferrère, D.; Flaminio, V.; Fraternali, M.; Gaillard, J.-M.; Gangler, E.; Geiser, A.; Geppert, D.; Gibin, D.; Gninenko, S.; Gomez-Cadenas, J.-J.; Gosset, J.; Gößling, C.; Gouanère, M.; Grant, A.; Graziani, G.; Guglielmi, A.; Hagner, C.; Hernando, J.; Hurst, P.; Hyett, N.; Iacopini, E.; Joseph, C.; Juget, F.; Kent, N.; Kim, J. J.; Kirsanov, M.; Klimov, O.; Kokkonen, J.; Kovzelev, A.; Krasnoperov, A.; Kulagin, S.; Lacaprara, S.; Lachaud, C.; Lakić, B.; Lanza, A.; La Rotonda, L.; Laveder, M.; Letessier-Selvon, A.; Levy, J.-M.; Ling, J.; Linssen, L.; Ljubič, A.; Long, J.; Lupi, A.; Lyubushkin, V.; Marchionni, A.; Martelli, F.; Méchain, X.; Mendiburu, J.-P.; Meyer, J.-P.; Mezzetto, M.; Moorhead, G. F.; Naumov, D.; Nédélec, P.; Nefedov, Yu.; Nguyen-Mau, C.; Orestano, D.; Pastore, F.; Peak, L. S.; Pennacchio, E.; Pessard, H.; Placci, A.; Polesello, G.; Pollmann, D.; Polyarush, A.; Poulsen, C.; Popov, B.; Rebuffi, L.; Rico, J.; Riemann, P.; Roda, C.; Rubbia, A.; Salvatore, F.; Samoylov, O.; Schahmaneche, K.; Schmidt, B.; Schmidt, T.; Sconza, A.; Seaton, M.; Sevior, M.; Sillou, D.; Soler, F. J. P.; Sozzi, G.; Steele, D.; Stiegler, U.; Stipčević, M.; Stolarczyk, Th.; Tareb-Reyes, M.; Taylor, G. N.; Tereshchenko, V.; Toropin, A.; Touchard, A.-M.; Tovey, S. N.; Tran, M.-T.; Tsesmelis, E.; Ulrichs, J.; Vacavant, L.; Valdata-Nappi, M.; Valuev, V.; Vannucci, F.; Varvell, K. E.; Veltri, M.; Vercesi, V.; Vidal-Sitjes, G.; Vieira, J.-M.; Vinogradova, T.; Weber, F. V.; Weisse, T.; Wilson, F. F.; Winton, L. J.; Yabsley, B. D.; Zaccone, H.; Zuber, K.; Zuccon, P.

    2008-02-01

    We present a measurement of the muon neutrino nucleon inclusive charged current cross section, off an isoscalar target, in the neutrino energy range 2.5⩽E⩽40 GeV. The significance of this measurement is its precision, ±4% in 2.5⩽E⩽10 GeV, and ±2.6% in 10⩽E⩽40 GeV regions, where significant uncertainties in previous experiments still exist, and its importance to the current and proposed long baseline neutrino oscillation experiments.

  2. Refining Automatically Extracted Knowledge Bases Using Crowdsourcing

    Directory of Open Access Journals (Sweden)

    Chunhua Li

    2017-01-01

    Full Text Available Machine-constructed knowledge bases often contain noisy and inaccurate facts. There exists significant work in developing automated algorithms for knowledge base refinement. Automated approaches improve the quality of knowledge bases but are far from perfect. In this paper, we leverage crowdsourcing to improve the quality of automatically extracted knowledge bases. As human labelling is costly, an important research challenge is how we can use limited human resources to maximize the quality improvement for a knowledge base. To address this problem, we first introduce a concept of semantic constraints that can be used to detect potential errors and do inference among candidate facts. Then, based on semantic constraints, we propose rank-based and graph-based algorithms for crowdsourced knowledge refining, which judiciously select the most beneficial candidate facts to conduct crowdsourcing and prune unnecessary questions. Our experiments show that our method improves the quality of knowledge bases significantly and outperforms state-of-the-art automatic methods under a reasonable crowdsourcing cost.

  3. Multiuser Successive Refinement and Multiple Description Coding

    CERN Document Server

    Tian, Chao; Diggavi, Suhas

    2007-01-01

    We consider the multiuser successive refinement (MSR) problem, where the users are connected to a central server via links with different noiseless capacities, and each user wishes to reconstruct in a successive-refinement fashion. An achievable region is given for the two-user two-layer case and it provides the complete rate-distortion region for the Gaussian source under the MSE distortion measure. The key observation is that this problem includes the multiple description (MD) problem (with two descriptions) as a subsystem, and the techniques useful in the MD problem can be extended to this case. We show that the coding scheme based on the universality of random binning is sub-optimal, because multiple Gaussian side informations only at the decoders do incur performance loss, in contrast to the case of single side information at the decoder. We further show that unlike the single user case, when there are multiple users, the loss of performance by a multistage coding approach can be unbounded for the Gaussi...

  4. Current status of rational design of pro-drugs targeting the intestinal di/tri-peptide transporter hPEPT1 (SLC15A1)

    DEFF Research Database (Denmark)

    Saaby, Lasse; Nielsen, Carsten Uhd; Steffansen, Bente;

    2013-01-01

    The intestinal di/tri-peptide transporter hPEPT1 has broad substrate specificity, accommodating uptake of the majority of investigated di- and tripeptides, as well as of a number of drug compounds. This transport system has a high capacity and it has been hypothesized that hPEPT1-mediated uptake ...... in the field, the present review aims at giving a brief overview of structure-activity relationships for hPEPT1, and to provide a critical evaluation of whether hPEPT1-targeted prodrugs can be rationally designed....

  5. Lossless, Near-Lossless, and Refinement Coding of Bi-level Images

    DEFF Research Database (Denmark)

    Martins, Bo; Forchhammer, Søren Otto

    1999-01-01

    We present general and unified algorithms for lossy/lossless coding of bi-level images. The compression is realized by applying arithmetic coding to conditional probabilities. As in the current JBIG standard the conditioning may be specified by a template.For better compression, the more general...... to the specialized soft pattern matching techniques which work better for text. Template based refinement coding is applied for lossy-to-lossless refinement. Introducing only a small amount of loss in halftoned test images, compression is increased by up to a factor of four compared with JBIG. Lossy, lossless......, and refinement decoding speed and lossless encoding speed are less than a factor of two slower than JBIG. The (de)coding method is proposed as part of JBIG2, an emerging international standard for lossless/lossy compression of bi-level images....

  6. X-ray structure refinement using aspherical atomic density functions obtained from quantum-mechanical calculations.

    Science.gov (United States)

    Jayatilaka, Dylan; Dittrich, Birger

    2008-05-01

    An approach is outlined for X-ray structure refinement using atomic density fragments obtained by Hirshfeld partitioning of quantum-mechanical density fragments. Results are presented for crystal structure refinements of urea and benzene using these 'Hirshfeld atoms'. Using this procedure, the quantum-mechanical non-spherical electron density is taken into account in the structural model based on the conformation found in the crystal. Contrary to current consensus in structure refinement, the anisotropic displacement parameters of H atoms can be reproduced from neutron diffraction measurements simply from a least-squares fit using the Hirshfeld atoms derived from the BLYP level of theory and including a simple point-charge model to treat the crystal environment.

  7. Overview on gold-refining technology%黄金精炼工艺综述

    Institute of Scientific and Technical Information of China (English)

    霍松龄

    2014-01-01

    The paper summarizes major methods of domestic gold-refining technology and current status of them , such as electrolytic refining ,extraction refining and electric control chlorination methods ,and analyzed the advantages and disadvantages each methods has ,and finally came up with the problems needing solving for the refinery work in the future .%综述了目前国内黄金精炼工艺的主要方法及现状,如电解精炼法、萃取精炼法、控电氯化法,并对各工艺方法的利弊进行了阐述,同时提出了未来精炼工艺需要解决的问题。

  8. 40 CFR 80.235 - How does a refiner obtain approval as a small refiner?

    Science.gov (United States)

    2010-07-01

    ... small refiner status, plus any subsidiary companies, any parent company and subsidiaries of the parent company, and any joint venture partners: (1)(i) A listing of the name and address of each location where... corporate contact person. (d) For joint ventures, the total number of employees includes the...

  9. Reintroducing electrostatics into macromolecular crystallographic refinement: application to neutron crystallography and DNA hydration.

    Science.gov (United States)

    Fenn, Timothy D; Schnieders, Michael J; Mustyakimov, Marat; Wu, Chuanjie; Langan, Paul; Pande, Vijay S; Brunger, Axel T

    2011-04-13

    Most current crystallographic structure refinements augment the diffraction data with a priori information consisting of bond, angle, dihedral, planarity restraints, and atomic repulsion based on the Pauli exclusion principle. Yet, electrostatics and van der Waals attraction are physical forces that provide additional a priori information. Here, we assess the inclusion of electrostatics for the force field used for all-atom (including hydrogen) joint neutron/X-ray refinement. Two DNA and a protein crystal structure were refined against joint neutron/X-ray diffraction data sets using force fields without electrostatics or with electrostatics. Hydrogen-bond orientation/geometry favors the inclusion of electrostatics. Refinement of Z-DNA with electrostatics leads to a hypothesis for the entropic stabilization of Z-DNA that may partly explain the thermodynamics of converting the B form of DNA to its Z form. Thus, inclusion of electrostatics assists joint neutron/X-ray refinements, especially for placing and orienting hydrogen atoms.

  10. Voltage-gated potassium currents are targets of diurnal changes in estradiol feedback regulation and kisspeptin action on gonadotropin-releasing hormone neurons in mice.

    Science.gov (United States)

    Pielecka-Fortuna, Justyna; DeFazio, R Anthony; Moenter, Suzanne M

    2011-11-01

    Estradiol has both negative and positive feedback actions upon gonadotropin-releasing hormone (GnRH) release; the latter actions trigger the preovulatory GnRH surge. Although neurobiological mechanisms of the transitions between feedback modes are becoming better understood, the roles of voltage-gated potassium currents, major contributors to neuronal excitability, are unknown. Estradiol alters two components of potassium currents in these cells: a transient current, I(A), and a sustained current, I(K). Kisspeptin is a potential mediator between estradiol and GnRH neurons and can act directly on GnRH neurons. We examined how estradiol, time of day, and kisspeptin interact to regulate these conductances in a mouse model exhibiting daily switches between estradiol negative (morning) and positive feedback (evening). Whole-cell voltage clamp recordings were made from GnRH neurons in brain slices from ovariectomized (OVX) mice and from OVX mice treated with estradiol (OVX+E). There were no diurnal changes in either I(A) or I(K) in GnRH neurons from OVX mice. In contrast, in GnRH neurons from OVX+E mice, I(A) and I(K) were greater during the morning when GnRH neuron activity is low and smaller in the evening when GnRH neuron activity is high. Estradiol increased I(A) in the morning and decreased it in the evening, relative to that in cells from OVX mice. Exogenously applied kisspeptin reduced I(A) regardless of time of day or estradiol status. Estradiol, interacting with time of day, and kisspeptin both depolarized I(A) activation. These findings extend our understanding of both the neurobiological mechanisms of estradiol negative vs. positive regulation of GnRH neurons and of kisspeptin action on these cells.

  11. Overview on the current status on virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part II.

    Science.gov (United States)

    Geromichalos, George D; Alifieris, Constantinos E; Geromichalou, Elena G; Trafalis, Dimitrios T

    2016-01-01

    Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anticancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery. A number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. In this part II we will review the role and methodology of ligand-, structure- and fragment-based computer-aided drug design computer aided drug desing (CADD), virtual high throughput screening (vHTS), de novo drug design, fragment-based design and structure-based molecular docking, homology modeling, combinatorial chemistry and library design, pharmacophore model chemistry and informatics in modern drug discovery.

  12. Systemic sclerosis: from pathogenesis to targeted therapy.

    Science.gov (United States)

    Denton, Christopher P

    2015-01-01

    Systemic sclerosis (scleroderma) leads to morbidity and mortality through a combination of inflammation, fibrosis and vascular damage leading to internal organ complications affecting the heart, lung, kidneys and bowel. More than half of those diagnosed ultimately die from the disease. Current treatments focus on broad spectrum immunosuppression or organ-based therapy for complication such as lung fibrosis, pulmonary or systemic hypertension. Targeting peptide mediators such as endothelin-1 have already led to licensed effective therapies for SSc vasculopathy. Outcomes are improving but as well as providing a major clinical challenge there are great opportunities for research translation that can be expected to improve understanding of the pathogenesis of SSc and also develop better and more targeted therapy. Key pathways and mediators can be identified within the skin and blood vessels and these are now being examined in early stage clinical trials. Promising results are emerging from targeting cytokine signalling, including IL-6, and from other immune-inflammatory therapies including lipid mediators such as LPA1. Other approaches to modulate TGFbeta and other profibrotic pathways also have potential although safety and toxicity remain to be determined. Since many profibrotic pathways have important physiological roles the assessment of safety and toxicity will be paramount. Nevertheless, advances in understanding the interplay between different pathological processes and progress in clinical trial design and patients stratification mean that targeted therapies are emerging and likely to be further developed and refined to have application in other important clinical contexts such as lung fibrosis.

  13. GRChombo: Numerical relativity with adaptive mesh refinement

    Science.gov (United States)

    Clough, Katy; Figueras, Pau; Finkel, Hal; Kunesch, Markus; Lim, Eugene A.; Tunyasuvunakool, Saran

    2015-12-01

    In this work, we introduce {\\mathtt{GRChombo}}: a new numerical relativity code which incorporates full adaptive mesh refinement (AMR) using block structured Berger-Rigoutsos grid generation. The code supports non-trivial ‘many-boxes-in-many-boxes’ mesh hierarchies and massive parallelism through the message passing interface. {\\mathtt{GRChombo}} evolves the Einstein equation using the standard BSSN formalism, with an option to turn on CCZ4 constraint damping if required. The AMR capability permits the study of a range of new physics which has previously been computationally infeasible in a full 3 + 1 setting, while also significantly simplifying the process of setting up the mesh for these problems. We show that {\\mathtt{GRChombo}} can stably and accurately evolve standard spacetimes such as binary black hole mergers and scalar collapses into black holes, demonstrate the performance characteristics of our code, and discuss various physics problems which stand to benefit from the AMR technique.

  14. Formal language theory: refining the Chomsky hierarchy

    Science.gov (United States)

    Jäger, Gerhard; Rogers, James

    2012-01-01

    The first part of this article gives a brief overview of the four levels of the Chomsky hierarchy, with a special emphasis on context-free and regular languages. It then recapitulates the arguments why neither regular nor context-free grammar is sufficiently expressive to capture all phenomena in the natural language syntax. In the second part, two refinements of the Chomsky hierarchy are reviewed, which are both relevant to the extant research in cognitive science: the mildly context-sensitive languages (which are located between context-free and context-sensitive languages), and the sub-regular hierarchy (which distinguishes several levels of complexity within the class of regular languages). PMID:22688632

  15. Algorithm refinement for stochastic partial differential equations.

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, F. J. (Francis J.); Garcia, Alejandro L.,; Tartakovsky, D. M. (Daniel M.)

    2001-01-01

    A hybrid particle/continuum algorithm is formulated for Fickian diffusion in the fluctuating hydrodynamic limit. The particles are taken as independent random walkers; the fluctuating diffusion equation is solved by finite differences with deterministic and white-noise fluxes. At the interface between the particle and continuum computations the coupling is by flux matching, giving exact mass conservation. This methodology is an extension of Adaptive Mesh and Algorithm Refinement to stochastic partial differential equations. A variety of numerical experiments were performed for both steady and time-dependent scenarios. In all cases the mean and variance of density are captured correctly by the stochastic hybrid algorithm. For a non-stochastic version (i.e., using only deterministic continuum fluxes) the mean density is correct, but the variance is reduced except within the particle region, far from the interface. Extensions of the methodology to fluid mechanics applications are discussed.

  16. Performance of a streaming mesh refinement algorithm.

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, David C.; Pebay, Philippe Pierre

    2004-08-01

    In SAND report 2004-1617, we outline a method for edge-based tetrahedral subdivision that does not rely on saving state or communication to produce compatible tetrahedralizations. This report analyzes the performance of the technique by characterizing (a) mesh quality, (b) execution time, and (c) traits of the algorithm that could affect quality or execution time differently for different meshes. It also details the method used to debug the several hundred subdivision templates that the algorithm relies upon. Mesh quality is on par with other similar refinement schemes and throughput on modern hardware can exceed 600,000 output tetrahedra per second. But if you want to understand the traits of the algorithm, you have to read the report!

  17. Refinement and stability of grain structure

    Energy Technology Data Exchange (ETDEWEB)

    John Humphreys, F.; Bate, P.S. [Manchester Univ. (United Kingdom). Manchester Materials Science Centre

    2001-07-01

    The various methods of producing fine-grained alloys are discussed and it is concluded that thermomechanical processing routes are most suitable for the economic production of the large quantities of material required for structural applications. The limits of grain refinement by conventional discontinuous recrystallization are considered, and the production of micron-grained alloys by continuous recrystallization processes during or after large strain deformation is discussed. The stability of highly deformed microstructures against recrystallization is analysed, and the effect of second-phase particles on grain growth is discussed. It is shown that perturbations of the Zener drag during high temperature deformation may lead to dynamic grain growth in two-phase alloys. (orig.)

  18. Error bounds from extra precise iterative refinement

    Energy Technology Data Exchange (ETDEWEB)

    Demmel, James; Hida, Yozo; Kahan, William; Li, Xiaoye S.; Mukherjee, Soni; Riedy, E. Jason

    2005-02-07

    We present the design and testing of an algorithm for iterative refinement of the solution of linear equations, where the residual is computed with extra precision. This algorithm was originally proposed in the 1960s [6, 22] as a means to compute very accurate solutions to all but the most ill-conditioned linear systems of equations. However two obstacles have until now prevented its adoption in standard subroutine libraries like LAPACK: (1) There was no standard way to access the higher precision arithmetic needed to compute residuals, and (2) it was unclear how to compute a reliable error bound for the computed solution. The completion of the new BLAS Technical Forum Standard [5] has recently removed the first obstacle. To overcome the second obstacle, we show how a single application of iterative refinement can be used to compute an error bound in any norm at small cost, and use this to compute both an error bound in the usual infinity norm, and a componentwise relative error bound. We report extensive test results on over 6.2 million matrices of dimension 5, 10, 100, and 1000. As long as a normwise (resp. componentwise) condition number computed by the algorithm is less than 1/max{l_brace}10,{radical}n{r_brace} {var_epsilon}{sub w}, the computed normwise (resp. componentwise) error bound is at most 2 max{l_brace}10,{radical}n{r_brace} {center_dot} {var_epsilon}{sub w}, and indeed bounds the true error. Here, n is the matrix dimension and w is single precision roundoff error. For worse conditioned problems, we get similarly small correct error bounds in over 89.4% of cases.

  19. Technical Considerations for Filler and Neuromodulator Refinements

    Science.gov (United States)

    Wilson, Anthony J.; Chang, Brian L.; Percec, Ivona

    2016-01-01

    Background: The toolbox for cosmetic practitioners is growing at an unprecedented rate. There are novel products every year and expanding off-label indications for neurotoxin and soft-tissue filler applications. Consequently, aesthetic physicians are increasingly challenged by the task of selecting the most appropriate products and techniques to achieve optimal patient outcomes. Methods: We employed a PubMed literature search of facial injectables from the past 10 years (2005–2015), with emphasis on those articles embracing evidence-based medicine. We evaluated the scientific background of every product and the physicochemical properties that make each one ideal for specific indications. The 2 senior authors provide commentary regarding their clinical experience with specific technical refinements of neuromodulators and soft-tissue fillers. Results: Neurotoxins and fillers are characterized by unique physical characteristics that distinguish each product. This results in subtle but important differences in their clinical applications. Specific indications and recommendations for the use of the various neurotoxins and soft-tissue fillers are reviewed. The discussion highlights refinements in combination treatments and product physical modifications, according to specific treatment zones. Conclusions: The field of facial aesthetics has evolved dramatically, mostly secondary to our increased understanding of 3-dimensional structural volume restoration. Our work reviews Food and Drug Administration–approved injectables. In addition, we describe how to modify products to fulfill specific indications such as treatment of the mid face, décolletage, hands, and periorbital regions. Although we cannot directly evaluate the duration or exact physical properties of blended products, we argue that “product customization” is safe and provides natural results with excellent patient outcomes. PMID:28018778

  20. Essays on refining markets and environmental policy

    Science.gov (United States)

    Oladunjoye, Olusegun Akintunde

    This thesis is comprised of three essays. The first two essays examine empirically the relationship between crude oil price and wholesale gasoline prices in the U.S. petroleum refining industry while the third essay determines the optimal combination of emissions tax and environmental research and development (ER&D) subsidy when firms organize ER&D either competitively or as a research joint venture (RJV). In the first essay, we estimate an error correction model to determine the effects of market structure on the speed of adjustment of wholesale gasoline prices, to crude oil price changes. The results indicate that market structure does not have a strong effect on the dynamics of price adjustment in the three regional markets examined. In the second essay, we allow for inventories to affect the relationship between crude oil and wholesale gasoline prices by allowing them to affect the probability of regime change in a Markov-switching model of the refining margin. We find that low gasoline inventory increases the probability of switching from the low margin regime to the high margin regime and also increases the probability of staying in the high margin regime. This is consistent with the predictions of the competitive storage theory. In the third essay, we extend the Industrial Organization R&D theory to the determination of optimal environmental policies. We find that RJV is socially desirable. In comparison to competitive ER&D, we suggest that regulators should encourage RJV with a lower emissions tax and higher subsidy as these will lead to the coordination of ER&D activities and eliminate duplication of efforts while firms internalize their technological spillover externality.

  1. Technical Considerations for Filler and Neuromodulator Refinements.

    Science.gov (United States)

    Montes, José Raúl; Wilson, Anthony J; Chang, Brian L; Percec, Ivona

    2016-12-01

    Background: The toolbox for cosmetic practitioners is growing at an unprecedented rate. There are novel products every year and expanding off-label indications for neurotoxin and soft-tissue filler applications. Consequently, aesthetic physicians are increasingly challenged by the task of selecting the most appropriate products and techniques to achieve optimal patient outcomes. Methods: We employed a PubMed literature search of facial injectables from the past 10 years (2005-2015), with emphasis on those articles embracing evidence-based medicine. We evaluated the scientific background of every product and the physicochemical properties that make each one ideal for specific indications. The 2 senior authors provide commentary regarding their clinical experience with specific technical refinements of neuromodulators and soft-tissue fillers. Results: Neurotoxins and fillers are characterized by unique physical characteristics that distinguish each product. This results in subtle but important differences in their clinical applications. Specific indications and recommendations for the use of the various neurotoxins and soft-tissue fillers are reviewed. The discussion highlights refinements in combination treatments and product physical modifications, according to specific treatment zones. Conclusions: The field of facial aesthetics has evolved dramatically, mostly secondary to our increased understanding of 3-dimensional structural volume restoration. Our work reviews Food and Drug Administration-approved injectables. In addition, we describe how to modify products to fulfill specific indications such as treatment of the mid face, décolletage, hands, and periorbital regions. Although we cannot directly evaluate the duration or exact physical properties of blended products, we argue that "product customization" is safe and provides natural results with excellent patient outcomes.

  2. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    Science.gov (United States)

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline.

  3. Effects and mechanisms of grain refinement in aluminium alloys

    Indian Academy of Sciences (India)

    K T Kashyap; T Chandrashekar

    2001-08-01

    Grain refinement plays a crucial role in improving characteristics and properties of cast and wrought aluminium alloys. Generally Al–Ti and Al–Ti–B master alloys are added to the aluminium alloys to grain refine the solidified product. The mechanism of grain refinement is of considerable controversy in the scientific literature. The nucleant effects i.e. which particle and its characteristics nucleate -Al, has been the subject of intensive research. Lately the solute effect i.e. the effect of dissolved titanium on grain refinement, has come into forefront of grain refinement research. The present paper attempts to review the literature on the nucleant effects and solute effects on grain refinement and addresses the importance of dissolved titanium in promoting nucleation of -Al on nucleant particles.

  4. On macromolecular refinement at subatomic resolution withinteratomic scatterers

    Energy Technology Data Exchange (ETDEWEB)

    Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.; Lunin, Vladimir Y.; Urzhumtsev, Alexandre

    2007-11-09

    A study of the accurate electron density distribution in molecular crystals at subatomic resolution, better than {approx} 1.0 {angstrom}, requires more detailed models than those based on independent spherical atoms. A tool conventionally used in small-molecule crystallography is the multipolar model. Even at upper resolution limits of 0.8-1.0 {angstrom}, the number of experimental data is insufficient for the full multipolar model refinement. As an alternative, a simpler model composed of conventional independent spherical atoms augmented by additional scatterers to model bonding effects has been proposed. Refinement of these mixed models for several benchmark datasets gave results comparable in quality with results of multipolar refinement and superior of those for conventional models. Applications to several datasets of both small- and macro-molecules are shown. These refinements were performed using the general-purpose macromolecular refinement module phenix.refine of the PHENIX package.

  5. Deformable elastic network refinement for low-resolution macromolecular crystallography.

    Science.gov (United States)

    Schröder, Gunnar F; Levitt, Michael; Brunger, Axel T

    2014-09-01

    Crystals of membrane proteins and protein complexes often diffract to low resolution owing to their intrinsic molecular flexibility, heterogeneity or the mosaic spread of micro-domains. At low resolution, the building and refinement of atomic models is a more challenging task. The deformable elastic network (DEN) refinement method developed previously has been instrumental in the determinion of several structures at low resolution. Here, DEN refinement is reviewed, recommendations for its optimal usage are provided and its limitations are discussed. Representative examples of the application of DEN refinement to challenging cases of refinement at low resolution are presented. These cases include soluble as well as membrane proteins determined at limiting resolutions ranging from 3 to 7 Å. Potential extensions of the DEN refinement technique and future perspectives for the interpretation of low-resolution crystal structures are also discussed.

  6. Refinement of herpesvirus B-capsid structure on parallel supercomputers.

    Science.gov (United States)

    Zhou, Z H; Chiu, W; Haskell, K; Spears, H; Jakana, J; Rixon, F J; Scott, L R

    1998-01-01

    Electron cryomicroscopy and icosahedral reconstruction are used to obtain the three-dimensional structure of the 1250-A-diameter herpesvirus B-capsid. The centers and orientations of particles in focal pairs of 400-kV, spot-scan micrographs are determined and iteratively refined by common-lines-based local and global refinement procedures. We describe the rationale behind choosing shared-memory multiprocessor computers for executing the global refinement, which is the most computationally intensive step in the reconstruction procedure. This refinement has been implemented on three different shared-memory supercomputers. The speedup and efficiency are evaluated by using test data sets with different numbers of particles and processors. Using this parallel refinement program, we refine the herpesvirus B-capsid from 355-particle images to 13-A resolution. The map shows new structural features and interactions of the protein subunits in the three distinct morphological units: penton, hexon, and triplex of this T = 16 icosahedral particle.

  7. Mirror of the refined topological vertex from a matrix model

    CERN Document Server

    Eynard, B

    2011-01-01

    We find an explicit matrix model computing the refined topological vertex, starting from its representation in terms of plane partitions. We then find the spectral curve of that matrix model, and thus the mirror symmetry of the refined vertex. With the same method we also find a matrix model for the strip geometry, and we find its mirror curve. The fact that there is a matrix model shows that the refined topological string amplitudes also satisfy the remodeling the B-model construction.

  8. [Current controversies in glycemic control targets. What do the results of the latest clinical trials tell us about the approach to type 2 diabetes mellitus?].

    Science.gov (United States)

    Mauricio, Dídac; Rius, Ferran

    2010-09-01

    The aim of this article is to discuss the implications of the results obtained in the latest large-scale clinical trials designed to evaluate the effect of intensive glycemic control on the vascular complications associated with type 2 diabetes mellitus. The current scientific evidence is reviewed and the implications of the ACCORD (The Action to Control Cardiovascular Risk in Diabetes study group), ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Control Evaluation) and VADT (Veterans Affairs Diabetes Trial) clinical trials are discussed. General concerns of the studies and their implications for clinical practice and the management of type 2 diabetes, as well as the questions which still need to be answered by future clinical research are discussed.

  9. Direct-space methods in phase extension and phase refinement. IV. The double-histogram method.

    Science.gov (United States)

    Refaat, L S; Tate, C; Woolfson, M M

    1996-03-01

    In the conventional histogram-matching technique for phase extension and refinement for proteins a simple one-to-one transformation is made in the protein region to modify calculated density so that it will have some target histogram in addition to solvent flattening. This work describes an investigation where the density modification takes into account not only the current calculated density at a grid point but also some characteristic of the environment of the grid point within some distance R. This characteristic can be one of the local maximum density, the local minimum density or the local variance of density. The grid points are divided into ten groups, each containing the same number of grid points, for ten different ranges of value of the local characteristic. The ten groups are modified to give different histograms, each corresponding to that obtained under the same circumstances from a structure similar to the one under investigation. This process is referred to as the double-histogram matching method. Other processes which have been investigated are the weighting of structure factors when calculating maps with estimated phases and also the use of a factor to dampen the change of density and so control the refinement process. Two protein structures were used in numerical trials, RNApl [Bezborodova, Ermekbaeva, Shlyapnikov, Polyakov & Bezborodov (1988). Biokhimiya, 53, 965-973] and 2-Zn insulin [Baker, Blundell, Cutfield, Cutfield, Dodson, Dodson, Hodgkin, Hubbard, lsaacs, Reynolds, Sakabe, Sakabe & Vijayan (1988). Philos. Trans. R. Soc. London Ser. B, 319, 456--469]. Comparison of the proposed procedures with the normal histogram-matching technique without structure-factor weighting or damping gives mean phase errors reduced by up to 10 degrees with map correlation coefficients improved by as much as 0.14. Compared to the normal histogram used with weighting of structure factors and damping, the improvement due to the use of the double-histogram method is

  10. Cardiac and electrophysiological effects of primary and refined extracts from Leonurus cardiaca L. (Ph.Eur.).

    Science.gov (United States)

    Ritter, Malte; Melichar, Kerstin; Strahler, Sabine; Kuchta, Kenny; Schulte, Jan; Sartiani, Laura; Cerbai, Elisabetta; Mugelli, Alessandro; Mohr, Friedrich-Wilhelm; Rauwald, Hans Wilhelm; Dhein, Stefan

    2010-04-01

    (Ca.L), sinoatrial node cells and ventricular myocytes isolated from adult guinea pigs to test effects on I(f) and action potential (AP) duration, as well as HERG-transfected HEK 293 cells to analyse the influence on the I (K.r). In these voltage clamp experiments LCRE exerted a calcium-antagonistic activity by I(Ca.L) blockade, reduced the repolarising current I(K.r), and prolonged the AP-duration, while I(Na) was not affected. Although LCRE displayed only weak effects on the I(f) amplitude and voltage dependence, it significantly prolonged the activation time constant of I(f). Thus, LCRE acts on multiple electrophysiological targets, specifically I(Ca.L), I(K.r), and I(f), observed both at whole organ and single cell level. Georg Thieme Verlag KG Stuttgart.New York.

  11. Physical model of aluminium refining process in URC-7000

    Directory of Open Access Journals (Sweden)

    M. Saternus

    2009-07-01

    Full Text Available The paper presents short characteristics of the most frequently used reactors for the continuous refining of aluminium and its alloys. Refining depends on the flow rate of refining gas. It influences the shape and size of gas bubbles. So the physical model was created to determine the level of gas bubble dispersion in liquids. Schemes of gas dispersion in liquid metal were presented taking into consideration that the gas flow rate is changing from 2 to 30 dm3/min. The range selection of the flow rate of refining gas value for five patterns of the dispersion (no dispersion, minimum, intimate, uniform and overdispersion was also done.

  12. New Process for Grain Refinement of Aluminum. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Joseph A. Megy

    2000-09-22

    A new method of grain refining aluminum involving in-situ formation of boride nuclei in molten aluminum just prior to casting has been developed in the subject DOE program over the last thirty months by a team consisting of JDC, Inc., Alcoa Technical Center, GRAS, Inc., Touchstone Labs, and GKS Engineering Services. The Manufacturing process to make boron trichloride for grain refining is much simpler than preparing conventional grain refiners, with attendant environmental, capital, and energy savings. The manufacture of boride grain refining nuclei using the fy-Gem process avoids clusters, salt and oxide inclusions that cause quality problems in aluminum today.

  13. Intra- and inter-clade cross-reactivity by HIV-1 Gag specific T-cells reveals exclusive and commonly targeted regions: implications for current vaccine trials.

    Directory of Open Access Journals (Sweden)

    Lycias Zembe

    Full Text Available The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128 and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001. Consistent with these results, the predicted Major Histocompatibility Complex Class I IC(50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p<0.0001, suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities.

  14. Interventions targeting sexual and reproductive health and rights outcomes of young people living with HIV: a comprehensive review of current interventions from sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Leandri Pretorius

    2015-11-01

    Full Text Available Background: A growing number of young people (ages 10–24 are living with HIV (YPLWH in sub-Saharan Africa (SSA. These YPLWH have particular needs and challenges related to their sexual and reproductive health and rights (SRHR. Contextual factors including gender inequalities, violence, stigma, and discrimination and lack of tailored services undermine YPLWH's SRHR. Objective: Understand the scope and impact of interventions targeting YPLWH to improve SRH-related outcomes in SSA. Design: We undertook a review to synthesise evaluated interventions (qualitative, quantitative, or mixed methods aimed at improving the SRH outcomes of YPLWH in SSA with outcomes based on a World Health Organization framework of comprehensive SRHR approaches for women living with HIV. Using inclusion criteria, only six interventions were identified. Results: Interventions sought to improve a range of direct and indirect SRH outcomes, including sexual behaviour, adherence, disclosure, and mental health. Four overarching issues emerged: 1 all interventions were structured according to cognitive behavioural therapy theories of behaviour change – while showing promise they do not tackle the wider gender, social, and economic contexts that shape YPLWH's SRH; 2 ‘significant others’ were included in two of the interventions, but further work needs to consider how to leverage parental/guardian support appropriately; 3 interventions only accessed young people who were already linked to care, participants were likely to have better SRH outcomes than those potentially more vulnerable YPLWH; and 4 none of the interventions explored the sexuality of young people. Conclusions: There have been a limited number of evaluated interventions to strengthen SRH of YPLWH in SSA, and gaps exist in addressing the SRHR needs of YPLWH. Intervention approaches require greater scope and depth, including the need to address structural and contextual challenges.

  15. Microstructural characterization and grain refinement of AA6082 gas tungsten arc welds by scandium modified fillers

    Energy Technology Data Exchange (ETDEWEB)

    Babu, N. Kishore, E-mail: nkishorebabu@gmail.com [Joining Technology Group, Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, Singapore 638075 (Singapore); Talari, Mahesh Kumar [Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam (Malaysia); Pan, D.; Sun, Z.; Wei, J. [Joining Technology Group, Singapore Institute of Manufacturing Technology, 71 Nanyang Drive, Singapore 638075 (Singapore); Sivaprasad, K. [Advanced Materials Processing Laboratory, Department of Metallurgical and Materials Engineering, National Institute of Technology, Tiruchirapalli 620015, Tamil Nadu (India)

    2012-12-14

    The refinement in weld metal grain size and shape results in both improved mechanical properties (ductility and toughness) as well as a significant improvement in weldability. In the present study, the influence of scandium (Sc) additions to the fillers on the structure and mechanical properties of AA6082 gas tungsten arc (GTA) weldments were investigated. Controlled amounts of scandium as grain refiner were introduced into the molten pool of AA6082 by pre-deposited cast inserts (AA4043 and AA5356) by GTA welding. Full penetration GTA welds were prepared using alternating current (AC). It was observed that grain size decreased with increasing amounts of scandium. The grain refinement is mainly caused by the Al{sub 3}Sc particles, which act as heterogeneous nucleation of {alpha}-Al grains. It has been shown that welds prepared with AA5356 cast insert exhibited high strength and ductility when compared with other welds. The observed grain refinement was shown to result in an appreciable increase in fusion zone hardness, strength and ductility. Post-weld aging treatment resulted in improved tensile strength and hardness of the weldments and this aging response could be attributed to the weld dilution from the base metal. The slow diffusion of Sc in Al matrix and stability of Al{sub 3}Sc precipitates at elevated temperatures were suggested to be responsible for the improved high temperature yield strength of welds made from Sc modified fillers. -- Highlights: Black-Right-Pointing-Pointer Primary Al{sub 3}Sc particles resulted in grain refinement by heterogeneous nucleation. Black-Right-Pointing-Pointer Weld metal strength and hardness improved due to grain refinement caused by Sc. Black-Right-Pointing-Pointer Weld metal responded to post-weld aging treatment due to dilution from base metal. Black-Right-Pointing-Pointer Sc addition improved the high temperature mechanical properties of welds.

  16. A comparison of spectral element and finite difference methods using statically refined nonconforming grids for the MHD island coalescence instability problem

    CERN Document Server

    Ng, C S; Germaschewski, K; Pouquet, A; Bhattacharjee, A

    2007-01-01

    A recently developed spectral-element adaptive refinement incompressible magnetohydrodynamic (MHD) code [Rosenberg, Fournier, Fischer, Pouquet, J. Comp. Phys. 215, 59-80 (2006)] is applied to simulate the problem of MHD island coalescence instability (MICI) in two dimensions. MICI is a fundamental MHD process that can produce sharp current layers and subsequent reconnection and heating in a high-Lundquist number plasma such as the solar corona [Ng and Bhattacharjee, Phys. Plasmas, 5, 4028 (1998)]. Due to the formation of thin current layers, it is highly desirable to use adaptively or statically refined grids to resolve them, and to maintain accuracy at the same time. The output of the spectral-element static adaptive refinement simulations are compared with simulations using a finite difference method on the same refinement grids, and both methods are compared to pseudo-spectral simulations with uniform grids as baselines. It is shown that with the statically refined grids roughly scaling linearly with effec...

  17. The Current Status of the Delineation and Determination of the Targets and the Radiation Protocols for Nasopharyngeal Cancer with Intensity-Modulated Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    IMRT has increased the local-regional control and decreased the complications from treating nasopharyngeal cancer (NPC).Therefore studying IMRT is important. CT and MRI are complementary, and their joint use is currently considered to be the optimal modality to delineate the extent of the primary spread of NPC. The key problem in delineation of the neck nodes is how to translate anatomic node regions into the CT boundaries. The consensus guideline which narrowed the gap among different cancer centers is recommended in delineating the boundary of the cervical lymph node regions. The definition of the NPC GTV is clear and almost the same among the main cancer centers in their IMRT planning protocols.The suggested biological dose to the GTV is close to or more than 80 Gy;the main differences are the definitions of the CTVs and their schemes for the prescribed dose, and also the dosage to the high cervical region is different among those centers. According to their long-term follow-up results, it is suggested that, besides adding 5~10 mm margins to the primary lesions,the immediate high-risk structures (including the entire nasopharyngeal cavity, retropharyngeal space, clivus, base of the skull, pterygoid plates and muscles, parapharyngeal space, the sphenoid and partial ethmoid sinuses,the posterior third of the maxillary sinuses and the nasal cavity) should also be included with a prescription of more than 60 Gy, and the bilateral Ib, Ⅱ and Ⅴa node levels should be ranked as high-risk regions and differentially prescribed for treatment with no less than 60 Gy.

  18. Ventral medial prefrontal cortex (vmPFC) as a target of the dorsolateral prefrontal modulation by transcranial direct current stimulation (tDCS) in drug addiction.

    Science.gov (United States)

    Nakamura-Palacios, Ester Miyuki; Lopes, Isabela Bittencourt Coutinho; Souza, Rodolpho Albuquerque; Klauss, Jaisa; Batista, Edson Kruger; Conti, Catarine Lima; Moscon, Janine Andrade; de Souza, Rodrigo Stênio Moll

    2016-10-01

    Here, we report some electrophysiologic and imaging effects of the transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) in drug addiction, notably in alcohol and crack-cocaine dependence. The low resolution electromagnetic tomography (LORETA) analysis obtained through event-related potentials (ERPs) under drug-related cues, more specifically in its P3 segment (300-500 ms) in both, alcoholics and crack-cocaine users, showed that the ventral medial prefrontal cortex (vmPFC) was the brain area with the largest change towards increasing activation under drug-related cues in those subjects that kept abstinence during and after the treatment with bilateral tDCS (2 mA, 35 cm(2), cathodal left and anodal right) over dlPFC, applied repetitively (five daily sessions). In an additional study in crack-cocaine, which showed craving decreases after repetitive bilateral tDCS, we examined data originating from diffusion tensor imaging (DTI), and we found increased DTI parameters in the left connection between vmPFC and nucleus accumbens (NAcc), such as the number of voxels, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), in tDCS-treated crack-cocaine users when compared to the sham-tDCS group. This increasing of DTI parameters was significantly correlated with craving decreasing after the repetitive tDCS. The vmPFC relates to the control of drug seeking, possibly by extinguishing this behavior. In our studies, the bilateral dlPFC tDCS reduced relapses and craving to the drug use, and increased the vmPFC activation under drug cues, which may be of a great importance in the control of drug use in drug addiction.

  19. GRChombo : Numerical Relativity with Adaptive Mesh Refinement

    CERN Document Server

    Clough, Katy; Finkel, Hal; Kunesch, Markus; Lim, Eugene A; Tunyasuvunakool, Saran

    2015-01-01

    Numerical relativity has undergone a revolution in the past decade. With a well-understood mathematical formalism, and full control over the gauge modes, it is now entering an era in which the science can be properly explored. In this work, we introduce GRChombo, a new numerical relativity code written to take full advantage of modern parallel computing techniques. GRChombo's features include full adaptive mesh refinement with block structured Berger-Rigoutsos grid generation which supports non-trivial "many-boxes-in-many-boxes" meshing hierarchies, and massive parallelism through the Message Passing Interface (MPI). GRChombo evolves the Einstein equation with the standard BSSN formalism, with an option to turn on CCZ4 constraint damping if required. We show that GRChombo passes all the standard "Apples-to-Apples" code comparison tests. We also show that it can stably and accurately evolve vacuum black hole spacetimes such as binary black hole mergers, and non-vacuum spacetimes such as scalar collapses into b...

  20. Time Critical Isosurface Refinement and Smoothing

    Energy Technology Data Exchange (ETDEWEB)

    Pascucci, V.; Bajaj, C.L.

    2000-07-10

    Multi-resolution data-structures and algorithms are key in Visualization to achieve real-time interaction with large data-sets. Research has been primarily focused on the off-line construction of such representations mostly using decimation schemes. Drawbacks of this class of approaches include: (i) the inability to maintain interactivity when the displayed surface changes frequently, (ii) inability to control the global geometry of the embedding (no self-intersections) of any approximated level of detail of the output surface. In this paper we introduce a technique for on-line construction and smoothing of progressive isosurfaces. Our hybrid approach combines the flexibility of a progressive multi-resolution representation with the advantages of a recursive sub-division scheme. Our main contributions are: (i) a progressive algorithm that builds a multi-resolution surface by successive refinements so that a coarse representation of the output is generated as soon as a coarse representation of the input is provided, (ii) application of the same scheme to smooth the surface by means of a 3D recursive subdivision rule, (iii) a multi-resolution representation where any adaptively selected level of detail surface is guaranteed to be free of self-intersections.

  1. Worldsheet realization of the refined topological string

    Energy Technology Data Exchange (ETDEWEB)

    Antoniadis, I., E-mail: ignatios.antoniadis@cern.ch [Department of Physics, CERN – Theory Division, CH-1211 Geneva 23 (Switzerland); Florakis, I., E-mail: florakis@mppmu.mpg.de [Max-Planck-Institut für Physik, Werner-Heisenberg-Institut, 80805 München (Germany); Hohenegger, S., E-mail: stefan.hohenegger@cern.ch [Department of Physics, CERN – Theory Division, CH-1211 Geneva 23 (Switzerland); Narain, K.S., E-mail: narain@ictp.trieste.it [High Energy Section, The Abdus Salam International Center for Theoretical Physics, Strada Costiera, 11-34014 Trieste (Italy); Zein Assi, A., E-mail: zeinassi@cern.ch [Department of Physics, CERN – Theory Division, CH-1211 Geneva 23 (Switzerland); Centre de Physique Théorique (UMR CNRS 7644), Ecole Polytechnique, 91128 Palaiseau (France)

    2013-10-01

    A worldsheet realization of the refined topological string is proposed in terms of physical string amplitudes that compute generalized N=2 F-terms of the form F{sub g,n}W{sup 2g}ϒ{sup 2n} in the effective supergravity action. These terms involve the chiral Weyl superfield W and a superfield ϒ defined as an N=2 chiral projection of a particular anti-chiral T{sup ¯}-vector multiplet. In Heterotic and Type I theories, obtained upon compactification on the six-dimensional manifold K3×T{sup 2}, T is the usual Kähler modulus of the T{sup 2} torus. These amplitudes are computed exactly at the one-loop level in string theory. They are shown to reproduce the correct perturbative part of the Nekrasov partition function in the field theory limit when expanded around an SU(2) enhancement point of the string moduli space. The two deformation parameters ϵ{sub −} and ϵ{sub +} of the Ω supergravity background are then identified with the constant field strength backgrounds for the anti-self-dual graviphoton and self-dual gauge field of the T{sup ¯} vector multiplet, respectively.

  2. Refining and blending of aviation turbine fuels.

    Science.gov (United States)

    White, R D

    1999-02-01

    Aviation turbine fuels (jet fuels) are similar to other petroleum products that have a boiling range of approximately 300F to 550F. Kerosene and No.1 grades of fuel oil, diesel fuel, and gas turbine oil share many similar physical and chemical properties with jet fuel. The similarity among these products should allow toxicology data on one material to be extrapolated to the others. Refineries in the USA manufacture jet fuel to meet industry standard specifications. Civilian aircraft primarily use Jet A or Jet A-1 fuel as defined by ASTM D 1655. Military aircraft use JP-5 or JP-8 fuel as defined by MIL-T-5624R or MIL-T-83133D respectively. The freezing point and flash point are the principle differences between the finished fuels. Common refinery processes that produce jet fuel include distillation, caustic treatment, hydrotreating, and hydrocracking. Each of these refining processes may be the final step to produce jet fuel. Sometimes blending of two or more of these refinery process streams are needed to produce jet fuel that meets the desired specifications. Chemical additives allowed for use in jet fuel are also defined in the product specifications. In many cases, the customer rather than the refinery will put additives into the fuel to meet their specific storage or flight condition requirements.

  3. FPGA Congestion-Driven Placement Refinement

    Energy Technology Data Exchange (ETDEWEB)

    Vicente de, J.

    2005-07-01

    The routing congestion usually limits the complete proficiency of the FPGA logic resources. A key question can be formulated regarding the benefits of estimating the congestion at placement stage. In the last years, it is gaining acceptance the idea of a detailed placement taking into account congestion. In this paper, we resort to the Thermodynamic Simulated Annealing (TSA) algorithm to perform a congestion-driven placement refinement on the top of the common Bounding-Box pre optimized solution. The adaptive properties of TSA allow the search to preserve the solution quality of the pre optimized solution while improving other fine-grain objectives. Regarding the cost function two approaches have been considered. In the first one Expected Occupation (EO), a detailed probabilistic model to account for channel congestion is evaluated. We show that in spite of the minute detail of EO, the inherent uncertainty of this probabilistic model impedes to relieve congestion beyond the sole application of the Bounding-Box cost function. In the second approach we resort to the fast Rectilinear Steiner Regions algorithm to perform not an estimation but a measurement of the global routing congestion. This second strategy allows us to successfully reduce the requested channel width for a set of benchmark circuits with respect to the widespread Versatile Place and Route (VPR) tool. (Author) 31 refs.

  4. Elliptic Solvers for Adaptive Mesh Refinement Grids

    Energy Technology Data Exchange (ETDEWEB)

    Quinlan, D.J.; Dendy, J.E., Jr.; Shapira, Y.

    1999-06-03

    We are developing multigrid methods that will efficiently solve elliptic problems with anisotropic and discontinuous coefficients on adaptive grids. The final product will be a library that provides for the simplified solution of such problems. This library will directly benefit the efforts of other Laboratory groups. The focus of this work is research on serial and parallel elliptic algorithms and the inclusion of our black-box multigrid techniques into this new setting. The approach applies the Los Alamos object-oriented class libraries that greatly simplify the development of serial and parallel adaptive mesh refinement applications. In the final year of this LDRD, we focused on putting the software together; in particular we completed the final AMR++ library, we wrote tutorials and manuals, and we built example applications. We implemented the Fast Adaptive Composite Grid method as the principal elliptic solver. We presented results at the Overset Grid Conference and other more AMR specific conferences. We worked on optimization of serial and parallel performance and published several papers on the details of this work. Performance remains an important issue and is the subject of continuing research work.

  5. Water Refining By the Membrane Separation Method

    Directory of Open Access Journals (Sweden)

    Zdenka Bolanca

    2000-03-01

    Full Text Available The investigations in this paper refer to the possibility of wastewater refining from deinking flotation process by the method of membrane separation. The offset impressions made with the conventional printing inks as wellas the models based on the raw materials of renewable origin were used in the recycling process. Before andafter the water treatment, the concentration of the sulphate, chloride, nitrate, total organic substance, oxygenconsumption, pH and electric conductivity was determinedin all the samples by standard analytical methods.The results point at the dependence of the concentration of the investigated inorganic and organic pollution with the characteristics of the prints used in the recycling process. The concentration decrease of the investigated pollution using the method of the membrane separation in relation to the boundary values of the water quality necessary for the paper production has been discussed. Besides the specific scientific contribution, the practical application of the investigation is the contribution to the closing of water circuit in paper production.

  6. The conditioned place preference test for assessing welfare consequences and potential refinements in a mouse bladder cancer model.

    Science.gov (United States)

    Roughan, John V; Coulter, Claire A; Flecknell, Paul A; Thomas, Huw D; Sufka, Kenneth J

    2014-01-01

    Most pre-clinical analgesic efficacy assays still involve nociceptive testing in rodents. This is despite concerns as to the relevance of these tests for evaluating the pain-preventative properties of drugs. More appropriate methods would target pain rather than nociception, but these are currently not available, so it remains unknown whether animal pain equates to the negatively affective and subjective/emotional state it causes in humans. Mouse cancer models are common despite the likelihood of substantial pain. We used Conditioned Place Preference (CPP) testing, assessments of thermal hyperalgesia and behaviour to determine the likelihood that MBT-2 bladder cancer impacts negatively on mouse welfare, such as by causing pain. There was no CPP to saline, but morphine preference in tumour bearing mice exceeded that seen in tumour-free controls. This occurred up to 10 days before the study end-point alongside reduced body weight, development of hyperalgesia and behaviour changes. These effects indicated mice experienced a negative welfare state caused by malaise (if not pain) before euthanasia. Due to the complexity of the assessments needed to demonstrate this, it is unlikely that this approach could be used for routine welfare assessment on a study-by-study basis. However, our results show mice in sufficiently similar studies are likely to benefit from more intensive severity assessment and re-evaluation of end-points with a view to implementing appropriate refinements. In this particular case, a refinement would have been to have euthanased mice at least 7 days earlier or possibly by provision of end-stage pain relief. CPP testing was found to be a helpful method to investigate the responses of mice to analgesics, possibly on a subjective level. These findings and those of other recent studies show it could be a valuable method of screening candidate analgesics for efficacy against cancer pain and possibly other pain or disease models.

  7. Cultural Competence Assessment Instrument: Initial Italian validation and proposed refinement.

    Science.gov (United States)

    Caricati, Luca; Dicembrino, Rita Bruna; Gionti, Luciano; Petre, Lucica; Ungurean, Liana

    2015-09-09

    Italy has become a target of immigration in the last three decades. Accordingly, the Italian population is progressively changing, becoming increasingly culturally different. Cultural competences are a fundamental requirement for many industries and, especially, for healthcare organizations. The aim of this paper is to propose an initial Italian validation of the Cultural Competence Assessment Instrument (CCAI) and to propose a refinement of this scale in terms of measured constructs. The CCAI was translated into Italian through a team-based iterative approach and then administered to a sample of 289 nurses with symbolic and realistic threat scale and social dominance orientation scale. An on-line cross-sectional survey questionnaire was used. Confirmatory factor analysis revealed that the original two dimensions of the CCAI can be divided into two other sub-scales, thus leaving us with the following dimensions: cultural awareness, cultural sensitivity, seeking information and active behavior. These dimensions appeared to be sufficiently reliable and independent one from another. Moreover, they showed specific and different correlations with other measured constructs. The Italian version of the CCAI would seem to be a useful instrument for measuring both attitudes and behavioral intention of nurses with respect to intercultural care. Using four dimensions instead of two appears to increase the understanding of professionals' cultural competence and supply a deeper picture of dimensions which compose cultural competence in healthcare settings.

  8. Fuel poverty in Scotland: refining spatial resolution in the Scottish Fuel Poverty Indicator using a GIS-based multiple risk index.

    Science.gov (United States)

    Morrison, Colin; Shortt, Niamh

    2008-12-01

    Fuel poverty describes a complex interaction between households with low income and energy inefficiency. The Scottish Executive has charged local Scottish authorities with the task of eradicating fuel poverty by 2016. In order to direct investment and tackle fuel poverty, a local authority must know which areas are more likely to contain fuel poor households. Currently, local area fuel poverty indicators, based on small area statistics, are used to identify target areas. This paper proposes an innovative methodology for refinement of the Scottish Fuel Poverty Indicator using GIS as a framework for integrating census data with georeferenced energy efficiency data on local housing stock. This allows a multi-scale mapping of fuel poverty risk at both a census output area level and an individual dwelling level. The proposed methodology highlights small areas, and households, possibly susceptible to fuel poverty previously masked by the aggregation of statistics to large geographic units.

  9. Refinements of the Weyl tensor classification in five dimensions

    NARCIS (Netherlands)

    Coley, A.; Hervik, S.; Ortaggio, M.; Wylleman, L.

    2012-01-01

    We refine the null alignment classification of the Weyl tensor of a five-dimensional spacetime. The paper focusses on the algebraically special alignment types N, III, II and D, while types I and G are briefly discussed. A first refinement is provided by the notion of spin type of the components of

  10. Crystal structure refinement a crystallographers guide to SHELXL

    CERN Document Server

    2006-01-01

    A crystallographers guide to SHELXL, covering various aspects of practical crystal structure refinement, from the treatment of hydrogen atoms to the assignment of atom types, and more. After an introduction to SHELXL, a brief survey of crystal structure refinement is provided.

  11. Optimization of Refining Craft for Vegetable Insulating Oil

    Science.gov (United States)

    Zhou, Zhu-Jun; Hu, Ting; Cheng, Lin; Tian, Kai; Wang, Xuan; Yang, Jun; Kong, Hai-Yang; Fang, Fu-Xin; Qian, Hang; Fu, Guang-Pan

    2016-05-01

    Vegetable insulating oil because of its environmental friendliness are considered as ideal material instead of mineral oil used for the insulation and the cooling of the transformer. The main steps of traditional refining process included alkali refining, bleaching and distillation. This kind of refining process used in small doses of insulating oil refining can get satisfactory effect, but can't be applied to the large capacity reaction kettle. This paper using rapeseed oil as crude oil, and the refining process has been optimized for large capacity reaction kettle. The optimized refining process increases the acid degumming process. The alkali compound adds the sodium silicate composition in the alkali refining process, and the ratio of each component is optimized. Add the amount of activated clay and activated carbon according to 10:1 proportion in the de-colorization process, which can effectively reduce the oil acid value and dielectric loss. Using vacuum pumping gas instead of distillation process can further reduce the acid value. Compared some part of the performance parameters of refined oil products with mineral insulating oil, the dielectric loss of vegetable insulating oil is still high and some measures are needed to take to further optimize in the future.

  12. Cavitation-aided grain refinement in aluminium alloys

    NARCIS (Netherlands)

    Atamanenko, T.V.

    2010-01-01

    This thesis deals with grain refinement under the influence of ultrasonic-driven cavitation in aluminium casting processes. Three major goals of this research were: (1) to identify the mechanism of the cavitation-aided grain refinement at different stages of solidification; (2) to reveal the

  13. Review and Prospect of China's Oil Refining Industry

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Driven by the steady and rapid development of domestic economy and the rapid growth of oil demand in recent years, China's oil refining industry has overcome the influence of fluctuating international crude oil price and international financial crisis, and witnessed rapid increase in refining capacity and continuous rising of processed crude oil and production of gasoline,

  14. The Analysis of the Refined Financial Management of Modern Enterprises

    Directory of Open Access Journals (Sweden)

    Li Ran

    2016-01-01

    Full Text Available This paper briefly introduces the concept of the refined financial management, elaborates on its characteristics and puts forward some main points about it. It also comes up with some personal suggestions for reference on effective ways of refining financial management.

  15. Cavitation-aided grain refinement in aluminium alloys

    NARCIS (Netherlands)

    Atamanenko, T.V.

    2010-01-01

    This thesis deals with grain refinement under the influence of ultrasonic-driven cavitation in aluminium casting processes. Three major goals of this research were: (1) to identify the mechanism of the cavitation-aided grain refinement at different stages of solidification; (2) to reveal the conditi

  16. REFMAC5 for the refinement of macromolecular crystal structures

    Energy Technology Data Exchange (ETDEWEB)

    Murshudov, Garib N., E-mail: garib@ysbl.york.ac.uk [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Skubák, Pavol [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Lebedev, Andrey A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Pannu, Navraj S. [Biophysical Structural Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden (Netherlands); Steiner, Roberto A. [Randall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London, London (United Kingdom); Nicholls, Robert A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom); Winn, Martyn D. [STFC Daresbury Laboratory, Warrington WA4 4AD (United Kingdom); Long, Fei; Vagin, Alexei A. [Structural Biology Laboratory, Department of Chemistry, University of York, Heslington, York YO10 5YW (United Kingdom)

    2011-04-01

    The general principles behind the macromolecular crystal structure refinement program REFMAC5 are described. This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part of the CCP4 suite. REFMAC5 utilizes different likelihood functions depending on the diffraction data employed (amplitudes or intensities), the presence of twinning and the availability of SAD/SIRAS experimental diffraction data. To ensure chemical and structural integrity of the refined model, REFMAC5 offers several classes of restraints and choices of model parameterization. Reliable models at resolutions at least as low as 4 Å can be achieved thanks to low-resolution refinement tools such as secondary-structure restraints, restraints to known homologous structures, automatic global and local NCS restraints, ‘jelly-body’ restraints and the use of novel long-range restraints on atomic displacement parameters (ADPs) based on the Kullback–Leibler divergence. REFMAC5 additionally offers TLS parameterization and, when high-resolution data are available, fast refinement of anisotropic ADPs. Refinement in the presence of twinning is performed in a fully automated fashion. REFMAC5 is a flexible and highly optimized refinement package that is ideally suited for refinement across the entire resolution spectrum encountered in macromolecular crystallography.

  17. RBT—A Tool for Building Refined Buneman Trees

    DEFF Research Database (Denmark)

    Besenbacher, Søren; Mailund; Westh-Nielsen, Lasse;

    2005-01-01

    We have developed a tool implementing an efficient algorithm for refined Buneman tree reconstruction. The algorithm—which has the same complexity as the neighbour-joining method and the (plain) Buneman tree construction—enables refined Buneman tree reconstruction on large taxa sets....

  18. CNPC Hits New High in Refining & Petrochemical Business

    Institute of Scientific and Technical Information of China (English)

    Luo Shichao

    2010-01-01

    @@ During the "11th Five-Year Plan" period, CNPC adjusts the distribution of refining territory, and increases processed crude oil steadily, which is significant to sustained and fast development of upstream, midstream and downstream business.Of the 28 main economic and technical indicators of refining and chemical business, 21 hit record high.

  19. Carpet: Adaptive Mesh Refinement for the Cactus Framework

    Science.gov (United States)

    Schnetter, Erik; Hawley, Scott; Hawke, Ian

    2016-11-01

    Carpet is an adaptive mesh refinement and multi-patch driver for the Cactus Framework (ascl:1102.013). Cactus is a software framework for solving time-dependent partial differential equations on block-structured grids, and Carpet acts as driver layer providing adaptive mesh refinement, multi-patch capability, as well as parallelization and efficient I/O.

  20. Refined analysis results for multimedia network costs and profits

    DEFF Research Database (Denmark)

    Tahkokorpi, M.; Falch, Morten; Skouby, Knud Erik

    This deliverable describes the techno-economic business model developed in EURORIM WP3 and presents the refined results of the multimedia service delivery cost-profit calculations......This deliverable describes the techno-economic business model developed in EURORIM WP3 and presents the refined results of the multimedia service delivery cost-profit calculations...

  1. Application of Thermodynamic Calculations to the Pyro-refining Process for Production of High Purity Bismuth

    Science.gov (United States)

    Mezbahul-Islam, Mohammad; Belanger, Frederic; Chartrand, Patrice; Jung, In-Ho; Coursol, Pascal

    2017-02-01

    The present work has been performed with the aim to optimize the existing process for the production of high purity bismuth (99.999 pct). A thermo-chemical database including most of the probable impurities of bismuth (Bi-X, X = Ag, Au, Al, Ca, Cu, Fe, Mg, Mn, Na, Ni, Pb, S, Sb, Sn, Si, Te, Zn) has been constructed to perform different thermodynamic calculations required for the refining process. Thermodynamic description for eight of the selected binaries, Bi-Ca, Cu, Mn, Ni, Pb, S, Sb, and Sn, has been given in the current paper. Using the current database, different thermodynamic calculations have been performed to explain the steps involved in the bismuth refining process.

  2. An approach of requirements tracing in formal refinement

    DEFF Research Database (Denmark)

    Jastram, Michael; Hallerstede, Stefan; Leuschel, Michael;

    2010-01-01

    results that we have obtained for tracing informal natural-language requirements into formal models across refinement levels. The approach uses the WRSPM reference model for requirements modeling, and Event-B for formal modeling and formal refinement. The combined use of WRSPM and Event-B is facilitated......Formal modeling of computing systems yields models that are intended to be correct with respect to the requirements that have been formalized. The complexity of typical computing systems can be addressed by formal refinement introducing all the necessary details piecemeal. We report on preliminary...... by the rudimentary refinement notion of WRSPM, which provides the foundation for tracing requirements to formal refinements. We assume that requirements are evolving, meaning that we have to cope with frequent changes of the requirements model and the formal model. Our approach is capable of dealing with frequent...

  3. Action Refinement for Real-Time Concurrent Processes with Urgency

    Institute of Scientific and Technical Information of China (English)

    Guang-Ping Qin; Jin-Zhao Wu

    2005-01-01

    Action refinement for real-time concurrent processes with urgent interactions is studied, where a partial-order setting, i.e., timed bundle event structures, is used as the system model and a real-time LOTOS-like process algebra is used as the specification language. It is shown that the proposed refinement approaches have the commonly expected properties:(1) the behaviour of the refined process can be inferred compositionally from the behaviour of the original process and from the behaviour of the processes substituted for actions; (2) the timed extensions of pomset (partially ordered multiset) trace equivalence and history preserving bisimulation equivalence are both congruences under the refinement; (3) the syntactic and semantic refinements coincide up to the aforementioned equivalence relations with respect to a cpo-based denotational semantics.

  4. Review and Prospect of China's Oil Refining Industry

    Institute of Scientific and Technical Information of China (English)

    Jin Yun; Zhu He

    2012-01-01

    Prospect of China's oil refining industry during the "12th Five-Year Plan" period The "12th Five-Year Plan" period is critical to China oil refining industry to transform growth mode and grow from big to strong. China oil refining industry will base itself on domestic market demand and maintain rapider development through construction and reconstruction. The total scale will continue to grow, crude runs and product oil output will rise steadily, and the structure and layout of refining units will be further adjusted and optimized. During the period, the number of 10-million-tonnage refineries will rise to about 30, the quality of oil products will be upgraded, overseas interest capability will be improved, and the diversified of oil refining industry will be market competition pattern developed further.

  5. Improvement of neutronic calculations on a Masurca core using adaptive mesh refinement capabilities

    Energy Technology Data Exchange (ETDEWEB)

    Fournier, D.; Archier, P.; Le Tellier, R.; Suteau, C., E-mail: damien.fournier@cea.fr, E-mail: pascal.archier@cea.fr, E-mail: romain.le-tellier@cea.fr, E-mail: christophe.suteau@cea.fr [CEA, DEN, DER/SPRC/LEPh, Cadarache, Saint Paul-lez-Durance (France)

    2011-07-01

    The simulation of 3D cores with homogenized assemblies in transport theory remains time and memory consuming for production calculations. With a multigroup discretization for the energy variable and a discrete ordinate method for the angle, a system of about 10{sup 4} coupled hyperbolic transport equations has to be solved. For these equations, we intend to optimize the spatial discretization. In the framework of the SNATCH solver used in this study, the spatial problem is dealt with by using a structured hexahedral mesh and applying a Discontinuous Galerkin Finite Element Method (DGFEM). This paper shows the improvements due to the development of Adaptive Mesh Refinement (AMR) methods. As the SNATCH solver uses a hierarchical polynomial basis, p−refinement is possible but also h−refinement thanks to non conforming capabilities. Besides, as the flux spatial behavior is highly dependent on the energy, we propose to adapt differently the spatial discretization according to the energy group. To avoid dealing with too many meshes, some energy groups are joined and share the same mesh. The different energy-dependent AMR strategies are compared to each other but also with the classical approach of a conforming and highly refined spatial mesh. This comparison is carried out on different quantities such as the multiplication factor, the flux or the current. The gain in time and memory is shown for 2D and 3D benchmarks coming from the ZONA2B experimental core configuration of the MASURCA mock-up at CEA Cadarache. (author)

  6. Refining Housing, Husbandry and Care for Animals Used in Studies Involving Biotelemetry

    Directory of Open Access Journals (Sweden)

    Penny Hawkins

    2014-06-01

    Full Text Available Biotelemetry can contribute towards reducing animal numbers and suffering in disciplines including physiology, pharmacology and behavioural research. However, the technique can also cause harm to animals, making biotelemetry a ‘refinement that needs refining’. Current welfare issues relating to the housing and husbandry of animals used in biotelemetry studies are single vs. group housing, provision of environmental enrichment, long term laboratory housing and use of telemetered data to help assess welfare. Animals may be singly housed because more than one device transmits on the same wavelength; due to concerns regarding damage to surgical sites; because they are wearing exteriorised jackets; or if monitoring systems can only record from individually housed animals. Much of this can be overcome by thoughtful experimental design and surgery refinements. Similarly, if biotelemetry studies preclude certain enrichment items, husbandry refinement protocols can be adapted to permit some environmental stimulation. Nevertheless, long-term laboratory housing raises welfare concerns and maximum durations should be defined. Telemetered data can be used to help assess welfare, helping to determine endpoints and refine future studies. The above measures will help to improve data quality as well as welfare, because experimental confounds due to physiological and psychological stress will be minimised.

  7. Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields.

    Science.gov (United States)

    Curioni, Alessandro; Mordasini, Tiziana; Andreoni, Wanda

    2004-12-01

    A methodology aimed at improving the accuracy of current docking-scoring procedures is proposed, and validated through detailed tests of its performance in predicting the activity of HIV-1 protease inhibitors. This methodology is based on molecular dynamics simulations using a force field whose effective charges are refined by means of a novel procedure that relies on quantum-mechanical calculations and preserves the internal consistency of the parameterization scheme.

  8. Keep it together: restraints in crystallographic refinement of macromolecule–ligand complexes

    Science.gov (United States)

    Steiner, Roberto A.; Tucker, Julie A.

    2017-01-01

    A short introduction is provided to the concept of restraints in macromolecular crystallographic refinement. A typical ligand restraint-generation process is then described, covering types of input, the methodology and the mechanics behind the software in general terms, how this has evolved over recent years and what to look for in the output. Finally, the currently available restraint-generation software is compared, concluding with some thoughts for the future. PMID:28177305

  9. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

    Directory of Open Access Journals (Sweden)

    Caleb Andrew Doll

    2014-02-01

    Full Text Available Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent developmental processes are specifically impaired in autism spectrum disorders (ASDs. ASD genetic models in both mouse and Drosophila have pioneered our insights into normal activity-dependent neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic Fragile X syndrome (FXS, a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in activity-dependent critical period processes. The Fragile X Mental Retardation Protein (FMRP is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the activity-dependent remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor activity-dependent processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of activity-dependent mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model.

  10. Refining personality disorder subtypes and classification using finite mixture modeling.

    Science.gov (United States)

    Yun, Rebecca J; Stern, Barry L; Lenzenweger, Mark F; Tiersky, Lana A

    2013-04-01

    The current Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic system for Axis II disorders continues to be characterized by considerable heterogeneity and poor discriminant validity. Such problems impede accurate personality disorder (PD) diagnosis. As a result, alternative assessment tools are often used in conjunction with the DSM. One popular framework is the object relational model developed by Kernberg and his colleagues (J. F. Clarkin, M. F. Lenzenweger, F. Yeomans, K. N. Levy, & O. F. Kernberg, 2007, An object relations model of borderline pathology, Journal of Personality Disorders, Vol. 21, pp. 474-499; O. F. Kernberg, 1984, Severe Personality Disorders, New Haven, CT: Yale University Press; O. F. Kernberg & E. Caligor, 2005, A psychoanalytic theory of personality disorders, in M. F. Lenzenweger & J. F. Clarkin, Eds., Major Theories of Personality Disorder, New York, NY: Guilford Press). Drawing on this model and empirical studies thereof, the current study attempted to clarify Kernberg's (1984) PD taxonomy and identify subtypes within a sample with varying levels of personality pathology using finite mixture modeling. Subjects (N = 141) were recruited to represent a wide range of pathology. The finite mixture modeling results indicated that 3 components were harbored within the variables analyzed. Group 1 was characterized by low levels of antisocial, paranoid, and aggressive features, and Group 2 was characterized by elevated paranoid features. Group 3 revealed the highest levels across the 3 variables. The validity of the obtained solution was then evaluated by reference to a variety of external measures that supported the validity of the identified grouping structure. Findings generally appear congruent with previous research, which argued that a PD taxonomy based on paranoid, aggressive, and antisocial features is a viable supplement to current diagnostic systems. Our study suggests that Kernberg's object relational model offers a

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

    Science.gov (United States)

    Koniges, Alice; Liu, Wangyi; Lidia, Steven; Schenkel, Thomas; Barnard, John; Friedman, Alex; Eder, David; Fisher, Aaron; Masters, Nathan

    2016-03-01

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

  12. Refined AFC-Enabled High-Lift System Integration Study

    Science.gov (United States)

    Hartwich, Peter M.; Shmilovich, Arvin; Lacy, Douglas S.; Dickey, Eric D.; Scalafani, Anthony J.; Sundaram, P.; Yadlin, Yoram

    2016-01-01

    A prior trade study established the effectiveness of using Active Flow Control (AFC) for reducing the mechanical complexities associated with a modern high-lift system without sacrificing aerodynamic performance at low-speed flight conditions representative of takeoff and landing. The current technical report expands on this prior work in two ways: (1) a refined conventional high-lift system based on the NASA Common Research Model (CRM) is presented that is more representative of modern commercial transport aircraft in terms of stall characteristics and maximum Lift/Drag (L/D) ratios at takeoff and landing-approach flight conditions; and (2) the design trade space for AFC-enabled high-lift systems is expanded to explore a wider range of options for improving their efficiency. The refined conventional high-lift CRM (HL-CRM) concept features leading edge slats and slotted trailing edge flaps with Fowler motion. For the current AFC-enhanced high lift system trade study, the refined conventional high-lift system is simplified by substituting simply-hinged trailing edge flaps for the slotted single-element flaps with Fowler motion. The high-lift performance of these two high-lift CRM variants is established using Computational Fluid Dynamics (CFD) solutions to the Reynolds-Averaged Navier-Stokes (RANS) equations. These CFD assessments identify the high-lift performance that needs to be recovered through AFC to have the CRM variant with the lighter and mechanically simpler high-lift system match the performance of the conventional high-lift system. In parallel to the conventional high-lift concept development, parametric studies using CFD guided the development of an effective and efficient AFC-enabled simplified high-lift system. This included parametric trailing edge flap geometry studies addressing the effects of flap chord length and flap deflection. As for the AFC implementation, scaling effects (i.e., wind-tunnel versus full-scale flight conditions) are addressed

  13. Refining the definition of hypereosinophilic syndrome

    OpenAIRE

    Simon, Hans-Uwe; Rothenberg, Marc E.; Bochner, Bruce S.; Weller, Peter Fahey; Wardlaw, Andrew J.; Wechsler, Michael E.; Rosenwasser, Lanny J.; Roufosse, Florence; Gleich, Gerald J.; Klion, Amy D.

    2010-01-01

    Because of advances in our understanding of the hypereosinophilic syndrome (HES) and the availability of novel therapeutic agents, the original criteria defining these disorders are becoming increasingly problematic. Here, we discuss shortcomings with the current definition of HES and recent developments in the classification of these disorders. Despite significant progress in our understanding of the pathogenesis of some forms of HES, the current state of knowledge is still insufficient to f...

  14. Main Development Targets for CNOOC in 2000

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    @@ In order to obtain stable reserves and create scope economic management, the China National Offshore Oil Corporation (CNOOC) officially put forward the main development target and main sci-tech sector target of the Ninth Five-Year Plan in July, 1995. These targets aim to make CNOOC as an international group corporation,including exploration and development of oil and gas,refining, petrochemicals, chemical fertilizer, power generation, unitizing sales network of up and down stream.

  15. The Glasgow Outcome Scale - 40 years of application and refinement.

    Science.gov (United States)

    McMillan, Tom; Wilson, Lindsay; Ponsford, Jennie; Levin, Harvey; Teasdale, Graham; Bond, Michael

    2016-08-01

    The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury.

  16. Refining the quantitative pathway of the Pathways to Mathematics model.

    Science.gov (United States)

    Sowinski, Carla; LeFevre, Jo-Anne; Skwarchuk, Sheri-Lynn; Kamawar, Deepthi; Bisanz, Jeffrey; Smith-Chant, Brenda

    2015-03-01

    In the current study, we adopted the Pathways to Mathematics model of LeFevre et al. (2010). In this model, there are three cognitive domains--labeled as the quantitative, linguistic, and working memory pathways--that make unique contributions to children's mathematical development. We attempted to refine the quantitative pathway by combining children's (N=141 in Grades 2 and 3) subitizing, counting, and symbolic magnitude comparison skills using principal components analysis. The quantitative pathway was examined in relation to dependent numerical measures (backward counting, arithmetic fluency, calculation, and number system knowledge) and a dependent reading measure, while simultaneously accounting for linguistic and working memory skills. Analyses controlled for processing speed, parental education, and gender. We hypothesized that the quantitative, linguistic, and working memory pathways would account for unique variance in the numerical outcomes; this was the case for backward counting and arithmetic fluency. However, only the quantitative and linguistic pathways (not working memory) accounted for unique variance in calculation and number system knowledge. Not surprisingly, only the linguistic pathway accounted for unique variance in the reading measure. These findings suggest that the relative contributions of quantitative, linguistic, and working memory skills vary depending on the specific cognitive task. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Refining moral agency: Insights from moral psychology and moral philosophy.

    Science.gov (United States)

    Milliken, Aimee

    2017-08-11

    Research in moral psychology has recently raised questions about the impact of context and the environment on the way the human mind works. In a 2012 call to action, Paley wrote: "If some of the conclusions arrived at by moral psychologists are true, they are directly relevant to the way nurses think about moral problems, and present serious challenges to favoured concepts in nursing ethics, such as the ethics of care, virtue, and the unity of the person" (p. 80). He urges nurse ethicists and scholars to evaluate the impact these findings may have for moral theory. In this paper, I review some of Paley's (Nursing Philosophy, 13, 2012, 80) critique, focusing on the argument that theories of nursing ethics have failed to account for the role of context; both in terms of its impact on the way nurses make moral judgements and in terms of the environment's influence on the way the mind works. I then examine nursing literature on moral agency, and focus on the role of the environment and context play within existing theory. I argue that theories of moral agency have often accounted for the role of context on the way nurses make decisions; however, less attention has been paid to its impact on the mind. With this background, I use insights from the fields of moral philosophy and moral psychology to refine the conceptualization of nurse moral agency in a way that is reflective of current cognitive, philosophical and nursing practice-based science. © 2017 John Wiley & Sons Ltd.

  18. Task Refinement for Autonomous Robots using Complementary Corrective Human Feedback

    Directory of Open Access Journals (Sweden)

    Cetin Mericli

    2011-06-01

    Full Text Available A robot can perform a given task through a policy that maps its sensed state to appropriate actions. We assume that a hand-coded controller can achieve such a mapping only for the basic cases of the task. Refining the controller becomes harder and gets more tedious and error prone as the complexity of the task increases. In this paper, we present a new learning from demonstration approach to improve the robot's performance through the use of corrective human feedback as a complement to an existing hand-coded algorithm. The human teacher observes the robot as it performs the task using the hand-coded algorithm and takes over the control to correct the behavior when the robot selects a wrong action to be executed. Corrections are captured as new state-action pairs and the default controller output is replaced by the demonstrated corrections during autonomous execution when the current state of the robot is decided to be similar to a previously corrected state in the correction database. The proposed approach is applied to a complex ball dribbling task performed against stationary defender robots in a robot soccer scenario, where physical Aldebaran Nao humanoid robots are used. The results of our experiments show an improvement in the robot's performance when the default hand-coded controller is augmented with corrective human demonstration.

  19. Model Refinement in the Model Driven Architecture Context

    Directory of Open Access Journals (Sweden)

    Paulo Cezar Stadzisz

    2012-01-01

    Full Text Available Problem statement: Model Driven Architecture (MDA is a software development approach based on the design and the transformation of models. In MDA, models are systematically translated to other models and to a source code. Model transformation plays a key role in MDA. Several model transformation languages have been launched lately, aiming to facilitate the translation of input models to output models. The employment of such languages in practical contexts has succeed, although quite often those languages cannot be directly applied to a particular type of model transformation, called refinement. Approach: This study provides a general overview on model refinement and investigates two approaches for model refinement based on Atlas Transformation Language (ATL referred to as: Refining mode and module superimposition. ATL is a widely adopted language for solving model transformation problems in the MDA approach. Results: This study presents the comparative results obtained from the analysis of the Refining Mode and the Module Superimposition approaches, emphasizing their application benefits. Conclusion: The increasing use of MDA for the design of software systems empowered researches on how developers may benefit from approaches that perform model refinement. The main advantages achieved with the use of the Module Superimposition technique are maintainability and reusability improvement, obtained through module composition and rule superimposition. In its turn, the Refining Mode stands out for its ease of use.

  20. Comparative Omics-Driven Genome Annotation Refinement: Application across Yersiniae

    Energy Technology Data Exchange (ETDEWEB)

    Rutledge, Alexandra C.; Jones, Marcus B.; Chauhan, Sadhana; Purvine, Samuel O.; Sanford, James; Monroe, Matthew E.; Brewer, Heather M.; Payne, Samuel H.; Ansong, Charles; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott; Motin, Vladimir L.; Adkins, Joshua N.

    2012-03-27

    Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. To date, the perceived value of manual curation for genome annotations is not offset by the real cost and time associated with the process. In order to balance the large number of sequences generated, the annotation process is now performed almost exclusively in an automated fashion for most genome sequencing projects. One possible way to reduce errors inherent to automated computational annotations is to apply data from 'omics' measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. This approach does require additional experimental and bioinformatics methods to include omics technologies; however, the approach is readily automatable and can benefit from rapid developments occurring in those research domains as well. The annotation process can be improved by experimental validation of transcription and translation and aid in the discovery of annotation errors. Here the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species, as is becoming common in sequencing efforts. Transcriptomic and proteomic data derived from three highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 previously incorrect protein-coding sequences (e.g., observed frameshifts, extended start sites, and translated pseudogenes) within the three current Yersinia genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent

  1. Refining the definition of hypereosinophilic syndrome

    Science.gov (United States)

    Simon, Hans-Uwe; Rothenberg, Marc E.; Bochner, Bruce S.; Weller, Peter F.; Wardlaw, Andrew J.; Wechsler, Michael E.; Rosenwasser, Lanny J.; Roufosse, Florence; Gleich, Gerald J.; Klion, Amy D.

    2012-01-01

    Because of advances in our understanding of the hypereosinophilic syndrome (HES) and the availability of novel therapeutic agents, the original criteria defining these disorders are becoming increasingly problematic. Here, we discuss shortcomings with the current definition of HES and recent developments in the classification of these disorders. Despite significant progress in our understanding of the pathogenesis of some forms of HES, the current state of knowledge is still insufficient to formulate a new comprehensive etiologic definition of HESs. Nevertheless, we suggest a new working definition that overcomes some of the most obvious limitations with the original definition. PMID:20639008

  2. Adaptive mesh refinement for stochastic reaction-diffusion processes

    Science.gov (United States)

    Bayati, Basil; Chatelain, Philippe; Koumoutsakos, Petros

    2011-01-01

    We present an algorithm for adaptive mesh refinement applied to mesoscopic stochastic simulations of spatially evolving reaction-diffusion processes. The transition rates for the diffusion process are derived on adaptive, locally refined structured meshes. Convergence of the diffusion process is presented and the fluctuations of the stochastic process are verified. Furthermore, a refinement criterion is proposed for the evolution of the adaptive mesh. The method is validated in simulations of reaction-diffusion processes as described by the Fisher-Kolmogorov and Gray-Scott equations.

  3. China Expands Oil Refining Capacity to Meet Rising Demand

    Institute of Scientific and Technical Information of China (English)

    Yin Yin

    2006-01-01

    @@ With the booming of China's auto market, the oil refining industry is falling over itself to boost capacity in the coastal regions. Sinochem Corporation is the latest out of the starting blocks. Its new oil refining project in southeastern Fujian Province will see it move into territory already occupied by the nation's big-three oil companies - China National Petrochemical Corporation(Sinopec), China's largest oil refiner,China National Petroleum Corporation (CNPC),the largest crude producer in the country, and China National Offshore Oil Corporation(CNOOC), the giant offshore oil player.

  4. Segmental Refinement: A Multigrid Technique for Data Locality

    KAUST Repository

    Adams, Mark F.

    2016-08-04

    We investigate a domain decomposed multigrid technique, termed segmental refinement, for solving general nonlinear elliptic boundary value problems. We extend the method first proposed in 1994 by analytically and experimentally investigating its complexity. We confirm that communication of traditional parallel multigrid is eliminated on fine grids, with modest amounts of extra work and storage, while maintaining the asymptotic exactness of full multigrid. We observe an accuracy dependence on the segmental refinement subdomain size, which was not considered in the original analysis. We present a communication complexity analysis that quantifies the communication costs ameliorated by segmental refinement and report performance results with up to 64K cores on a Cray XC30.

  5. Refining the risk estimate for transfusion-transmission of occult hepatitis B virus.

    Science.gov (United States)

    Seed, C R; Kiely, P; Hoad, V C; Keller, A J

    2017-01-01

    We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. In our original model, the OBI risk, p(OBI), was defined by the rate of 'non-detection' by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission). We revised the model by integrating three refinements: that donations with anti-HBs levels of >10 IU/l, or donations solely for manufactured plasma products, be excluded from the risk calculation, and an updated estimate of p(transmission). Refining our OBI RR model resulted in a more than 10-fold reduction in the reported RR risk to recipients from OBI in our donor population. Based on the use of a common data set, the mean OBI RR risk decreased from 1 in 374 354 donations (95% CI: 1 in 191 940-1 072 681) to 1 in 3 984 033 (95% CI: 1 in 1 146 188-65 268 257) for the refined model. Our model refinements provide a more realistic measure of the HBV RR in the donor population. Unlike the previous model, the new model demonstrates that the risk of HBV due to OBI in the Australian blood donor population is negligible, and further potentially cost-ineffective risk management strategies are not currently warranted. © 2016 International Society of Blood Transfusion.

  6. Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    David Cheng

    2011-10-01

    Full Text Available Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  7. Refined Aluminum Industry Suffers From Deficit and Western Investment Accelerates

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>Under the backdrop of loss of the entire refined aluminum industry,the investment in electrolytic aluminum accelerates.The reporter learnt from a recent survey that,many companies including Shandong Xinfa Group,East Hope

  8. Biorthogonal multiple wavelets generated by vector refinement equation

    Institute of Scientific and Technical Information of China (English)

    Song LI; Jun XIAN

    2007-01-01

    Biorthogonal multiple wavelets are generated from refinable function vectors by using the multiresolution analysis. In this paper we provide a general method for the construction of compactly supported biorthogonal multiple wavelets by refinable function vectors which are the solutions of vector refinement equations of the formψ(x) =∑α∈Zs α(α)ψ(Mx-α), x ∈ Rs,sequence of r × r matrices called the refinement mask, and M is an s × s integer matrix such that limn→∞ M-n = 0. Our characterizations are in the general setting and the main results of this paper are the real extensions of some known results.

  9. Biorthogonal multiple wavelets generated by vector refinement equation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Biorthogonal multiple wavelets are generated from refinable function vectors by using the multiresolution analysis.In this paper we provide a general method for the construction of compactly supported biorthogonal multiple wavelets by refinable function vectors which are the solutions of vector refinement equations of the form (?)(x)=(?)a(α)(?)(Mx-α),x∈Rs, where the vector of functions(?)=((?)1,...,(?)r)T is in(L2(Rs))r,a=:(a(α))α∈Zsis a finitely supported sequence of r×r matrices called the refinement mask,and M is an s×s integer matrix such that limn→∞M-n=0.Our characterizations are in the general setting and the main results of this paper are the real extensions of some known results.

  10. Recent Development and Status of CNPC's Refining and Chemical Industry

    Institute of Scientific and Technical Information of China (English)

    Zhou Weiyong

    1997-01-01

    @@ In the past one and halfyear since carrying China National Petroleum Corporation's (CNPC) Ninth Five-Year Plan (1996-2000), CNPC's oil refining and chemical industry has made considerable progress.

  11. Latest Development in China's Oil Refining & Petrochemical Sector

    Institute of Scientific and Technical Information of China (English)

    Xia Zuhua

    2008-01-01

    @@ China's big-three oil companies-CNPC, Sinopec and CNOOC-have intensified their competition in the domestic oil refining and petrochemical sector in recent years so as to better position themselves in the oil products market at home.

  12. Value Source of Integrated Refining/Chemical Plant

    Institute of Scientific and Technical Information of China (English)

    Zhao Jianwei

    2009-01-01

    Based on an integrated refining/chemical plant processing 15 Mt/a of crude and manufacturing 1.0 Mt/a of ethylene under the guideline of"engaging in refining, olefins and aromatics by whatever appropriate means" to maximize the overall value of the integrated refining/chemical plant, it is necessary to concentrate on working on the flow diagram and the solution for mutual supply of materials between the refinery and ethylene plant. After analyzing the feedstock slate, the composition and properties of products, it is proposed to optimize the integrated refining/chemical plant in order to reduce investment and operating cost to realize maximization of the value of the integrated plant.

  13. ADAPTIVE MODEL REFINEMENT FOR THE IONOSPHERE AND THERMOSPHERE

    Data.gov (United States)

    National Aeronautics and Space Administration — ADAPTIVE MODEL REFINEMENT FOR THE IONOSPHERE AND THERMOSPHERE ANTHONY M. D’AMATO∗, AARON J. RIDLEY∗∗, AND DENNIS S. BERNSTEIN∗∗∗ Abstract. Mathematical models of...

  14. High resolution single particle refinement in EMAN2.1.

    Science.gov (United States)

    Bell, James M; Chen, Muyuan; Baldwin, Philip R; Ludtke, Steven J

    2016-05-01

    EMAN2.1 is a complete image processing suite for quantitative analysis of grayscale images, with a primary focus on transmission electron microscopy, with complete workflows for performing high resolution single particle reconstruction, 2-D and 3-D heterogeneity analysis, random conical tilt reconstruction and subtomogram averaging, among other tasks. In this manuscript we provide the first detailed description of the high resolution single particle analysis pipeline and the philosophy behind its approach to the reconstruction problem. High resolution refinement is a fully automated process, and involves an advanced set of heuristics to select optimal algorithms for each specific refinement task. A gold standard FSC is produced automatically as part of refinement, providing a robust resolution estimate for the final map, and this is used to optimally filter the final CTF phase and amplitude corrected structure. Additional methods are in-place to reduce model bias during refinement, and to permit cross-validation using other computational methods.

  15. Risk Assessment: Perchloroethylene Dry Cleaners Refined Human Health Risk Characterization

    Science.gov (United States)

    This November 2005 memo and appendices describe the methods by which EPA conducted its refined risk assessment of the Major Source and Area Source facilities within the perchloroethylene (perc) dry cleaners source category.

  16. Refinement of reduced-models for dynamic systems

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A refinement procedure for the reduced models of structural dynamic systems is presented in this article. The refinement procedure is to "tune" the parameters of a reduced model, which could be obtained from any traditional model reduction scheme, into an improved reduced model. Upon the completion of the refinement, the improved reduced model matches the dynamic characteristics - the chosen structural frequencies and their mode shapes - of the full order model. Mathematically, the procedure to implement the model refinement technique is an application of the recently developed cross-model cross-mode (CMCM) method for model updating. A numerical example of reducing a 5-DOF (degree-of-freedom) classical mass-spring (or shear-building) model into a 3-DOF generalized mass-spring model is demonstrated in this article.

  17. Refinement of macromolecular structures against neutron data with SHELXL2013.

    Science.gov (United States)

    Gruene, Tim; Hahn, Hinrich W; Luebben, Anna V; Meilleur, Flora; Sheldrick, George M

    2014-02-01

    Some of the improvements in SHELX2013 make SHELXL convenient to use for refinement of macromolecular structures against neutron data without the support of X-ray data. The new NEUT instruction adjusts the behaviour of the SFAC instruction as well as the default bond lengths of the AFIX instructions. This work presents a protocol on how to use SHELXL for refinement of protein structures against neutron data. It includes restraints extending the Engh & Huber [Acta Cryst. (1991), A47, 392-400] restraints to H atoms and discusses several of the features of SHELXL that make the program particularly useful for the investigation of H atoms with neutron diffraction. SHELXL2013 is already adequate for the refinement of small molecules against neutron data, but there is still room for improvement, like the introduction of chain IDs for the refinement of macromolecular structures.

  18. CITGO Petroleum Corporation and PDV Midwest Refining, LLC Settlement

    Science.gov (United States)

    CITGO Petroleum Corporation and PDV Midwest Refining, LLC (collectively, CITGO) have agreed to pay a $1,955,000 civil penalty, perform environmental projects totaling more than $2 million, and spend an estimated $42 million in injunctive relief to resolve.

  19. REFINABLE DISTRIBUTIONS SUPPORTED ON SELF-AFFINE TILES

    Institute of Scientific and Technical Information of China (English)

    DaiXinrong

    2002-01-01

    In this paper,some conditions which assure the compactly supported refinable distributions supported on a self-affine tile to be Lebesgue-Stieltjes measures or absolutely continuous measures with respect to Lebesgue-Stieltjes measures are given.

  20. Rack gasoline and refining margins - wanted: a summer romance

    Energy Technology Data Exchange (ETDEWEB)

    1988-04-13

    For the first time since late 1987, apparent refining margins on the US benchmark crude oil (based on spot purchase prices) are virtually zero. This felicitous bit of news comes loaded with possibilities of positive (maybe even good.) margins in coming months, if the differential between crude buying prices and the value of the refined barrel continues to improve. What refiners in the US market are watching most closely right now are motorists. This issue also contains the following: (1) ED refining netback data for the US Gulf and Western Coasts, Rotterdam, and Singapore, prices for early April 1988; and (2) ED fuel price/tax series for countries of the Western Hemisphere, April 1988 edition. 5 figures, 5 tables.

  1. On the application of grits to thermomechanical pulp refining

    Energy Technology Data Exchange (ETDEWEB)

    Somboon, P.

    2009-07-01

    The objective of this thesis was to develop a mechanical pulping process capable of producing good-quality pulp, while consuming less electrical energy. The study focused on applying of grits to TMP refining to enhance the breaking of the fiber cell wall promoting faster development of pulp fibers to the desired quality for papermaking. The study comprises tests at laboratory scale and development of an application for industrial, including trials at pilot scale A preliminary trial with the grit application in TMP refining was conducted at laboratory scale. The results showed that the grits should be introduced between the first and second stages in TMP refining. The grit treatment on the TMP fibers caused disruption of the wall structure, opening of the outer layers and peeling-off of the cell wall. The efficient disruption with minimal shortening and weakening of fibers was found to be operated at a low-intensity and high-frequency of treatment. According to an experiment with first-stage TMP pulp, the disrupted pulp developed faster during subsequent refining, while the energy consumption was reduced by up to 30% without a significant loss of pulp quality. With the aim of developing an industrial application, the refiner segments were modified by applying grits on the refiner segment surfaces. The grits were made from self-fluxing tungsten-carbide powder and a Ni-base alloy powder, which were laser-clad onto the surface of breaker bars, the inner part of a segment. Trials with grit segments were carried out on a pilot refiner. The grit segments were applied in first-stage TMP refining, followed by treatment with base segments operated under normal mill conditions. The grit segments were found to have no negative effects on the refining system. A refiner equipped with grit segments, operated at a speed of 2400 rpm, produced pulp with a higher level of disruption of fiber cell walls than a refiner equipped with the reference segments. According to the results, the

  2. Reverse mechanical after effect during hydrogenation of zone refined iron

    Energy Technology Data Exchange (ETDEWEB)

    Spivak, L.V.; Skryabina, N.E.; Kurmaeva, L.D.; Smirnov, L.V. (Permskij Gosudarstvennyj Univ. (USSR); AN SSSR, Sverdlovsk. Inst. Fiziki Metallov)

    1984-12-01

    The relationship between the process of hydrogenation and the reverse mechanical after effect (RMA) microplastic deformation in the zone refined iron has been studied. Metallographic investigations and mechanical testing of the samples hydrogenated under torsional strain have been performed. It is shown that in the zone refined iron the formation of voids responsible for irreversible hydrogen embrittlement does not occur, but the hydrogen-initiated RMA strain is conserved, i. e. the RMA effects are independent of the presence of discontinuities.

  3. Refinements and Social Order Beliefs: A Unified Survey

    OpenAIRE

    Atsushi Kajii; Stephen Morris

    1997-01-01

    This paper presents a simple framework that allows us to survey and relate some different strands of the game theory literature. We describe a "canonical" way of adding incomplete information to a complete information game. This framework allows us to give a simple "complete theory" interpretation (Kreps 1990) of standard normal form refinements such as perfection, and to relate refinements both to the "higher order beliefs literature" (Rubinstein 1989; Monderer and Samet 1989; Morris, Rob an...

  4. Refinement of Fourier Coefficients from the Stokes Deconvoluted Profile

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Computer-aided experimental technique was used to study the Stokes deconvolution of X-ray diffraction profile.Considerable difference can be found between the Fourier coefficients obtained from the deconvolutions of singlet and doublet experimental profiles. Nevertheless, the resultant physical profiles corresponding to singlet and doublet profiles are identical. An approach is proposed to refine the Fourier coefficients, and the refined Fourier coefficients coincide well with that obtained from the deconvolution of singlet experimental profile.

  5. A Simple Method for Grain Refinement of Pure Aluminium

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    In order to produce the fully equiaxed and fine grained pure Al, a simple casting process that used cooling slope was examined and compared with conventional casting process under same casting conditions. By using cooling slope,grains over the whole section of castings were suddenly refined and ability of grain refinement kept up at very high mold temperature up to 550℃ in examined casting conditions.

  6. Two stage bioethanol refining with multi litre stacked microbial fuel cell and microbial electrolysis cell.

    Science.gov (United States)

    Sugnaux, Marc; Happe, Manuel; Cachelin, Christian Pierre; Gloriod, Olivier; Huguenin, Gérald; Blatter, Maxime; Fischer, Fabian

    2016-12-01

    Ethanol, electricity, hydrogen and methane were produced in a two stage bioethanol refinery setup based on a 10L microbial fuel cell (MFC) and a 33L microbial electrolysis cell (MEC). The MFC was a triple stack for ethanol and electricity co-generation. The stack configuration produced more ethanol with faster glucose consumption the higher the stack potential. Under electrolytic conditions ethanol productivity outperformed standard conditions and reached 96.3% of the theoretically best case. At lower external loads currents and working potentials oscillated in a self-synchronized manner over all three MFC units in the stack. In the second refining stage, fermentation waste was converted into methane, using the scale up MEC stack. The bioelectric methanisation reached 91% efficiency at room temperature with an applied voltage of 1.5V using nickel cathodes. The two stage bioethanol refining process employing bioelectrochemical reactors produces more energy vectors than is possible with today's ethanol distilleries.

  7. Single-Pass GPU-Raycasting for Structured Adaptive Mesh Refinement Data

    CERN Document Server

    Kaehler, Ralf

    2012-01-01

    Structured Adaptive Mesh Refinement (SAMR) is a popular numerical technique to study processes with high spatial and temporal dynamic range. It reduces computational requirements by adapting the lattice on which the underlying differential equations are solved to most efficiently represent the solution. Particularly in astrophysics and cosmology such simulations now can capture spatial scales ten orders of magnitude apart and more. The irregular locations and extensions of the refined regions in the SAMR scheme and the fact that different resolution levels partially overlap, poses a challenge for GPU-based direct volume rendering methods. kD-trees have proven to be advantageous to subdivide the data domain into non-overlapping blocks of equally sized cells, optimal for the texture units of current graphics hardware, but previous GPU-supported raycasting approaches for SAMR data using this data structure required a separate rendering pass for each node, preventing the application of many advanced lighting sche...

  8. On the impact of a refined stochastic model for airborne LiDAR measurements

    Science.gov (United States)

    Bolkas, Dimitrios; Fotopoulos, Georgia; Glennie, Craig

    2016-09-01

    Accurate topographic information is critical for a number of applications in science and engineering. In recent years, airborne light detection and ranging (LiDAR) has become a standard tool for acquiring high quality topographic information. The assessment of airborne LiDAR derived DEMs is typically based on (i) independent ground control points and (ii) forward error propagation utilizing the LiDAR geo-referencing equation. The latter approach is dependent on the stochastic model information of the LiDAR observation components. In this paper, the well-known statistical tool of variance component estimation (VCE) is implemented for a dataset in Houston, Texas, in order to refine the initial stochastic information. Simulations demonstrate the impact of stochastic-model refinement for two practical applications, namely coastal inundation mapping and surface displacement estimation. Results highlight scenarios where erroneous stochastic information is detrimental. Furthermore, the refined stochastic information provides insights on the effect of each LiDAR measurement in the airborne LiDAR error budget. The latter is important for targeting future advancements in order to improve point cloud accuracy.

  9. Some theoretical comparisons of refined Ritz vectors and Ritz vectors

    Institute of Scientific and Technical Information of China (English)

    JIA Zhongxiao

    2004-01-01

    Refined projection methods proposed by the author have received attention internationally. We are concerned with a conventional projection method and its refined counterpart for computing approximations to a simple eigenpair (λ,x)of a large matrix A. Given a subspace w that contains anapproximation to x, these two methods compute approximations(μ(x~)) and (μ(x^)) to (λ,x),respectively. We establish three results. First, the refinedeigenvector approximation or simply the refined Ritz vector (x^) is unique as the deviation of x from w approaches zero if λ is simple. Second, interms of residual norm of the refined approximate eigenpair (μ,(x^)), we derive lower and upper bounds for the sine of the angle betweenthe Ritz vector (x~) and the refined eigenvector approximation (x^), and we prove that (x~)≠(x^) unless (x^)=x. Third, we establish relationships between theresidual norm ‖A(x~)-μ(x^)‖ of the conventionalmethods and the residual norm ‖A(x^)-μ(x^)‖ of therefined methods, and we show that the latter is always smallerthan the former if (μ,(x^)) is not an exact eigenpair ofA, indicating that the refined projection method is superiorto the corresponding conventional counterpart.

  10. Some theoretical comparisons of refined Ritz vectors and Ritz vectors

    Institute of Scientific and Technical Information of China (English)

    JIA; Zhongxiao

    2004-01-01

    Refined projection methods proposed by the author have received attention internationally. We are concerned with a conventional projection method and its refined counterpart for computing approximations to a simple eigenpair (λ,x)of a large matrix A. Given a subspace w that contains anapproximation to x, these two methods compute approximations(μ(x~)) and (μ(x)) to (λ,x),respectively. We establish three results. First, the refinedeigenvector approximation or simply the refined Ritz vector (x) is unique as the deviation of x from w approaches zero if λ is simple. Second, interms of residual norm of the refined approximate eigenpair (μ,(x)), we derive lower and upper bounds for the sine of the angle betweenthe Ritz vector (x~) and the refined eigenvector approximation (x), and we prove that (x~)≠(x) unless (x)=x. Third, we establish relationships between theresidual norm ‖A(x~)-μ(x)‖ of the conventionalmethods and the residual norm ‖A(x)-μ(x)‖ of therefined methods, and we show that the latter is always smallerthan the former if (μ,(x)) is not an exact eigenpair ofA, indicating that the refined projection method is superiorto the corresponding conventional counterpart.

  11. Effect of refining on quality and composition of sunflower oil.

    Science.gov (United States)

    Pal, U S; Patra, R K; Sahoo, N R; Bakhara, C K; Panda, M K

    2015-07-01

    An experimental oil refining unit has been developed and tested for sunflower oil. Crude pressed sunflower oil obtained from a local oil mill was refined using chemical method by degumming, neutralization, bleaching and dewaxing. The quality and composition of crude and refined oil were analysed compared. Reduction in phosphorous content from 6.15 ppm to 0, FFA content from 1.1 to 0.24 % (oleic acid), peroxide value from 22.5 to 7.9 meq/kg, wax content from 1,420 to 200 ppm and colour absorbance value from 0.149 to 0.079 (in spectrophotometer at 460 nm) were observed from crude to refined oil. It was observed that refining did not have significant effect on fatty acid compositions as found in the percentage peak area in the GC-MS chromatogram. The percentage of unsaturated fatty acid in both the oils were recorded to be about 95 % containing 9-Octadecenoic acid (Oleic acid) and 11,14-Eicosadienoic acid (elongated form of linoleic acid). The research results will be useful to small entrepreneurs and farmers for refining of sunflower oil for better marketability.

  12. A Refined Count of BPS States in the D1/D5 System

    CERN Document Server

    Benjamin, Nathan

    2016-01-01

    We examine the low-lying quarter BPS spectrum of a 2d conformal field theory with target Sym$^N(K3)$ at various points in the moduli space, and look at a more refined count than the ordinary elliptic genus. We compute growth of the spectrum at both the symmetric orbifold point, as well as at the supergravity point in the moduli space. Finally we do a decomposition of the spectra into $\\mathcal{N}=4$ characters and discuss possible relations to interesting symmetry groups. A similar analysis is done with $T^4$.

  13. REFINEMENT OF THE NEPHELINE DISCRIMINATOR: RESULTS OF A PHASE II STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K; Tommy Edwards, T

    2008-11-21

    Twenty five glass compositions were selected for a Phase II study to assess the potential for reducing the conservatism in the nepheline discriminator. The glass compositions were restricted to regions that fell within the validation ranges of the DWPF PCCS models. In addition, the liquidus temperature model was used to restrict the glass compositions so that they could all be melted at the same temperature. The nepheline discriminator was used to force the glass compositions into regions where nepheline formation was predicted to occur. The glasses were fabricated in the laboratory and characterized for crystallization and chemical durability after both quenching and slow cooling. Chemical analysis showed that the fabricated glasses met the target compositions. Nepheline was identified in one of the quenched glasses and several of the CCC glasses. There was no clear relationship between the types of crystallization that occurred in a particular glass and its location on the Al{sub 2}O{sub 3}-Na{sub 2}O-SiO{sub 2} ternary diagram. A partitioning algorithm was used to identify trends in crystallization behavior based on glass composition. Generally, for the CCC glasses MnO influenced the crystallization of spinels and B{sub 2}O{sub 3} and SiO{sub 2} influenced the crystallization of nepheline. Measured durability responses varied from acceptable to unacceptable depending on the glass composition and type and extent of crystallization that occurred. It was not possible to identify any linear effects of composition on chemical durability performance for this set of study glasses. The results were not sufficient to recommend modification of the current nepheline discriminator at this time. It is recommended that the next series of experiments continue to focus not only on compositional regions where the PCCS models are considered applicable (i.e., the model validation ranges), but also be restricted to compositional regions where acceptable glasses are predicted to be

  14. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  15. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  16. State Quo and Future of China's Refining Sector%State Quo and Future of China's Refining Sector

    Institute of Scientific and Technical Information of China (English)

    Zhu He

    2012-01-01

    Ever since the beginning of the 21st century and China's entering into the WTO, China's refining sector has made great strides with the support of a rapid economic growth and a strong demand for petroleum despite the fact that the industry has been facing a fiercer international competition, higher oil prices, policy-related losses (losses caused by the fact that refined oil prices strangely lower than that of the crude), international financial crisis, unstable energy geopolitics, and etc.

  17. Refining Approximating Betweenness Centrality Based on Samplings

    CERN Document Server

    Ji, Shiyu

    2016-01-01

    Betweenness Centrality (BC) is an important measure used widely in complex network analysis, such as social network, web page search, etc. Computing the exact BC values is highly time consuming. Currently the fastest exact BC determining algorithm is given by Brandes, taking $O(nm)$ time for unweighted graphs and $O(nm+n^2\\log n)$ time for weighted graphs, where $n$ is the number of vertices and $m$ is the number of edges in the graph. Due to the extreme difficulty of reducing the time complexity of exact BC determining problem, many researchers have considered the possibility of any satisfactory BC approximation algorithms, especially those based on samplings. Bader et al. give the currently best BC approximation algorithm, with a high probability to successfully estimate the BC of one vertex within a factor of $1/\\varepsilon$ using $\\varepsilon t$ samples, where $t$ is the ratio between $n^2$ and the BC value of the vertex. However, some of the algorithmic parameters in Bader's work are not yet tightly boun...

  18. Refined exposure assessment of Brown HT (E 155

    Directory of Open Access Journals (Sweden)

    European Food Safety Authority

    2014-05-01

    Full Text Available The European Food Safety Authority (EFSA carried out an exposure assessment of Brown HT (E 155 taking into account additional information on its use in foods as consumed. In 2010, the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS adopted a scientific opinion on the re-evaluation of Brown HT and concluded that dietary exposure in both adults and 1-10 year old children at the high level may exceed the Acceptable Daily Intake (ADI for Brown HT of 1.5 mg/kg body weight (bw/day at the upper end of the range. Following this conclusion, the European Commission requested EFSA to perform a refined exposure assessment for this food colour. Data on the presence of Brown HT in foods were requested from relevant stakeholders through a call for usage and concentration data. Usage levels were provided to EFSA for six out of 37 food categories in which Brown HT is authorised. A limited number of analytical results were also reported to EFSA, all below the limit of detection (LOD or limit of quantification (LOQ. Exposure assessment was performed using the EFSA Comprehensive Food Consumption Database. Three different scenarios were considered, including i exposure estimates based on Maximum Permitted Levels (MPLs, ii a combination of MPLs and reported maximum use levels and iii reported maximum use levels only. Considering the first two scenarios, high exposure levels (95th percentile exceeded the ADI for all age groups, with exception for the elderly. In comparison to the previous assessment, for both children and adults, the current mean exposure estimates are of the same order of magnitude, while the 95th percentile exposure is lower, particularly in adults. The mean and high level exposure estimates of Brown HT are below the ADI for all population groups when considering the reported use levels only.

  19. Nonequilibrium Solidification, Grain Refinements, and Recrystallization of Deeply Undercooled Ni-20 At. Pct Cu Alloys: Effects of Remelting and Stress

    Science.gov (United States)

    Xu, Xiaolong; Hou, Hua; Zhao, Yuhong; Liu, Feng

    2017-10-01

    Grain refinement phenomena during the microstructural evolution upon nonequilibrium solidification of deeply undercooled Ni-20 at. pct Cu melts were systematically investigated. The dendrite growth in the bulk undercooled melts was captured by a high-speed camera. The first kind of grain refinement occurring in the low undercooling regimes was explained by a current grain refinement model. Besides, for the dendrite melting mechanism, the stress originating from the solidification contraction and thermal strain in the FMZ during rapid solidification could be a main mechanism causing the second kind of grain refinement above the critical undercooling. This internal stress led to the distortion and breakup of the primary dendrites and was semiquantitatively described by a corrected stress accumulation model. It was found that the stress-induced recrystallization could make the primary microstructures refine substantially after recalescence. A new method, i.e., rapidly quenching the deeply undercooled alloy melts before recalescence, was developed in the present work to produce crystalline alloys, which were still in the cold-worked state and, thus, had the driven force for recrystallization.

  20. Mathematical Modeling of the Vacuum Circulation Refining Processof Molten Steel

    Institute of Scientific and Technical Information of China (English)

    魏季和

    2003-01-01

    The available studies in the literature on mathematical modeling of the vacuum circulation (RH) refining process of molten steel have briefly been reviewed. The latest advances obtained by the author with his research group have been Summarized. On the basis of the mass and momentum balances in the system, a new mathematical model for decarburization and degassing during the RH and RH-KTB refining processes of molten steel was proposed and developed. The refining roles of the three reaction sites, i.e. the up-snorkel zone, the droplet group and steel bath in the vacuum vessel, were considered in the model. It was assumed that the mass transfer of reactive components in the molten steel is the rate control step of the refining reactions. And the friction losses and drags of flows in the snorkels and vacuum vessel were all counted. The model was applied to the refining of molten steel in a multifunction RH degasser of 90 t capacity. The decarburization and degassing processes in the degasser under the RH and RH-KTB operating condi-tions were modeled and analyzed using this model. Besides, proceeded from the two-resistance mass transfer theory and the mass bal-ance of sulphur in the system, a kinetic model for the desulphurization by powder injection and blowing in the RH refining of molten steel was developed. Modeling and predictions of the process of injecting and blowing the lime based powder flux under assumed oper-ating modes with the different initial contents of sulphur and amounts of powder injected and blown in a RH degasser of 300 t capacity were carried out using the model. It was demonstrated that for the RH and RH-KTB refining processes, and the desulphurization by powder injection and blowing in the RH refining, the results predicted by the models were all in good agreement respectively with data from industrial experiments and practice. These models may be expected to offer some useful information and a reliable basis for de-termining and optimizing

  1. Microstructure and tensile properties of magnesium alloy modified by Si/Ca based refiner

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhi-chao; SUN Yang-shan; WEI Yu; DU Wen-wen; XUE Feng; ZHU Tian-bai

    2005-01-01

    Microstructure and mechanical properties of pure magnesium and AZ31 alloy with Ca/Si based refiner addition were investigated. The results indicate that addition of Ca/Si based refiners to pure magnesium and AZ31 alloy results in remarkable microstructure refinement. With proper amount of refiner addition, the grain size in as cast ingots can be one order of magnitude lower than that without refiner addition. Small amount of refiner addition to AZ31 alloy increases both ultimate strength and yield strength significantly, while the ductility of the alloy with refiner addition is similar to that without refiner addition. Addition of refiner improves the deformability of AZ31 alloy and extruded or hot rolled specimens (rods or sheets) with refiner addition exhibit higher surface quality and mechanical properties than those without refiner addition.

  2. η-INVARIANT AND CHERN-SIMONS CURRENT

    Institute of Scientific and Technical Information of China (English)

    ZHANG WEIPING

    2005-01-01

    The author presents an alternate proof of the Bismut-Zhang localization formula of ηinvariants, when the target manifold is a sphere, by using ideas of mod k index theory instead of the difficult analytic localization techniques of Bismut-Lebeau. As a consequence, it is shown that the R/Z part of the aualytically defined η invariant of Atiyah-Patodi-Singer for a Dirac operator on an odd dimensional closed spin manifold can be expressed purely geometrically through a stable Chern-Simons current on a higher dimensional sphere. As a preliminary application, the author discusses the relation with the Atiyah-Patodi-Singer R/Z index theorem for unitary flat vector bundles,and proves an R refinement in the case where the Dirac operator is replaced by the Signature operator.

  3. Adaptive mesh refinement for shocks and material interfaces

    Energy Technology Data Exchange (ETDEWEB)

    Dai, William Wenlong [Los Alamos National Laboratory

    2010-01-01

    There are three kinds of adaptive mesh refinement (AMR) in structured meshes. Block-based AMR sometimes over refines meshes. Cell-based AMR treats cells cell by cell and thus loses the advantage of the nature of structured meshes. Patch-based AMR is intended to combine advantages of block- and cell-based AMR, i.e., the nature of structured meshes and sharp regions of refinement. But, patch-based AMR has its own difficulties. For example, patch-based AMR typically cannot preserve symmetries of physics problems. In this paper, we will present an approach for a patch-based AMR for hydrodynamics simulations. The approach consists of clustering, symmetry preserving, mesh continuity, flux correction, communications, management of patches, and load balance. The special features of this patch-based AMR include symmetry preserving, efficiency of refinement across shock fronts and material interfaces, special implementation of flux correction, and patch management in parallel computing environments. To demonstrate the capability of the AMR framework, we will show both two- and three-dimensional hydrodynamics simulations with many levels of refinement.

  4. REFINING BEHAVIOR OF BAMBOO LONG FIBER FRACTION PULP

    Institute of Scientific and Technical Information of China (English)

    Nishi K.Bhardwaj; S.V.Subrahmanyam; A.G.Kulkarni

    2004-01-01

    Refining of pulp significantly contributes to papermaking process by affecting the runnability of the stock and quality of end product. The greater the production rates of a paper, the greater are the effects of machine downtime through breaks. A correct approach towards refining treatment is very essential for energy savings and product with desired properties. Papermakers are being encouraged to use non-wood fibres for a variety of reasons - the environment, changing agricultural policy and long-term fibre supply. Compared with wood fibres,there is less knowledge on how to treat non-wood fibres for optimum performance. Laboratory studies aimed at understanding the behaviour of unbleached bamboo long fibre fraction pulp on refining in Escher Wyss Laborefiner under simulated process conditions included investigations of the important parameters like wet web tensile, wet web elongation, water retention value and paper strength properties. The paper describes the influence of two specific edge loads, 1000 and 1500 Ws/km on refining of pulp.Bamboo long fibre fraction pulp responds better to lower intensity refining to develop pulp strength.

  5. Optimal modifying and refining processes for A356 aluminium alloys

    Institute of Scientific and Technical Information of China (English)

    ZUO Xiu-rong; ZHONG Zhi-guo

    2006-01-01

    The influence of Ti, B, RE (cerium-rich mixtures of rare earth) and Sr, applied in modification and refining processes, on A356 aluminum alloys has been studied with the aids of OM, etc. The results show that the grain refining efficiency of Grain-Refining Aluminium Ingot (GRAI) and Al-Ti master alloys is similar. But the Ti addition from GRAI has lower costs than that with Al-Ti master alloys. So A356 aluminum alloys produced with GRAI are feasible in economy.Grain refining with GRAI with 0.01%Ti plus additional 0.03% B offers significant advantages over that from GRAI with 0.1% Ti only in A356 aluminum alloys, which made the dendrite α (Al) grain structure transform into equiaxed α (Al) grain structure, plus a partially modified eutectic silicon structure. RE addition to A356 aluminum alloys with Sr modifier is enable to achieve small DAS,reduced pores, well-refined fibrous silicon, small and dispersive eutectic colonies.

  6. Bayesian ensemble refinement by replica simulations and reweighting.

    Science.gov (United States)

    Hummer, Gerhard; Köfinger, Jürgen

    2015-12-28

    We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss their practical application. With ensemble refinement, the properties of dynamic and partially disordered (bio)molecular structures can be characterized by integrating a wide range of experimental data, including measurements of ensemble-averaged observables. We start from a Bayesian formulation in which the posterior is a functional that ranks different configuration space distributions. By maximizing this posterior, we derive an optimal Bayesian ensemble distribution. For discrete configurations, this optimal distribution is identical to that obtained by the maximum entropy "ensemble refinement of SAXS" (EROS) formulation. Bayesian replica ensemble refinement enhances the sampling of relevant configurations by imposing restraints on averages of observables in coupled replica molecular dynamics simulations. We show that the strength of the restraints should scale linearly with the number of replicas to ensure convergence to the optimal Bayesian result in the limit of infinitely many replicas. In the "Bayesian inference of ensembles" method, we combine the replica and EROS approaches to accelerate the convergence. An adaptive algorithm can be used to sample directly from the optimal ensemble, without replicas. We discuss the incorporation of single-molecule measurements and dynamic observables such as relaxation parameters. The theoretical analysis of different Bayesian ensemble refinement approaches provides a basis for practical applications and a starting point for further investigations.

  7. REFINING BEHAVIOUR OF BAMBOO LONG FIBRE FRACTION PULP

    Institute of Scientific and Technical Information of China (English)

    NishiK.Bhardwaj; S.V.Subrahmanyam; A.G.Kulkarni

    2004-01-01

    Refining of pulp significantly contributes to papermaking process by affecting the runnability of the stock and quality of end product. The greater the production rates of a paper, the greater are the effects of machine downtime through breaks. A correct approach towards refining treatment is very essential for energy savings and product with desired properties. Papermakers are being encouraged to use non-wood fibres for a variety of reasons - the environment, changing agricultural policy and long-term fibre supply. Compared with wood fibres, there is less knowledge on how to treat non-wood fibres for optimum performance. Laboratory studies aimed at understanding the behaviour of unbleached bamboo long fibre fraction pulp on refining in Escher Wyss Laborefmer under simulated process conditions included investigations of the important parameters like wet web tensile, wet web elongation, water retention value and paper strength properties. The paper describes the influence of two specific edge loads, 1000 and 1500 Ws/km on refining of pulp. Bamboo long fibre fraction pulp responds better to lower intensity refining to develop pulp strength.

  8. Refined food addiction: a classic substance use disorder.

    Science.gov (United States)

    Ifland, J R; Preuss, H G; Marcus, M T; Rourke, K M; Taylor, W C; Burau, K; Jacobs, W S; Kadish, W; Manso, G

    2009-05-01

    Overeating in industrial societies is a significant problem, linked to an increasing incidence of overweight and obesity, and the resultant adverse health consequences. We advance the hypothesis that a possible explanation for overeating is that processed foods with high concentrations of sugar and other refined sweeteners, refined carbohydrates, fat, salt, and caffeine are addictive substances. Therefore, many people lose control over their ability to regulate their consumption of such foods. The loss of control over these foods could account for the global epidemic of obesity and other metabolic disorders. We assert that overeating can be described as an addiction to refined foods that conforms to the DSM-IV criteria for substance use disorders. To examine the hypothesis, we relied on experience with self-identified refined foods addicts, as well as critical reading of the literature on obesity, eating behavior, and drug addiction. Reports by self-identified food addicts illustrate behaviors that conform to the 7 DSM-IV criteria for substance use disorders. The literature also supports use of the DSM-IV criteria to describe overeating as a substance use disorder. The observational and empirical data strengthen the hypothesis that certain refined food consumption behaviors meet the criteria for substance use disorders, not unlike tobacco and alcohol. This hypothesis could lead to a new diagnostic category, as well as therapeutic approaches to changing overeating behaviors.

  9. Refining signal decomposition for GRETINA detectors

    Science.gov (United States)

    Prasher, V. S.; Campbell, C. M.; Cromaz, M.; Crawford, H. L.; Wiens, A.; Lee, I. Y.; Macchiavelli, A. O.; Lister; Merchan, E.; Chowdhury, P.; Radford, D. C.

    2013-04-01

    The reconstruction of the original direction and energy of gamma rays through locating their interaction points in solid state detectors is a crucial evolving technology for nuclear physics, space science and homeland security. New arrays AGATA and GRETINA have been built for nuclear science based on highly segmented germanium crystals. The signal decomposition process fits the observed waveform from each crystal segment with a linear combination of pre-calculated basis signals. This process occurs on an event-by-event basis in real time to extract the position and energy of γ-ray interactions. The methodology for generating a basis of pulse shapes, varying according to the position of the charge generating interactions, is in place. Improvements in signal decomposition can be realized by better modeling the crystals. Specifically, a better understanding of the true impurity distributions, internal electric fields, and charge mobilities will lead to more reliable bases, more precise definition of the interaction points, and hence more reliable tracking. In this presentation we will cover the current state-of-the-art for basis generation and then discuss the sensitivity of the predicted pulse shapes when varying some key parameters.

  10. Whether integrating refining and petrochemical business can provide opportunities for development of petrochemical industry in Serbia

    Directory of Open Access Journals (Sweden)

    Popović Zoran M.

    2016-01-01

    Full Text Available Since the beginning of 90s of last century both the petroleum industry and petrochemical industry have operated in difficult circumstances. In particularly, margins of petroleum and petrochemical industry were exacerbated during global economic crisis in 2008-2009 years. At that time, as one option that could be the solution, the global analysts had started to more intense investigate the benefits of Refining-Petrochemical Integration. Shortly afterwards, more and more petroleum refineries and petrochemical manufacturers began to see the future in this kind of operational, managerial, marketing and commercial connection. This paper evaluates, in particular, the achieved level of integration of refinery and petrochemical businesses in Central and South-Eastern Europe. And specifically, the paper identifies current capabilities and future chances of linking this kind of integration between Serbian refining and petrochemical players. The viability of integration between possible actors and benefits of every single refining-petrochemical interface in Serbia depend on many factors, and therefore each integrated system is unique and requires prior serious Cost Benefit Analysis.

  11. Reaching Adolescent Gay, Bisexual, and Queer Men Online: Development and Refinement of a National Recruitment Strategy

    Science.gov (United States)

    Prescott, Tonya L; Phillips II, Gregory; DuBois, L. Zachary; Bull, Sheana S; Mustanski, Brian

    2016-01-01

    Background Using social networking websites to recruit research participants is increasingly documented in the literature, although few studies have leveraged these sites to reach those younger than 18 years. Objective To discuss the development and refinement of a recruitment protocol to reach and engage adolescent gay, bisexual, and other teenaged men who have sex with men (AGBM). Participants were recruited for development and evaluation activities related to Guy2Guy, a text messaging–based human immunodeficiency virus infection prevention program. Methods Eligibility criteria included being between 14 to 18 years old; being a cisgender male; self-identifying as gay, bisexual, and/or queer; being literate in English, exclusively owning a cell phone, enrolled in an unlimited text messaging plan, intending to keep their current phone number over the next 6 months, and having used text messaging for at least the past 6 months. Recruitment experiences and subsequent steps to refine the Internet-based recruitment strategy are discussed for 4 research activities: online focus groups, content advisory team, beta test, and randomized controlled trial (RCT). Recruitment relied primarily on Facebook advertising. To a lesser extent, Google AdWords and promotion through partner organizations working with AGBM youth were also utilized. Results Facebook advertising strategies were regularly adjusted based on preidentified recruitment targets for race, ethnicity, urban-rural residence, and sexual experience. The result was a diverse sample of participants, of whom 30% belonged to a racial minority and 20% were Hispanic. Facebook advertising was the most cost-effective method, and it was also able to reach diverse recruitment goals: recruitment for the first focus group cost an average of US $2.50 per enrolled participant, and it took 9 days to enroll 40 participants; the second focus group cost an average of US $6.96 per enrolled participant, and it took 11 days to enroll 40

  12. Reaching Adolescent Gay, Bisexual, and Queer Men Online: Development and Refinement of a National Recruitment Strategy.

    Science.gov (United States)

    Prescott, Tonya L; Phillips Ii, Gregory; DuBois, L Zachary; Bull, Sheana S; Mustanski, Brian; Ybarra, Michele L

    2016-08-04

    Using social networking websites to recruit research participants is increasingly documented in the literature, although few studies have leveraged these sites to reach those younger than 18 years. To discuss the development and refinement of a recruitment protocol to reach and engage adolescent gay, bisexual, and other teenaged men who have sex with men (AGBM). Participants were recruited for development and evaluation activities related to Guy2Guy, a text messaging-based human immunodeficiency virus infection prevention program. Eligibility criteria included being between 14 to 18 years old; being a cisgender male; self-identifying as gay, bisexual, and/or queer; being literate in English, exclusively owning a cell phone, enrolled in an unlimited text messaging plan, intending to keep their current phone number over the next 6 months, and having used text messaging for at least the past 6 months. Recruitment experiences and subsequent steps to refine the Internet-based recruitment strategy are discussed for 4 research activities: online focus groups, content advisory team, beta test, and randomized controlled trial (RCT). Recruitment relied primarily on Facebook advertising. To a lesser extent, Google AdWords and promotion through partner organizations working with AGBM youth were also utilized. Facebook advertising strategies were regularly adjusted based on preidentified recruitment targets for race, ethnicity, urban-rural residence, and sexual experience. The result was a diverse sample of participants, of whom 30% belonged to a racial minority and 20% were Hispanic. Facebook advertising was the most cost-effective method, and it was also able to reach diverse recruitment goals: recruitment for the first focus group cost an average of US $2.50 per enrolled participant, and it took 9 days to enroll 40 participants; the second focus group cost an average of US $6.96 per enrolled participant, and it took 11 days to enroll 40 participants. Recruitment for the

  13. Flow induced/ refined solution crystallization of a semiconducting polymer

    Science.gov (United States)

    Nguyen, Ngoc A.

    Organic photovoltaics, a new generation of solar cells, has gained scientific and economic interests due to the ability of solution-processing and potentially low-cost power production. Though, the low power conversion efficiency of organic/ plastic solar cells is one of the most pertinent challenges that has appealed to research communities from many different fields including materials science and engineering, electrical engineering, chemical engineering, physics and chemistry. This thesis focuses on investigating and controlling the morphology of a semi-conducting, semi-crystalline polymer formed under shear-flow. Molecular structures and processing techniques are critical factors that significantly affect the morphology formation in the plastic solar cells, thus influencing device performance. In this study, flow-induced solution crystallization of poly (3-hexylthiophene) (P3HT) in a poor solvent, 2-ethylnapthalene (2-EN) was utilized to make a paint-like, structural liquid. The polymer crystals observed in this structured paint are micrometers long, nanometers in cross section and have a structure similar to that formed under quiescent conditions. There is pi-pi stacking order along the fibril axis, while polymer chain folding occurs along the fibril width and the order of the side-chain stacking is along fibril height. It was revealed that shear-flow not only induces P3HT crystallization from solution, but also refines and perfects the P3HT crystals. Thus, a general strategy to refine the semiconducting polymer crystals from solution under shear-flow has been developed and employed by simply tuning the processing (shearing) conditions with respect to the dissolution temperature of P3HT in 2-EN. The experimental results demonstrated that shear removes defects and allows more perfect crystals to be formed. There is no glass transition temperature observed in the crystals formed using the flow-induced crystallization indicating a significantly different

  14. Docking with PIPER and refinement with SDU in rounds 6-11 of CAPRI.

    Science.gov (United States)

    Shen, Yang; Brenke, Ryan; Kozakov, Dima; Comeau, Stephen R; Beglov, Dmitri; Vajda, Sandor

    2007-12-01

    Our approach to protein-protein docking includes three main steps. First we run PIPER, a new rigid body docking program. PIPER is based on the Fast Fourier Transform (FFT) correlation approach that has been extended to use pairwise interactions potentials, thereby substantially increasing the number of near-native structures generated. The interaction potential is also new, based on the DARS (Decoys As the Reference State) principle. In the second step, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the conformations are refined by a new medium-range optimization method SDU (Semi-Definite programming based Underestimation). SDU has been developed to locate global minima within regions of the conformational space in which the energy function is funnel-like. The method constructs a convex quadratic underestimator function based on a set of local energy minima, and uses this function to guide future sampling. The combined method performed reliably without the direct use of biological information in most CAPRI problems that did not require homology modeling, providing acceptable predictions for targets 21, and medium quality predictions for targets 25 and 26.

  15. Microstructure refinement and enhanced critical current density in binary doped SmFeAsO superconductor

    Energy Technology Data Exchange (ETDEWEB)

    Anooja, J. B.; Aswathy, P. M.; Varghese, Neson; Syamaprasad, U., E-mail: syamcsir@gmail.com [National Institute for Interdisciplinary Science and Technology (CSIR), Trivandrum- 695 019 (India); Aloysius, R. P. [National Physical Laboratory (CSIR), Delhi-110012 (India)

    2014-04-24

    The iron-pnictide Sm{sub 1−x}Ca{sub x}FeAsO{sub 1−2x}F{sub 2x} superconductor was prepared and the combined effect of electron and hole doping was studied in detail. It is observed that the binary doping using CaF{sub 2} improves the microstructure tremendously with a preferred orientation of the (00l) planes. Moreover, a maximum T{sub C} of 53.8 K and a transport J{sub C} of 880 A/cm{sup 2} (12 K), which is double to that of the F-doped sample, are achieved. The dopant CaF{sub 2} seems to be a potential candidate for solving the grain-connectivity concerns in iron-pnictides paving the way towards conductor development.

  16. Study on Laboratory Method for Refining of SR Diesel Fuel

    Institute of Scientific and Technical Information of China (English)

    Li Junling; Zheng Tinglu; Han Zhaping

    2006-01-01

    The method for refining the straight-run diesel fuel was studied in laboratory scale in order to make the acid number of diesel fraction comply with the standard while removing the naphthenic acids contained in diesel without causing environmental pollution. After comparing the effect of refining using three solvents, the isopropyl alcohol-HOA was specified as the best solvent. Meanwhile, the relationship between the acid number of diesel fraction and the amount of solvent used and the relationship between the concentration of solvent and temperature and the stability of diesel in terms of its acid number were also investigated. Experimental results had shown that when the mass fraction of the HOA-IPA solvent was 20% at a dosage of 17 mL of the solvent and a temperature of 30℃, the acid number of the refined diesel fraction was 0.015 mg KOH/g with a good stability of acidity in the diesel traction.

  17. System refinement for content based satellite image retrieval

    Directory of Open Access Journals (Sweden)

    NourElDin Laban

    2012-06-01

    Full Text Available We are witnessing a large increase in satellite generated data especially in the form of images. Hence intelligent processing of the huge amount of data received by dozens of earth observing satellites, with specific satellite image oriented approaches, presents itself as a pressing need. Content based satellite image retrieval (CBSIR approaches have mainly been driven so far by approaches dealing with traditional images. In this paper we introduce a novel approach that refines image retrieval process using the unique properties to satellite images. Our approach uses a Query by polygon (QBP paradigm for the content of interest instead of using the more conventional rectangular query by image approach. First, we extract features from the satellite images using multiple tiling sizes. Accordingly the system uses these multilevel features within a multilevel retrieval system that refines the retrieval process. Our multilevel refinement approach has been experimentally validated against the conventional one yielding enhanced precision and recall rates.

  18. Toward parallel, adaptive mesh refinement for chemically reacting flow simulations

    Energy Technology Data Exchange (ETDEWEB)

    Devine, K.D.; Shadid, J.N.; Salinger, A.G. Hutchinson, S.A. [Sandia National Labs., Albuquerque, NM (United States); Hennigan, G.L. [New Mexico State Univ., Las Cruces, NM (United States)

    1997-12-01

    Adaptive numerical methods offer greater efficiency than traditional numerical methods by concentrating computational effort in regions of the problem domain where the solution is difficult to obtain. In this paper, the authors describe progress toward adding mesh refinement to MPSalsa, a computer program developed at Sandia National laboratories to solve coupled three-dimensional fluid flow and detailed reaction chemistry systems for modeling chemically reacting flow on large-scale parallel computers. Data structures that support refinement and dynamic load-balancing are discussed. Results using uniform refinement with mesh sequencing to improve convergence to steady-state solutions are also presented. Three examples are presented: a lid driven cavity, a thermal convection flow, and a tilted chemical vapor deposition reactor.

  19. The refined theory of transversely isotropic piezoelectric rectangular beams

    Institute of Scientific and Technical Information of China (English)

    GAO; Yang; WANG; Minzhong

    2006-01-01

    The problem of deducing one-dimensional theory from two-dimensional theory for a transversely isotropic piezoelectric rectangular beam is investigated. Based on the piezoelasticity theory, the refined theory of piezoelectric beams is derived by using the general solution of transversely isotropic piezoelasticity and Lur'e method without ad hoc assumptions. Based on the refined theory of piezoelectric beams, the exact equations for the beams without transverse surface loadings are derived, which consist of two governing differential equations: the fourth-order equation and the transcendental equation. The approximate equations for the beams under transverse loadings are derived directly from the refined beam theory. As a special case, the governing differential equations for transversely isotropic elastic beams are obtained from the corresponding equations of piezoelectric beams. To illustrate the application of the beam theory developed, a uniformly loaded and simply supported piezoelectric beam is examined.

  20. Steam refining as an alternative to steam explosion.

    Science.gov (United States)

    Schütt, Fokko; Westereng, Bjørge; Horn, Svein J; Puls, Jürgen; Saake, Bodo

    2012-05-01

    In steam pretreatment the defibration is usually achieved by an explosion at the end of the treatment, but can also be carried out in a subsequent refiner step. A steam explosion and a steam refining unit were compared by using the same raw material and pretreatment conditions, i.e. temperature and time. Smaller particle size was needed for the steam explosion unit to obtain homogenous slurries without considerable amounts of solid chips. A higher amount of volatiles could be condensed from the vapour phase after steam refining. The results from enzymatic hydrolysis showed no significant differences. It could be shown that, beside the chemical changes in the cell wall, the decrease of the particle size is the decisive factor to enhance the enzymatic accessibility while the explosion effect is not required.

  1. Future prospects for palm oil refining and modifications

    Directory of Open Access Journals (Sweden)

    Gibon Véronique

    2009-07-01

    Full Text Available Palm oil is rich in minor components that impart unique nutritional properties and need to be preserved. In this context, refining technologies have been improved, with the dual temperature deodorizer, the double condensing unit and the ice condensing system. The DOBI is a good tool to assess quality of the crude palm oil and its ability to be properly refined. Specially refined oils open a market for new high quality products (golden palm oil, red palm oil, white soaps, etc.. Palm oil is a good candidate for the multi-step dry fractionation process, aiming to the production of commodity oils and specialty fats (cocoa butter replacers. New technological developments allow quality and yield improvements. Palm oil and fractions are also valuable feedstock for enzymatic interesterification in which applications are for commodity oil (low-trans margarines and shortenings and for special products (cocoa butter equivalents, infant formulation, ….

  2. RNA Structure Refinement using the ERRASER-Phenix pipeline

    Science.gov (United States)

    Chou, Fang-Chieh; Echols, Nathaniel; Terwilliger, Thomas C.; Das, Rhiju

    2015-01-01

    Summary The final step of RNA crystallography involves the fitting of coordinates into electron density maps. The large number of backbone atoms in RNA presents a difficult and tedious challenge, particularly when experimental density is poor. The ERRASER-Phenix pipeline can improve an initial set of RNA coordinates automatically based on a physically realistic model of atomic-level RNA interactions. The pipeline couples diffraction-based refinement in Phenix with the Rosetta-based real-space refinement protocol ERRASER (Enumerative Real-Space Refinement ASsisted by Electron density under Rosetta). The combination of ERRASER and Phenix can improve the geometrical quality of RNA crystallographic models while maintaining or improving the fit to the diffraction data (as measured by Rfree). Here we present a complete tutorial for running ERRASER-Phenix through the Phenix GUI, from the command-line, and via an application in the Rosetta On-line Server that Includes Everyone (ROSIE). PMID:26227049

  3. Evolutions in 3D numerical relativity using fixed mesh refinement

    CERN Document Server

    Schnetter, E; Hawke, I; Schnetter, Erik; Hawley, Scott H.; Hawke, Ian

    2004-01-01

    We present results of 3D numerical simulations using a finite difference code featuring fixed mesh refinement (FMR), in which a subset of the computational domain is refined in space and time. We apply this code to a series of test cases including a robust stability test, a nonlinear gauge wave and an excised Schwarzschild black hole in an evolving gauge. We find that the mesh refinement results are comparable in accuracy, stability and convergence to unigrid simulations with the same effective resolution. At the same time, the use of FMR reduces the computational resources needed to obtain a given accuracy. Particular care must be taken at the interfaces between coarse and fine grids to avoid a loss of convergence at high resolutions. This FMR system, "Carpet", is a driver module in the freely available Cactus computational infrastructure, and is able to endow existing Cactus simulation modules ("thorns") with FMR with little or no extra effort.

  4. Elliptic Solvers with Adaptive Mesh Refinement on Complex Geometries

    Energy Technology Data Exchange (ETDEWEB)

    Phillip, B.

    2000-07-24

    Adaptive Mesh Refinement (AMR) is a numerical technique for locally tailoring the resolution computational grids. Multilevel algorithms for solving elliptic problems on adaptive grids include the Fast Adaptive Composite grid method (FAC) and its parallel variants (AFAC and AFACx). Theory that confirms the independence of the convergence rates of FAC and AFAC on the number of refinement levels exists under certain ellipticity and approximation property conditions. Similar theory needs to be developed for AFACx. The effectiveness of multigrid-based elliptic solvers such as FAC, AFAC, and AFACx on adaptively refined overlapping grids is not clearly understood. Finally, a non-trivial eye model problem will be solved by combining the power of using overlapping grids for complex moving geometries, AMR, and multilevel elliptic solvers.

  5. Targeted screening for colorectal cancer in high-risk individuals.

    Science.gov (United States)

    Wong, Martin C S; Wong, Sunny H; Ng, Siew C; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2015-12-01

    The idea of targeted screening for colorectal cancer based on risk profiles originates from its benefits to improve detection yield and optimize screening efficiency. Clinically, it allows individuals to be more aware of their own risk and make informed decisions on screening choice. From a public health perspective, the implementation of risk stratification strategies may better justify utilization of colonoscopic resources, and facilitate resource-planning in the formulation of population-based screening programmes. There are several at-risk groups who should receive earlier screening, and colonoscopy is more preferred. This review summarizes the currently recommended CRC screening strategies among subjects with different risk factors, and introduces existing risk scoring systems. Additional genetic, epidemiological, and clinical parameters may be needed to enhance their performance to risk-stratify screening participants. Future research studies should refine these scoring systems, and explore the adaptability, feasibility, acceptability, and user-friendliness of their use in clinical practice among different population groups.

  6. By-products of palm oil extraction and refining

    Directory of Open Access Journals (Sweden)

    Tan Yew-Ai

    2006-01-01

    Full Text Available This paper outlines the utilisation of by-products resulting from the extraction and refining of palm oil. It summarises research by the Malaysian Palm Oil Board (MPOB directed at producing zero waste from the palm oil industry. MPOB regards by-products of the palm oil industry not as waste but resources. It will be evident that by-products from the palm oil industry can be and have been used extensively and that the research carried out is relevant to both the milling and refining sectors.

  7. The Algorithm for Rule-base Refinement on Fuzzy Set

    Institute of Scientific and Technical Information of China (English)

    LI Feng; WU Cui-hong; DING Xiang-wu

    2006-01-01

    In the course of running an artificial intelligent system many redundant rules are often produced. To refine the knowledge base, viz. to remove the redundant rules, can accelerate the reasoning and shrink the rule base. The purpose of the paper is to present the thinking on the topic and design the algorithm to remove the redundant rules from the rule base.The "abstraction" of "state variable", redundant rules and the least rule base are discussed in the paper. The algorithm on refining knowledge base is also presented.

  8. Refinement-based verification of sequential implementations of Stateflow charts

    CERN Document Server

    Miyazawa, Alvaro; 10.4204/EPTCS.55.5

    2011-01-01

    Simulink/Stateflow charts are widely used in industry for the specification of control systems, which are often safety-critical. This suggests a need for a formal treatment of such models. In previous work, we have proposed a technique for automatic generation of formal models of Stateflow blocks to support refinement-based reasoning. In this article, we present a refinement strategy that supports the verification of automatically generated sequential C implementations of Stateflow charts. In particular, we discuss how this strategy can be specialised to take advantage of architectural features in order to allow a higher level of automation.

  9. Crystal structural refinement for NdAlSi

    Institute of Scientific and Technical Information of China (English)

    HE Wei; ZHANG Jiliang; ZENG Lingmin; ZHUANG Yinghong

    2006-01-01

    The compound NdAlSi was studied using X-ray powder diffraction technique and refined by the Rietveld method. The compound NdAlSihas tetragonal α-ThSi2-type structure, space group I41/amd (No.141), Z = 4, and the lattice parameters a = 0.41991(1) nm, c = 1.44916(3) nm. The Smith and Snyder figure of merit FN is F30= 103.1(36). The R-factors of Rietveld refinement are Rp= 0.113 and Rwp= 0.148, respectively. The X-ray powder diffraction data is presented in this article.

  10. Targeting Immune Suppression to Refine Dendritic Cell-based Immunotherapy in Mesothelioma

    NARCIS (Netherlands)

    J.D. Veltman (Joris)

    2010-01-01

    textabstractMalignant mesothelioma (MM) is a highly aggressive neoplasm caused by neoplastic transformation of mesothelial cells that line the body’s serous cavities and the internal organs. In the majority of patients mesothelioma is localized within the pleural cavity. At this moment, no curative

  11. REFINEMENT OF THE NEPHELINE DISCRIMINATOR: RESULTS OF A PHASE I STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K; James Newell, J; Tommy Edwards, T; David Best, D; Irene Reamer, I; Phyllis Workman, P

    2008-02-13

    studied HLW glasses with relatively high Al{sub 2}O{sub 3} compositions of 25 wt % or greater and nepheline discriminator values well below 0.62 have been shown to be free of nepheline crystallization upon quenching and slow cooling. Thus, the current nepheline discriminator equation also appears to be conservative for some HLW glass compositions. Refining the nepheline discriminator to include other important components and to reduce conservatism may provide access to high Al{sub 2}O{sub 3} concentration glass compositions for the DWPF, which could in turn allow access to higher waste loadings, decreased washing and improved waste throughput. The objective of this study was to develop and characterize a series of HLW glass compositions based on a projected composition of Sludge Batch 5 (SB5), the next sludge batch to be processed in the DWPF. The selected glass compositions all had nepheline discriminator values below the current limit of 0.62. They cover a range of locations on the SiO{sub 2}-Na{sub 2}O-Al{sub 2}O{sub 3} diagram. They also include varying amounts of B{sub 2}O{sub 3} and CaO to support an evaluation of the impact of these components on the propensity for nepheline crystallization. The results described in this report confirm that some conservatism exists in the current nepheline discriminator. Several glass compositions, particularly compositions that target higher Al{sub 2}O{sub 3} concentrations, were shown to be very durable (i.e., PCT responses that were more than an order of magnitude better than that of the Environmental Assessment benchmark glass) while their nepheline discriminator values were well below the current nepheline discriminator limit of 0.62. Increased concentrations of B{sub 2}O{sub 3} and increased concentrations of CaO were shown to improve durability responses and suppress the formation of nepheline. This provides incentive to revise the nepheline discriminator to reduce some of this conservatism and incorporate the influence of B

  12. Grain refinement and improved properties through electromagnetic stirring in AI alloy MIG welds

    Institute of Scientific and Technical Information of China (English)

    Chang Yunlong; Yang Xu; Che Xiaoping; Li Duo

    2008-01-01

    This paper described the effects of external excitatory parameters of current and frequency on the microstructure and mechanical properties of weld metal in M1G welding with longitudinal electromagnetic field. With a high speed video camera capturing the images of arc shape, the mechanism of arc rotation and how the periodic contraction and expansion of arc affected the movement of molten pool were investigated. The technique resulted in fine equiaxed grains in weld metal and optimum parameters of electromagnetic stirring were suggested based on the extent of refinement. Fine-grained weld metal exhibited better yield strength and significant improvement in elongation.

  13. Bandwidth Study on Energy Use and Potential Energy Savings Opportunities in U.S. Petroleum Refining

    Energy Technology Data Exchange (ETDEWEB)

    Sabine Brueske, Caroline Kramer, Aaron Fisher

    2015-06-01

    Energy bandwidth studies of U.S. manufacturing sectors can serve as foundational references in framing the range (or bandwidth) of potential energy savings opportunities. This bandwidth study examines energy consumption and potential energy savings opportunities in U.S. petroleum refining. The study relies on multiple sources to estimate the energy used in nine individual process areas, representing 68% of sector-wide energy consumption. Energy savings opportunities for individual processes are based on technologies currently in use or under development; these potential savings are then extrapolated to estimate sector-wide energy savings opportunity.

  14. PetroChina's Sichuan Refining/Chemical Proiect Will Adopt UOP's Technology

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ UOP has been selected by PetroChina's Sichuan Petrochemical Company to provide technology,basic engineering design services and equipment to the integrated refining/chemical project near Chendu,Sichuan province.Currently this project is in the engineering design phase.This integrated project will manufacture fuel and petrochemical products,including a 600 kt/a paraxylene (PX) unit using UOP's ParexTM process and a 350 kt/a benzene unit.It is projected that in the future ten years to come the demand for PX will increase by 11% a year.

  15. Targeted Cancer Screening in Average-Risk Individuals.

    Science.gov (United States)

    Marcus, Pamela M; Freedman, Andrew N; Khoury, Muin J

    2015-11-01

    Targeted cancer screening refers to use of disease risk information to identify those most likely to benefit from screening. Researchers have begun to explore the possibility of refining screening regimens for average-risk individuals using genetic and non-genetic risk factors and previous screening experience. Average-risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without comorbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. In this paper, we describe the goals of targeted cancer screening in average-risk individuals, present factors on which cancer screening has been targeted, discuss inclusion of targeting in screening guidelines issued by major U.S. professional organizations, and present evidence to support or question such inclusion. Screening guidelines for average-risk individuals currently target age; smoking (lung cancer only); and, in some instances, race; family history of cancer; and previous negative screening history (cervical cancer only). No guidelines include common genomic polymorphisms. RCTs suggest that targeting certain ages and smoking histories reduces disease-specific cancer mortality, although some guidelines extend ages and smoking histories based on statistical modeling. Guidelines that are based on modestly elevated disease risk typically have either no or little evidence of an ability to affect a mortality benefit. In time, targeted cancer screening is likely to include genetic factors and past screening experience as well as non-genetic factors other than age, smoking, and race, but it is of utmost importance that clinical implementation be evidence-based.

  16. Automatic methods for the refinement of system models from the specification to the implementation

    CERN Document Server

    Seiter, Julia; Drechsler, Rolf

    2017-01-01

    This book provides a comprehensive overview of automatic model refinement, which helps readers close the gap between initial textual specification and its desired implementation. The authors enable readers to follow two “directions” for refinement: Vertical refinement, for adding detail and precision to single description for a given model and Horizontal refinement, which considers several views on one level of abstraction, refining the system specification by dedicated descriptions for structure or behavior. The discussion includes several methods which support designers of electronic systems in this refinement process, including verification methods to check automatically whether a refinement has been conducted as intended.

  17. Analysis of Environment for Development of Oil Refining Business in China

    Institute of Scientific and Technical Information of China (English)

    Song Aiping; Yang Weijun

    2006-01-01

    This articles focuses on analysis of the changing trend relating to crude supply and petroleum products demand inside China, while introducing the preliminary progress resulted from restructuring of China' s refining industry and dynamics of competition among Chinese refining enterprises. This article has made a preliminary judgment and analysis on the situation facing China's refining industry and may serve as a reference to refiners intending to develop refining business inside China.

  18. Action Relations. Basic Design Concepts for Behaviour Modelling and Refinement.

    NARCIS (Netherlands)

    Quartel, Dick

    This thesis presents basic design concepts, design methods and a basic design language for distributed system behaviours. This language is based on two basic concepts: the action concept and the causality relation concept. Our methods focus on behaviour refinement, which consists of replacing an

  19. A refinement of the A-polynomial of quivers

    CERN Document Server

    Villegas, Fernando Rodriguez

    2011-01-01

    We study a refinement of the A-polynomial in the case of the g-loop quiver. We give an explicit formula for its value at q=1. Conjecturally this implies a formula for the middle Betti number of the moduli space of Higgs bundles or equivalently of the character variety of a Riemann surface of genus g.

  20. Refining the classification criteria for primary Sjogren syndrome

    NARCIS (Netherlands)

    Vissink, Arjan; Bootsma, Hendrika

    2017-01-01

    The 2016 ACR-EULAR classification criteria for primary Sjogren syndrome, which are intended to facilitate uniform classification of patients for enrolment in clinical studies, combine features of previous criteria sets. These new criteria are a step in the right direction, but further refinement wou