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Sample records for californium 254 target

  1. Californium-252 progress, report No. 7, April 1971

    Energy Technology Data Exchange (ETDEWEB)

    1971-12-31

    This report contains discusses of the following topics on Californium-252: First sales of californium-252; encapsulation services discussed; three new participants in market evaluation program; summer training programs to use californium; Californium-252 shipping casks available; Californium-252 questions and answers, radiotherapy; neutron radiography; natural resources exploration; nuclear safeguards; process control; dosimetry; neutron radiography; neutron shielding; and nuclear safeguards.

  2. Historical review of californium-252 discovery and development

    Science.gov (United States)

    Stoddard, D. H.

    This paper discusses the discovery and history of californium 252. This isotope may be synthesized by irradiating plutonium 239, plutonium 242, americium 243, or curium 244 with neutrons in a nuclear reactor. Various experiments and inventions involving (252)Cf conducted at the Savannah River Plant are discussed. The evolution of radiotherapy using californium 252 is reviewed.

  3. Californium-252: a remarkable versatile radioisotope

    Energy Technology Data Exchange (ETDEWEB)

    Osborne-Lee, I.W.; Alexander, C.W.

    1995-10-10

    A product of the nuclear age, Californium-252 ({sup 252}Cf) has found many applications in medicine, scientific research, industry, and nuclear science education. Californium-252 is unique as a neutron source in that it provides a highly concentrated flux and extremely reliable neutron spectrum from a very small assembly. During the past 40 years, {sup 252}Cf has been applied with great success to cancer therapy, neutron radiography of objects ranging from flowers to entire aircraft, startup sources for nuclear reactors, fission activation for quality analysis of all commercial nuclear fuel, and many other beneficial uses, some of which are now ready for further growth. Californium-252 is produced in the High Flux Isotope Reactor (HFIR) and processed in the Radiochemical Engineering Development Center (REDC), both of which are located at the Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee. The REDC/HFIR facility is virtually the sole supplier of {sup 252}Cf in the western world and is the major supplier worldwide. Extensive exploitation of this product was made possible through the {sup 252}Cf Market Evaluation Program, sponsored by the United States Department of Energy (DOE) [then the Atomic Energy Commission (AEC) and later the Energy Research and Development Administration (ERDA)]. This program included training series, demonstration centers, seminars, and a liberal loan policy for fabricated sources. The Market Evaluation Program was instituted, in part, to determine if large-quantity production capability was required at the Savannah River Laboratory (SRL). Because of the nature of the product and the means by which it is produced, {sup 252}Cf can be produced only in government-owned facilities. It is evident at this time that the Oak Ridge research facility can meet present and projected near-term requirements. The production, shipment, and sales history of {sup 252}Cf from ORNL is summarized herein.

  4. Production, Distribution, and Applications of Californium-252 Neutron Sources

    Energy Technology Data Exchange (ETDEWEB)

    Balo, P.A.; Knauer, J.B.; Martin, R.C.

    1999-10-03

    The radioisotope {sup 252}Cf is routinely encapsulated into compact, portable, intense neutron sources with a 2.6-year half-life. A source the size of a person's little finger can emit up to 10{sup 11} neutrons/s. Californium-252 is used commercially as a reliable, cost-effective neutron source for prompt gamma neutron activation analysis (PGNAA) of coal, cement, and minerals, as well as for detection and identification of explosives, laud mines, and unexploded military ordnance. Other uses are neutron radiography, nuclear waste assays, reactor start-up sources, calibration standards, and cancer therapy. The inherent safety of source encapsulations is demonstrated by 30 years of experience and by U.S. Bureau of Mines tests of source survivability during explosions. The production and distribution center for the U. S Department of Energy (DOE) Californium Program is the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory (ORNL). DOE sells The radioisotope {sup 252}Cf is routinely encapsulated into compact, portable, intense neutron sources with a 2.6- year half-life. A source the size of a person's little finger can emit up to 10 neutrons/s. Californium-252 is used commercially as a reliable, cost-effective neutron source for prompt gamma neutron activation analysis (PGNAA) of coal, cement, and minerals, as well as for detection and identification of explosives, laud mines, and unexploded military ordnance. Other uses are neutron radiography, nuclear waste assays, reactor start-up sources, calibration standards, and cancer therapy. The inherent safety of source encapsulations is demonstrated by 30 years of experience and by U.S. Bureau of Mines tests of source survivability during explosions. The production and distribution center for the U. S Department of Energy (DOE) Californium Program is the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory(ORNL). DOE sells {sup 252}Cf to commercial

  5. Unusual structure, bonding and properties in a californium borate

    Energy Technology Data Exchange (ETDEWEB)

    Polinski, Matthew J.; Garner, Edward B.; Maurice, Rémi; Planas, Nora; Stritzinger, Jared T.; Parker, T. Gannon; Cross, Justin N.; Green, Thomas D.; Alekseev, Evgeny V.; Van Cleve, Shelley M.; Depmeier, Wulf; Gagliardi, Laura; Shatruk, Michael; Knappenberger, Kenneth L.; Liu, Guokui; Skanthakumar, S.; Soderholm, Lynda; Dixon, David A.; Albrecht-Schmitt, Thomas E.

    2014-03-23

    The participation of the valence orbitals of actinides in bonding has been debated for decades. Recent experimental and computational investigations demonstrated the involvement of 6p, 6d and/or 5f orbitals in bonding. However, structural and spectroscopic data, as well as theory, indicate a decrease in covalency across the actinide series, and the evidence points to highly ionic, lanthanide-like bonding for late actinides. Here we show that chemical differentiation between californium and lanthanides can be achieved by using ligands that are both highly polarizable and substantially rearrange on complexation. A ligand that suits both of these desired properties is polyborate. We demonstrate that the 5f, 6d and 7p orbitals are all involved in bonding in a Cf(III) borate, and that large crystal-field effects are present. Synthetic, structural and spectroscopic data are complemented by quantum mechanical calculations to support these observations.

  6. Extraction of Trivalent Actinides and Lanthanides from Californium Campaign Rework Solution Using TODGA-based Solvent Extraction System

    Energy Technology Data Exchange (ETDEWEB)

    Benker, Dennis [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Delmau, Laetitia Helene [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dryman, Joshua Cory [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-07-01

    This report presents the studies carried out to demonstrate the possibility of quantitatively extracting trivalent actinides and lanthanides from highly acidic solutions using a neutral ligand-based solvent extraction system. These studies stemmed from the perceived advantage of such systems over cationexchange- based solvent extraction systems that require an extensive feed adjustment to make a low-acid feed. The targeted feed solutions are highly acidic aqueous phases obtained after the dissolution of curium targets during a californium (Cf) campaign. Results obtained with actual Cf campaign solutions, but highly diluted to be manageable in a glove box, are presented, followed by results of tests run in the hot cells with Cf campaign rework solutions. It was demonstrated that a solvent extraction system based on the tetraoctyl diglycolamide molecule is capable of quantitatively extracting trivalent actinides from highly acidic solutions. This system was validated using actual feeds from a Cf campaign.

  7. 27 CFR 44.254 - Shipping containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Shipping containers. 44.254 Section 44.254 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Requirements § 44.254 Shipping containers. Each shipping case, crate, or other container, in which cigars are...

  8. 38 CFR 17.254 - Applications.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Applications. 17.254 Section 17.254 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Grants for Exchange of Information § 17.254 Applications. Each application for a grant shall be submitted to the Under...

  9. 36 CFR 254.25 - Survey.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Survey. 254.25 Section 254.25... National Forest Townsites § 254.25 Survey. The authorized Forest Service official shall conduct or provide for the necessary tract survey and boundary posting of National Forest System land. ...

  10. 20 CFR 632.254 - Program startup.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Program startup. 632.254 Section 632.254 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR INDIAN AND NATIVE AMERICAN EMPLOYMENT AND TRAINING PROGRAMS Summer Youth Employment and Training Programs § 632.254 Program startup...

  11. Biomedical neutron research at the Californium User Facility for neutron science

    Energy Technology Data Exchange (ETDEWEB)

    Martin, R.C. [Oak Ridge National Lab., TN (United States); Byrne, T.E. [Roane State Community College, Harriman, TN (United States); Miller, L.F. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-04-01

    The Californium User Facility for Neutron Science has been established at Oak Ridge National Laboratory (ORNL). The Californium User Facility (CUF) is a part of the larger Californium Facility, which fabricates and stores compact {sup 252}Cf neutron sources for worldwide distribution. The CUF can provide a cost-effective option for research with {sup 252}Cf sources. Three projects at the CUF that demonstrate the versatility of {sup 252}Cf for biological and biomedical neutron-based research are described: future establishment of a {sup 252}Cf-based neutron activation analysis system, ongoing work to produce miniature high-intensity, remotely afterloaded {sup 252}Cf sources for tumor therapy, and a recent experiment that irradiated living human lung cancer cells impregnated with experimental boron compounds to test their effectiveness for boron neutron capture therapy.

  12. Beyond Californium-A Neutron Generator Alternative for Dosimetry and Instrument Calibration in the U.S.

    Science.gov (United States)

    Piper, Roman K; Mozhayev, Andrey V; Murphy, Mark K; Thompson, Alan K

    2017-09-01

    Evaluations of neutron survey instruments, area monitors, and personal dosimeters rely on reference neutron radiations, which have evolved from the heavy reliance on (α,n) sources to a shared reliance on (α,n) and the spontaneous fission neutrons of californium-252 (Cf). Capable of producing high dose equivalent rates from an almost point source geometry, the characteristics of Cf are generally more favorable when compared to the use of (α,n) and (γ,n) sources or reactor-produced reference neutron radiations. Californium-252 is typically used in two standardized configurations: unmoderated, to yield a fission energy spectrum; or with the capsule placed within a heavy-water moderating sphere to produce a softened spectrum that is generally considered more appropriate for evaluating devices used in nuclear power plant work environments. The U.S. Department of Energy Cf Loan/Lease Program, a longtime origin of affordable Cf sources for research, testing and calibration, was terminated in 2009. Since then, high-activity sources have become increasingly cost-prohibitive for laboratories that formerly benefited from that program. Neutron generators, based on the D-T and D-D fusion reactions, have become economically competitive with Cf and are recognized internationally as important calibration and test standards. Researchers from the National Institute of Standards and Technology and the Pacific Northwest National Laboratory are jointly considering the practicality and technical challenges of implementing neutron generators as calibration standards in the U.S. This article reviews the characteristics of isotope-based neutron sources, possible isotope alternatives to Cf, and the rationale behind the increasing favor of electronically generated neutron options. The evaluation of a D-T system at PNNL has revealed characteristics that must be considered in adapting generators to the task of calibration and testing where accurate determination of a dosimetric quantity is

  13. 36 CFR 254.10 - Bargaining; arbitration.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bargaining; arbitration. 254... LANDOWNERSHIP ADJUSTMENTS Land Exchanges § 254.10 Bargaining; arbitration. (a) Unless the parties to an exchange... exchange, the appraisal(s), at the initiative of either party, must be submitted to arbitration, unless, in...

  14. Apparatus for the measurement of total body nitrogen using prompt neutron activation analysis with californium-252.

    Science.gov (United States)

    Mackie, A; Hannan, W J; Smith, M A; Tothill, P

    1988-01-01

    Details of clinical apparatus designed for the measurement of total body nitrogen (as an indicator of body protein), suitable for the critically ill, intensive-care patient are presented. Californium-252 radio-isotopic neutron sources are used, enabling a nitrogen measurement by prompt neutron activation analysis to be made in 40 min with a precision of +/- 3.2% for a whole body dose equivalent of 0.145 mSv. The advantages of Californium-252 over alternative neutron sources are discussed. A comparison between two irradiation/detection geometries is made, leading to an explanation of the geometry adopted for the apparatus. The choice of construction and shielding materials to reduce the count rate at the detectors and consequently to reduce the pile-up contribution to the nitrogen background is discussed. Salient features of the gamma ray spectroscopy system to reduce spectral distortion from pulse pile-up are presented.

  15. Safety Analysis Report for Packaging (SARP) of the Oak Ridge National Laboratory TRU Californium Shipping Container

    Energy Technology Data Exchange (ETDEWEB)

    Box, W.D.; Shappert, L.B.; Seagren, R.D.; Klima, B.B.; Jurgensen, M.C.; Hammond, C.R.; Watson, C.D.

    1980-01-01

    An analytical evaluation of the Oak Ridge National Laboratory TRU Californium Shipping Container was made in order to demonstrate its compliance with the regulations governing off-site shipment of packages that contain radioactive material. The evaluation encompassed five primary categories: structural integrity, thermal resistance, radiation shielding, nuclear criticality safety, and quality assurance. The results of this evaluation demonstrate that the container complies with the applicable regulations.

  16. 48 CFR 53.303-DD-254 - Department of Defense DD Form 254, Contract Security Classification Specification.

    Science.gov (United States)

    2010-10-01

    ... Illustrations of Forms 53.303-DD-254 Department of Defense DD Form 254, Contract Security Classification... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Department of Defense DD Form 254, Contract Security Classification Specification. 53.303-DD-254 Section 53.303-DD-254 Federal...

  17. cdc-25.4, a Caenorhabditis elegans Ortholog of cdc25, Is Required for Male Mating Behavior

    Directory of Open Access Journals (Sweden)

    Sangmi Oh

    2016-12-01

    Full Text Available Cell division cycle 25 (cdc25 is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25.4 mutant males. We also found that cdc-25.4 is expressed in many neuronal cells throughout development. The turning defect in cdc-25.4 mutant males was recovered by cdc-25.4 transgenic expression in neuronal cells, suggesting that cdc-25.4 functions in neurons for male mating. However, the neuronal morphology of cdc-25.4 mutant males appeared to be normal, as examined with several neuronal markers. Also, RNAi depletion of wee-1.3, a C. elegans ortholog of Wee1/Myt1 kinase, failed to suppress the mating defects of cdc-25.4 mutant males. These findings suggest that, for successful male mating, cdc-25.4 does not target cell cycles that are required for neuronal differentiation and development. Rather, cdc-25.4 likely regulates noncanonical substrates in neuronal cells.

  18. Dicty_cDB: CHR254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available CH (Link to library) CHR254 (Link to dictyBase) - - - Contig-U11845-1 | Contig-U13149-1 CHR...254P (Link to Original site) CHR254F 130 CHR254Z 620 CHR254P 730 - - Show CHR254 Library CH (Link to library) Clone ID CHR...45-1 | Contig-U13149-1 Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/CH/CHR2-C/CHR...254Q.Seq.d/ Representative seq. ID CHR254P (Link to Original site) Representative DNA sequence >CHR254 (CHR...254Q) /CSM/CH/CHR2-C/CHR254Q.Seq.d/ CNNAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAACCCCCCCCCNTTTTTTTT

  19. 36 CFR 254.2 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... disposal of National Forest System lands administered by the Secretary of Agriculture. Reserved interest... Secretary of the Interior to allow for the orderly administration of the Federal lands. Statement of value... ADJUSTMENTS Land Exchanges § 254.2 Definitions. For the purposes of this subpart, the following terms have the...

  20. 50 CFR 216.254 - Mitigation.

    Science.gov (United States)

    2010-10-01

    ... detecting marine mammals, detonation must be delayed until adequate sea conditions exist for aerial..., DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Taking Marine Mammals Incidental to Conducting Precision Strike Weapon Missions in the Gulf of Mexico § 216.254...

  1. 14 CFR 254.5 - Notice requirement.

    Science.gov (United States)

    2010-01-01

    ... REGULATIONS DOMESTIC BAGGAGE LIABILITY § 254.5 Notice requirement. In any flight segment using large aircraft... large aircraft, an air carrier shall provide to passengers, by conspicuous written material included on... passengers; or (b) The following notice: “Federal rules require any limit on an airline's baggage liability...

  2. 38 CFR 21.254 - Supportive services.

    Science.gov (United States)

    2010-07-01

    ...-employment as defined in § 21.257(b) if VA determines that the following conditions are met: (1) The...) VOCATIONAL REHABILITATION AND EDUCATION Vocational Rehabilitation and Employment Under 38 U.S.C. Chapter 31 Employment Services § 21.254 Supportive services. (a) General. Supportive services which may be provided...

  3. Inactivation of oxytocin by 254 nm radiation

    Energy Technology Data Exchange (ETDEWEB)

    Erndt, A.; Karolczyk-Kostuch, S.; Polaczek, E.

    1975-01-01

    Irradiation of oxytocin in diluted solutions with 254 nm light reduced markedly the hormone activity. The decrease in activity in the range between 0 and 20 percent was nearly proportional to the increase in sulfhydryl group concentration. In view of the fundamental role of cystyl residue in holding the oxytocin native backbone conformation the results suggest that disulfide bond cleavage makes an essential contribution to photoinactivation of this hormone under the conditions used.

  4. 36 CFR 254.11 - Exchanges at approximately equal value.

    Science.gov (United States)

    2010-07-01

    ... attributes; and (4) There are no significant elements of value requiring complex analysis. (b) The authorized... equal value. 254.11 Section 254.11 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE LANDOWNERSHIP ADJUSTMENTS Land Exchanges § 254.11 Exchanges at approximately equal value. (a) The...

  5. 29 CFR 1910.254 - Arc welding and cutting.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 5 2010-07-01 2010-07-01 false Arc welding and cutting. 1910.254 Section 1910.254 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Welding, Cutting and Brazing § 1910.254 Arc welding and cutting. (a... following limits shall not be exceeded: (i) Alternating-current machines (A) Manual arc welding and cutting...

  6. 36 CFR 254.34 - Mineral survey fractions.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Mineral survey fractions. 254... LANDOWNERSHIP ADJUSTMENTS Conveyance of Small Tracts § 254.34 Mineral survey fractions. (a) Mineral survey fractions subject to conveyance under this subpart are limited to those tracts which: (1) Cannot be...

  7. Application of TSH bioindicator for studying the biological efficiency of neutrons from californium-252 source

    Energy Technology Data Exchange (ETDEWEB)

    Cebulska-Wasilewska, A.; Rekas, K. [Institute of Nuclear Physics, Cracow (Poland); Kim, J.K. [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of)

    1997-12-31

    The effectiveness of neutrons from a Californium-252 source in the induction of various abnormalities in the Tradescantia clone 4430 stamen hair cells (TSH-assay) was studied. The special attention was paid to check whether any enhancement in effects caused by process of boron neutron capture is visible in the cells enriched with boron ions. Two chemicals (borax and BSH) were applied to introduce boron-10 ions into cells. Inflorescence, normal or pretreated with chemicals containing boron, were irradiated in the air with neutrons from a Cf-252 source at KAERI, Taejon, Korea. To estimate the relative biological effectiveness (RBE) in the induction of gene mutations of the neutron beam under the study, Tradescantia inflorescences, without any chemical pretreatment, were irradiated with various doses of X-rays. The ranges of radiation doses used were 0-0.1 Gy in neutrons and 0-0.5 Gy in X-rays. After the time needed to complete the postirradiation repair Tradescantia cuttings were transferred to Cracow, where screening of gene and lethal; mutations, cell cycle alterations in somatic cells have been done, and dose response relationships were figured. The maximal RBE values were estimated in the range of 4.6-6.8. Alterations of RBE value were observed; from 6.8 to 7.8 in the case of plants pretreated with 240 ppm of B-10 from borax, and 4.6 to 6.1 in the case of 400 ppm of B-10 from BSH. Results showed a slight, although statistically insignificant increase in biological efficacy of radiation from the Cf-252 source in samples pretreated with boron containing chemicals. (author)

  8. Study of the shielding for spontaneous fission sources of Californium-252; Estudio de blindaje para fuentes de fision espontanea de Californio-252

    Energy Technology Data Exchange (ETDEWEB)

    Davila R, I

    1991-06-15

    A shielding study is made to attenuate, until maximum permissible levels, the neutrons radiation and photons emitted by spontaneous fission coming from a source of Californium-252. The compound package by a database (Library DLC-23) and the ANISNW code is used, in it version for personal computer. (Author)

  9. Susceptibility to Stress Corrosion Cracking of 254SMO SS

    Directory of Open Access Journals (Sweden)

    De Micheli Lorenzo

    2002-01-01

    Full Text Available The susceptibility to stress corrosion cracking (SCC of solubilized and sensitized 254SMO SS was studied in sodium chloride, and sodium fluoride solutions at 80 °C and sulfuric acid solutions in presence of sodium chloride at 25 °C. The influence of salt concentration, pH values and the addition of thiosulfate was examined. The susceptibility to SCC was evaluated by Slow Strain Rate Tests (SSRT, at 1.5 x 10-6 s-1 strain rate. The behavior of 254SMO was compared to those of AISI 316L SS and Hastelloy C276. 254SMO showed an excellent resistance to SCC in all conditions, except in the more acidic solutions (pH <= 1 where, in the sensitized conditions, intergranular stress corrosion cracking occurred.

  10. Simulation and design of an electron beam ion source charge breeder for the californium rare isotope breeder upgrade

    Directory of Open Access Journals (Sweden)

    Clayton Dickerson

    2013-02-01

    Full Text Available An electron beam ion source (EBIS will be constructed and used to charge breed ions from the californium rare isotope breeder upgrade (CARIBU for postacceleration into the Argonne tandem linear accelerator system (ATLAS. Simulations of the EBIS charge breeder performance and the related ion transport systems are reported. Propagation of the electron beam through the EBIS was verified, and the anticipated incident power density within the electron collector was identified. The full normalized acceptance of the charge breeder with a 2 A electron beam, 0.024π  mm mrad for nominal operating parameters, was determined by simulating ion injection into the EBIS. The optics of the ion transport lines were carefully optimized to achieve well-matched ion injection, to minimize emittance growth of the injected and extracted ion beams, and to enable adequate testing of the charge bred ions prior to installation in ATLAS.

  11. Californium-252 Brachytherapy Combined With External-Beam Radiotherapy for Cervical Cancer: Long-Term Treatment Results

    Energy Technology Data Exchange (ETDEWEB)

    Lei Xin; Qian Chengyuan; Qing Yi; Zhao Kewei; Yang Zhengzhou; Dai Nan; Zhong Zhaoyang; Tang Cheng; Li Zheng; Gu Xianqing; Zhou Qian; Feng Yan; Xiong Yanli; Shan Jinlu [Cancer Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing (China); Wang Dong, E-mail: dongwang64@hotmail.com [Cancer Center, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing (China)

    2011-12-01

    Purpose: To observe, by retrospective analysis, the curative effects and complications due to californium-252 ({sup 252}Cf) neutron intracavitary brachytherapy (ICBT) combined with external-beam radiotherapy (EBRT) in the treatment of cervical cancer. Methods and Materials: From February 1999 to December 2007, 696 patients with cervical cancer (Stages IB to IIIB) were treated with {sup 252}Cf-ICBT in combination of EBRT. Of all, 31 patients were at Stage IB, 104 at IIA, 363 at IIB, 64 at IIIA, and 134 at IIIB. Californium-252 ICBT was delivered at 7-12 Gy per insertion per week, with a total dose of 29-45 Gy to reference point A in three to five insertions. The whole pelvic cavity was treated with 8-MV X-ray external irradiation at 2 Gy per fraction, four times per week. After 16-38 Gy of external irradiation, the center of the whole pelvic field was blocked with a 4-cm-wide lead shield, with a total external irradiation dose of 44-56 Gy. The total treatment course was 5 to 6 weeks. Results: Overall survival rate at 3 and 5 years for all patients was 76.0% and 64.9%, respectively. Disease-free 3- and 5-year survival rates of patients were 71.2% and 58.4%, respectively. Late complications included vaginal contracture and adhesion, radiation proctitis, radiation cystitis, and inflammatory bowel, which accounted for 5.8%, 7.1%, 6.2%, and 4.9%, respectively. Univariate analysis results showed significant correlation of stage, age, histopathologic grade, and lymph node status with overall survival. Cox multiple regression analysis showed that the independent variables were stage, histopathologic grade, tumor size, and lymphatic metastasis in all patients. Conclusion: Results of this series suggest that the combined use of {sup 252}Cf-ICBT with EBRT is an effective method for treatment of cervical cancer.

  12. 7 CFR 1220.254 - Patents, copyrights, inventions, and publications.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, and publications... Miscellaneous § 1220.254 Patents, copyrights, inventions, and publications. (a) Any patents, copyrights..., franchising, or other uses of such patents, copyrights, inventions, or publications, inure to the benefit of...

  13. 19 CFR 10.254 - Certificate of Origin.

    Science.gov (United States)

    2010-04-01

    ... article described in § 10.253(a) being exported from an ATPDEA beneficiary country to the United States... TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. Andean Trade Promotion and Drug Eradication Act Extension of Atpa Benefits to Tuna and Certain Other Non-Textile Articles § 10.254 Certificate...

  14. Cold valleys in the radioactive decay of 248−254Cf isotopes

    Indian Academy of Sciences (India)

    Geiger–Nuttal plots of log10(T1/2) vs. Q−1/2 for 48−52Ca emitting from various californium isotopes. Acknowledgement. One of the authors (KPS) would like to thank University Grants Commis- sion, Govt. of India for the financial support under project No. MRP(S)-. 352/2005(X Plan)/KLKA 002/UGC-SWRO. References.

  15. Photodegradation and ecotoxicology of acyclovir in water under UV254and UV254/H2O2processes.

    Science.gov (United States)

    Russo, Danilo; Siciliano, Antonietta; Guida, Marco; Galdiero, Emilia; Amoresano, Angela; Andreozzi, Roberto; Reis, Nuno M; Li Puma, Gianluca; Marotta, Raffaele

    2017-10-01

    The photochemical and ecotoxicological fate of acyclovir (ACY) through UV 254 direct photolysis and in the presence of hydroxyl radicals (UV 254 /H 2 O 2 process) were investigated in a microcapillary film (MCF) array photoreactor, which provided ultrarapid and accurate photochemical reaction kinetics. The UVC phototransformation of ACY was found to be unaffected by pH in the range from 4.5 to 8.0 and resembled an apparent autocatalytic reaction. The proposed mechanism included the formation of a photochemical intermediate (ϕ ACY  = (1.62 ± 0.07)·10 -3  mol ein -1 ) that further reacted with ACY to form by-products (k' = (5.64 ± 0.03)·10 -3  M -1  s -1 ). The photolysis of ACY in the presence of hydrogen peroxide accelerated the removal of ACY as a result of formation of hydroxyl radicals. The kinetic constant for the reaction of OH radicals with ACY (k OH/ACY ) determined with the kinetic modeling method was (1.23 ± 0.07)·10 9  M -1  s -1 and with the competition kinetics method was (2.30 ± 0.11)·10 9  M -1  s -1 with competition kinetics. The acute and chronic effects of the treated aqueous mixtures on different living organisms (Vibrio fischeri, Raphidocelis subcapitata, D. magna) revealed significantly lower toxicity for the samples treated with UV 254 /H 2 O 2 in comparison to those collected during UV 254 treatment. This result suggests that the addition of moderate quantity of hydrogen peroxide (30-150 mg L -1 ) might be a useful strategy to reduce the ecotoxicity of UV 254 based sanitary engineered systems for water reclamation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Phenotype abnormality: 254 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available 254 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u760i delayed whole p...lant flowering stage in presence of gibberellin in presence of gibberellins http://metadb.riken.jp/db/SciNetS_ria224i/cria224u2ria224u46i ... delayed ... whole plant flowering stage ...

  17. 16 CFR 254.3 - Misrepresentation of extent or nature of accreditation or approval.

    Science.gov (United States)

    2010-01-01

    ... to an accredited institution of higher education. (b) It is deceptive for an industry member to... accreditation or approval. 254.3 Section 254.3 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES FOR PRIVATE VOCATIONAL AND DISTANCE EDUCATION SCHOOLS § 254.3 Misrepresentation of...

  18. 47 CFR 1.254 - Nature of the hearing; burden of proof.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Nature of the hearing; burden of proof. 1.254 Section 1.254 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Hearing Proceedings Hearing and Intermediate Decision § 1.254 Nature of the hearing; burden of proof. Any hearing upon...

  19. 37 CFR 2.54 - Requirements for drawings submitted on paper.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Requirements for drawings submitted on paper. 2.54 Section 2.54 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES Drawing § 2.54 Requirements for...

  20. Long-term effects of an intracavitary treatment with californium-252 on normal tissue. [Swine, /sup 226/Ra

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, M.F.; Beamer, J.L.; Mahony, T.D.; Cross, F.T.; Lund, J.E.; Endres, G.W.R.

    1976-01-01

    About one hundred fifty swine were exposed to either radium-226 or californium-252 sources in the uterine cervix to determine an RBE for both acute and long-term effects. That value for early changes in the tissues at risk in the treatment of cervical cancer was between 6.2 and 6.8. The incidence of complications increased with time after exposure, especially among animals treated with /sup 252/Cf. Analysis of rectal injury showed that ulceration occurred frequently within a year postexposure at doses between 1600 and 2400 rad calculated at 2 cm lateral to the source midline. Fat necrosis and smooth muscle atrophy, resulting in a local rectal stricture, were delayed changes observed in some animals. The lower ureter was the site for a greater frequency of complications than the GI tract. Ureteral stricture often occurred at doses of 1200 rad from /sup 252/Cf and 7000 rad from /sup 226/Ra. Observation of delayed effects in the uterine-cervix in animals held up to 4 years postexposure indicate that the RBE for /sup 252/Cf may be increased to a value as high as 18, while repair may have even decreased it to about 5.6 in the rectum. Fifty swine are still being observed for long-term effects after doses above 800 rad from /sup 252/Cf and 5000 rad from /sup 226/Ra.

  1. Ab initio full-potential study of mechanical properties and magnetic phase stability of californium monopnictides (CfN and CfP)

    Energy Technology Data Exchange (ETDEWEB)

    Amari, S., E-mail: siham_amari@yahoo.fr [Faculté des Sciences de la Nature et de la Vie, Université Hassiba Benbouali, Chlef, 02000 (Algeria); Bouhafs, B. [Laboratoire de Modélisation et Simulation en Sciences des Matériaux, Université Djillali Liabès de Sidi Bel-Abbés, Sidi Bel-Abbés, 22000 (Algeria)

    2016-09-15

    Based on the first-principles methods, the structural, elastic, electronic, properties and magnetic ordering of californium monopnictides CfX (X = P) have been studied using the full-potential augmented plane wave plus local orbitals (FP-L/APW + lo) method within the framework of density functional theory (DFT). The electronic exchange correlation energy is described by generalized gradient approximation GGA and GGA+U (U is the Hubbard correction). The GGA+U method is applied to the rare-earth 5f states. We have calculated the lattice parameters, bulk modulii and the first pressure derivatives of the bulk modulii. The elastic properties of the studied compounds are only investigated in the most stable calculated phase. In order to gain further information, we have calculated Young’s modulus, shear modulus, anisotropy factor and Kleinman parameter by the aid of the calculated elastic constants. The results mainly show that californium monopnictides CfX (X = P) have an antiferromagnetic spin ordering. Density of states (DOS) and charge densities for both compounds are also computed in the NaCl (B1) structure.

  2. Low-Dose-Rate Californium-252 Neutron Intracavitary Afterloading Radiotherapy Combined With Conformal Radiotherapy for Treatment of Cervical Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Min [Department of Oncology, Armed Police Hospital of Hangzhou, Hangzhou, Zhejiang Province (China); Xu Hongde [Cancer Center, Armed Police Hospital of Hangzhou, Hangzhou, Zhejiang Province (China); Pan Songdan; Lin Shan; Yue Jianhua [Department of Oncology, Armed Police Hospital of Hangzhou, Hangzhou, Zhejiang Province (China); Liu Jianren, E-mail: liujianren0571@hotmail.com [Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province (China)

    2012-07-01

    Purpose: To study the efficacy of low-dose-rate californium-252 ({sup 252}Cf) neutron intracavitary afterloading radiotherapy (RT) combined with external pelvic RT for treatment of cervical cancer. Methods and Materials: The records of 96 patients treated for cervical cancer from 2006 to 2010 were retrospectively reviewed. For patients with tumors {<=}4 cm in diameter, external beam radiation was performed (1.8 Gy/day, five times/week) until the dose reached 20 Gy, and then {sup 252}Cf neutron intracavitary afterloading RT (once/week) was begun, and the frequency of external beam radiation was changed to four times/week. For patients with tumors >4 cm, {sup 252}Cf RT was performed one to two times before whole-pelvis external beam radiation. The tumor-eliminating dose was determined by using the depth limit of 5 mm below the mucosa as the reference point. In all patients, the total dose of the external beam radiation ranged from 46.8 to 50 Gy. For {sup 252}Cf RT, the dose delivered to point A was 6 Gy/fraction, once per week, for a total of seven times, and the total dose was 42 Gy. Results: The mean {+-} SD patient age was 54.7 {+-} 13.7 years. Six patients had disease assessed at stage IB, 13 patients had stage IIA, 49 patients had stage IIB, 3 patients had stage IIIA, 24 patients had stage IIIB, and 1 patient had stage IVA. All patients obtained complete tumor regression (CR). The mean {+-} SD time to CR was 23.5 {+-} 3.4 days. Vaginal bleeding was fully controlled in 80 patients within 1 to 8 days. The mean {+-} SD follow-up period was 27.6 {+-} 12.7 months (range, 6-48 months). Five patients died due to recurrence or metastasis. The 3-year survival and disease-free recurrence rates were 89.6% and 87.5 %, respectively. Nine patients experienced mild radiation proctitis, and 4 patients developed radiocystitis. Conclusions: Low-dose-rate {sup 252}Cf neutron RT combined with external pelvic RT is effective for treating cervical cancer, with a low incidence of

  3. 29 CFR 25.4 - Contents of requests; service on other parties; answer; intervention.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Contents of requests; service on other parties; answer; intervention. 25.4 Section 25.4 Labor Office of the Secretary of Labor RULES FOR THE NOMINATION OF ARBITRATORS...; intervention. (a) Requests for nominations 1 shall be in triplicate and contain the following information: 1...

  4. 48 CFR 53.303-254-53.303-347 - Illustration of agency forms.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Illustration of agency... FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES AND FORMS FORMS Illustrations of Forms 53.303-254—53.303-347 Illustration of agency forms. Editorial Note: The forms appearing in sections 53.303-DD-254...

  5. 48 CFR 53.204-1 - Safeguarding classified information within industry (DD Form 254, DD Form 441).

    Science.gov (United States)

    2010-10-01

    ... information within industry (DD Form 254, DD Form 441). 53.204-1 Section 53.204-1 Federal Acquisition....204-1 Safeguarding classified information within industry (DD Form 254, DD Form 441). The following... specified in subpart 4.4 and the clause at 52.204-2: (a) DD Form 254 (Department of Defense (DOD)), Contract...

  6. 30 CFR 254.46 - Whom do I notify if an oil spill occurs?

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Whom do I notify if an oil spill occurs? 254.46... Outer Continental Shelf Facilities § 254.46 Whom do I notify if an oil spill occurs? (a) You must immediately notify the National Response Center (1-800-424-8802) if you observe: (1) An oil spill from your...

  7. Degradation of highly consumed fluoroquinolones, penicillins and cephalosporins in distilled water and simulated hospital wastewater by UV254 and UV254/persulfate processes.

    Science.gov (United States)

    Serna-Galvis, Efraím A; Ferraro, Franklin; Silva-Agredo, Javier; Torres-Palma, Ricardo A

    2017-10-01

    In this work, three penicillins (ampicillin "AMP", oxacillin "OXA" and cloxacillin "CLO"), two cephalosporins (cephalexin "CPX" and cephadroxyl "CPD") and three fluoroquinolones (levofloxacin "LEV", norfloxacin "NOR" and ciprofloxacin "CIP") were initially treated by UV254 and persulfate activated by UV254 (UV/PS). Significant differences in degradation kinetics under UV254 irradiation were found. Photodegradation followed the order: OXA > CPX > CPD > CLO > CIP > NOR > AMP ≫ LEV. Then, in order to study the participation of direct photolysis and reactive oxygen species (ROS) in photodegradation a model antibiotic of each class (OXA, CPX and CIP) was considered. OXA and CPX were mainly degraded by direct photolysis, whereas the CIP removal involved ROS and photolysis. On the other hand, the persulfate addition (UV/PS process) improved the removals due to sulfate radical formation, especially, in the case of antibiotics with lower photodegradation levels (i.e. LEV, AMP and NOR). Computational calculations on the representative antibiotics were applied to determine the regions susceptible to electrophilic attacks by degrading agents. The functional groups of OXA and CPX followed the reactivity order: thioether ≫ β-lactam ring > benzene ring. For CIP, the piperazyl moiety presented higher reactivity than the quinolone ring. Also, the antimicrobial activity (AA) evolution during the treatments was tested. In the cases of CPX and CIP, both UV254 and UV/PS removed the AA; which were associated with structural changes in their reactive moieties: β-lactam ring and piperazyl ring, respectively. However, in the case of OXA only the UV/PS system decreased AA, which was attributed to transformations in its penicillin electron-rich nucleus (thioether + β-lactam). Finally, the applicability of UV254 and UV/PS was assessed using synthetic hospital wastewater (HWW). The processes comparison showed that for practical purposes, OXA and CIP in HWW should be

  8. Cross section limits for the Cm248(Mg25,4n-5n)Hs268,269 reactions

    Science.gov (United States)

    Dvorak, J.; Brüchle, W.; Düllmann, Ch. E.; Dvorakova, Z.; Eberhardt, K.; Eichler, R.; Jäger, E.; Nagame, Y.; Qin, Z.; Schädel, M.; Schausten, B.; Schimpf, E.; Schuber, R.; Semchenkov, A.; Thörle, P.; Türler, A.; Wegrzecki, M.; Yakushev, A.

    2009-03-01

    We report on an attempt to produce and detect Hs268 and Hs269 in the nuclear fusion reaction Mg25+Cm248 using the gas phase chemistry apparatus COMPACT. No decay chains attributable to the decay of hassium isotopes were observed during the course of this experiment. From the nonobservation of Hs269 we derive a cross section limit of 0.4 pb (63% confidence limit) for the reaction Cm248(Mg25,4n)Hs269 at a center-of-target beam energy of 140 MeV. The evaluated cross section limit for the Cm248(Mg25,5n)Hs268 reaction depends on the assumed half-life of unknown Hs268. Current systematics of the half-lives for even-even Hs isotopes suggests a value of 0.5 s, resulting in a cross section limit of 1.3 pb.

  9. Enhanced escape rate for Hg 254 nm resonance radiation in fluorescent lamps

    Science.gov (United States)

    Lawler, James E.; Raizen, Mark G.

    2013-10-01

    The potential of the low-cost MAGIS isotopic separation method to improve fluorescent lamp efficacy is explored using resonance radiation transport simulations. New Hg isotopic mixes are discovered that yield escape rates for 254 nm Hg I resonance radiation equal to 117% to 122% of the rate for a natural isotopic mix under the same lamp conditions.

  10. 6 CFR 25.4 - Designation of qualified anti-terrorism technologies.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Designation of qualified anti-terrorism... REGULATIONS TO SUPPORT ANTI-TERRORISM BY FOSTERING EFFECTIVE TECHNOLOGIES § 25.4 Designation of qualified anti-terrorism technologies. (a) General. The Under Secretary may Designate as a Qualified Anti-Terrorism...

  11. Cold valleys in the radioactive decay of 248− 254Cf isotopes

    Indian Academy of Sciences (India)

    Based on the concept of cold valley in cold fission and fusion, we have investigated the cluster decay process in 248-254Cf isotopes. In addition to alpha particle minima, other deep minima occur for S, Ar and Ca clusters. It is found that inclusion of proximity potential does not change the position of minima but minima ...

  12. Californium-252 neutron intracavity brachytherapy alone for T1N0 low-lying rectal adenocarcinoma: A definitive anal sphincter-preserving radiotherapy

    Science.gov (United States)

    Xiong, Yanli; Shan, Jinlu; Liu, Jia; Zhao, Kewei; Chen, Shu; Xu, Wenjing; Zhou, Qian; Yang, Mei; Lei, Xin

    2017-01-01

    This study evaluated the 4-year results of 32 patients with T1N0 low-lying rectal adenocarcinoma treated solely with californium-252 (Cf-252) neutron intracavity brachytherapy (ICBT). Patients were solicited into the study from January 2008 to June 2011. All the patients had refused surgery or surgery was contraindicated. The patients were treated with Cf-252 neutron ICBT using a novel 3.5-cm diameter off-axis 4-channel intrarectal applicator designed by the authors. The dose reference point was defined on the mucosa surface, with a total dose of 55–62 Gy-eq/4 f (13–16 Gy-eq/f/wk). All the patients completed the radiotherapy in accordance with our protocol. The rectal lesions regressed completely, and the acute rectal toxicity was mild (≤G2). The 4-year local control, overall survival, disease-free survival, and late complication (≥G2) rates were 96.9%, 90.6%, 87.5% and 15.6%, respectively. No severe late complication (≥G3) occurred. The mean follow-up was 56.1 ± 16.0 months. At the end of last follow-up, 29 patients remained alive. The mean survival time was 82.1 ± 2.7 months. Cf-252 neutron ICBT administered as the sole treatment (without surgery) for patients with T1N0 low-lying rectal adenocarcinoma is effective with acceptable late complications. Our study and method offers a definitive anal sphincter-preserving radiotherapy for T1N0 low-lying rectal adenocarcinoma patients. PMID:28094790

  13. Coulomb dissociation of {sup 8}B at 254 A MeV

    Energy Technology Data Exchange (ETDEWEB)

    Suemmerer, K.; Boue, F.; Baumann, T.; Geissel, H.; Hellstroem, M.; Koczon, P.; Schwab, E.; Schwab, W.; Senger, P.; Surowiecz, A. [Gesellschaft fuer Schwerionenforschung (GSI), Darmstadt (Germany); Iwasa, N.; Ozawa, A. [Gesellschaft fuer Schwerionenforschung (GSI), Darmstadt (Germany)]|[RIKEN Institute of Physical and Chemical Research, Saitama (Japan); Surowka, G. [Gesellschaft fuer Schwerionenforschung (GSI), Darmstadt (Germany)]|[Jagiellonian Univ., Krakow (Poland). Inst. of Physics; Blank, B.; Czajkowski, S.; Marchand, C.; Pravikoff, M.S. [Centre d`Etudes Nucleaires de Bordeaux-Gradignan, 33 (France); Foerster, A.; Lauer, F.; Oeschler, H.; Speer, J.; Sturm, C.; Uhlig, F.; Wagner, A. [Technische Univ. Darmstadt (Germany); Gai, M. [Connecticut Univ., Storrs, CT (United States). Dept. of Physics; Grosse, E. [Inst. fuer Kern- und Hadronenphysik, Forschungszentrum Rossendorf, Dresden (Germany); Kohlmeyer, B. [Philipps Univ., Marburg (Germany). Fachbereich Physik; Kulessa, R.; Walus, W. [Jagiellonian Univ., Krakow (Poland). Inst. of Physics; Motobayashi, T. [Rikkyo Univ., Tokyo (Japan). Dept. of Physics; Teranishi, T. [RIKEN Institute of Physical and Chemical Research, Saitama (Japan)

    1998-06-01

    As an alternative method for determining the astrophysical S-factor for the {sup 7}Be(p,{gamma}){sup 8}B reaction we have measured the Coulomb dissociation of {sup 8}B at 254 A MeV. From our preliminary results, we obtain good agreement with both the accepted direct-reaction measurements and the low-energy Coulomb dissociation study of Iwasa et al. performed at about 50 A MeV. (orig.)

  14. Ferric ion mediated photochemical decomposition of perfluorooctanoic acid (PFOA) by 254 nm UV light

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yuan [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Science, Chinese Academy of Science, Beijing 100085 (China); Department of Environmental Science and Engineering, Tsinghua University, Beijing 100084 (China); Zhang Pengyi [Department of Environmental Science and Engineering, Tsinghua University, Beijing 100084 (China)], E-mail: zpy@tsinghua.edu.cn; Pan Gang; Chen Hao [State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Science, Chinese Academy of Science, Beijing 100085 (China)

    2008-12-15

    The great enhancement of ferric ion on the photochemical decomposition of environmentally persistent perfluorooctanoic acid (PFOA) under 254 nm UV light was reported. In the presence of 10 {mu}M ferric ion, 47.3% of initial PFOA (48 {mu}M) was decomposed and the defluorination ratio reached 15.4% within 4 h reaction time. While the degradation and defluorination ratio greatly increased to 80.2% and 47.8%, respectively, when ferric ion concentration increased to 80 {mu}M, and the corresponding half-life was shortened to 103 min. Though the decomposition rate was significantly lowered under nitrogen atmosphere, PFOA was efficiently decomposed too. Other metal ions like Cu{sup 2+} and Zn{sup 2+} also slightly improved the photochemical decomposition of PFOA under irradiation of 254 nm UV light. Besides fluoride ion, other intermediates during PFOA decomposition including formic acid and five shorter-chain perfluorinated carboxylic acids (PFCAs) with C7, C6, C5, C4 and C3, respectively, were identified and quantified by IC or LC/MS. The mixture of PFOA and ferric ion had strong absorption around 280 nm. It is proposed that PFOA coordinates with ferric ion to form a complex, and its excitation by 254 nm UV light leads to the decomposition of PFOA in a stepwise way.

  15. Bibliography of ground-water references for all 254 counties in Texas, 1886-2001

    Science.gov (United States)

    Baker, E.T.

    2005-01-01

    PrefaceThis bibliography comprises more than 10,000 citations of ground-water references involving all 254 counties in Texas. The reference citations date from 1886 and extend into 2001. Publications and reports from more than 30 agencies, universities, water districts, geological societies, cities, consultants, and private publication outlets are included in the bibliography. The bibliographic listing is, first, alphabetical by county and, second, chronological by date of the report, from oldest to most recent. The passing years have seen a proliferation in both published and unpublished reports, and such proliferation continues to expand at an accelerating pace. All 254 counties have had groundwater studies, either cursory or detailed. Investigation and development of the ground-water resources of the State of Texas resulted in reports that appear in a variety of formats, including Federal, State, and local agency reports; scholarly, professional, and trade journals; conference proceedings; guidebooks; maps; and theses and dissertations. The end result for the person seeking ground-water information about specific Texas counties is the increasing difficulty in locating pertinent data among the many and diverse ground-water reports in which the information is recorded. This bibliography, covering a span of 115 years, should have considerable utility in guiding those individuals seeking ground-water information.

  16. Action spectra (254-302 nm) for four human photosensitive cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Coohill, T.P.; Moore, S.P.; Grider, R.A. (Western Kentucky Univ., Bowling Green (USA))

    1983-07-01

    The inactivation of cellular viral capacity for Herpes simplex type I growth in six separate wavelengths (254-302 nm) was measured in five human cell lines. These consisted of one ''normal''-skin fibroblast line (KD), and four photosensitive lines. Two lines of Xeroderma pigmentosum, one of Bloom's syndrome, and one of Cockayne's syndrome cells were used. Similar relative sensitivity were observed for the Bloom's syndrome. Xeroderma pigmentosum, and normal cell lines. The Cockayne's syndrome-line became relatively more sensitive at 289 nm and longer wavelengths. Absolute sensitivities varied. Some divergence in response was noted at the longest wavelength tested, 302 nm.

  17. Printed wax masks for 254 nm deep-UV pattering of PMMA-based microfluidics

    KAUST Repository

    Fan, Yiqiang

    2012-01-13

    This paper reports a new technique for masking deep-UV exposure of poly(methyl methacrylate) (PMMA) using a printed wax mask. This technique provides an inexpensive and bulk fabrication method for PMMA structures. The technique involves the direct printing of the mask onto a polymer sheet using a commercial wax printer. The wax layer was then transferred to a PMMA substrate using a thermal laminator, exposed using deep-UV (with a wavelength of 254 nm), developed in an IPA:water solution, and completed by bonding on a PMMA cap layer. A sample microfluidic device fabricated with this method is also presented, with the microchannel as narrow as 50 μm. The whole process is easy to perform without the requirement for any microfabrication facilities. © 2012 IOP Publishing Ltd.

  18. Kinetics and mechanism investigation on the destruction of oxytetracycline by UV-254 nm activation of persulfate

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yiqing [Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu 611756 (China); Environmental Engineering and Science Program, University of Cincinnati, Cincinnati, OH 45221-0012 (United States); He, Xuexiang [Environmental Engineering and Science Program, University of Cincinnati, Cincinnati, OH 45221-0012 (United States); Fu, Yongsheng [Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu 611756 (China); Dionysiou, Dionysios D., E-mail: dionysios.d.dionysiou@uc.edu [Environmental Engineering and Science Program, University of Cincinnati, Cincinnati, OH 45221-0012 (United States)

    2016-03-15

    Highlights: • The most effective destruction of OTC by UV/PS was achieved at near neutral pH. • Deprotonated HOTC{sup −} had the highest second-order rate constant with SO{sub 4}·{sup −}. • Presence of HCO{sub 3}{sup −} or Cu{sup 2+} enhanced the removal of OTC in UV/PS system. • Total organic carbon was degraded slowly during the mineralization of OTC. • Studies on the degradation mechanism revealed four different reaction pathways. - Abstract: Oxytetracycline (OTC), an important broad-spectrum antibiotic, has been detected extensively in various environmental systems, which may have a detrimental impact on ecosystem and human health through the development of drug resistant bacteria and pathogens. In this study, the degradation of OTC was evaluated by UV-254 nm activated persulfate (PS). The observed UV fluence based pseudo first-order rate constant (k{sub obs}) was found to be the highest at near neutral pH conditions (pH 5.5–8.5). Presence of various natural water constituents had different effects on OTC degradation, with a significant enhancement in the presence of bicarbonate or Cu{sup 2+}. Limited elimination of total organic carbon (TOC) and PS was observed during the mineralization of OTC. Transformation byproducts in the presence and absence of hydroxyl radical scavenging agent tert-butanol (t-BuOH) were identified using ultra-high definition accurate-mass quadrupole time-of-flight liquid chromatography/mass spectrometer (LC-QTOF/MS). Potential OTC degradation mechanism was subsequently proposed revealing four different reaction pathways by SO{sub 4}·{sup −} reaction including hydroxylation (+16 Da), demethylation (−14 Da), decarbonylation (−28 Da) and dehydration (−18 Da). This study suggests that UV-254 nm/PS is a promising treatment technology for the control of water pollution caused by emerging contaminants such as OTC.

  19. Spitzer Observations of the Massive Star-forming Complex S254-S258: Structure and Evolution

    Science.gov (United States)

    Chavarría, Luis A.; Allen, Lori E.; Hora, Joseph L.; Brunt, Christopher M.; Fazio, Giovanni G.

    2008-07-01

    We present Spitzer IRAC, NOAO 2.1 m Flamingos, Keck NIRC, and FCRAO SEQUOIA observations of the massive star-forming complex S254-S258, covering an area of 25' × 20'. Using a combination of the IRAC and NIR data, we identify and classify the young stellar objects (YSOs) in the complex. We detect 510 sources with near- or mid-IR excess, and we classify 87 Class I and 165 Class II sources. The YSOs are found in clusters surrounded by isolated YSOs in a low-density distributed population. The ratio of clustered to total YSOs is 0.8. We identify six new clusters in the complex. One of them, G192.63-00, is located around the ionizing star of the H II region S255. We hypothesize that the ionizing star of S255 was formed in this cluster. We also detect a southern component of the cluster in H II region S256. The cluster G192.54-0.15, located inside H II region S254 has a VLSR of 17 km s-1 with respect to the main cloud, and we conclude that it is located in the background of the complex. The structure of the molecular cloud is examined using 12CO and 13CO , as well as a near-IR extinction map. The main body of the molecular cloud has VLSR between 5 and 9 km s-1. The arc-shaped structure of the molecular cloud following the border of the H II regions and the high column density in the border of the H II regions support the idea that the material has been swept up by the expansion of the H II regions.

  20. Californium-252 Program Equipment Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Chattin, Fred Rhea [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wilson, Kenton [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ezold, Julie G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-12-01

    To successfully continue the 252Cf production and meet the needs of the customers, a comprehensive evaluation of the Building 7920 processing equipment was requested to identify equipment critical to the operational continuity of the program.

  1. Yeast Interacting Proteins Database: YOR269W, YLR254C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available hway; targets dynein to microtubule tips, which is necessary for sliding of microtubules along bud cortex; s...tin pathway; targets dynein to microtubule tips, which is necessary for sliding of microtubules along bud co

  2. A prospective study on time to recovery in 254 injured novice runners.

    Directory of Open Access Journals (Sweden)

    Rasmus Oestergaard Nielsen

    Full Text Available Describe the diagnoses and the time to recovery of running-related injuries in novice runners.Prospective cohort study on injured runners.This paper is a secondary data analysis of a 933-person cohort study (DANO-RUN aimed at characterizing risk factors for injury in novice runners. Among those sustaining running-related injuries, the types of injuries and time to recovery is described in the present paper. All injured runners were diagnosed after a thorough clinical examination and then followed prospectively during their recovery. If they recovered completely from injury, time to recovery of each injury was registered.A total of 254 runners were injured. The proportion of runners diagnosed with medial tibial stress syndrome was 15%, 10% for patellofemoral pain, 9% for medial meniscal injury, 7% for Achilles tendinopathy and 5% for plantar fasciitis. Among the 220 runners (87% recovering from their injury, the median time to recovery was 71 days (minimum  = 9 days, maximum  = 617 days.Medial tibial stress syndrome was the most common injury followed by patellofemoral pain, medial meniscal injury and Achilles tendinopathy. Half of the injured runners were unable to run 2×500 meters without pain after 10 weeks. Almost 5% of the injured runners received surgical treatment.

  3. A prospective study on time to recovery in 254 injured novice runners.

    Science.gov (United States)

    Nielsen, Rasmus Oestergaard; Rønnow, Lotte; Rasmussen, Sten; Lind, Martin

    2014-01-01

    Describe the diagnoses and the time to recovery of running-related injuries in novice runners. Prospective cohort study on injured runners. This paper is a secondary data analysis of a 933-person cohort study (DANO-RUN) aimed at characterizing risk factors for injury in novice runners. Among those sustaining running-related injuries, the types of injuries and time to recovery is described in the present paper. All injured runners were diagnosed after a thorough clinical examination and then followed prospectively during their recovery. If they recovered completely from injury, time to recovery of each injury was registered. A total of 254 runners were injured. The proportion of runners diagnosed with medial tibial stress syndrome was 15%, 10% for patellofemoral pain, 9% for medial meniscal injury, 7% for Achilles tendinopathy and 5% for plantar fasciitis. Among the 220 runners (87%) recovering from their injury, the median time to recovery was 71 days (minimum  = 9 days, maximum  = 617 days). Medial tibial stress syndrome was the most common injury followed by patellofemoral pain, medial meniscal injury and Achilles tendinopathy. Half of the injured runners were unable to run 2×500 meters without pain after 10 weeks. Almost 5% of the injured runners received surgical treatment.

  4. Photodegradation of iodinated trihalomethanes in aqueous solution by UV 254 irradiation.

    Science.gov (United States)

    Xiao, Yongjun; Fan, Rongli; Zhang, Lifeng; Yue, Junqi; Webster, Richard D; Lim, Teik-Thye

    2014-02-01

    Photodegradation of 6 iodinated trihalomethanes (ITHMs) under UV irradiation at 254 nm was investigated in this study. ITHMs underwent a rapid photodegradation process through cleavage of carbon-halogen bond with first-order rate constants in the range of 0.1-0.6 min(-1). The effects of matrix species including nitrate, humic acid (HA), bicarbonate, sulfate, and chloride were evaluated. The degradation rate increased slightly in the presence of nitrate possibly due to generation of HO at a low quantum yield via direct photolysis of nitrate, while HA lowered the photodegradation rate of ITHMs due to its competitive UV absorption. Moreover, bicarbonate, sulfate, and chloride had no significant effect on photodegradation kinetics, as there is no UV absorption for these 3 species. In the study using surface water, treated water, and secondary effluent from a wastewater treatment plant, high turbidity and natural organic matters present in the water inhibited the photodegradation of ITHMs. The degradation rates of 6 ITHMs in UV/H2O2 system were rather comparable and significantly higher than those achieved in the UV system without H2O2. To develop a quantitative structure-reactivity relationship (QSAR) model, the logarithm of measured first-order rate constants was correlated with a number of molecular descriptors. The best correlation was obtained with a combination of 3 molecular descriptors, namely the bond strength of carbon-halogen to be broken in the rate-determining step, steric and electronic effects of all substituents to the carbon center. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Manganese determination om minerals by activation analysis, using the californium-252 as a neutron source; Determinacao de manganes em minerios, por analise por ativacao, usando californio-252 como fonte de neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Cardoso, Antonio

    1976-07-01

    Neutron Activation Analysis, using a Californium-252 neutron source, has been applied for the determination of manganese in ores such as pyrolusite, rodonite (manganese silicate)' and blending used in dry-batteries The favorable nuclear properties of manganese, such as high thermal neutron cross-section for the reaction {sup 55}Mn (n.gamma){sup 56} Mn, high concentration of manganese in the matrix and short half - life of {sup 56}Mn, are an ideal combination for non-destructive analysis of manganese in ores. Samples and standards of manganese dioxide were irradiated for about 20 minutes, followed by a 4 to 15 minutes decay and counted in a single channel pulse-height discrimination using a NaI(Tl) scintillation detector. Counting time was equal to 10 minutes. The interference of nuclear reactions {sup 56}Fe(n,p){sup 56}Mn and {sup 59} Co (n, {alpha}){sup 56} were studied, as well as problems in connection with neutron shadowing during irradiation, gamma-rays attenuation during counting and influence of granulometry of samples. One sample,was also analysed by wet-chemical method (sodium bismuthate) in order to compare results. As a whole, i t was shown that the analytical method of neutron activation for manganese in ores and blending, is a method simple, rapid and with good precision and accuracy. (author)

  6. Design of a homogeneous subcritical nuclear reactor based on thorium with a source of californium 252; Diseno de un reactor nuclear subcritico homogeneo a base de Torio con una fuente de Californio 252

    Energy Technology Data Exchange (ETDEWEB)

    Delgado H, C. E.; Vega C, H. R. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas, Zac. (Mexico); Sajo B, L., E-mail: ce_delgado89@hotmail.com [Universidad Simon Bolivar, Laboratorio de Fisica Nuclear, Apdo. 89000, 1080A Caracas (Venezuela, Bolivarian Republic of)

    2015-10-15

    Full text: One of the energy alternatives to fossil fuels which do not produce greenhouse gases is the nuclear energy. One of the drawbacks of this alternative is the generation of radioactive wastes of long half-life and its relation to the generation of nuclear materials to produce weapons of mass destruction. An option to these drawbacks of nuclear energy is to use Thorium as part of the nuclear fuel which it becomes in U{sup 233} when capturing neutrons, that is a fissile material. In this paper Monte Carlo methods were used to design a homogeneous subcritical reactor based on thorium. As neutron reflector graphite was used. The reactor core is homogeneous and is formed of 70% light water as moderator, 12% of enriched uranium UO{sub 2}(NO{sub 3}){sub 4} and 18% of thorium Th(NO{sub 3}){sub 4} as fuel. To start the nuclear fission chain reaction an isotopic source of californium 252 was used with an intensity of 4.6 x 10{sup 7} s{sup -1}. In the design the value of the effective multiplication factor, whose value turned out k{sub eff} <1 was calculated. Also, the neutron spectra at different distances from the source and the total fluence were calculated, as well as the values of the ambient dose equivalent in the periphery of the reactor. (Author)

  7. Induction of micronuclei by 2-hydroxypyridine in water and elimination of solution genotoxicity by UVC (254 nm) photolysis

    Energy Technology Data Exchange (ETDEWEB)

    Skoutelis, Charalambos G. [Department of Environmental and Natural Resources Management, University of Ioannina, Seferi 2, Agrinio 30100 (Greece); Vlastos, Dimitris, E-mail: dvlastos@cc.uoi.gr [Department of Environmental and Natural Resources Management, University of Ioannina, Seferi 2, Agrinio 30100 (Greece); Kortsinidou, Marianna C.; Theodoridis, Ioannis T.; Papadaki, Maria I. [Department of Environmental and Natural Resources Management, University of Ioannina, Seferi 2, Agrinio 30100 (Greece)

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer 2-Hydroxypyridine (2-HPY) is the major metabolite of 2-halogenated pyridines photolysis. Black-Right-Pointing-Pointer We examine the genotoxicity of 2-HPY in cultured human lymphocytes applying the micronucleus assay. Black-Right-Pointing-Pointer 2-HPY was found to be genotoxic. Black-Right-Pointing-Pointer Aqueous solutions of 2-HPY were irradiated by UV at 254 nm. Black-Right-Pointing-Pointer Solution genotoxicity can be completely removed after prolonged phototreatment. - Abstract: 2-Hydroxypyridine (2-HPY) is a major first-stage product formed upon the photolytic destruction of 2-halogenated pyridines. Genotoxicity of 2-HPY in water was studied as a function of concentration. Aqueous solutions of 2-HPY were irradiated by ultraviolet (UV) at 254 nm. 2-HPY concentration, solution total organic carbon (TOC) concentration and solution genotoxicity were measured as a function of treatment time and their profile as a function of time is presented in this work. 2-HPY was found to be genotoxic at all concentrations in the range of 5-400 {mu}g ml{sup -1}. 2-HPY mineralises completely upon prolonged UV irradiation. All untreated and irradiated solution samples, taken at different photo-treatment times, were tested in cultured human lymphocytes applying the cytokinesis block micronucleus (CBMN) assay. The genotoxicity of the solution was reduced near to the control level after prolonged UV irradiation.

  8. Closure Report for Corrective Action Unit 254: Area 25, R-MAD Decontamination Facility, Nevada Test Site, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    G. N. Doyle

    2002-02-01

    Corrective Action Unit (CAU) 254 is located in Area 25 of the Nevada Test Site (NTS), approximately 100 kilometers (km) (62 miles) northwest of Las Vegas, Nevada. The site is located within the Reactor Maintenance, Assembly and Disassembly (R-MAD) compound and consists of Building 3126, two outdoor decontamination pads, and surrounding areas within an existing fenced area measuring approximately 50 x 37 meters (160 x 120 feet). The site was used from the early 1960s to the early 1970s as part of the Nuclear Rocket Development Station program to decontaminate test-car hardware and tooling. The site was reactivated in the early 1980s to decontaminate a radiologically contaminated military tank. This Closure Report (CR) describes the closure activities performed to allow un-restricted release of the R-MAD Decontamination Facility.

  9. Induction of micronuclei by 2-hydroxypyridine in water and elimination of solution genotoxicity by UVC (254 nm) photolysis.

    Science.gov (United States)

    Skoutelis, Charalambos G; Vlastos, Dimitris; Kortsinidou, Marianna C; Theodoridis, Ioannis T; Papadaki, Maria I

    2011-12-15

    2-Hydroxypyridine (2-HPY) is a major first-stage product formed upon the photolytic destruction of 2-halogenated pyridines. Genotoxicity of 2-HPY in water was studied as a function of concentration. Aqueous solutions of 2-HPY were irradiated by ultraviolet (UV) at 254 nm. 2-HPY concentration, solution total organic carbon (TOC) concentration and solution genotoxicity were measured as a function of treatment time and their profile as a function of time is presented in this work. 2-HPY was found to be genotoxic at all concentrations in the range of 5-400 μg ml(-1). 2-HPY mineralises completely upon prolonged UV irradiation. All untreated and irradiated solution samples, taken at different photo-treatment times, were tested in cultured human lymphocytes applying the cytokinesis block micronucleus (CBMN) assay. The genotoxicity of the solution was reduced near to the control level after prolonged UV irradiation. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. 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,...

  11. A clinico-radiological study on 254 cases of pontine high signals on magnetic resonance imaging in relation to brain stem semiology

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-11-01

    A total of 254 patients who were proved to have pontine high intensity areas on T[sub 2]-weighted magnetic resonance imaging (MRI) were analyzed in relation to brain stem semiology. A comparative study on MRI and MR angiography was made between 254 patients with pontine high signals and 276 control cases showing no abnormality either on T[sub 1] or T[sub 2]-weighted images. Of the 254 patients, 62 had transient subjective complaints such as vertigo-dizziness. Supratentorial high signals, basilar artery tortuousness and vertebral artery asymmetry on MR angiography were seen more frequently in patients with pontine high signals than in the controls. In conclusion, pontine high signals may result from diffuse arteriosclerosis and MR angiography is considered to be a useful screening method. (author).

  12. Comparison of the disinfection effects of vacuum-UV (VUV) and UV light on Bacillus subtilis spores in aqueous suspensions at 172, 222 and 254 nm.

    Science.gov (United States)

    Wang, Ding; Oppenländer, Thomas; El-Din, Mohamed Gamal; Bolton, James R

    2010-01-01

    The efficacy of UV and vacuum-UV (VUV) disinfection of Bacillus subtilis spores in aqueous suspensions at wavelengths of 172, 222 and 254 nm was evaluated. A Xe(2)* excilamp, a KrCl* excilamp and a low-pressure mercury lamp were used as almost monochromatic light sources at these three wavelengths. The first-order inactivation rate constants at 172, 222 and 254 nm were 0.0023, 0.122 and 0.069 cm(2) mJ(-1), respectively. Therefore, a 2 log reduction of B. subtilis spores was reached with fluences (UV doses) of 870, 21.6 and 40.4 mJ cm(-2) at these individual wavelengths. Consequently, for the inactivation of B. subtilis spores, VUV exposure at 172 nm is much less efficient than exposure at the other two wavelengths, while exposure at 222 nm is more efficient than that at 254 nm, which is probably because triplet energy transfer from DPA to thymine bases at 222 nm is higher than that at 254 nm. This research indicated quantitatively that VUV light is not practicable for microorganism disinfection in water and wastewater treatment. However, in comparison with other advanced oxidation processes (e.g. UV/TiO(2), UV/H(2)O(2) or O(3)/H(2)O(2)) the VUV-initiated photolysis of water is likely more efficient in generating hydroxyl radicals and more effective for the inactivation of microorganisms.

  13. Added value of interpreter experience in occult and suspect hip fractures: a retrospective analysis of 254 patients.

    Science.gov (United States)

    Collin, David; Göthlin, Jan H; Nilsson, Martin; Hellström, Mikael; Geijer, Mats

    2016-06-01

    The influence of experience in categorizing suspect and occult fractures on radiography compared to MRI and clinical outcome has not been studied. The aim of this study is to evaluate the importance of experience in diagnosing normal or suspect hip radiographs compared to MRI. Primarily reported normal or suspect radiography in 254 patients with low-energy hip trauma and subsequent MRI was re-evaluated by two experienced reviewers. Primary readings and review were compared. The prevalence of fractures among normal and suspect radiographic studies was assessed. Clinical outcome was used as reference. At review of radiography, 44 fractures (17 %) were found. Significantly more fractures were found among suspect cases than among normal cases. At MRI, all 44 fractures were confirmed, and further 64 fractures were detected (25 %). MRI detected all fractures with no missed fractures revealed at follow-up. There were a significantly higher proportion of fractures at MRI among the suspect radiographic diagnoses for both the primary report and at review than among occult cases. The more experienced reviewers classified radiography examinations with higher accuracy than primary reporting general radiologists. There was almost complete agreement on MRI diagnoses.

  14. Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010).

    Science.gov (United States)

    Bellumori, Thomas P; Famula, Thomas R; Bannasch, Danika L; Belanger, Janelle M; Oberbauer, Anita M

    2013-06-01

    To determine the proportion of mixed-breed and purebred dogs with common genetic disorders. Case-control study. 27,254 dogs with an inherited disorder. Electronic medical records were reviewed for 24 genetic disorders: hemangiosarcoma, lymphoma, mast cell tumor, osteosarcoma, aortic stenosis, dilated cardiomyopathy, hypertrophic cardiomyopathy, mitral valve dysplasia, patent ductus arteriosus, ventricular septal defect, hyperadrenocorticism, hypoadrenocorticism, hypothyroidism, elbow dysplasia, hip dysplasia, intervertebral disk disease, patellar luxation, ruptured cranial cruciate ligament, atopy or allergic dermatitis, bloat, cataracts, epilepsy, lens luxation, and portosystemic shunt. For each disorder, healthy controls matched for age, body weight, and sex to each affected dog were identified. Genetic disorders differed in expression. No differences in expression of 13 genetic disorders were detected between purebred dogs and mixed-breed dogs (ie, hip dysplasia, hypo- and hyperadrenocorticism, cancers, lens luxation, and patellar luxation). Purebred dogs were more likely to have 10 genetic disorders, including dilated cardiomyopathy, elbow dysplasia, cataracts, and hypothyroidism. Mixed-breed dogs had a greater probability of ruptured cranial cruciate ligament. Prevalence of genetic disorders in both populations was related to the specific disorder. Recently derived breeds or those from similar lineages appeared to be more susceptible to certain disorders that affect all closely related purebred dogs, whereas disorders with equal prevalence in the 2 populations suggested that those disorders represented more ancient mutations that are widely spread through the dog population. Results provided insight on how breeding practices may reduce prevalence of a disorder.

  15. International travel in the immunocompromised patient: a cross-sectional survey of travel advice in 254 consecutive patients.

    Science.gov (United States)

    Bialy, C; Horne, K; Dendle, C; Kanellis, J; Littlejohn, G; Ratnam, I; Woolley, I

    2015-06-01

    Our primary aim was to determine the rate of overseas travel in immunocompromised individuals attending appropriate clinics at an Australian tertiary care hospital. We also aimed to characterise health-seeking behaviour prior to travel and investigated sources of pre-travel advice, compared travel patterns and activities between three specific immunosuppressed groups, and examined pre-immunosuppression patient serology. We implemented a cross-sectional survey of patients between February and August 2012. This survey was implemented among three outpatient populations at Monash Medical Centre, an Australian tertiary care hospital. We recruited 254 immunosuppressed adults from three patient populations: human immunodeficiency virus-positive individuals, renal transplant patients and rheumatology patients requiring immunosuppressive therapy. No clinical intervention was performed. In the 10 years preceding the survey, 153 (60.2%) participants reported international travel. Of these, 105 (68.6%) were immunosuppressed at the time of travel. These patients were 47.6% male and 60% Australian born. Forty per cent were visiting friends and relatives as part of their travel. Fifty-four per cent of those immunocompromised at the time of travel were going to high-risk destinations. Pathology files indicated that serological screening was frequently not performed prior to immunosuppression in the renal transplant and rheumatology groups. Immunocompromised patients often travel to high-risk destinations with limited or inadequate pre-travel preparations. Doctors caring for the immunocompromised should be aware of travel risks, suitable vaccination protocols and when to refer to specialist travel clinics. © 2015 Royal Australasian College of Physicians.

  16. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  17. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  18. Chemical, optical and other data collected aboard the THOMAS G. THOMPSON during cruise TN254 in the Coastal Waters of SE Alaska and North Pacific Ocean from 2010-09-09 to 2010-10-11 (NODC Accession 0104359)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0104359 includes chemical, optical and other data collected aboard the THOMAS G. THOMPSON during cruise TN254 in the Coastal Waters of SE Alaska and...

  19. Surface modification of Sylgard 184 polydimethylsiloxane by 254 nm excimer radiation and characterization by contact angle goniometry, infrared spectroscopy, atomic force and scanning electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Waddell, Emanuel A. [University of Alabama in Huntsville, Huntsville, AL (United States)], E-mail: ewaddell@chemistry.uah.edu; Shreeves, Stephen [University of Alabama in Huntsville, Huntsville, AL (United States); Carrell, Holly; Perry, Christopher [Oakwood College, Huntsville, AL (United States); Reid, Branden A. [Morgan State University, Baltimore, MD (United States); McKee, James [University of Alabama in Birmingham, Birmingham, AL (United States)

    2008-06-30

    The modification of polydimethylsiloxane (PDMS) by narrow band 254 nm excimer radiation under a nitrogen atmosphere was characterized by contact angle goniometry, attenuated total reflectance infrared spectroscopy, atomic force and scanning electron microscopy. UV irradiation results in the formation of the carboxylic acids that influences the wettability of the surface. Continued exposure results in the formation of an inorganic surface (SiO{sub x} (1 < x < 2)) which hinders the ability to continually increase the wettability. The continuity of this inorganic layer is disrupted by the formation of surface cracks. These results have implications in the fabrication and chemical modification of microfluidic or micro-electro-mechanical systems.

  20. Surface modification of Sylgard 184 polydimethylsiloxane by 254 nm excimer radiation and characterization by contact angle goniometry, infrared spectroscopy, atomic force and scanning electron microscopy

    Science.gov (United States)

    Waddell, Emanuel A.; Shreeves, Stephen; Carrell, Holly; Perry, Christopher; Reid, Branden A.; McKee, James

    2008-06-01

    The modification of polydimethylsiloxane (PDMS) by narrow band 254 nm excimer radiation under a nitrogen atmosphere was characterized by contact angle goniometry, attenuated total reflectance infrared spectroscopy, atomic force and scanning electron microscopy. UV irradiation results in the formation of the carboxylic acids that influences the wettability of the surface. Continued exposure results in the formation of an inorganic surface (SiO x (1 < x < 2)) which hinders the ability to continually increase the wettability. The continuity of this inorganic layer is disrupted by the formation of surface cracks. These results have implications in the fabrication and chemical modification of microfluidic or micro-electro-mechanical systems.

  1. Cytochrome P450 CYP716A254 catalyzes the formation of oleanolic acid from β-amyrin during oleanane-type triterpenoid saponins biosynthesis in Anemone flaccida.

    Science.gov (United States)

    Zhan, Chuansong; Ahmed, Shakeel; Hu, Sheng; Dong, Shuang; Cai, Qian; Yang, Tewu; Wang, Xuekui; Li, Xiaohua; Hu, Xuebo

    2018-01-01

    Anemone flaccida Fr. Shmidt (Ranunculaceae), known as 'Di Wu' in China, is a perennial herb which has long been used to treat arthritis. The rhizome of A. flaccida contains pharmacologically active components i.e. oleanane-type triterpenoid saponins. Oleanolic acid is natural triterpenoid in plants with diverse biological activities. The biosynthesis of oleanolic acid involves cyclization of 2,3-oxidosqualene to the oleanane-type triterpenoid skeleton, followed by a series of oxidation reactions catalyzed by cytochrome P450 monooxygenase (CYP450). Previously, we identified four possible cytochrome P450 genes belonging to CYP716A subfamily from the transcriptome of A. flaccida. In this study, we identified one of those genes "CYP716A254" encoding a cytochrome P450 monooxygenase from A. flaccida that catalyzes the conversion of the β-amyrin into oleanolic acid. The heterologous expression of CYP716A254 in yeast resulted in oxidation of β-amyrin at the C-18 position to oleanolic acid production. These results provide an important basis for further studies of oleanane-type triterpenoid saponins synthesis in A. flaccida. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The fate of silica based Stöber particles soaked into growth media (RPMI and M254): A DLS and ζ-potential study.

    Science.gov (United States)

    Branda, Francesco; Silvestri, Brigida; Costantini, Aniello; Luciani, Giuseppina

    2015-11-01

    Understanding the mechanisms involved in the interaction of biological systems with inorganic materials is of great importance and interest in both fundamental and applied disciplines in several different fields such as astrobiology, ecology, biology, biotechnology, engineering, and medicine. In this context, this paper investigates the interaction of biomacromolecules with submicrometric silica gel particles (NP) obtained through the Stöber method. Surprisingly, particles size reduction is observed after their dispersion into two different reconstituted growth media (RPMI and M254). This effect was related to the nature of the Stöber particles and the mechanism of their formation. The experimental results can be explained arguing that a biomacromolecule corona rapidly forms on NP incubated in both RPMI and M254 growth media. The results suggest that hydrolytic attack at incompletely condensed internal surface valence sites as well as interactions between NPs surface and the components of the growth media reverse the aggregation process, giving smaller disaggregated particles surrounded by a biomacromolecule corona. Moreover it was assessed that, at longer incubation time, the particles slightly grow probably due to interlocking of biomacromolecules in the corona. Furthermore, experimental results confirm that formation of this corona is a competitive and dynamic process. The present paper shows that the described effects (as size changes) are strongly dependent on the nature of the growth medium. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Actinide targets for the synthesis of super-heavy elements

    Energy Technology Data Exchange (ETDEWEB)

    Roberto, J.B., E-mail: robertojb@ornl.gov; Alexander, C.W.; Boll, R.A.; Burns, J.D.; Ezold, J.G.; Felker, L.K.; Hogle, S.L.; Rykaczewski, K.P.

    2015-12-15

    Since 2000, six new super-heavy elements with atomic numbers 113 through 118 have been synthesized in hot fusion reactions of {sup 48}Ca beams on actinide targets. These target materials, including {sup 242}Pu, {sup 244}Pu, {sup 243}Am, {sup 245}Cm, {sup 248}Cm, {sup 249}Cf, and {sup 249}Bk, are available in very limited quantities and require specialized production and processing facilities resident in only a few research centers worldwide. This report describes the production and chemical processing of heavy actinide materials for super-heavy element research, current availabilities of these materials, and related target fabrication techniques. The impact of actinide materials in super-heavy element discovery is reviewed, and strategies for enhancing the production of rare actinides including {sup 249}Bk, {sup 251}Cf, and {sup 254}Es are described.

  4. SU-F-T-254: Dose Volume Histogram (DVH) Analysis of Breath Hold Vs Free Breathing Techniques for Esophageal Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Badkul, R; Doke, K; Pokhrel, D; Aguilera, N; Lominska, C [University of Kansas Medical Center, Kansas City, KS (United States)

    2016-06-15

    Purpose: Lung and heart doses and associated toxicity are of concern in radiotherapy for esophageal cancer. This study evaluates the dosimetry of deep-inspiration-breath-hold (DIBH) technique as compared to freebreathing( FB) using 3D-conformal treatment(3D-CRT) of esophageal cancer. Methods: Eight patients were planned with FB and DIBH CT scans. DIBH scans were acquired using Varian RPM system. FB and DIBH CTs were contoured per RTOG-1010 to create the planning target volume(PTV) as well as organs at risk volumes(OAR). Two sets of gross target volumes(GTV) with 5cm length were contoured for each patient: proximal at the level of the carina and distal at the level of gastroesophageal junction and were enlarged with appropriate margin to generate Clinical Target Volume and PTV. 3D-CRT plans were created on Eclipse planning system for 45Gy to cover 95% of PTV in 25 fractions for both proximal and distal tumors on FB and DIBH scans. For distal tumors celiac nodes were covered electively. DVH parameters for lung and heart OARs were generated and analyzed. Results: All DIBH DVH parameters were normalized to FB plan values. Average of heart-mean and heart-V40 was 0.70 and 0.66 for proximal lesions. For distal lesions ratios were 1.21 and 2.22 respectively. For DIBH total lung volume increased by 2.43 times versus FB scan. Average of lung-mean, V30, V20, V10, V5 are 0.82, 0.92, 0.76, 0.77 and 0.79 for proximal lesions and 1.17,0.66,0.87,0.93 and 1.03 for distal lesions. Heart doses were lower for breath-hold proximal lesions but higher for distal lesions as compared to free-breathing plans. Lung doses were lower for both proximal and distal breath-hold lesions except mean lung dose and V5 for distal lesions. Conclusion: This study showed improvement of OAR doses for esophageal lesions at mid-thoracic level utilizing DIBH vs FB technique but did not show consistent OAR sparing with DIBH for distal lesions.

  5. Abundancias químicas de la compañera visible del agujero negro binario V4641 Sgr (XTE J1819-254)

    Science.gov (United States)

    Cúneo, V. A.; Jofré, E.; Pintado, O. I.; Gómez, M. N.

    2015-08-01

    In this work we expose an analysis of the chemical abundances of the optical companion of the confirmed black hole binary V4641 Sgr (XTE J1819-254) from GMOS spectra obtained with the Gemini North telescope. This analysis allowed to observe an enhancement of N, O, Mg and Si, attributed to the contamination of heavy elements generated during the supernova explosion that gave birth to the black hole. It was also observed that Cr and Fe were subabundant. The aim of this study is to test the formation scenario of a binary system containing a black hole as remnant of the supernova explosion of a massive star, and to provide information to better understand the final stages in the evolution of massive stars and black hole progenitors.

  6. Mitotic recombination and inactivation in Saccharomyces cerevisiae induced by UV-radiation (254 nm) and hyperthermia depend on UV fluence rate.

    Science.gov (United States)

    Petin, V G; Kim, J K; Rassokhina, A V; Zhurakovskaya, G P

    2001-07-01

    In experiments with wild-type diploid yeast cells of Saccharomyces cerevisiae, the synergistic interaction of ultraviolet (UV) light (wavelength, 254 nm) and heat (45--60 degrees C) was studied both for mutagenic and inactivation effects. Simultaneous hyperthermia and UV light treatments increase the frequency of UV-induced mitotic intergenic recombination (crossing-over) and cell inactivation. The enhancing effect was a function of UV light fluence rate. It is concluded that the effect of hyperthermia on low fluence UV or high fluence UV irradiation results in comparable effects on survival and mitotic recombination suggesting similar modulation by hyperthermia of the effects induced by UV at different fluence rates. The interpretation of the data obtained was carried out within the widely accepted point of view considering the synergistic effects as a result of repair ability damage.

  7. Atomic gas temperature in a nonequilibrium high-intensity discharge lamp determined from the red wing of the resonance mercury line 254 nm

    Energy Technology Data Exchange (ETDEWEB)

    Drakakis, E. [Technological Educational Institute, Department of Electrical Engineering, 71004 Heraklion (Greece); Karabourniotis, D. [Institute of Plasma Physics, Department of Physics, University of Crete, 71003 Heraklion (Greece)

    2012-09-01

    For developing low-wattage high intensity discharge (HID) lamps, a better understanding of the relatively unexplored nonequilibrium phenomena is essential. This needs interpretation of diagnostic results by methods free from equilibrium assumptions. In this paper, the atomic temperature is determined from the simulation of a quasistatic broadened resonance line by distinguishing between atomic temperature and excitation temperature in the equation of radiative transfer. The proposed method is applied to the red wing of the resonance mercury line 254 nm emitted from a HID lamp working on ac. The experimental results show severe deviation from local thermodynamic equilibrium. More than one thousand degrees difference was obtained between atomic and electron temperatures at the maximum current phase.

  8. MEET ISOLDE - Target Production

    CERN Multimedia

    2017-01-01

    MEET ISOLDE - Target Production. Everything at ISOLDE starts with a target and the target production team realise on more then 50 years of experience to build and develop new targets for ISOLDE’s wide physics program.

  9. The minimal domain of adipose triglyceride lipase (ATGL ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively.

    Directory of Open Access Journals (Sweden)

    Irina Cornaciu

    Full Text Available Adipose triglyceride lipase (ATGL is the rate-limiting enzyme of lipolysis. ATGL specifically hydrolyzes triacylglycerols (TGs, thereby generating diacylglycerols and free fatty acids. ATGL's enzymatic activity is co-activated by the protein comparative gene identification-58 (CGI-58 and inhibited by the protein G0/G1 switch gene 2 (G0S2. The enzyme is predicted to act through a catalytic dyad (Ser47, Asp166 located within the conserved patatin domain (Ile10-Leu178. Yet, neither an experimentally determined 3D structure nor a model of ATGL is currently available, which would help to understand how CGI-58 and G0S2 modulate ATGL's activity. In this study we determined the minimal active domain of ATGL. This minimal fragment of ATGL could still be activated and inhibited by CGI-58 and G0S2, respectively. Furthermore, we show that this minimal domain is sufficient for protein-protein interaction of ATGL with its regulatory proteins. Based on these data, we generated a 3D homology model for the minimal domain. It strengthens our experimental finding that amino acids between Leu178 and Leu254 are essential for the formation of a stable protein domain related to the patatin fold. Our data provide insights into the structure-function relationship of ATGL and indicate higher structural similarities in the N-terminal halves of mammalian patatin-like phospholipase domain containing proteins, (PNPLA1, -2,- 3 and -5 than originally anticipated.

  10. Prospective analysis of the use of OnabotulinumtoxinA (BOTOX) in the treatment of chronic migraine; real-life data in 254 patients from Hull, U.K.

    Science.gov (United States)

    Khalil, Modar; Zafar, Hassan W; Quarshie, Victoria; Ahmed, Fayyaz

    2014-09-01

    Chronic migraine affects 2% of the population. It results in substantial disability and reduced quality of life. Medications used for prophylaxis in episodic migraine may also work in chronic migraine. The efficacy and safety of OnabotulinumtoxinA (BOTOX) in adults with chronic migraine was confirmed in the PREEMPT programme. However, there are few real-life data of its use. 254 adults with chronic migraine were injected with OnabotulinumtoxinA BOTOX as per PREEMPT Protocol between July 2010 and May 2013, their headache data were collected using the Hull headache diary and analysed to look for headache, migraine days decrements, crystal clear days increment in the month post treatment, we looked at the 50% responder rate as well. Our prospective analysis shows that OnabotulinumtoxinA, significantly, reduced the number of headache and migraine days, and increased the number of headache free days. OnabotulinumtoxinA Botox also improved patients' quality of life. We believe that these results represent the largest post-marketing cohort of patients treated with OnabotulinumtoxinA in the real-life clinical setting. OnabotulinumtoxinA is a valuable addition to current treatment options in patients with chronic migraine. Our results support findings of PREEMPT study in a large cohort of patients, we believe, is representative of the patients seen in an average tertiary headache centre. While it can be used as a first line prophylaxis its cost may restrict its use to more refractory patients who failed three oral preventive treatments.

  11. Use of mussel casts from archaeological sites as paleoecological indicators: An example from CA-MRN-254, Marin County, Alta California

    Science.gov (United States)

    McGann, Mary; Starratt, Scott W.; Powell, Charles L.; Bieling, David G

    2016-01-01

    Archaeological investigations at prehistoric site CA-MRN-254 at the Dominican University of California in Marin County, California, revealed evidence of Native American occupation spanning the past 1,800 years. A dominant source of food for the inhabitants in the San Francisco Bay area was the intertidal, quiet-water dwelling blue mussel (Mytilus trossulus), although rare occurrences of the open coast-dwelling California mussel (Mytilus californianus) suggest that this species was also utilized sporadically. On rare occasions, cultural horizons at this site contain abundant sediment-filled casts of the smaller mussel Modiolus sp. These casts were formed soon after death when the shells filled with sediment and were roasted along with living bivalve shellfish for consumption. Thin sections of these mussel casts display sedimentological and microbiological constituents that shed light on the paleoenvironmental conditions when they were alive. Fine-grained sediment and pelletal muds comprising these casts suggest that the mussels were collected in a low energy, inner bay environment. The rare presence of the diatoms Triceratium dubium and Thalassionema nitzschioides indicate more normal marine (35 psu) and possibly warmer conditions than presently exist in San Francisco Bay. Radiocarbon dating of charcoal associated with the mussel casts containing these diatoms correlates with a 600-year period of warming from ca. A.D. 700–1300, known as the Medieval Climatic Anomaly. Results of this mussel cast study demonstrate that they have great potential for providing paleoenvironmental information at this and other archaeological sites.

  12. Investigation of Free-Standing Plasmonic Mesoporous Ag/CMK-8-Nafion Composite Membrane for the Removal of Organic Pollutants with 254-nm UV Irradiation

    Science.gov (United States)

    Tseng, Chuan Ming; Chen, Hsin Liang; Lai, Sz Nian; Chen, Ming Shiung; Peng, Chien Jung; Li, Chia Jui; Hung, Wei Hsuan

    2017-05-01

    "Carbon-based material" has demonstrated a great potential on water purification due to its strong physical adsorption to organic pollutants in the water. Three-dimensional cubic ordered mesoporous carbon (CMK-8), one of the well-known ordered mesoporous carbons, was prepared by using nanocasting method with mesoporous silica (KIT-6) as the template. In this study, CMK-8 blended with Nafion polymer to form a free-standing mesoporous CMK-8-Nafion composite membrane. The synthesis of high crystallinity CMK-8 was characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). More than 80% methyl orange (MO) removal efficiency was observed under 254-nm UV irradiation after 120 min. Ninety-two percent recycling performance was remained after four recycling tests, which indicated a reliable servicing lifetime for the water purification. Furthermore, an additional layer of plasmonic silver nanoparticles (Ag NPs) was integrated into this CMK-8-Nafion membrane for higher pollutant removal efficiency, attributing from the generation of plasmon-resonance hot electrons from Ag NPs. A 4-in. CMK-8-Nafion composite membrane was also fabricated for the demonstration of potential large-scale utilization.

  13. DD Form 254 Preparation Guide

    Science.gov (United States)

    1994-07-01

    DATA is iequired. e. INTELLIGENCE INFORMATION. This information is tinder the jurisdiction and control of the Directo : of Central Intelligence (DCI...une this cort •b. ia•r otosubl .t y qusetone for Inter•retat•jo• of this ggdacn• tothe *Offldasl imufleid below Ft•d"rIg final decision. the 0• n sol

  14. A "Dock and Lock" Approach to Preparation of Targeted Liposomes.

    Science.gov (United States)

    Backer, Marina V; Backer, Joseph M

    2017-01-01

    We developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. This strategy is based on "dock and lock" interactions between two mutated fragments of human RNase I, a 1-15 aa fragment with the R4C amino acid substitution (Cys-tag), and a 21-127-aa fragment with the V118C substitution, (Ad-C). Upon binding to each other, Cys-tag and Ad-C spontaneously form a disulfide bond between the complementary 4C and 118C residues. Therefore, any targeting protein expressed with Cys-tag can be easily coupled to liposomes decorated with Ad-C. Here we describe the preparation of Ad-liposomes followed by coupling them to two Cys-tagged targeted proteins, human vascular endothelial growth factor expressed with N-terminal Cys-tag and a 254-aa long N-terminal fragment of anthrax lethal factor carrying C-terminal Cys-tag. Both proteins retain functional activity after coupling to Ad-C-decorated drug-loaded liposomes. We expect that our "dock and lock" strategy will open new opportunities for development of targeted therapeutic liposomes for research and clinical use.

  15. Flow measurements in ONKALO at Olkiluoto probe holes and investigation holes ONK-PP201, -PP254, -PP262, -PP263, -PP274, -PVA8 and -KR13

    Energy Technology Data Exchange (ETDEWEB)

    Pekkanen, J. [Poeyry Finland Oy, Vantaa (Finland)

    2011-10-15

    The Posiva Flow Log, Difference Flow Method (PFL DIFF) uses a flowmeter that incorporates a flow guide and can be used for relatively quick determination of hydraulic conductivity and hydraulic head in fractures/fractured zones in cored drillholes. This report presents the principles of the method and the results of measurements carried out in several drillholes during the excavation of the underground access tunnel ONKALO at Olkiluoto. Phase 1, phase 2, phase 3 and phase 4 of the probe hole measurements in the access tunnel started when the tunnel was 15 m long and finished at the tunnel length of 3976 m. The results of phases 1, 2, 3 and 4 are presented in reports 2006-65 (Phase 1) (Reiman, M., Vaeisaesvaara, J and Poellaenen, J. 2006), 2008-37 (Phase 2) (Pekkanen, J., 2008), 2010-02 (Phase 3) (Pekkanen, J and Vaeisaesvaara, J., 2010) and 2010-32 (Phase 4) (Pekkanen, J, 2010). Probe hole measurements were continued normally in phase 5. The phase 5 results are presented in this report. Flow measurements started on July 15, 2010 when tunnel length was 4357 m and ended on February 3, 2011, at tunnel length 4399 m. Probe hole measurements will continue normally below 4399 m. The probe hole measurements were continued after the phase 4 with a manual device. The flow along the probe hole was measured using manual measurement setup with a 1.0 m point interval. In addition to probe holes, shallow core-drilled drillholes were also measured in ONKALO. The drillholes discussed in this report are ONK-PP201, ONK-PP254, ONKPP262, ONK-PP263, ONK-PP274, ONK-PVA8 and ONK-KR13. The PFL DIFF probe was used to detect flow within single fractures in the drillhole. The method utilizes rubber disks to isolate the flow in a test section from that in the rest of the drillhole. Core-drilled drillholes were measured using a 0.5 m section length (the distance isolated with the rubber disks). Alternatively the flow along the drillhole were measured without the lower rubber disks. The

  16. Effect of Key Parameters on the Photocatalytic Oxidation of Toluene at Low Concentrations in Air under 254 + 185 nm UV Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Quici, Natalia; Vera, Maria L.; Choi, Hyeok; Puma, Gianluca Li; Dionysiou, Dionysios D.; Litter, Marta I.; Destaillats, Hugo

    2009-07-01

    The effect of key experimental parameters on the removal of toluene under 254 + 185 nm irradiation was investigated using a benchtop photocatalytic flow reactor. Toluenewas introduced at low concentrations between 10 and 500 ppbv, typical of indoorenvironments, and reacted on TiO2-coated Raschig rings. Two different TiO2-coated rings were prepared: in one case, by dip-coating using a P25 aqueous suspension and, on the other, using an organic/inorganic sol-gel method that produced thin films of mesoporous anatase. Flow rates in the photoreactor varied between 4 L min-1 and 125 mL min-1, leading to residence times in the range 100 ms< tau< 2 s. For these conditions, toluene removal efficiencies were between 30 and 90percent, indicating that the system did not achieve total conversion in any case. For each air flow rate, the conversion oftoluene was significantly higher when the reactor length was 10 cm, as compared with 5 cm; however, only marginal increases in conversions were achieved in the two reactor lengths at equal residence time and different concentration of toluene, suggesting that that the reactor is effectively behaving as an ideal reactor and that the reaction is first-order in the concentration of toluene. Experiments were carried out between 0 and 66percent relative humidity (RH), the fastest reaction rate being observed at moderately low humidity conditions (10percent RH), with respect to both dry air and higher humidity levels. Formaldehyde was formed as a partial oxidation byproduct at low and at high residence times (240 and 960 ms), although higher formaldehyde molar yields (up to 20percent) were observed at low tau (240 ms) and moderate humidity conditions (10 and 33percent), suggesting that both tau and RH can be optimized toreduce the formation of harmful intermediates. Toluene removal efficiency increased with the TiO2 thickness (i.e., mass) until a maximum value of 500 nm, beyond which the removal efficiency decreased. This should be

  17. Targeted therapies for cancer

    Science.gov (United States)

    ... so they cannot spread. How Does Targeted Therapy Work? Targeted therapy drugs work in a few different ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  18. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — ABSTRACT: Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590...

  19. Reflectance Reference Targets (OTTER)

    Data.gov (United States)

    National Aeronautics and Space Administration — Spectral reflectance measurements of flat field targets as reference points representative of pseudo-invariant targets as measured by Spectron SE590 spectrophotometer

  20. Targets for Precision Measurements

    Science.gov (United States)

    Loveland, W.; Yao, L.; Asner, D. M.; Baker, R. G.; Bundgaard, J.; Burgett, E.; Cunningham, M.; Deaven, J.; Duke, D. L.; Greife, U.; Grimes, S.; Heffner, M.; Hill, T.; Isenhower, D.; Klay, J. L.; Kleinrath, V.; Kornilov, N.; Laptev, A. B.; Massey, T. N.; Meharchand, R.; Qu, H.; Ruz, J.; Sangiorgio, S.; Selhan, B.; Snyder, L.; Stave, S.; Tatishvili, G.; Thornton, R. T.; Tovesson, F.; Towell, D.; Towell, R. S.; Watson, S.; Wendt, B.; Wood, L.

    2014-05-01

    The general properties needed in targets (sources) for high precision, high accuracy measurements are reviewed. The application of these principles to the problem of developing targets for the Fission TPC is described. Longer term issues, such as the availability of actinide materials, improved knowledge of energy losses and straggling and the stability of targets during irradiation are also discussed.

  1. Setting Asset Performance Targets

    NARCIS (Netherlands)

    Green, D.; Hodkiewicz, M.; Masschelein, S.; Schoenmaker, R.; Muruvan, S.

    2015-01-01

    Setting targets is a common way for organisations to establish performance expectations. However the validity of targets is challenged when performance is influenced by factors beyond the control of the manager. This project examines the issue of target setting for a single asset performance measure

  2. Automated absolute activation analysis with californium-252 sources

    Energy Technology Data Exchange (ETDEWEB)

    MacMurdo, K.W.; Bowman, W.W.

    1978-09-01

    A 100-mg /sup 252/Cf neutron activation analysis facility is used routinely at the Savannah River Laboratory for multielement analysis of many solid and liquid samples. An absolute analysis technique converts counting data directly to elemental concentration without the use of classical comparative standards and flux monitors. With the totally automated pneumatic sample transfer system, cyclic irradiation-decay-count regimes can be pre-selected for up to 40 samples, and samples can be analyzed with the facility unattended. An automatic data control system starts and stops a high-resolution gamma-ray spectrometer and/or a delayed-neutron detector; the system also stores data and controls output modes. Gamma ray data are reduced by three main programs in the IBM 360/195 computer: the 4096-channel spectrum and pertinent experimental timing, counting, and sample data are stored on magnetic tape; the spectrum is then reduced to a list of significant photopeak energies, integrated areas, and their associated statistical errors; and the third program assigns gamma ray photopeaks to the appropriate neutron activation product(s) by comparing photopeak energies to tabulated gamma ray energies. Photopeak areas are then converted to elemental concentration by using experimental timing and sample data, calculated elemental neutron capture rates, absolute detector efficiencies, and absolute spectroscopic decay data. Calculational procedures have been developed so that fissile material can be analyzed by cyclic neutron activation and delayed-neutron counting procedures. These calculations are based on a 6 half-life group model of delayed neutron emission; calculations include corrections for delayed neutron interference from /sup 17/O. Detection sensitivities of < or = 400 ppB for natural uranium and 8 ppB (< or = 0.5 (nCi/g)) for /sup 239/Pu were demonstrated with 15-g samples at a throughput of up to 140 per day. Over 40 elements can be detected at the sub-ppM level.

  3. Metastable charge-transfer state of californium(iii) compounds.

    Science.gov (United States)

    Liu, Guokui; Cary, Samantha K; Albrecht-Schmitt, Thomas E

    2015-06-28

    Among a series of anomalous physical and chemical properties of Cf(iii) compounds revealed by recent investigations, the present work addresses the characteristics of the optical spectra of An(HDPA)3·H2O (An = Am, Cm, and Cf), especially the broadband photoluminescence from Cf(HDPA)3·H2O induced by ligand-to-metal charge transfer (CT). As a result of strong ion-ligand interactions and the relative ease of reducing Cf(iii) to Cf(ii), a CT transition occurs at low energy (transfer state undergoes radiative and non-radiative relaxations. Broadening of the CT transition arises from strong vibronic coupling and hole-charge interactions in the valence band. The non-radiative relaxation of the metastable CT state results from a competition between phonon-relaxation and thermal tunneling that populates the excited states of Cf(iii).

  4. Development of distributed target

    CERN Document Server

    Yu Hai Jun; Li Qin; Zhou Fu Xin; Shi Jin Shui; Ma Bing; Chen Nan; Jing Xiao Bing

    2002-01-01

    Linear introduction accelerator is expected to generate small diameter X-ray spots with high intensity. The interaction of the electron beam with plasmas generated at the X-ray converter will make the spot on target increase with time and debase the X-ray dose and the imaging resolving power. A distributed target is developed which has about 24 pieces of thin 0.05 mm tantalum films distributed over 1 cm. due to the structure adoption, the distributed target material over a large volume decreases the energy deposition per unit volume and hence reduces the temperature of target surface, then reduces the initial plasma formalizing and its expansion velocity. The comparison and analysis with two kinds of target structures are presented using numerical calculation and experiments, the results show the X-ray dose and normalized angle distribution of the two is basically the same, while the surface of the distributed target is not destroyed like the previous block target

  5. Corrective Action Investigation Plan for Corrective Action Unit 254: Area 25 R-MAD Decontamination Facility, Nevada Test Site, Nevada (includes ROTC No. 1, date 01/25/1999)

    Energy Technology Data Exchange (ETDEWEB)

    DOE/NV

    1999-07-29

    This Corrective Action Investigation Plan contains the US Department of Energy, Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 254 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 254 consists of Corrective Action Site (CAS) 25-23-06, Decontamination Facility. Located in Area 25 at the Nevada Test Site (NTS), CAU 254 was used between 1963 through 1973 for the decontamination of test-car hardware and tooling used in the Nuclear Rocket Development Station program. The CAS is composed of a fenced area measuring approximately 119 feet by 158 feet that includes Building 3126, an associated aboveground storage tank, a potential underground storage area, two concrete decontamination pads, a generator, two sumps, and a storage yard. Based on site history, the scope of this plan is to resolve the problem statement identified during the Data Quality Objectives process that decontamination activities at this CAU site may have resulted in the release of contaminants of concern (COCs) onto building surfaces, down building drains to associated leachfields, and to soils associated with two concrete decontamination pads located outside the building. Therefore, the scope of the corrective action field investigation will involve soil sampling at biased and random locations in the yard using a direct-push method, scanning and static radiological surveys, and laboratory analyses of all soil/building samples. Historical information provided by former NTS employees indicates that solvents and degreasers may have been used in the decontamination processes; therefore, potential COCs include volatile/semivolatile organic compounds, Resource Conservation and Recovery Act metals, petroleum hydrocarbons, polychlorinated biphenyls, pesticides, asbestos, gamma-emitting radionuclides, plutonium, uranium, and strontium-90. The results of this

  6. Inertial Confinement fusion targets

    Science.gov (United States)

    Hendricks, C. D.

    1982-01-01

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

  7. Target Window Reliability

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    The target window design implemented and tested in experiments at ANL have performed without failure for the available beam of 6 mm FWHM on a 12 mm diameter target. However, scaling that design to a 25 mm diameter target size for a 12 mm FWHM beam has proven problematic. Combined thermal and mechanical (pressure induced) stresses and strains are too high to maintain the small coolant gaps and provide adequate fatigue lifetime.

  8. The ISOLDE target robots

    CERN Multimedia

    Maximilein Brice

    2002-01-01

    ISOLDE targets need to be changed frequently, around 80 times per year. The high radiation levels do not permit this to be done by human hands and the target changes are effected by 2 industrial robots (picture _01). On the left, in the distance, the front-end of the GPS (General Purpose Separator) is seen, while the HRS (High Resolution Separator) is at the right. Also seen are the doors to the irradiated-target storage.

  9. Targeting the tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

  10. Target Assembly Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Target Assembly Facility integrates new armor concepts into actual armored vehicles. Featuring the capability ofmachining and cutting radioactive materials, it...

  11. Target visibility for multiple maneuvering target tracking

    Science.gov (United States)

    Sabordo, Madeleine G.; Aboutanios, Elias

    2015-05-01

    We present a recursion of the probability of target visibility and its applications to analysis of track life and termination in the context of Global Nearest Neighbour (GNN) approach and Probability Hypothesis Density (PHD) filter. In the presence of uncertainties brought about by clutter; decisions to retain a track, terminate it or initialise a new track are based on probability, rather than on distance criterion or estimation error. The visibility concept is introduced into a conventional data-association-oriented multitarget tracker, the GNN; and a random finite set based-tracker, the PHD filter, to take into account instances when targets become invisible or occluded by obstacles. We employ the natural logarithmof the Dynamic Error Spectrum to assess the performance of the trackers with and without probability of visibility incorporated. Simulation results show that the performance of the GNN tracker with visibility concept incorporated is significantly enhanced.

  12. A abordagem sociotécnica na investigação e na prevenção de acidentes aéreos: o caso do vôo RG-254

    Directory of Open Access Journals (Sweden)

    Vitor Alexandre de Freitas Cardoso

    Full Text Available Este artigo apresenta estudo de caso do acidente ocorrido com o vôo RG-254 da Varig, em setembro de 1989. Partindo de informações de investigações oficiais, publicações, material audiovisual, entrevistas com envolvidos no acidente e especialistas em segurança de vôo, os autores re-analisam o acidente com enfoque sociotécnico referenciado na teoria ator-rede e no conceito de acidente "normal". O texto apresenta novo entendimento para a investigação de acidentes na aviação criticando a tradicional repartição de causas entre os chamados fatores "humanos", "técnicos" e "operacionais" e sugere aplicação do conceito de multicausalidade que não se restringe à mera listagem de "fatores contribuintes", mas que analisa as relações entre atores-redes envolvidos no sistema de aviação em que ocorreu o acidente. O acidente do RG-254 é descrito como sintoma do rompimento de relações entre os atores que atuam no sistema.

  13. Frozen spin targets

    CERN Document Server

    Parsons, A S L

    1976-01-01

    Describes six projects which use the frozen-spin principle: Helium-3 R.M.S. and longitudinally polarized frozen spin targets at Rutherford Laboratory, and the frozen spin targets at KEK, Saclay and the one used by the CERN-Helsinki collaboration. (7 refs).

  14. Seedling root targets

    Science.gov (United States)

    Diane L. Haase

    2011-01-01

    Roots are critical to seedling performance after outplanting. Although root quality is not as quick and simple to measure as shoot quality, target root characteristics should be included in any seedling quality assessment program. This paper provides a brief review of root characteristics most commonly targeted for operational seedling production. These are: root mass...

  15. Strategic Targeted Advertising

    NARCIS (Netherlands)

    A. Galeotti; J.L. Moraga-Gonzalez (José Luis)

    2003-01-01

    textabstractWe present a strategic game of pricing and targeted-advertising. Firms can simultaneously target price advertisements to different groups of customers, or to the entire market. Pure strategy equilibria do not exist and thus market segmentation cannot occur surely. Equilibria exhibit

  16. Segmented Target Design

    Science.gov (United States)

    Merhi, Abdul Rahman; Frank, Nathan; Gueye, Paul; Thoennessen, Michael; MoNA Collaboration

    2013-10-01

    A proposed segmented target would improve decay energy measurements of neutron-unbound nuclei. Experiments like this have been performed at the National Superconducting Cyclotron Laboratory (NSCL) located at Michigan State University. Many different nuclei are produced in such experiments, some of which immediately decay into a charged particle and neutron. The charged particles are bent by a large magnet and measured by a suite of charged particle detectors. The neutrons are measured by the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). With the current target setup, a nucleus in a neutron-unbound state is produced with a radioactive beam impinged upon a beryllium target. The resolution of these measurements is very dependent on the target thickness since the nuclear interaction point is unknown. In a segmented target using alternating layers of silicon detectors and Be-targets, the Be-target in which the nuclear reaction takes place would be determined. Thus the experimental resolution would improve. This poster will describe the improvement over the current target along with the status of the design. Work supported by Augustana College and the National Science Foundation grant #0969173.

  17. The CNGS target

    CERN Multimedia

    Patrice Loïez

    2005-01-01

    The CERN Neutrinos to Gran Sasso (CNGS) target ‘magazine’ of five target units. Each unit contains a series of 10-cm long graphite rods distributed over a length of 2 m. It is designed to maximize the number of secondary particles produced and hence the number of neutrinos. One unit is used at a time to prevent over heating.

  18. Targeted therapy in lymphoma

    Directory of Open Access Journals (Sweden)

    Cavalli Franco

    2010-11-01

    Full Text Available Abstract Discovery of new treatments for lymphoma that prolong survival and are less toxic than currently available agents represents an urgent unmet need. We now have a better understanding of the molecular pathogenesis of lymphoma, such as aberrant signal transduction pathways, which have led to the discovery and development of targeted therapeutics. The ubiquitin-proteasome and the Akt/mammalian target of rapamycin (mTOR pathways are examples of pathological mechanisms that are being targeted in drug development efforts. Bortezomib (a small molecule protease inhibitor and the mTOR inhibitors temsirolimus, everolimus, and ridaforolimus are some of the targeted therapies currently being studied in the treatment of aggressive, relapsed/refractory lymphoma. This review will discuss the rationale for and summarize the reported findings of initial and ongoing investigations of mTOR inhibitors and other small molecule targeted therapies in the treatment of lymphoma.

  19. Targets and teamwork

    DEFF Research Database (Denmark)

    Skinner, Timothy C; Lange, Karin S; Hoey, Hilary

    2017-01-01

    with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. Conclusions: The diabetes care....... Research Design and Methods: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed...... questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring. Results: Totally 1113 (53% male) children (mean age 8.0±2.1years) from 18 centers in 17 countries, along with parents and 113 health-care professionals, participated. There were substantial...

  20. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing of stainless steel. At the entrance to the target assembly was a scintillator screen, imprinted with circles every 5 mm in radius, which allowed to precisely aim the 26 GeV high-intensity proton beam from the PS onto the centre of the target rod. The scintillator screen was a 1 mm thick plate of Cr-doped alumina. See also 7903034 and 7905091.

  1. Target Price Accuracy

    Directory of Open Access Journals (Sweden)

    Alexander G. Kerl

    2011-04-01

    Full Text Available This study analyzes the accuracy of forecasted target prices within analysts’ reports. We compute a measure for target price forecast accuracy that evaluates the ability of analysts to exactly forecast the ex-ante (unknown 12-month stock price. Furthermore, we determine factors that explain this accuracy. Target price accuracy is negatively related to analyst-specific optimism and stock-specific risk (measured by volatility and price-to-book ratio. However, target price accuracy is positively related to the level of detail of each report, company size and the reputation of the investment bank. The potential conflicts of interests between an analyst and a covered company do not bias forecast accuracy.

  2. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available This research describes a quantitative methodology for deriving optimal exploration target zones based on a probabilistic mineral prospectivity map. In order to arrive at out objective, we provide a plausible answer to the following question: "Which...

  3. Delays in thick targets

    CERN Document Server

    Bennett, J R J

    2002-01-01

    The delays in the emission of radioactive particles from a thick target bombarded by high-energy protons is discussed in relation to the basic physical processes of diffusion and effusion through the target and ioniser. The delay time, relative to the decay time, is crucial to the efficiency of particle release at the exit of the ioniser. The principles of minimizing the delay times are discussed with reference to a mathematical model of the process, and some experimental examples are given.

  4. Cross-species analysis of Fc engineered anti-Lewis-Y human IgG1 variants in human neonatal receptor transgenic mice reveal importance of S254 and Y436 in binding human neonatal Fc receptor

    Science.gov (United States)

    Burvenich, Ingrid J. G.; Farrugia, William; Lee, Fook T.; Catimel, Bruno; Liu, Zhanqi; Makris, Dahna; Cao, Diana; O'Keefe, Graeme J.; Brechbiel, Martin W.; King, Dylan; Spirkoska, Violeta; Allan, Laura C.; Ramsland, Paul A.; Scott, Andrew M.

    2016-01-01

    ABSTRACT IgG has a long half-life through engagement of its Fc region with the neonatal Fc receptor (FcRn). The FcRn binding site on IgG1 has been shown to contain I253 and H310 in the CH2 domain and H435 in the CH3 domain. Altering the half-life of IgG has been pursued with the aim to prolong or reduce the half-life of therapeutic IgGs. More recent studies have shown that IgGs bind differently to mouse and human FcRn. In this study we characterize a set of hu3S193 IgG1 variants with mutations in the FcRn binding site. A double mutation in the binding site is necessary to abrogate binding to murine FcRn, whereas a single mutation in the FcRn binding site is sufficient to no longer detect binding to human FcRn and create hu3S193 IgG1 variants with a half-life similar to previously studied hu3S193 F(ab')2 (t1/2β, I253A, 12.23 h; H310A, 12.94; H435A, 12.57; F(ab')2, 12.6 h). Alanine substitutions in S254 in the CH2 domain and Y436 in the CH3 domain showed reduced binding in vitro to human FcRn and reduced elimination half-lives in huFcRn transgenic mice (t1/2β, S254A, 37.43 h; Y436A, 39.53 h; wild-type, 83.15 h). These variants had minimal effect on half-life in BALB/c nu/nu mice (t1/2β, S254A, 119.9 h; Y436A, 162.1 h; wild-type, 163.1 h). These results provide insight into the interaction of human Fc by human FcRn, and are important for antibody-based therapeutics with optimal pharmacokinetics for payload strategies used in the clinic. PMID:27030023

  5. Cross-species analysis of Fc engineered anti-Lewis-Y human IgG1 variants in human neonatal receptor transgenic mice reveal importance of S254 and Y436 in binding human neonatal Fc receptor.

    Science.gov (United States)

    Burvenich, Ingrid J G; Farrugia, William; Lee, Fook T; Catimel, Bruno; Liu, Zhanqi; Makris, Dahna; Cao, Diana; O'Keefe, Graeme J; Brechbiel, Martin W; King, Dylan; Spirkoska, Violeta; Allan, Laura C; Ramsland, Paul A; Scott, Andrew M

    2016-01-01

    IgG has a long half-life through engagement of its Fc region with the neonatal Fc receptor (FcRn). The FcRn binding site on IgG1 has been shown to contain I253 and H310 in the CH2 domain and H435 in the CH3 domain. Altering the half-life of IgG has been pursued with the aim to prolong or reduce the half-life of therapeutic IgGs. More recent studies have shown that IgGs bind differently to mouse and human FcRn. In this study we characterize a set of hu3S193 IgG1 variants with mutations in the FcRn binding site. A double mutation in the binding site is necessary to abrogate binding to murine FcRn, whereas a single mutation in the FcRn binding site is sufficient to no longer detect binding to human FcRn and create hu3S193 IgG1 variants with a half-life similar to previously studied hu3S193 F(ab')2 (t1/2β, I253A, 12.23 h; H310A, 12.94; H435A, 12.57; F(ab')2, 12.6 h). Alanine substitutions in S254 in the CH2 domain and Y436 in the CH3 domain showed reduced binding in vitro to human FcRn and reduced elimination half-lives in huFcRn transgenic mice (t1/2β, S254A, 37.43 h; Y436A, 39.53 h; wild-type, 83.15 h). These variants had minimal effect on half-life in BALB/c nu/nu mice (t1/2β, S254A, 119.9 h; Y436A, 162.1 h; wild-type, 163.1 h). These results provide insight into the interaction of human Fc by human FcRn, and are important for antibody-based therapeutics with optimal pharmacokinetics for payload strategies used in the clinic.

  6. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    A good dozen different targets are available for ISOLDE, made of different materials and equipped with different kinds of ion-sources, according to the needs of the experiments. Each separator (GPS: general purpose; HRS: high resolution) has its own target. Because of the high radiation levels, robots effect the target changes, about 80 times per year. In the standard unit shown in picture _01, the target is the cylindrical object in the front. It contains uranium-carbide kept at a temperature of 2200 deg C, necessary for the isotopes to be able to escape. At either end, one sees the heater current leads, carrying 700 A. The Booster beam, some 3E13 protons per pulse, enters the target from left. The evaporated isotope atoms enter a hot-plasma ion source (the black object behind the target). The whole unit sits at 60 kV potential (pulsed in synchronism with the arrival of the Booster beam) which accelerates the ions (away from the viewer) towards one of the 2 separators.

  7. Burglar Target Selection

    Science.gov (United States)

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  8. The Sinuous Target

    Energy Technology Data Exchange (ETDEWEB)

    Zwaska, R. [Fermilab

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  9. Setting reference targets

    Energy Technology Data Exchange (ETDEWEB)

    Ruland, R.E.

    1997-04-01

    Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets.

  10. Targeted Therapy of CLL.

    Science.gov (United States)

    Al-Sawaf, Othman; Fischer, Kirsten; Eichhorst, Barbara; Hallek, Michael

    2016-01-01

    The landscape of chronic lymphocytic leukemia (CLL) has undergone profound changes in the past years. First, the addition of CD20-targeting antibodies to conventional chemotherapy has improved the therapeutic outcome in the majority of CLL patients. Since the establishment of the critical role of the B cell receptor signaling pathway in the pathogenesis of CLL, several agents have been developed to target this pathway. Ibrutinib and idelalisib, 2 potent kinase inhibitors, have both become available for CLL therapy in the first and second line. Additionally, the observation of high expression levels of the anti-apoptotic mitochondrial protein Bcl-2 in CLL has led to the development of venetoclax, a BH3 mimetic compound that inhibits Bcl-2 and has shown high efficacy in CLL. This short review summarizes preclinical and clinical data on currently available agents in CLL and provides an outlook on upcoming new challenges in the targeted therapy of CLL. © 2016 S. Karger GmbH, Freiburg.

  11. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    Hill, Amanda Louise; Leinikka Dall, Ole; Andersen, Frits M.

    2014-01-01

    Within the European Union (EU) a paradigm shift is currently occurring in the waste sector, where EU waste directives and national waste strategies are placing emphasis on resource efficiency and recycling targets. The most recent Danish resource strategy calculates a national recycling rate of 22......% for household waste, and sets an ambitious goal of a 50% recycling rate by 2020. This study integrates the recycling target into the FRIDA model to project how much waste and from which streams should be diverted from incineration to recycling in order to achieve the target. Furthermore, it discusses how...... the existing technological, organizational and legislative frameworks may affect recycling activities. The results of the analysis show that with current best practice recycling rates, the 50% recycling rate cannot be reached without recycling of household biowaste. It also shows that all Danish municipalities...

  12. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available , Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results Optimal Exploration Target Zones Pravesh Debba1, Emmanual M.J. Carranza2, Alfred Stein2, Freek D. van der Meer2 1CSIR, Logistics... and Quantitative Methods, CSIR Built Environment 2International Institute for Geo-Information Science and Earth Observation (ITC), Hengelosestraat 99, P.O. Box 6, 7500AA Enschede, The Netherlands Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer...

  13. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

    The first version of the antiproton production target was a tungsten rod, 11 cm long (actually a row of 11 rods, each 1 cm long) and 3 mm in diameter. The rod was embedded in graphite, pressure-seated into an outer casing made of stainless steel. The casing had fins for forced-air cooling. In this picture, the 26 GeV high-intensity beam from the PS enters from the right, where a scintillator screen, with circles every 5 mm in radius, permits precise aim at the target centre. See also 7903034 and 7905094.

  14. An Assessment of Database-Validated microRNA Target Genes in Normal Colonic Mucosa: Implications for Pathway Analysis.

    Science.gov (United States)

    Slattery, Martha L; Herrick, Jennifer S; Stevens, John R; Wolff, Roger K; Mullany, Lila E

    2017-01-01

    Determination of functional pathways regulated by microRNAs (miRNAs), while an essential step in developing therapeutics, is challenging. Some miRNAs have been studied extensively; others have limited information. In this study, we focus on 254 miRNAs previously identified as being associated with colorectal cancer and their database-identified validated target genes. We use RNA-Seq data to evaluate messenger RNA (mRNA) expression for 157 subjects who also had miRNA expression data. In the replication phase of the study, we replicated associations between 254 miRNAs associated with colorectal cancer and mRNA expression of database-identified target genes in normal colonic mucosa. In the discovery phase of the study, we evaluated expression of 18 miR-NAs (those with 20 or fewer database-identified target genes along with miR-21-5p, miR-215-5p, and miR-124-3p which have more than 500 database-identified target genes) with expression of 17 434 mRNAs to identify new targets in colon tissue. Seed region matches between miRNA and newly identified targeted mRNA were used to help determine direct miRNA-mRNA associations. From the replication of the 121 miRNAs that had at least 1 database-identified target gene using mRNA expression methods, 97.9% were expressed in normal colonic mucosa. Of the 8622 target miRNA-mRNA associations identified in the database, 2658 (30.2%) were associated with gene expression in normal colonic mucosa after adjusting for multiple comparisons. Of the 133 miRNAs with database-identified target genes by non-mRNA expression methods, 97.2% were expressed in normal colonic mucosa. After adjustment for multiple comparisons, 2416 miRNA-mRNA associations remained significant (19.8%). Results from the discovery phase based on detailed examination of 18 miRNAs identified more than 80 000 miRNA-mRNA associations that had not previously linked to the miRNA. Of these miRNA-mRNA associations, 15.6% and 14.8% had seed matches for CRCh38 and CRCh37

  15. Aquaporin-2 membrane targeting

    DEFF Research Database (Denmark)

    Olesen, Emma T B; Fenton, Robert A

    2017-01-01

    The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis...

  16. ISOLDE back on target

    CERN Multimedia

    Anaïs Schaeffer

    2014-01-01

    Today, Friday 1 August, the ISOLDE installation, supplied by the beams of the PS Booster, restarted its physics programme. After a shutdown of almost a year and a half, there was a real buzz in the air as the first beam of protons hit the target of the first post-LS1 ISOLDE experiment.   One of the new target-handling robots installed by ISOLDE during LS1. Many improvements have been made to the ISOLDE installation during LS1. One of the main projects was the installation of new robots for handling the targets (see photo 1). “Our targets are bombarded by protons from the PS Booster’s beams and become very radioactive,” explains Maria Jose Garcia Borge, spokesperson for the ISOLDE collaboration. “They therefore need to be handled carefully, which is where the robots come in. The robots we had until now were already over 20 years old and were starting to suffer from the effects of radiation. So LS1 was a perfect opportunity to replace them with more moder...

  17. Microenvironmental targets in sarcoma

    Directory of Open Access Journals (Sweden)

    Monika eEhnman

    2015-11-01

    Full Text Available Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

  18. Target Heart Rates

    Science.gov (United States)

    ... is your level of intensity? When is the best time of day to work out? Target Heart Rates Warm Up, Cool Down See More >> Getting Active Getting Started - Tips for Long-term Exercise Success Get Moving: Easy Tips to Get Active! ...

  19. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, Thomas [Alphamed, Jackson, TN (United States); Moore, Herbert [Alphamed, Jackson, TN (United States)

    2016-12-05

    The research project, entitled ”Targeted Therapy for Melanoma,” was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the 212Pb/203Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg11)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of 212Pb labeled DOTA-Re(Arg11)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter 212Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  20. Target Chamber Manipulator

    Science.gov (United States)

    Tantillo, Anthony; Watson, Matthew

    2015-11-01

    A system has been developed to allow remote actuation of sensors in a high vacuum target chamber used with a particle accelerator. Typically, sensors of various types are placed into the target chamber at specific radial and angular positions relative to the beam line and target. The chamber is then evacuated and the experiments are performed for those sensor positions. Then, the chamber is opened, the sensors are repositioned to new angles or radii, and the process is repeated, with a separate pump-down cycle for each set of sensor positions. The new sensor positioning system allows scientists to pre-set the radii of up to a dozen sensors, and then remotely actuate their angular positions without breaking the vacuum of the target chamber. This reduces the time required to reposition sensors from 6 hours to 1 minute. The sensors are placed into one of two tracks that are separately actuated using vacuum-grade stepping motors. The positions of the sensors are verified using absolute optical rotary encoders, and the positions are accurate to 0.5 degrees. The positions of the sensors are electronically recorded and time-stamped after every change. User control is through a GUI using LabVIEW.

  1. Active Target Simulation

    Science.gov (United States)

    Smith, Nathan; Draznik, Peter; Frank, Nathan

    2012-10-01

    We have simulated an existing experimental design to determine the resolution improvement upon energy measurements of neutron unbound nuclei. A number of experiments of this type have been performed at the National Superconducting Cyclotron Laboratory (NSCL), located at Michigan State University. An excited nucleus is typically produced with a radioactive beam interacting with a passive Beryllium target. Many different nuclei are produced in experiment, each of which immediately decays into a charged particle and neutron. The charged particles are detected and the neutrons interact in scintillation detectors such as the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). In our simulation, we have constructed an active target that provides additional information such that the point of nuclear interaction within the target may be determined. This information improves the resolution in decay energy measurements of neutron unbound isotopes. This presentation will cover some aspects of the simulation process, as well as showing some of the results that demonstrate the simulated improvement over a passive target.

  2. Physics of polarized targets

    CERN Document Server

    Niinikoski, Tapio

    2014-01-01

    For developing, building and operating solid polarized targets we need to understand several fields of physics that have seen sub stantial advances during the last 50 years. W e shall briefly review a selection of those that are important today. These are: 1) quantum statistical methods to describe saturation and relaxation in magnetic resonance; 2) equal spin temperature model for dy namic nuclear polarization; 3 ) weak saturation during NMR polarization measurement; 4 ) refrigeration using the quantum fluid properties of helium isotopes. These, combined with superconducting magnet technologies, permit today to reach nearly complete pola rization of almost any nuclear spins. Targets can be operated in frozen spin mode in rather low and inhomogeneous field of any orientation, and in DNP mode in beams of high intensity. Beyond such experiments of nuclear and particle physics, applications a re also emerging in macromolecular chemistry and in magnetic resonance imaging. This talk is a tribute to Michel Borghini...

  3. Emerging Targets in Photopharmacology.

    Science.gov (United States)

    Lerch, Michael M; Hansen, Mickel J; van Dam, Gooitzen M; Szymanski, Wiktor; Feringa, Ben L

    2016-09-05

    The field of photopharmacology uses molecular photoswitches to establish control over the action of bioactive molecules. It aims to reduce systemic drug toxicity and the emergence of resistance, while achieving unprecedented precision in treatment. By using small molecules, photopharmacology provides a viable alternative to optogenetics. We present here a critical overview of the different pharmacological targets in various organs and a survey of organ systems in the human body that can be addressed in a non-invasive manner. We discuss the prospects for the selective delivery of light to these organs and the specific requirements for light-activatable drugs. We also aim to illustrate the druggability of medicinal targets with recent findings and emphasize where conceptually new approaches have to be explored to provide photopharmacology with future opportunities to bring "smart" molecular design ultimately to the realm of clinical use. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Inflation Targeting: Provisional Results

    Directory of Open Access Journals (Sweden)

    Cerna, Silviu

    2010-06-01

    Full Text Available Inflation targeting monetary policy framework that requires the central bank to achieve a low inflation has contributed to price stability in industrialized countries. As well as the other developing countries, ex communist countries have also tried to apply this strategy, which was susceptible to increase monetary policy transparency and to determine authorities to make necessary reforms in order to pass from a planned to a market economy. In Romania, inflation targeting has contributed, to a large extent, to price increase smoothening, without affecting economic growth. Knowing the factors that have determined this unquestionable success allows for not only understanding the Romanian transition process, but also draw some useful conclusions in view of the necessary actions for adopting the euro.

  5. Foucault on targets.

    Science.gov (United States)

    Lynch, John

    2004-01-01

    This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict.

  6. Antibodies Targeting EMT

    Science.gov (United States)

    2017-10-01

    VLDL uptake and redistribution of lipids to cells for energy metabolism and cell signaling. ApoE overexpression has shown to be associated with a...involved in testosterone and estradiol biosynthesis, as well as prostaglandin F synthesis and has previously been implicated in cancer progression, AKR1C2...is involved in androgen metabolism and is a potential drug target for prostate cancer. AKR1C4 is involved in bile acid synthesis but has not yet

  7. Explosive Target Balances

    OpenAIRE

    Potrafke, Niklas; Reischmann, Markus

    2013-01-01

    Using the new unit root test by Phillips et al. (2011) we show that the Target balances of the German Bundesbank have been exploding from the beginning of 2009 to the beginning of 2013. By implementing a full-allotment policy and reducing the required minimum quality of collaterals in October 2008, the European Central Bank (ECB) refinanced credits in the GIIPS countries to a large extent. Private capital flowed out of the GIIPS countries (Greece, Italy, Ireland, Portugal and Spain), and the ...

  8. Implementing Target Value Design.

    Science.gov (United States)

    Alves, Thais da C L; Lichtig, Will; Rybkowski, Zofia K

    2017-04-01

    An alternative to the traditional way of designing projects is the process of target value design (TVD), which takes different departure points to start the design process. The TVD process starts with the client defining an allowable cost that needs to be met by the design and construction teams. An expected cost in the TVD process is defined through multiple interactions between multiple stakeholders who define wishes and others who define ways of achieving these wishes. Finally, a target cost is defined based on the expected profit the design and construction teams are expecting to make. TVD follows a series of continuous improvement efforts aimed at reaching the desired goals for the project and its associated target value cost. The process takes advantage of rapid cycles of suggestions, analyses, and implementation that starts with the definition of value for the client. In the traditional design process, the goal is to identify user preferences and find solutions that meet the needs of the client's expressed preferences. In the lean design process, the goal is to educate users about their values and advocate for a better facility over the long run; this way owners can help contractors and designers to identify better solutions. This article aims to inform the healthcare community about tools and techniques commonly used during the TVD process and how they can be used to educate and support project participants in developing better solutions to meet their needs now as well as in the future.

  9. Inflation targeting and core inflation

    OpenAIRE

    Julie Smith

    2005-01-01

    This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

  10. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  11. Meeting the Aichi targets

    DEFF Research Database (Denmark)

    Funk, Stephan M; Conde, Dalia Amor; Lamoreux, John

    2017-01-01

    &s), is an excellent opportunity to achieve the Aichi 2020 Targets T11 (protected areas) and T12 (preventing species extinctions). AZE taxa have small, single-site populations that are especially vulnerable to human-induced extinctions, particularly for the many amphibians. We show that AZEs&s can be protected...... feasibly and cost-effectively, but action is urgent. We argue that the Alliance, whose initial main aim was to identify AZEs&s, must be followed up by a second-generation initiative that directs and co-ordinates AZE conservation activities on the ground. The prominent role of zoos, conservation NGOs...

  12. Polarized scintillator targets

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2000-05-01

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as "live" polarized targets in nuclear physics experiments.

  13. Polarized scintillator targets

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, B. van den E-mail: vandenbrandt@psi.ch; Bunyatova, E.I.; Hautle, P.; Konter, J.A.; Mango, S

    2000-05-21

    The hydrogen nuclei in an organic scintillator have been polarized to more than 80% and the deuterons in its fully deuterated version to 24%. The scintillator, doped with TEMPO, has been polarized dynamically in a field of 2.5 T in a vertical dilution refrigerator in which a plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat. Sizeable solid samples with acceptable optical properties and light output have been prepared and successfully operated as 'live' polarized targets in nuclear physics experiments.

  14. Targeting Prostate Cancer Metastasis

    Science.gov (United States)

    2015-09-01

    achieve this goal, we cultured high-invasive prostate cancer PC3 cells and treated them with the drugs/inhibitors that were proposed to target WASF3...groups (treated by DMSO), either treated by 100 μM CYT997 or 10 μM Dasatinib suppressed the cells to spread throughout the fish body (Fig. 4). As...have scr eened t he e f fect s o f mor e t han 40 drugs on invasion using cul tur ed prost ate cancer cells and f ound t hat tar geting multiple

  15. Targeting Nuclear Thymidylate Biosynthesis

    Science.gov (United States)

    Chon, James; Stover, Patrick J.; Field, Martha S.

    2016-01-01

    Thymidylate (dTMP) biosynthesis plays an essential and exclusive function in DNA synthesis and proper cell division, and therefore has been an attractive therapeutic target. Folate analogues, known as antifolates, and nucleotide analogs that inhibit the enzymatic action of the de novo thymidylate biosynthesis pathway and are commonly used in cancer treatment. In this review, we examine the mechanisms by which the antifolate 5-fluorouracil, as well as other dTMP synthesis inhibitors, function in cancer treatment in light of emerging evidence that dTMP synthesis occurs in the nucleus. Nuclear localization of the de novo dTMP synthesis pathway requires modification of the pathway enzymes by the small ubiquitin-like modifier (SUMO) protein. SUMOylation is required for nuclear localization of the de novo dTMP biosynthesis pathway, and disruption in the SUMO pathway inhibits cell proliferation in several cancer models. We summarize evidence that the nuclear localization of the dTMP biosynthesis pathway is a critical factor in the efficacy of antifolate-based therapies that target dTMP synthesis. PMID:27876557

  16. Targeted corneal transplantation.

    Science.gov (United States)

    Jhanji, Vishal; Mehta, Jod S; Sharma, Namrata; Sharma, Bhavana; Vajpayee, Rasik B

    2012-07-01

    Corneal transplantation surgery has moved from an era of conventional penetrating keratoplasty to selective replacement of the diseased corneal layer with complementary healthy donor corneal tissue. Anterior lamellar transplantation surgeries do not involve replacement of corneal endothelium, consequently eliminating the occurrence of endothelial rejection. Similarly, in diseases affecting the corneal endothelium, selective replacement with a lamellar lenticule bearing healthy endothelium provides better outcomes in terms of ocular surface, lesser astigmatism and quick visual recovery. In addition to the advantages of enhanced surgical outcomes, targeted corneal transplantation allows the use of one donor cornea for more than one recipient, thereby offering a viable solution to the problem of paucity of donor corneas. Evolving techniques of corneal transplantation have enabled better utilization of donor corneal tissue. Anterior lamellar as well as endothelial keratoplasty surgeries have become first-choice surgeries in appropriately selected cases. This review briefly discusses some of these novel surgical techniques. A better understanding of targeted corneal transplantation would lead to adaptation of the concept of component corneal surgery. This would further enable the corneal surgeons to circumvent the problem of donor corneal shortage especially in the developing world.

  17. Fixed target beams

    CERN Document Server

    Kain, V; Cettour-Cave, S; Cornelis, K; Fraser, M A; Gatignon, L; Goddard, B; Velotti, F

    2017-01-01

    The CERN SPS (Super Proton Synchrotron) serves asLHC injector and provides beam for the North Area fixedtarget experiments. At low energy, the vertical acceptancebecomes critical with high intensity large emittance fixed tar-get beams. Optimizing the vertical available aperture is a keyingredient to optimize transmission and reduce activationaround the ring. During the 2016 run a tool was developed toprovide an automated local aperture scan around the entirering.The flux of particles slow extracted with the1/3inte-ger resonance from the Super Proton Synchrotron at CERNshould ideally be constant over the length of the extractionplateau, for optimum use of the beam by the fixed target ex-periments in the North Area. The extracted intensity is con-trolled in feed-forward correction of the horizontal tune viathe main SPS quadrupoles. The Mains power supply noiseat 50 Hz and harmonics is also corrected in feed-forwardby small amplitude tune modulation at the respective fre-quencies with a dedicated additional quad...

  18. Old Drug, New Target

    Science.gov (United States)

    Andrews, William J.; Panova, Tatiana; Normand, Christophe; Gadal, Olivier; Tikhonova, Irina G.; Panov, Konstantin I.

    2013-01-01

    Transcription by RNA polymerase I (Pol-I) is the main driving force behind ribosome biogenesis, a fundamental cellular process that requires the coordinated transcription of all three nuclear polymerases. Increased Pol-I transcription and the concurrent increase in ribosome biogenesis has been linked to the high rates of proliferation in cancers. The ellipticine family contains a number of potent anticancer therapeutic agents, some having progressed to stage I and II clinical trials; however, the mechanism by which many of the compounds work remains unclear. It has long been thought that inhibition of Top2 is the main reason behind the drugs antiproliferative effects. Here we report that a number of the ellipticines, including 9-hydroxyellipticine, are potent and specific inhibitors of Pol-I transcription, with IC50 in vitro and in cells in the nanomolar range. Essentially, the drugs did not affect Pol-II and Pol-III transcription, demonstrating a high selectivity. We have shown that Pol-I inhibition occurs by a p53-, ATM/ATR-, and Top2-independent mechanism. We discovered that the drug influences the assembly and stability of preinitiation complexes by targeting the interaction between promoter recognition factor SL1 and the rRNA promoter. Our findings will have an impact on the design and development of novel therapeutic agents specifically targeting ribosome biogenesis. PMID:23293027

  19. Quantum state targeting

    Science.gov (United States)

    Rudolph, Terry; Spekkens, Robert W.

    2004-11-01

    We introduce a primitive for quantum cryptography that we term “state targeting.” We show that increasing one’s probability of success in this task above a minimum amount implies an unavoidable increase in the probability of a particular kind of failure. This is analogous to the unavoidable disturbance to a quantum state that results from gaining information about its identity, and can be shown to be a purely quantum effect. We solve various optimization problems for state targeting that are useful for the security analysis of two-party cryptographic tasks implemented between remote antagonistic parties. Although we focus on weak coin flipping, the results are significant for other two-party protocols, such as strong coin flipping, partially binding and concealing bit commitment, and bit escrow. Furthermore, the results have significance not only for the traditional notion of security in cryptography, that of restricting a cheater’s ability to bias the outcome of the protocol, but also for a different notion of security that arises only in the quantum context, that of cheat sensitivity. Finally, our analysis leads to some interesting secondary results, namely, a generalization of Uhlmann’s theorem and an operational interpretation of the fidelity between two mixed states.

  20. Target Housing Material Options

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-02-11

    With gas cooling, heat transfer coefficients are low compared to water. The benefit of gas from a heat transfer point of view is that there is really no upper temperature limit for the coolant, as compared to water, which is limited ultimately by the critical point, and in practice the critical heat flux. In our case with parallel flow channels, water is limited to even lower operating limits by nucleate boiling. So gas can get as hot as the containment material will allow, but to get the density and heat transfer up to something reasonable, we must also increase pressure, thus increasing stress on the containment, namely the front and back faces. We are designing to ASME BPVC, which, for most materials allows a maximum stress of UTS/3. So we want the highest possible UTS. For reference, the front face stress in the 12 mm target at 300 psi was about 90 MPa. The inconel 718 allowable stress at 900°C is 1/3 of 517 or 172 MPa. So we are in a very safe place, but the uTS is dropping rapidly with temperature above 900°C. As we increase target diameter, the challenge will be to keep the stress down. We are probably looking at keeping the allowable at or above the present value, and at as high a temperature as possible.

  1. Targeting adipose tissue

    Directory of Open Access Journals (Sweden)

    Haas Bodo

    2012-10-01

    Full Text Available Abstract Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT is generally known and stores excess energy in the form of triacylglycerol (TG, insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP. The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET, however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs, activators of peroxisome proliferator-activated receptor γ (PPARγ a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  2. Targeting adipose tissue.

    Science.gov (United States)

    Haas, Bodo; Schlinkert, Paul; Mayer, Peter; Eckstein, Niels

    2012-10-27

    Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor γ (PPARγ) a 'master' regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  3. Low intensity beam target unit

    CERN Multimedia

    CERN PhotoLab

    1976-01-01

    This is a wheel fitted with many targets around its periphery (each with three longitudinally arranged thin rods) of which one is placed into the beam via a rotation of the wheel. Upstream of each target is placed a luminescent screen, aligbed on each target axis and viewed with a TV camera, to make sure that one is hitting the target. This target unit was probably used to study target's behaviour (like beam heating). Gualtiero Del Torre stands on the left, Pierre Gerdil on the right.

  4. Reference: 254 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available ers A et al. 2005 Sep. Plant Cell 17(9):2554-63. TIP GROWTH DEFECTIVE1 (TIP1) of Arabidopsis thaliana affects...rol of protein hydrophobicity and affects protein association with membranes, signal transduction, and vesic

  5. 36 CFR 254.40 - Applications.

    Science.gov (United States)

    2010-07-01

    ... System land must be made in writing to the District Ranger or the Forest Supervisor who has administrative jurisdiction over the land. (b) The applicant shall bear all reasonable costs of administration...

  6. Publications | Page 254 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Through books, articles, research publications, and studies, we aim to widen the impact of our investment and advance development research. ... This important and well-researched book examines the challenges to private sector growth in 12 Middle East and North African countries, assessing comparative performance ...

  7. 30 CFR 254.6 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... injection into a pipeline. It does not include petroleum, including crude oil or any fraction thereof, which... and greases and fish and marine mammal oils, within the meaning of paragraph (2) of section 61(a) of... Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OIL-SPILL RESPONSE REQUIREMENTS...

  8. Publications | Page 254 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Much of this biodiversity is highly vulnerable to climate change. So too are the rainfed agriculture,... Understanding adaptation decisions in Morocco's plains and mountains. In Morocco, the threat posed by climate change has been recognized for some time by decision-makers at national and provincial levels. Erratic rainfall ...

  9. 36 CFR 254.9 - Appraisals.

    Science.gov (United States)

    2010-07-01

    ... Acquisition Conference 1992 (Washington, DC, 1992), ISBN 0-16-038050-2 when appraising the values of the..., impartial, and has training and experience in appraising property similar to the property involved in the...: (i) Determine the highest and best use of the property to be appraised; (ii) Estimate the value of...

  10. 36 CFR 254.3 - Requirements.

    Science.gov (United States)

    2010-07-01

    ... supporting rationale shall be documented and made part of the administrative record. (c) Equal value... appraisal(s), through bargaining based on appraisal(s), through other acceptable and commonly recognized... in the exchange and shall provide notice of known storage, release, or disposal of hazardous...

  11. Publications | Page 254 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Seeing climate vulnerabilities through lived experience in Madagascar. Madagascar, the world's fourth largest island, is home to an astonishing range of life forms found nowhere else on the planet. Much of this biodiversity is highly vulnerable to climate change. So too are the rainfed agriculture,... CCAA resources on M&E.

  12. 254-IJBCS-Article-Prof. Msafiri Jackson

    African Journals Online (AJOL)

    Dr Gatsing

    Atomic Absorption Spectrometric methods were correspondingly used for analysis of NO2, SPM, and particulate lead. Results have shown that ... junction, and bus stations and quantified air pollutants such as sulphur dioxide (SO2), ... pollutants include industries (large and small scale), construction, traffic, open burning of.

  13. Issues in Target Tracking

    Science.gov (United States)

    2010-05-01

    simulations we take as ground truth that the target moves at 10m/s heading west and 5m/s heading north, starting from ( 5000m , 35000m). The emitted frequency is... runs , the estimated initial and final positions fall into the 99% confidence region. −1 −0.8 −0.6 −0.4 −0.2 0 0.2 0.4 0.6 0.8 1 x 10 4 0 0.5 1 1.5 2 2.5...position of trajectories. “F”: final position of trajectories. Right: The true and estimated trajectories from 100 Monte Carlo runs for Johnson noise

  14. Bradycardia During Targeted Temperature Management

    DEFF Research Database (Denmark)

    Thomsen, Jakob Hartvig; Nielsen, Niklas; Hassager, Christian

    2016-01-01

    OBJECTIVES: Bradycardia is common during targeted temperature management, likely being a physiologic response to lower body temperature, and has recently been associated with favorable outcome following out-of-hospital cardiac arrest in smaller observational studies. The present study sought...... to confirm this finding in a large multicenter cohort of patients treated with targeted temperature management at 33°C and explore the response to targeted temperature management targeting 36°C. DESIGN: Post hoc analysis of a prospective randomized study. SETTING: Thirty-six ICUs in 10 countries. PATIENTS......: We studied 447 (targeted temperature management = 33°C) and 430 (targeted temperature management = 36°C) comatose out-of-hospital cardiac arrest patients with available heart rate data, randomly assigned in the targeted temperature management trial from 2010 to 2013. INTERVENTIONS: Targeted...

  15. Characterization of solid hydrogen targets

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, M.C. [British Columbia Univ., Vancouver, BC (Canada); Bailey, J.M.; Mulhauser, F. [Chester Technology (United Kingdom); Beer, G.A.; Douglas, J.L.; Knowles, P.E.; Maier, M.; Mason, G.R.; Olin, A.; Porcelli, T.A. [Victoria Univ., BC (Canada); Beveridge, J.L.; Marshall, G.M. [British Columbia Univ., Vancouver, BC (Canada). TRIUMF Facility; Huber, T.M. [Gustavus Adolphus Coll., St. Peter, MN (United States); Jacot-Guillarmod, R. [Fribourg Univ. (Switzerland); Kammel, P. [Lawrence Berkeley Lab., CA (United States); Kim, S.K. [Jeonbuk National Univ., Jeonju City (Korea, Republic of); Kunselman, A.R. [Wyoming Univ., Laramie, WY (United States); Martoff, C.J. [Temple Univ., Philadelphia, PA (United States); Petitjean, C. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Zmeskal, J. [Oesterreichische Akademie der Wissenschaften, Vienna (Austria)

    1996-10-01

    In experiments using the TRIUMF solid hydrogen target system, the knowledge of the target thickness and uniformity is often essential in order to extract physical parameters from the data. We have characterized the thickness and uniformity of frozen targets using the energy loss of alpha particles. An accuracy of {approx}5% was achieved, a limit imposed by the uncertainty in the stopping powers. The details of the method are described, and the thickness calibration of the target is presented. (orig.). 11 refs.

  16. Target noise in overlay metrology

    Science.gov (United States)

    Seligson, Joel L.; Adel, Mike E.; Izikson, Pavel; Levinski, Vladimir; Yaffe, Dan

    2004-05-01

    We have developed a method for calculating the statistical effects of spatial noise on the overlay measurement extracted from a given overlay target. The method has been applied to two kinds of overlay targets on three process layers, and the new metric, Target Noise, has been shown to correlate well to the random component of Overlay Mark Fidelity. A significant difference in terms of robustness has been observed between AIM targets and conventional Frame-in-Frame targets. The results fit well into the spatial noise hierarchy presented in this paper.

  17. EURISOL High Power Targets

    CERN Document Server

    Kadi, Y; Lindroos, M; Ridikas, D; Stora, T; Tecchio, L; CERN. Geneva. BE Department

    2009-01-01

    Modern Nuclear Physics requires access to higher yields of rare isotopes, that relies on further development of the In-flight and Isotope Separation On-Line (ISOL) production methods. The limits of the In-Flight method will be applied via the next generation facilities FAIR in Germany, RIKEN in Japan and RIBF in the USA. The ISOL method will be explored at facilities including ISAC-TRIUMF in Canada, SPIRAL-2 in France, SPES in Italy, ISOLDE at CERN and eventually at the very ambitious multi-MW EURISOL facility. ISOL and in-flight facilities are complementary entities. While in-flight facilities excel in the production of very short lived radioisotopes independently of their chemical nature, ISOL facilities provide high Radioisotope Beam (RIB) intensities and excellent beam quality for 70 elements. Both production schemes are opening vast and rich fields of nuclear physics research. In this article we will introduce the targets planned for the EURISOL facility and highlight some of the technical and safety cha...

  18. The target effect: visual memory for unnamed search targets.

    Science.gov (United States)

    Thomas, Mark D; Williams, Carrick C

    2014-01-01

    Search targets are typically remembered much better than other objects even when they are viewed for less time. However, targets have two advantages that other objects in search displays do not have: They are identified categorically before the search, and finding them represents the goal of the search task. The current research investigated the contributions of both of these types of information to the long-term visual memory representations of search targets. Participants completed either a predefined search or a unique-object search in which targets were not defined with specific categorical labels before searching. Subsequent memory results indicated that search target memory was better than distractor memory even following ambiguously defined searches and when the distractors were viewed significantly longer. Superior target memory appears to result from a qualitatively different representation from those of distractor objects, indicating that decision processes influence visual memory.

  19. Guidance and targeting for the Strategic Target System

    Science.gov (United States)

    White, John E.

    Guidance algorithms and targeting procedures for the Strategic Target System (STARS) launch vehicle are described. The STARS vehicle is a three stage booster, based partly upon retired Polaris A3 missile assets, which is intended to support development and testing of the Strategic Defense Initiative by delivering target payloads to the vicinity of the Kwajalein Atoll. STARS will be launched from the Kauai Test Facility located on Kauai, Hawaii. The STARS guidance objective is to deliver payloads to a prescribed target location with maximum accuracy at intercontinental ballistic missile velocities. Mission objectives are achieved with a combination of guidance algorithms.

  20. Oxide Fiber Targets at ISOLDE

    CERN Document Server

    Köster, U; Carminati, D; Catherall, R; Cederkäll, J; Correia, J G; Crepieux, B; Dietrich, M; Elder, K; Fedosseev, V; Fraile-Prieto, L M; Franchoo, S; Fynbo, H O U; Georg, U; Giles, T; Joinet, A; Jonsson, O C; Kirchner, R; Lau, C; Lettry, Jacques; Maier, H J; Mishin, V I; Oinonen, M; Peräjärvi, K; Ravn, H L; Rinaldi, T; Santana-Leitner, M; Wahl, U; Weissman, L

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxyde fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points. The experience with various oxyde fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process or by burning commercial gas lantern mantle cloth. In the future a beryllia fiber target could be used to produce...

  1. Therapeutic Targeting of Telomerase

    Directory of Open Access Journals (Sweden)

    Kathrin Jäger

    2016-07-01

    Full Text Available Telomere length and cell function can be preserved by the human reverse transcriptase telomerase (hTERT, which synthesizes the new telomeric DNA from a RNA template, but is normally restricted to cells needing a high proliferative capacity, such as stem cells. Consequently, telomerase-based therapies to elongate short telomeres are developed, some of which have successfully reached the stage I in clinical trials. Telomerase is also permissive for tumorigenesis and 90% of all malignant tumors use telomerase to obtain immortality. Thus, reversal of telomerase upregulation in tumor cells is a potential strategy to treat cancer. Natural and small-molecule telomerase inhibitors, immunotherapeutic approaches, oligonucleotide inhibitors, and telomerase-directed gene therapy are useful treatment strategies. Telomerase is more widely expressed than any other tumor marker. The low expression in normal tissues, together with the longer telomeres in normal stem cells versus cancer cells, provides some degree of specificity with low risk of toxicity. However, long term telomerase inhibition may elicit negative effects in highly-proliferative cells which need telomerase for survival, and it may interfere with telomere-independent physiological functions. Moreover, only a few hTERT molecules are required to overcome senescence in cancer cells, and telomerase inhibition requires proliferating cells over a sufficient number of population doublings to induce tumor suppressive senescence. These limitations may explain the moderate success rates in many clinical studies. Despite extensive studies, only one vaccine and one telomerase antagonist are routinely used in clinical work. For complete eradication of all subpopulations of cancer cells a simultaneous targeting of several mechanisms will likely be needed. Possible technical improvements have been proposed including the development of more specific inhibitors, methods to increase the efficacy of vaccination

  2. Target Acquisition Methodology Enhancement (TAME)

    Science.gov (United States)

    1989-03-01

    acquisition probability from COMINT, PCOM , against all communications type targets, is determined offline by a stochastic model for subsequent...of PN over all replications. F-4 f. Computes overall acquisition probability, PCOM , against all communications type targets as C: PCOM = (1. - PN...NNET where NNET denotes the number of nets which the target is in. F-6. TOTAL ACQUISITION PROBABILITY. With PNCj and PCOM computed as above, the

  3. Guidance system for laser targets

    Science.gov (United States)

    Porter, Gary D.; Bogdanoff, Anatoly

    1978-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  4. Targeted nanotechnology for cancer imaging.

    Science.gov (United States)

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B; Karathanasis, Efstathios

    2014-09-30

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Targets and Secondary Beam Extraction

    Science.gov (United States)

    Noah, Etam

    2014-02-01

    Several applications make use of secondary beams of particles generated by the interaction of a primary beam of particles with a target. Spallation neutrons, bremsstrahlung photon-produced neutrons, radioactive ions and neutrinos are available to users at state-of-the-art facilities worldwide. Plans for even higher secondary beam intensities place severe constraints on the design of targets. This article reports on the main targetry challenges and highlights a variety of solutions for targetry and secondary beam extraction. Issues related to target station layout, instrumentation at the beam-target interface, safety and radioprotection are also discussed.

  6. Achieving Plant CRISPR Targeting that Limits Off-Target Effects

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Wolt

    2016-11-01

    Full Text Available The CRISPR-Cas9 system (clustered regularly interspaced short palindromic repeats with associated Cas9 protein has been used to generate targeted changes for direct modification of endogenous genes in an increasing number of plant species; but development of plant genome editing has not yet fully considered potential off-target mismatches that may lead to unintended changes within the genome. Assessing the specificity of CRISPR-Cas9 for increasing editing efficiency as well as the potential for unanticipated downstream effects from off-target mutations is an important regulatory consideration for agricultural applications. Increasing genome-editing specificity entails developing improved design methods that better predict the prevalence of off-target mutations as a function of genome composition and design of the engineered ribonucleoprotein (RNP. Early results from CRISPR-Cas9 genome editing in plant systems indicate that the incidence of off-target mutation frequencies is quite low; however, by analyzing CRISPR-edited plant lines and improving both computational tools and reagent design, it may be possible to further decrease unanticipated effects at potential mismatch sites within the genome. This will provide assurance that CRISPR-Cas9 reagents can be designed and targeted with a high degree of specificity. Improved and experimentally validated design tools for discriminating target and potential off-target positions that incorporate consideration of the designed nuclease fidelity and selectivity will help to increase confidence for regulatory decision making for genome-edited plants.

  7. Literature evidence in open targets - a target validation platform.

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

    We present the Europe PMC literature component of Open Targets - a target validation platform that integrates various evidence to aid drug target identification and validation. The component identifies target-disease associations in documents and ranks the documents based on their confidence from the Europe PMC literature database, by using rules utilising expert-provided heuristic information. The confidence score of a given document represents how valuable the document is in the scope of target validation for a given target-disease association by taking into account the credibility of the association based on the properties of the text. The component serves the platform regularly with the up-to-date data since December, 2015. Currently, there are a total number of 1168365 distinct target-disease associations text mined from >26 million PubMed abstracts and >1.2 million Open Access full text articles. Our comparative analyses on the current available evidence data in the platform revealed that 850179 of these associations are exclusively identified by literature mining. This component helps the platform's users by providing the most relevant literature hits for a given target and disease. The text mining evidence along with the other types of evidence can be explored visually through https://www.targetvalidation.org and all the evidence data is available for download in json format from https://www.targetvalidation.org/downloads/data .

  8. Transverse target spin asymmetries on a proton target at COMPASS

    CERN Document Server

    Richter, Andreas

    2009-01-01

    Transversity and transverse momentum-dependent parton distribution functions (TMDs) are been measured in semi-inclusive deep inelastic scattering (SIDIS) by using a transversely polarized target at the COMPASS experiment. COMPASS is a fixed target experiment at the CERN M2 beamline, which provides a 160GeV/c polarized m+ beam. In the years 2002-2004 COMPASS has collected data with a transversely polarized deuteron 6LiD target. In 2007, COMPASS has used for the first time a proton NH3 target. To access transversity COMPASS has used three different quark polarimeters: the Collins effect, responsible for an azimuthal asymmetry in the single hadron distribution, azimuthal target spin asymmetries of charged hadron pairs and the transverse polarisation of L hyperons. Beside this also the Sivers asymmetry arising from the correlation between the transverse nucleon spin and the quark intrinsic transverse momentum was measured. European

  9. Degradation kinetics and mechanism of β-lactam antibiotics by the activation of H{sub 2}O{sub 2} and Na{sub 2}S{sub 2}O{sub 8} under UV-254 nm irradiation

    Energy Technology Data Exchange (ETDEWEB)

    He, Xuexiang [Environmental Engineering and Science Program, University of Cincinnati, Cincinnati, OH 45221-0012 (United States); Department of Civil and Environmental Engineering and Nireas-International Water Research Centre, School of Engineering, University of Cyprus, PO Box 20537, 1678 Nicosia (Cyprus); Mezyk, Stephen P. [Department of Chemistry and Biochemistry, California State University Long Beach, 1250 Bellflower Blvd., Long Beach, CA 90840 (United States); Michael, Irene; Fatta-Kassinos, Despo [Department of Civil and Environmental Engineering and Nireas-International Water Research Centre, School of Engineering, University of Cyprus, PO Box 20537, 1678 Nicosia (Cyprus); Dionysiou, Dionysios D., E-mail: dionysios.d.dionysiou@uc.edu [Environmental Engineering and Science Program, University of Cincinnati, Cincinnati, OH 45221-0012 (United States); Department of Civil and Environmental Engineering and Nireas-International Water Research Centre, School of Engineering, University of Cyprus, PO Box 20537, 1678 Nicosia (Cyprus)

    2014-08-30

    Graphical abstract: - Highlights: • Removal efficiency was comparable at different UV fluence rates but same fluence. • Reducing pH to 3 or 2 did not inhibit the removal of nitrobenzene by UV/S{sub 2}O{sub 8}{sup 2−}. • 1.84 × 10{sup −14} M [HO{sup •} ]{sub ss} and 3.10 × 10{sup −13} M [SO{sub 4}{sup •} {sup −}]{sub ss} in UV/S{sub 2}O{sub 8}{sup 2−} were estimated. • HO{sup •} reacted faster with the β-lactams than SO{sub 4}{sup •} {sup −} but sharing similar byproducts. • Transformation pathways included hydroxylation, hydrolysis and decarboxylation. - Abstract: The extensive production and usage of antibiotics have led to an increasing occurrence of antibiotic residuals in various aquatic compartments, presenting a significant threat to both ecosystem and human health. This study investigated the degradation of selected β-lactam antibiotics (penicillins: ampicillin, penicillin V, and piperacillin; cephalosporin: cephalothin) by UV-254 nm activated H{sub 2}O{sub 2} and S{sub 2}O{sub 8}{sup 2−} photochemical processes. The UV irradiation alone resulted in various degrees of direct photolysis of the antibiotics; while the addition of the oxidants improved significantly the removal efficiency. The steady-state radical concentrations were estimated, revealing a non-negligible contribution of hydroxyl radicals in the UV/S{sub 2}O{sub 8}{sup 2−} system. Mineralization of the β-lactams could be achieved at high UV fluence, with a slow formation of SO{sub 4}{sup 2−} and a much lower elimination of total organic carbon (TOC). The transformation mechanisms were also investigated showing the main reaction pathways of hydroxylation (+16 Da) at the aromatic ring and/or the sulfur atom, hydrolysis (+18 Da) at the β-lactam ring and decarboxylation (–44 Da) for the three penicillins. Oxidation of amine group was also observed for ampicillin. This study suggests that UV/H{sub 2}O{sub 2} and UV/S{sub 2}O{sub 8}{sup 2−} advanced

  10. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS...

  11. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R

    2016-01-01

    BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this t...

  12. Saccadic adaptation to moving targets.

    Directory of Open Access Journals (Sweden)

    Katharina Havermann

    Full Text Available Saccades are so called ballistic movements which are executed without online visual feedback. After each saccade the saccadic motor plan is modified in response to post-saccadic feedback with the mechanism of saccadic adaptation. The post-saccadic feedback is provided by the retinal position of the target after the saccade. If the target moves after the saccade, gaze may follow the moving target. In that case, the eyes are controlled by the pursuit system, a system that controls smooth eye movements. Although these two systems have in the past been considered as mostly independent, recent lines of research point towards many interactions between them. We were interested in the question if saccade amplitude adaptation is induced when the target moves smoothly after the saccade. Prior studies of saccadic adaptation have considered intra-saccadic target steps as learning signals. In the present study, the intra-saccadic target step of the McLaughlin paradigm of saccadic adaptation was replaced by target movement, and a post-saccadic pursuit of the target. We found that saccadic adaptation occurred in this situation, a further indication of an interaction of the saccadic system and the pursuit system with the aim of optimized eye movements.

  13. Saccadic adaptation to moving targets.

    Science.gov (United States)

    Havermann, Katharina; Volcic, Robert; Lappe, Markus

    2012-01-01

    Saccades are so called ballistic movements which are executed without online visual feedback. After each saccade the saccadic motor plan is modified in response to post-saccadic feedback with the mechanism of saccadic adaptation. The post-saccadic feedback is provided by the retinal position of the target after the saccade. If the target moves after the saccade, gaze may follow the moving target. In that case, the eyes are controlled by the pursuit system, a system that controls smooth eye movements. Although these two systems have in the past been considered as mostly independent, recent lines of research point towards many interactions between them. We were interested in the question if saccade amplitude adaptation is induced when the target moves smoothly after the saccade. Prior studies of saccadic adaptation have considered intra-saccadic target steps as learning signals. In the present study, the intra-saccadic target step of the McLaughlin paradigm of saccadic adaptation was replaced by target movement, and a post-saccadic pursuit of the target. We found that saccadic adaptation occurred in this situation, a further indication of an interaction of the saccadic system and the pursuit system with the aim of optimized eye movements.

  14. Target recognition by wavelet transform

    CERN Document Server

    Li Zheng Dong; He Wu Liang; Pei Chun Lan; Peng Wen; SongChen; Zheng Xiao Dong

    2002-01-01

    Wavelet transform has an important character of multi-resolution power, which presents pyramid structure, and this character coincides the way by which people distinguish object from coarse to fineness and from large to tiny. In addition to it, wavelet transform benefits to reducing image noise, simplifying calculation, and embodying target image characteristic point. A method of target recognition by wavelet transform is provided

  15. ISOLDE target zone control room

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  16. Targeted marketing and public health.

    Science.gov (United States)

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

  17. Oxide fiber targets at ISOLDE

    DEFF Research Database (Denmark)

    Köster, U.; Bergmann, U.C.; Carminati, D.

    2003-01-01

    Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxide fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some...... contact points. The experience with various oxide fiber targets (titania, zirconia, ceria and thoria) used in the last years at ISOLDE is reviewed. For short-lived isotopes of Cu, Ga and Xe the zirconia and ceria targets respectively provided significantly higher yields than any other target (metal foils......, oxide powders, etc.) tested before. Titania fibers, which were not commercially available, were produced in a relic process by impregnation of a rayon felt in a titanium chloride solution and subsequent calcination by heating the dried felt in air. Thoria fibers were obtained either by the same process...

  18. The Bering Target Tracking Instrumentation

    DEFF Research Database (Denmark)

    Denver, Troelz; Jørgensen, John Leif; Betto, Maurizio

    2003-01-01

    The key science instrument on the Bering satellite mission is a relative small telescope with an entrance aperture of 300 mm and a focal length between 500 and 1000 mm. The detection of potential targets is performed by one of the target scanning advanced stellar compasses (ASCs). This procedure...... results in a simple prioritized list of right ascension, declination, proper motion and intensity of each prospective target. The telescope itself has a dedicated ASC Camera Head Unit (CHU) mounted on the secondary mirror, largely co-aligned with the telescope. This CHU accurately determines the telescope......'s pointing direction. To achieve fast tracking over a large solid angle, the telescope pointing is achieved by means of a folding mirror in the optical pathway. When a prospective target approaches the telescope FOV, the ASC on the secondary will guide the folding mirror into position such that the target...

  19. High speed cryogenic monodisperse targets

    Science.gov (United States)

    Boukharov, A.; Vishnevkii, E.

    2017-11-01

    The basic possibility of creation of high speed cryogenic monodisperse targets is shown. According to calculations at input of thin liquid cryogenic jets with a velocity of bigger 100 m/s in vacuum the jets don’t manage to freeze at distance to 1 mm and can be broken into monodisperse drops. Drops due to evaporation are cooled and become granules. High speed cryogenic monodisperse targets have the following advantages: direct input in vacuum (there is no need for a chamber of a triple point chamber and sluices), it is possible to use the equipment of a cluster target, it is possible to receive targets with a diameter of D 100m/s), exact synchronization of the target hitting moment in a beam with the moment of sensors turning on.

  20. Target Selection and Deselection at the Berkeley StructuralGenomics Center

    Energy Technology Data Exchange (ETDEWEB)

    Chandonia, John-Marc; Kim, Sung-Hou; Brenner, Steven E.

    2005-03-22

    At the Berkeley Structural Genomics Center (BSGC), our goalis to obtain a near-complete structural complement of proteins in theminimal organisms Mycoplasma genitalium and M. pneumoniae, two closelyrelated pathogens. Current targets for structure determination have beenselected in six major stages, starting with those predicted to be mosttractable to high throughput study and likely to yield new structuralinformation. We report on the process used to select these proteins, aswell as our target deselection procedure. Target deselection reducesexperimental effort by eliminating targets similar to those recentlysolved by the structural biology community or other centers. We measurethe impact of the 69 structures solved at the BSGC as of July 2004 onstructure prediction coverage of the M. pneumoniae and M. genitaliumproteomes. The number of Mycoplasma proteins for which thefold couldfirst be reliably assigned based on structures solved at the BSGC (24 M.pneumoniae and 21 M. genitalium) is approximately 25 percent of the totalresulting from work at all structural genomics centers and the worldwidestructural biology community (94 M. pneumoniae and 86M. genitalium)during the same period. As the number of structures contributed by theBSGC during that period is less than 1 percent of the total worldwideoutput, the benefits of a focused target selection strategy are apparent.If the structures of all current targets were solved, the percentage ofM. pneumoniae proteins for which folds could be reliably assigned wouldincrease from approximately 57 percent (391 of 687) at present to around80 percent (550 of 687), and the percentage of the proteome that could beaccurately modeled would increase from around 37 percent (254 of 687) toabout 64 percent (438 of 687). In M. genitalium, the percentage of theproteome that could be structurally annotated based on structures of ourremaining targets would rise from 72 percent (348 of 486) to around 76percent (371 of 486), with the

  1. Tracking Target and Spiral Waves

    DEFF Research Database (Denmark)

    Jensen, Flemming G.; Sporring, Jon; Nielsen, Mads

    2002-01-01

    A new algorithm for analyzing the evolution of patterns of spiral and target waves in large aspect ratio chemical systems is introduced. The algorithm does not depend on finding the spiral tip but locates the center of the pattern by a new concept, called the spiral focus, which is defined...... by the evolutes of the actual spiral or target wave. With the use of Gaussian smoothing, a robust method is developed that permits the identification of targets and spirals foci independently of the wave profile. Examples of an analysis of long image sequences from experiments with the Belousov...

  2. Hydrophobically Modified Glycol Chitosan Nanoparticles for Targeting Breast Cancer Microcalcification Using Alendronate Probes

    Science.gov (United States)

    Vishnu, Kamalakannan

    In 2016, invasive breast cancer was diagnosed in about 246,660 women and 2,600 men. An additional 61,000 new cases of in situ breast cancer was diagnosed in women. Microcalcifications are most common abnormalities detected by mammography for breast cancer, present in about 30% of all malignant breast lesions. Tumor specific biomarkers are used for targeting these abnormalities. Nanoparticles with multimodal and combinatorial therapies and conjunction of bio-ligands for specific molecular targeting using surface modifications effectually deliver a variety of drugs and are simultaneously used to image tumor progression. Alendronate, a germinal bisphosphonate conjugation as a targeting ligand would improve the nanoparticle's direct binding to hydroxyapatite (HA) mimicking calcified spots in breast cancer lesions. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was modified with alendronate surface functionalization using a biotin-avidin interaction to improve the nanomicelle's calcification targeting ability. Biotinylated, avidinlyated hydrophobically modified iv glycol chitosan particles were linked to biotinylated alendronate via a strong biotin-avidin linkage. Cyanine 3, a red fluorescent dye was conjugated to the amine groups on HGC for visualization of micelles. The size of the nanoparticles measured was 254.0 +/- 0.43 nm and 209.7 +/- 1.0 nm for Cy3- BHGCA and Cy3-BHGCA-BALN nanoparticles respectively. The average surface charge was measured to be +26.9 +/- 0.19 mV and +27.68 +/- 0.20 mV for Cy3-BHGCA and Cy3-BHGCA- BALN nanoparticles respectively. Binding affinity using hydroxyapatite (HA) revealed that both Cy3 BHGCA BALN and Cy3 BHGCA nanoparticles displayed 95% binding in 24 hours. However, the biotin quenched nanoparticle Cy3 BHGCAB displayed 68% binding in 24 hours. The synthesis and binding chemistry was verified using Fourier transform infrared spectroscopy (FTIR).

  3. Targeted intraoperative radiotherapy in oncology

    CERN Document Server

    Keshtgar, Mohammed; Wenz, Frederik

    2014-01-01

    Targeted intraoperative radiotherapy is a major advance in the management of cancer patients. With an emphasis on practical aspects, this book offers an ideal introduction to this innovative  technology for clinicians.

  4. Hyperspectral-Augmented Target Tracking

    National Research Council Canada - National Science Library

    Soliman, Neil A

    2008-01-01

    ... air with the capability to seek, monitor, and destroy mobile terrorist targets in hostile territory. One such capability recognizes and persistently tracks multiple moving vehicles in complex, highly ambiguous urban environments...

  5. After treat-to-target

    DEFF Research Database (Denmark)

    Wakefield, Richard J; D'Agostino, Maria Antonietta; Naredo, Esperanza

    2012-01-01

    have recently formed a research network - the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted...... defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found...... in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who...

  6. After treat-to-target

    DEFF Research Database (Denmark)

    Wakefield, Richard J; D'Agostino, Maria Antonietta; Naredo, Esperanza

    2012-01-01

    have recently formed a research network--the Targeted Ultrasound Initiative (TUI) group. The statement proposes that targeting therapy to PD activity provides superior outcomes compared with treating to clinical targets alone and introduces the rationale for a new randomised trial using targeted...... defined by clinical remission criteria (disease activity score, simplified disease activity index, etc) does not always equate to the complete absence of inflammation as measured by new sensitive imaging techniques such as ultrasound (US) . There is evidence that imaging synovitis is frequently found...... in these patients and associated with adverse clinical and functional outcomes. This article reviews the data regarding remission, ultrasound imaging and outcomes in patients with RA to provide the background to a consensus statement from an international collaboration of ultrasonographers and rheumatologists who...

  7. Targeted therapy for pediatric glioma

    NARCIS (Netherlands)

    Olow, A.K.

    2015-01-01

    This thesis assesses molecular underpinnings of responses to promising targeted agents for pediatric tumors of Central Nervous System (CNS), incorporating preclinical testing of novel and translatable combination therapies to define the best therapy for each tumor cell specific molecular aberration.

  8. Physics of Automatic Target Recognition

    CERN Document Server

    Sadjadi, Firooz

    2007-01-01

    Physics of Automatic Target Recognition addresses the fundamental physical bases of sensing, and information extraction in the state-of-the art automatic target recognition field. It explores both passive and active multispectral sensing, polarimetric diversity, complex signature exploitation, sensor and processing adaptation, transformation of electromagnetic and acoustic waves in their interactions with targets, background clutter, transmission media, and sensing elements. The general inverse scattering, and advanced signal processing techniques and scientific evaluation methodologies being used in this multi disciplinary field will be part of this exposition. The issues of modeling of target signatures in various spectral modalities, LADAR, IR, SAR, high resolution radar, acoustic, seismic, visible, hyperspectral, in diverse geometric aspects will be addressed. The methods for signal processing and classification will cover concepts such as sensor adaptive and artificial neural networks, time reversal filt...

  9. National Ignition Facility Target Chamber

    Energy Technology Data Exchange (ETDEWEB)

    Wavrik, R W; Cox, J R; Fleming, P J

    2000-10-05

    On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The two isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This

  10. Theoretical aspects of inflation targeting

    Directory of Open Access Journals (Sweden)

    Obradović Jelena

    2014-01-01

    Full Text Available Inflation targeting is one of the possible strategies used by central banks during conducting monetary policy. The basic characteristics, advantages and disadvantages of inflation targeting will be presented in this paper. The focus is on the the presentation and interpretation of the understanding of this strategy from the perspective of monetarist and Keynesian theory, the theory of rational expectations, and methodological analysis of the strategy in light of the game theory using payoff matrix.

  11. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  12. Targeting the nuclear RNA exosome

    DEFF Research Database (Denmark)

    Meola, Nicola; Jensen, Torben Heick

    2017-01-01

    Centrally positioned in nuclear RNA metabolism, the exosome deals with virtually all transcript types. This 3'-5' exo- and endo-nucleolytic degradation machine is guided to its RNA targets by adaptor proteins that enable substrate recognition. Recently, the discovery of the 'Poly(A) tail exosome...... targeting (PAXT)' connection as an exosome adaptor to human nuclear polyadenylated transcripts has relighted the interest of poly(A) binding proteins (PABPs) in both RNA productive and destructive processes....

  13. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Denver, Troelz; Betto, Maurizio

    2003-01-01

    An autonomous asteroid target detection and tracking method has been developed. The method features near omnidirectionality and focus on high speed operations and completeness of search of the near space rather than the traditional faint object search methods, employed presently at the larger...... telescopes. The method has proven robust in operation and is well suited for use onboard spacecraft. As development target for the method and the associated instrumentation the asteroid research mission Bering has been used. Onboard a spacecraft, the autonomous detection is centered around the fully...... autonomous star tracker the Advanced Stellar Compass (ASC). One feature of this instrument is that potential targets are registered directly in terms of date, right ascension, declination, and intensity, which greatly facilitates both tracking search and registering. Results from ground and inflight tests...

  14. Pharmacogenomics of GPCR Drug Targets

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

    2017-01-01

    Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

  15. INFLATION TARGETING IN EASTERN EUROPE

    Directory of Open Access Journals (Sweden)

    Laurian Lungu

    2006-05-01

    Full Text Available This paper addresses the inflation targeting approach in three transition economies, namely Hungary, Poland and the Czech Republic with the use of Taylor rules as benchmarks. The three economies considered have been successful at achieving disinflation, but deviations of inflation from its target have been persistent in all cases. Except for the Czech Republic, deviations from the Taylor rule are large and persistent, with Hungary displaying the largest fluctuations. Polish interest rates have consistently exceeded those suggested by the Taylor rule and given the prevalence of high unemployment, these undershootings do not augur well for the stability of monetary policy. Finally, the behaviour of Czech interest rates can be remarkably captured by the simple Taylor rule proposed in this paper, suggesting that the Czech National Bank has been the most successful at stabilising inflation and output around their target levels.

  16. Targeting Angiogenesis in Childhood Sarcomas

    Directory of Open Access Journals (Sweden)

    Hemant K. Bid

    2011-01-01

    Full Text Available Angiogenesis and vasculogenesis constitute two processes in the formation of new blood vessels and are essential for progression of solid tumors. Consequently, targeting angiogenesis, and to a lesser extent vasculogenesis, has become a major focus in cancer drug development. Angiogenesis inhibitors are now being tested in pediatric populations whereas inhibitors of vasculogenesis are in an earlier stage of development. Despite the initial enthusiasm for targeting angiogenesis for treatment of cancer, clinical trials have shown only incremental increases in survival, and agents have been largely cytostatic rather than inducing tumor regressions. Consequently, the role of such therapeutic approaches in the context of curative intent for childhood sarcomas is less clear. Here we review the literature on blood vessel formation in sarcomas with a focus on pediatric sarcomas and developments in targeting angiogenesis for treatment of these rare cancers.

  17. Ribosome Assembly as Antimicrobial Target

    Directory of Open Access Journals (Sweden)

    Rainer Nikolay

    2016-05-01

    Full Text Available Many antibiotics target the ribosome and interfere with its translation cycle. Since translation is the source of all cellular proteins including ribosomal proteins, protein synthesis and ribosome assembly are interdependent. As a consequence, the activity of translation inhibitors might indirectly cause defective ribosome assembly. Due to the difficulty in distinguishing between direct and indirect effects, and because assembly is probably a target in its own right, concepts are needed to identify small molecules that directly inhibit ribosome assembly. Here, we summarize the basic facts of ribosome targeting antibiotics. Furthermore, we present an in vivo screening strategy that focuses on ribosome assembly by a direct fluorescence based read-out that aims to identify and characterize small molecules acting as primary assembly inhibitors.

  18. Progress with developing a target for magnetized target fusion

    Energy Technology Data Exchange (ETDEWEB)

    Wysocki, F.J.; Chrien, R.E.; Idzorek, G.; Oona, H.; Whiteson, D.O.; Kirkpatrick, R.C.; Lindemuth, I.R.; Sheehey, P.T.

    1997-09-01

    Magnetized Target Fusion (MTF) is an approach to fusion where a preheated and magnetized plasma is adiabatically compressed to fusion conditions. Successful MTF requires a suitable initial target plasma with an embedded magnetic field of at least 5 T in a closed-field-line topology, a density of roughly 10{sup 18} cm{sup {minus}3}, a temperature of at least 50 eV, and must be free of impurities which would raise radiation losses. Target plasma generation experiments are underway at Los Alamos National Laboratory using the Colt facility; a 0.25 MJ, 2--3 {micro}s rise-time capacitor bank. The goal of these experiments is to demonstrate plasma conditions meeting the minimum requirements for a MTF initial target plasma. In the first experiments, a Z-pinch is produced in a 2 cm radius by 2 cm high conducting wall using a static gas-fill of hydrogen or deuterium gas in the range of 0.5 to 2 torr. Thus far, the diagnostics include an array of 12 B-dot probes, framing camera, gated OMA visible spectrometer, time-resolved monochrometer, filtered silicon photodiodes, neutron yield, and plasma-density interferometer. These diagnostics show that a plasma is produced in the containment region that lasts roughly 10 to 20 {micro}s with a maximum plasma density exceeding 10{sup 18} cm{sup {minus}3}. The experimental design and data are presented.

  19. Targeted Therapies for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Idoroenyi Amanam

    2018-01-01

    Full Text Available Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies.

  20. Harnessing off-target effects

    DEFF Research Database (Denmark)

    Saginc, Gaye; Voellmy, Franziska; Linding, Rune

    2017-01-01

    The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.......The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action....

  1. The OPERA experiment Target Tracker

    CERN Document Server

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

    2007-01-01

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

  2. Target-Centric Network Modeling

    DEFF Research Database (Denmark)

    Mitchell, Dr. William L.; Clark, Dr. Robert M.

    In Target-Centric Network Modeling: Case Studies in Analyzing Complex Intelligence Issues, authors Robert Clark and William Mitchell take an entirely new approach to teaching intelligence analysis. Unlike any other book on the market, it offers case study scenarios using actual intelligence......, and collaborative sharing in the process of creating a high-quality, actionable intelligence product. The case studies reflect the complexity of twenty-first century intelligence issues by dealing with multi-layered target networks that cut across political, economic, social, technological, and military issues....... Working through these cases, students will learn to manage and evaluate realistic intelligence accounts....

  3. Achievement of NKF/K-DOQI recommended target values for bone and mineral metabolism in incident hemodialysis patients: results of the FARO-2 cohort.

    Science.gov (United States)

    Cozzolino, Mario; Messa, Piergiorgio; Brancaccio, Diego; Cannella, Giuseppe; Bolasco, Piergiorgio; Di Luca, Marina; Costanzo, Anna Maria; Paparatti, Umberto di Luzio; Festa, Vincenzo; Gualberti, Giuliana; Mazzaferro, Sandro

    2014-01-01

    Mineral Bone Disorders (MBD) is prevalent in hemodialysis (HD) patients and associated with increased cardiovascular mortality. The FARO-2 study evaluated the achievement of the NKF/K-DOQI guidelines on recommended target values for serum calcium (Ca), phosphorous (P) and intact parathyroid hormone (PTH) levels on survival in incident HD patients. Data were collected by questionnaire from 568 incident HD patients followed prospectively over a 3-year period from 26 Italian dialysis units. The cumulative probability of time-to-death for CKD-MBD treatment characteristics was determined by the Kaplan-Meier curves. Serum PTH levels (median values at 6 months vs. 36 months; 225 vs. 254 pg/ml), Ca (8.8 vs. 8.9 g/dl) and P (5.1 vs. 4.8 mg/dl) were not significantly different at 6 months versus follow-up. The majority of incident HD patients (60-70%) who were followed up for 36 months did not achieve the NKF/K-DOQI recommended target values. Survival rates were higher in patients on target for three parameters versus patients off target (survival at 24 months: at target 95.7% (95% CI: 84.0-98.9) versus not on target 71.1% (95% CI: 66.3-75.4, p < 0.01)). The 30.1% of patients on target for three MBD parameters at least once during the follow-up period had better survival rates compared to those not reaching these targets (survival at 24 months: at least once 88.0% (95% CI: 81.9-92.1); 67.7% (95% CI: 61.9-72.8, p < 0.01)). Our findings indicate that incident HD patients who achieved target levels (for three MBD parameters) for at least one visit have a lower risk of mortality. © 2014 S. Karger AG, Basel.

  4. TARGET Imbalances at Record Levels

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    TARGET is the payments system for making settlements between euro area economies and five other EU economies. Cross-border transactions generate claims/surpluses and liabilities/deficits among national central banks which “net out” for the system as a whole. These imbalances are manageable in rel...

  5. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  6. Communicating to heterogeneous target groups

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    very often have to communicate to rather heterogeneous target groups that have little more in common than a certain geographical habitat. That goes against most schoolbook teaching in the field of communication, but is none the less the terms with which that kind of communication has to live...

  7. Emerging targets in treating pain.

    Science.gov (United States)

    Chang, David S; Raghavan, Rahul; Christiansen, Sandy; Cohen, Steven P

    2015-08-01

    To provide an overview on drug targets and emerging pharmacological treatment options for chronic pain. Chronic pain poses an enormous socioeconomic burden for the more than 30% of people who suffer from it, costing over $600 billion per year in the USA. In recent years, there has been a surge in preclinical and clinical research endeavors to try to stem this epidemic. Preclinical studies have identified a wide array of potential targets, with some of the most promising translational research being performed on novel opioid receptors, cannabinoid receptors, selective ion channel blockers, cytokine inhibitors, nerve growth factor inhibitors, N-methyl-D-aspartate receptor antagonists, glial cell inhibitors, and bisphosphonates. There are many obstacles for the development of effective medications to treat chronic pain, including the inherent challenges in identifying pathophysiological mechanisms, the overlap and multiplicity of pain pathways, and off-target adverse effects stemming from the ubiquity of drug target receptor sites and the lack of highly selective receptor ligands. Despite these barriers, the number and diversity of potential therapies have continued to grow, to include disease-modifying and individualized drug treatments.

  8. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    Udaya Kiran eMarelli

    2013-08-01

    Full Text Available Selective and targeted delivery of drugs to tumors is a major challenge for an effective cancer therapy and also to overcome the side effects associated with current treatments. Overexpression of various receptors on tumor cells is a characteristic structural and biochemical aspect of tumors and distinguishes them from physiologically normal cells. This abnormal feature is therefore suitable for selectively directing anticancer molecules to tumors by using ligands that can preferentially recognize such receptors. Several subtypes of integrin receptors that are crucial for cell adhesion, cell signaling, cell viability and motility have been shown to have an upregulated expression on cancer cells. Thus, ligands that recognize specific integrin subtypes represent excellent candidates to be conjugated to drugs or drug carrier systems and be targeted to tumors. In this regard, integrins recognizing the RGD cell adhesive sequence have been extensively targeted for tumor specific drug delivery. Here we review key recent examples on the presentation of RGD-based integrin ligands by means of distinct drug delivery systems, and discuss the prospects of such therapies to specifically target tumor cells.

  9. How are inflation targets set?

    Czech Academy of Sciences Publication Activity Database

    Horváth, R.; Matějů, Jakub

    -, č. 426 (2010), s. 1-35 ISSN 1211-3298 Grant - others:MŠk(CZ) SVV-2010-261801 Institutional research plan: CEZ:MSM0021620846 Keywords : inflation targeting * central bank * credibility Subject RIV: AH - Economics http://www.cerge-ei.cz/pdf/wp/Wp426.pdf

  10. High power neutron production targets

    Energy Technology Data Exchange (ETDEWEB)

    Wender, S. [Los Alamos National Lab., NM (United States)

    1996-06-01

    The author describes issues of concern in the design of targets and associated systems for high power neutron production facilities. The facilities include uses for neutron scattering, accelerator driven transmutation, accelerator production of tritium, short pulse spallation sources, and long pulse spallation sources. Each of these applications requires a source with different design needs and consequently different implementation in practise.

  11. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could ...

  12. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  13. The Automatic Measurement of Targets

    DEFF Research Database (Denmark)

    Höhle, Joachim

    1997-01-01

    The automatic measurement of targets is demonstrated by means of a theoretical example and by an interactive measuring program for real imagery from a réseau camera. The used strategy is a combination of two methods: the maximum correlation coefficient and the correlation in the subpixel range...

  14. Polarized Scintillating Targets at Psi

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.; Mango, S.

    2001-02-01

    Scintillating polarized targets are now routinely available: blocks of 18×18×5 mm scintillating organic polymer, doped with TEMPO, polarized dynamically in a field of 2.5 T in a vertical 3He-4He dilution refrigerator. A 19 mm diameter plastic lightguide transports the scintillation light from the sample in the mixing chamber to a photomultiplier outside the cryostat.

  15. Aptamers for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Partha Ray

    2010-05-01

    Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  16. Targeted Advertising and Social Status

    NARCIS (Netherlands)

    N. Vikander (Nick)

    2010-01-01

    textabstractThis paper shows how a firm can use non-targeted advertising to exploit consumers' desire for social status. A monopolist sells multiple varieties of a good to consumers who each care about what others believe about his wealth. Advertising allows consumers both to buy different varieties

  17. Polarimetric imaging of underwater targets

    Science.gov (United States)

    Gilerson, Alex; Carrizo, Carlos; Tonizzo, Alberto; Ibrahim, Amir; El-Habashi, Ahmed; Foster, Robert; Ahmed, Samir

    2013-06-01

    Underwater imaging is challenging because of the significant attenuation of light due to absorption and scattering of light in water. Using polarization properties of light is one of the options for improving image quality. We present results of imaging of a polarized target in open ocean (Curacao) and coastal (NY Bight) waters. The target in the shape of a square is divided into several smaller squares, each of which is covered with a polarizing film with different polarization orientations or transmission coefficients was placed on a mirror and imaged under water by a green-band full-Stokes polarimetric video camera at the full range of azimuth angles against the Sun. The values of the Stokes vector components from the images are compared with the modeled image of the target using radiative transfer code for the atmosphere-ocean system combined with the simple imaging model. It is shown that even in clear water the impact of the water body on the polarized underwater image is very significant and retrieval of target polarization characteristics from the image is extremely challenging.

  18. Target selection for direct marketing.

    NARCIS (Netherlands)

    Bult, Jan Roelf

    1993-01-01

    In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of

  19. Uranium briquettes for irradiation target

    Energy Technology Data Exchange (ETDEWEB)

    Saliba-Silva, Adonis Marcelo; Garcia, Rafael Henrique Lazzari; Martins, Ilson Carlos; Carvalho, Elita Fontenele Urano de; Durazzo, Michelangelo, E-mail: saliba@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Direct irradiation on targets inside nuclear research or multiple purpose reactors is a common route to produce {sup 99}Mo-{sup 99m}Tc radioisotopes. Nevertheless, since the imposed limits to use LEU uranium to prevent nuclear armament production, the amount of uranium loaded in target meats has physically increased and new processes have been proposed for production. Routes using metallic uranium thin film and UAl{sub x} dispersion have been used for this purpose. Both routes have their own issues, either by bringing difficulties to disassemble the aluminum case inside hot cells or by generating great amount of alkaline radioactive liquid rejects. A potential route might be the dispersion of powders of LEU metallic uranium and nickel, which are pressed as a blend inside a die and followed by pulse electroplating of nickel. The electroplating provides more strength to the briquettes and creates a barrier for gas evolution during neutronic disintegration of {sup 235}U. A target briquette platted with nickel encapsulated in an aluminum case to be irradiated may be an alternative possibility to replace other proposed targets. This work uses pulse Ni-electroplating over iron powder briquette to simulate the covering of uranium by nickel. The following parameters were applied 10 times for each sample: 900Hz, -0.84A/square centimeters with duty cycle of 0.1 in Watts Bath. It also presented the optical microscopy analysis of plated microstructure section. (author)

  20. Collisional disruptions of rotating targets

    Science.gov (United States)

    Ševeček, Pavel; Broz, Miroslav

    2017-10-01

    Collisions are key processes in the evolution of the Main Asteroid Belt and impact events - i.e. target fragmentation and gravitational reaccumulation - are commonly studied by numerical simulations, namely by SPH and N-body methods. In our work, we extend the previous studies by assuming rotating targets and we study the dependence of resulting size-distributions on the pre-impact rotation of the target. To obtain stable initial conditions, it is also necessary to include the self-gravity already in the fragmentation phase which was previously neglected.To tackle this problem, we developed an SPH code, accelerated by SSE/AVX instruction sets and parallelized. The code solves the standard set of hydrodynamic equations, using the Tillotson equation of state, von Mises criterion for plastic yielding and scalar Grady-Kipp model for fragmentation. We further modified the velocity gradient by a correction tensor (Schäfer et al. 2007) to ensure a first-order conservation of the total angular momentum. As the intact target is a spherical body, its gravity can be approximated by a potential of a homogeneous sphere, making it easy to set up initial conditions. This is however infeasible for later stages of the disruption; to this point, we included the Barnes-Hut algorithm to compute the gravitational accelerations, using a multipole expansion of distant particles up to hexadecapole order.We tested the code carefully, comparing the results to our previous computations obtained with the SPH5 code (Benz and Asphaug 1994). Finally, we ran a set of simulations and we discuss the difference between the synthetic families created by rotating and static targets.

  1. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

    To test the hypothesis that resveratrol, a grape derived polyphenol, exerts its chemopreventive properties against prostate cancer by interacting with specific cellular targets, denoted resveratrol targeting proteins (RTPs...

  2. North Pacific Targets Program Environmental Assessment

    National Research Council Canada - National Science Library

    2001-01-01

    .... The STPO would provide the Strategic Target System launch vehicle for strategic target launch services from Kodiak Launch Complex, Kodiak Island, Alaska, a commercial rocket launch facility operated...

  3. Targeted nanosystems: Advances in targeted dendrimers for cancer therapy.

    Science.gov (United States)

    Yang, Hu

    2016-02-01

    Dendrimers possess discrete highly compact nanostructures constituted of successive branched layers. Soon after the inception of dendrimers, recognition of their tunable structures and biologically favorable properties provoked a great enthusiasm in delving deeply into the utility of dendrimers for biomedical and pharmaceutical applications. One of the most important nanotechnology applications is the development of nanomedicines for targeted cancer therapies. Tremendous success in targeted therapies has been achieved with the use of dendrimer-based nanomedicines. This article provides a concise review on latest advances in the utility of dendrimers in immunotherapies and hormone therapies. Much basic and clinical research has been done since the invention of dendrimers, which are highly branched nano-sized molecules with the ability to act as carriers in nanomedicine. In this concise review article, the authors highlighted the current use of dendrimers in immunotherapies and hormone therapies in the fight against cancers. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Emerging targets in human lymphoma: targeting the MYD88 mutation

    Directory of Open Access Journals (Sweden)

    Wang JQ

    2013-08-01

    Full Text Available James Q Wang,* Yogesh S Jeelall,* Keisuke Horikawa* Department of Immunology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia *All authors contributed equally to this manuscript Abstract: B cell neoplasms co-opt the molecular machinery of normal B cells for their survival. Technological advances in cancer genomics has significantly contributed to uncovering the root cause of aggressive lymphomas, revealing a previously unknown link between TLR signaling and B cell neoplasm. Recurrent oncogenic mutations in MYD88 have been found in 39% of the activated B cell-like subtype of diffuse large B cell lymphoma (ABC DLBCL. Interestingly, 29% of ABC DLBCL have a single amino acid substitution of proline for the leucine at position 265 (L265P, and the exact same variant has also been identified in a number of lymphoid malignancies. The MYD88 L265P variant was recently identified in 90% of Wadenstrom's macroglobulinemia patients. These recent developments warrant the need for novel diagnostic tools as well as targeted therapeutics. In this review, we discuss the physiological functions of MYD88 and focus on its role in B cell lymphomas, evaluating the potential for targeting oncogenic MYD88 in lymphoma. Keywords: MYD88, L265P mutation, lymphoma, targeted therapy

  5. Targeting an efficient target-to-target interval for P300 speller brain–computer interfaces

    Science.gov (United States)

    Sellers, Eric W.; Wang, Xingyu

    2013-01-01

    Longer target-to-target intervals (TTI) produce greater P300 event-related potential amplitude, which can increase brain–computer interface (BCI) classification accuracy and decrease the number of flashes needed for accurate character classification. However, longer TTIs requires more time for each trial, which will decrease the information transfer rate of BCI. In this paper, a P300 BCI using a 7 × 12 matrix explored new flash patterns (16-, 18- and 21-flash pattern) with different TTIs to assess the effects of TTI on P300 BCI performance. The new flash patterns were designed to minimize TTI, decrease repetition blindness, and examine the temporal relationship between each flash of a given stimulus by placing a minimum of one (16-flash pattern), two (18-flash pattern), or three (21-flash pattern) non-target flashes between each target flashes. Online results showed that the 16-flash pattern yielded the lowest classification accuracy among the three patterns. The results also showed that the 18-flash pattern provides a significantly higher information transfer rate (ITR) than the 21-flash pattern; both patterns provide high ITR and high accuracy for all subjects. PMID:22350331

  6. Newer targeted therapies in psoriasis

    Directory of Open Access Journals (Sweden)

    Sujay Khandpur

    2013-01-01

    Full Text Available Psoriasis is a common, chronic, inflammatory skin disease that can have a significant impact on the quality of life of those who are afflicted due to chronicity of the disease and frequent remissions and relapses. Many available systemic therapies, however, are unsuitable for chronic administration due to the risk of cumulative toxicity. Recent advances in the understanding of the pathophysiology of psoriasis have led to the development of new, genetically engineered, targeted therapies for this disease. These include approaches targeting antigen presentation and co-stimulation, T-cell activation and leukocyte adhesion, action on pro-inflammatory mediators, and modulating the cytokine balance. Although only preliminary data are available so far and there is limited data supporting their use, these trials contribute to a further understanding of the disease and will eventually lead to new therapeutic options for psoriasis.

  7. Moulding calixarenes for biomacromolecule targeting.

    Science.gov (United States)

    Giuliani, Marta; Morbioli, Ilaria; Sansone, Francesco; Casnati, Alessandro

    2015-09-28

    After their successful use as a preorganized platform for the preparation of receptors for metal ions and small neutral molecules over the last 15 years, calixarenes are enjoying a renaissance of popularity as scaffolds for ligands that are able to efficiently and selectively target macromolecules such as proteins/enzymes, nucleic acids and lipids. This feature article summarizes the peculiar factors characterizing the calixarene structure and properties, as well as outlines the main rules that can be used to turn such macrocycles into efficient and successful ligands for these classes of biomacromolecules. Factors that affect the multivalent properties of calixarenes, such as the size, conformation and stereochemical presentation of binding groups or their amphiphilicity and hybrid character, are described in detail with the use of a few selected examples from the literature. Perspectives and applications of these ligands in bionanotechnology and nanomedicine, such as protein sensing and inhibition, gene-delivery, targeted drug-delivery and cell imaging, are also discussed.

  8. Swimbladder on Fish Target Strength

    Directory of Open Access Journals (Sweden)

    Sunardi

    2008-08-01

    Full Text Available This paper discusses of target strength (TS for the Selar boops (Oxeye scad and Megalaspis cordyla (Torpedo scad, the most commercially fish in Malaysia. TS can be determined from in situ measurements and acoustic calculation of fish model. TS value, depth, and position (x-y-z of targeted fish can be viewed from echogram using FQ-80 Analyzer by in situ measurement. X-ray imaged can be deployed to develop the acoustic fish model. The percentage of length and upper surface area for swimbladder to body fish of Selar boops more than Megalaspis cordyla can be measured after X-ray process. The percentage of width and volume of swimbladders to its each body are no significantly difference for both fish. These data of swimbladder physic support the result of in situ measurement which TS of Megalaspis cordyla stronger Selar boops.

  9. Recurring Utterances - Targeting a Breakthrough

    Directory of Open Access Journals (Sweden)

    Jacqueline Stark

    2014-05-01

    The most interesting phenomenon is KB’s production of words from former sessions indicating that they are still ‘active’ and the production of completely novel incorrect words. The observable features indicate that immediate auditory processing is possible in the form of repeating target words. However, as soon as KB must retrieve information from the (semantic lexicon, even after being able to correctly ‘repeat’ the target word several times, he responds with a RU, perseveration, or paraphasia. Several of his productions can be characterized as aphasic confabulations which stem from a memory gap. Thus, although KB’s language impairment is severe, his responses across time indicate that step-by-step a breakthrough is being made.

  10. Remote moving target indication assessment

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.

    1996-10-01

    The objective of this project was to design and test key components of a sensor to be used on remotely piloted vehicles, aircraft, or satellites for the detection of moving vehicles in cluttered backgrounds. The proposed sensor uses modern large-array focal planes to provide multiple infrared observations of moving targets and capable on-board computers to integrate multiple observations to detect moving targets in background clutter. This combination reduces the size, weight, and cost of the sensor to levels that can be flown on many small unmanned platforms. This effort selected the actual components, integrated them into a test bed, tested the performance of the sensor against realistic generated scenes, and designed a proof-of-concept prototype.

  11. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    to be far superior to that of B-cells and macrophages. DC are localized at strategic places in the body at sites used by pathogens to enter the organism, and are thereby in an optimal position to capture antigens. In general, vaccination strategies try to mimic the invasiveness of the pathogens. DC...... are considered to play a central role for the provocation of primary immune responses by vaccination. A rational way of improving the potency and safety of new and already existing vaccines could therefore be to direct vaccines specifically to DC. There is a need for developing multifunctional vaccine drug...... delivery systems (DDS) with adjuvant effect that target DC directly and induce optimal immune responses. This paper will review the current knowledge of DC physiology as well as the progress in the field of novel vaccination strategies that directly or indirectly aim at targeting DC....

  12. Poverty, inequality, and geographic targeting

    OpenAIRE

    Simler, Kenneth R.; Nhate, Virgulino

    2005-01-01

    "This paper applies small area estimation techniques to Mozambican data to develop high resolution (subdistrictlevel) poverty and inequality maps...The picture that emerges is one of considerable local-level economic heterogeneity, with the poor living alongside the nonpoor. Rather than finding stark pockets of intense poverty traps in one part of the country and a relative absence of poverty in other parts, the situation is much more nuanced. This suggests that targeting antipoverty efforts ...

  13. Targeting phenotypically tolerant Mycobacterium tuberculosis

    Science.gov (United States)

    Gold, Ben; Nathan, Carl

    2016-01-01

    While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

  14. Medium size polarised deuteron target

    Energy Technology Data Exchange (ETDEWEB)

    Kiselev, Yu.F.; Polyakov, V.V.; Kovalev, A.I.; Bunyatova, E.I.; Borisov, N.S.; Trautman, V.Yu.; Werner, K.; Kozlenko, N.G.

    1984-03-01

    A frozen polarised deuteron target based on ethanediol with a high percentage of deuterium is described. Analytical expressions for the NMR spectrum correction for non-linearity of the Q-meter are obtained and a method for the determination of the asymmetry is developed. Experimental results confirm the thermal mixing theory for deuteron and proton spin systems with a dipole-dipole reservoir of electron spins.

  15. Peptide-targeted polymer cancerostatics

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert

    2016-01-01

    Roč. 65, Suppl. 2 (2016), S153-S164 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LO1507 Institutional support: RVO:61389013 Keywords : HPMA copolymers * tumor targeting * peptides Subject RIV: CD - Macromolecular Chemistry Impact factor: 1.461, year: 2016 http://www.biomed.cas.cz/physiolres/pdf/65%20Suppl%202/65_S153.pdf

  16. Coherent Communications, Imaging and Targeting

    Energy Technology Data Exchange (ETDEWEB)

    Stappaerts, E; Baker, K; Gavel, D; Wilks, S; Olivier, S; Brase, J; Olivier, S; Brase, J

    2003-10-03

    Laboratory and field demonstration results obtained as part of the DARPA-sponsored Coherent Communications, Imaging and Targeting (CCIT) program are reviewed. The CCIT concept uses a Phase Conjugation Engine based on a quadrature receiver array, a hologram processor and a spatial light modulator (SLM) for high-speed, digital beam control. Progress on the enabling MEMS SLM, being developed by a consortium consisting of LLNL, academic institutions and small businesses, is presented.

  17. Theranostics Targeting Metastatic Breast Cancer

    Science.gov (United States)

    2016-10-01

    What opportunities for training and professional development has the project provided? Two graduate students and one postdoctoral research associate...hostile immune reaction toward FR-expressing tumors. A series of vaccinations with hapten fluorescein (EC90 vaccine ) admin- istrated with an adjuvant...FITC-conjugated (FITC is flu - orescein isothiocyanate) CA inhibitor acetalozamide (AAZ) targeted CA-IX positive cells (Kd = 12.6 nM). The biodistribution

  18. Targeting inflammation in metabolic syndrome.

    Science.gov (United States)

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K

    2016-01-01

    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Targeting distress in rheumatic diseases

    OpenAIRE

    Vriezekolk, J.E.

    2011-01-01

    Psychological distress is highly prevalent in patients with rheumatic diseases. It is associated with a variety of negative outcomes, including pain, fatigue, disability, and maladaptive cognitive behavioural coping strategies. In this thesis, psychological distress was studied both as an outcome measure and as a therapeutic target in the context of multidisciplinary rehabilitation. The longitudinal role of coping in psychological distress was systematically reviewed, a questionnaire to asses...

  20. Novel therapies targeting vascular endothelium.

    Science.gov (United States)

    Tousoulis, Dimitris; Antoniades, Charalambos; Koumallos, Nikolaos; Marinou, Kyriakoula; Stefanadi, Elli; Latsios, George; Stefanadis, Christodoulos

    2006-01-01

    Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature may improve the long-term outcome in healthy individuals, high-risk subjects, or patients with advanced atherosclerosis. Several therapeutic strategies are now available, targeting both the synthesis and oxidative inactivation of nitric oxide (NO) in human vasculature. Statins seem to be currently the most powerful category of these agents, improving endothelial function and decreasing cardiovascular risk after long-term administration. Other cardiovascular agents improving endothelial function in humans are angiotensin-converting enzyme inhibitors/angiotensin receptors blockers, which increase NO bioavailability by modifying the rennin-angiotensin-aldosterone system. Newer therapeutic approaches targeting endothelial dysfunction in specific disease states include insulin sensitizers, L-arginine (the substrate for endothelial NO synthase [eNOS]) as well as substances that target eNOS "coupling," such as folates or tetrahydrobiopterin. Although there are a variety of strategies to improve NO bioavailability in human endothelium, it is still unclear whether they have any direct benefit at a clinical level.

  1. Targeted gene flow for conservation.

    Science.gov (United States)

    Kelly, Ella; Phillips, Ben L

    2016-04-01

    Anthropogenic threats often impose strong selection on affected populations, causing rapid evolutionary responses. Unfortunately, these adaptive responses are rarely harnessed for conservation. We suggest that conservation managers pay close attention to adaptive processes and geographic variation, with an eye to using them for conservation goals. Translocating pre-adapted individuals into recipient populations is currently considered a potentially important management tool in the face of climate change. Targeted gene flow, which involves moving individuals with favorable traits to areas where these traits would have a conservation benefit, could have a much broader application in conservation. Across a species' range there may be long-standing geographic variation in traits or variation may have rapidly developed in response to a threatening process. Targeted gene flow could be used to promote natural resistance to threats to increase species resilience. We suggest that targeted gene flow is a currently underappreciated strategy in conservation that has applications ranging from the management of invasive species and their impacts to controlling the impact and virulence of pathogens. © 2015 Society for Conservation Biology.

  2. Targeted Treatment Options in Mastocytosis

    Directory of Open Access Journals (Sweden)

    Mélanie Vaes

    2017-07-01

    Full Text Available Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM or in various organs (systemic mastocytosis, SM. This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia. In addition, SM may be associated with hematological neoplasms (AHN. While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN. Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy.

  3. Unmanned Aircraft Systems (UAS) Sensor and Targeting

    Science.gov (United States)

    2010-07-27

    mission, a pre-determined number of different targets should be shuffled between the target locations in the array. Example targets for this subtest are...UNFOV Ultra Narrow Field of View UTM Universal Transverse Mercator VBLSS Video-Based Laser Scoring System VRT Vertical Reference Target WFOV

  4. Progress with developing a target for magnetized target fusion

    Energy Technology Data Exchange (ETDEWEB)

    Wysocki, F.J.; Chrien, B.E.; Idzorek, G.; Oona, H.; Whiteson, D.O.; Kirkpatrick, R.C.; Lindemuth, I.R.; Sheehey, P.T. [Los Alamos National Lab., NM (United States)

    1997-12-31

    Magnetized Target Fusion (MTF) is an approach to fusion where a preheated and magnetized plasma is adiabatically compressed to fusion conditions. Successful MTF requires a suitable initial target plasma with an embedded magnetic field of at least 5 T in a closed-field-line topology, a density of roughly 10{sup 18} cm{sup {minus}3}, a temperature of at least 50 eV, and must be free of impurities which would raise radiation losses. Target plasma generation experiments are underway at Los Alamos National Laboratory using the Colt facility; a 0.25 MJ, 2--3 {micro}s rise-time capacitor bank. In the first experiments, a Z-pinch is produced in a 2 cm radius by 2 cm high conducting wall using a static gas-fill of hydrogen or deuterium gas in the range of 0.5 to 2 torr. Follow-on experiments will use a frozen deuterium fiber along the axis (without a gas-fill). The diagnostics include B-dot probes, framing camera, gated OMA visible spectrometer, time-resolved monochrometer, silicon photodiodes, neutron yield, and plasma-density interferometer. Operation to date has been with drive current ranging from 0.8 MA to 1.9 MA. Optical diagnostics show that the plasma produced in the containment region lasts roughly 20 to 30 {micro}s, and the B-dot probes show a broad current-profile in the containment region. The experimental design and data will be presented.

  5. Targeted advertising, platform competition and privacy

    OpenAIRE

    Henk Kox; Bas Straathof; Gijsbert Zwart

    2014-01-01

    Targeted advertising can benefit consumers through lower prices for access to websites. Yet, if consumers dislike that websites collect their personal information, their welfare may go down. We study competition for consumers between websites that can show targeted advertisements. We find that more targeting increases competition and reduces the websites' profits, but yet in equilibrium websites choose maximum targeting as they cannot credibly commit to low targeting. A privacy protection pol...

  6. Non-viral gene therapy that targets motor neurons in vivo

    Directory of Open Access Journals (Sweden)

    Mary-Louise eRogers

    2014-10-01

    Full Text Available A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS. We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by ‘immunogene’ nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12 as DNA carrier was conjugated to an antibody (MLR2 to the neurotrophin receptor p75 (p75NTR. We used a plasmid (pVIVO2 designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP. MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0 % of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo.

  7. Hospitals: Soft Target for Terrorism?

    Science.gov (United States)

    De Cauwer, Harald; Somville, Francis; Sabbe, Marc; Mortelmans, Luc J

    2017-02-01

    In recent years, the world has been rocked repeatedly by terrorist attacks. Arguably, the most remarkable were: the series of four coordinated suicide plane attacks on September 11, 2001 on buildings in New York, Virginia, and Pennsylvania, USA; and the recent series of two coordinated attacks in Brussels (Belgium), on March 22, 2016, involving two bombings at the departure hall of Brussels International Airport and a bombing at Maalbeek Metro Station located near the European Commission headquarters in the center of Brussels. This statement paper deals with different aspects of hospital policy and disaster response planning that interface with terrorism. Research shows that the availability of necessary equipment and facilities (eg, personal protective clothing, decontamination rooms, antidotes, and anti-viral drugs) in hospitals clearly is insufficient. Emergency teams are insufficiently prepared: adequate and repetitive training remain necessary. Unfortunately, there are many examples of health care workers and physicians or hospitals being targeted in both political or religious conflicts and wars. Many health workers were kidnapped and/or killed by insurgents of various ideology. Attacks on hospitals also could cause long-term effects: hospital units could be unavailable for a long time and replacing staff could take several months, further compounding hospital operations. Both physical and psychological (eg, posttraumatic stress disorder [PTSD]) after-effects of a terrorist attack can be detrimental to health care services. On the other hand, physicians and other hospital employees have shown to be involved in terrorism. As data show that some offenders had a previous history with the location of the terror incident, the possibility of hospitals or other health care services being targeted by insiders is discussed. The purpose of this report was to consider how past terrorist incidents can inform current hospital preparedness and disaster response planning

  8. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  9. High-frequency jet ventilation for complete target immobilization and reduction of planning target volume in stereotactic high single-dose irradiation of stage I non-small cell lung cancer and lung metastases.

    Science.gov (United States)

    Fritz, Peter; Kraus, Hans-Jörg; Mühlnickel, Werner; Sassmann, Volker; Hering, Werner; Strauch, Konstantin

    2010-09-01

    To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTV enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of >or=20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  10. Downstream targets of WRKY33

    DEFF Research Database (Denmark)

    Petersen, Klaus; Fiil, Berthe Katrine; Mundy, John

    2008-01-01

    Innate immunity signaling pathways in both animals and plants are regulated by mitogen-activated protein kinase (MAPK) cascades. In a recent publication we show that MPK4 and its substrate MKS1 interact with WRKY33 in vivo, and that WRKY33 is released from complexes with MPK4 upon infection. Tran...... immunoprecipitation confirmed that WRKY33 bound the promoter of PAD3 when plants were inoculated with pathogens. Here we further discuss the involvement of two other targets of WRKY33, NUDT6 and ROF2 in defense responses against invading pathogens....

  11. Performance Targets and External Benchmarking

    DEFF Research Database (Denmark)

    Friis, Ivar; Hansen, Allan; Vámosi, Tamás S.

    Research on relative performance measures, transfer pricing, beyond budgeting initiatives, target costing, piece rates systems and value based management has for decades underlined the importance of external benchmarking in performance management. Research conceptualises external benchmarking...... of the ‘inside’ costs of the sub-component, technical specifications of the product, opportunistic behavior from the suppliers and cognitive limitation. These are all aspects that easily can dismantle the market mechanism and make it counter-productive in the organization. Thus, by directing more attention...

  12. The challenge of targeting metastasis.

    Science.gov (United States)

    Fidler, Isaiah J; Kripke, Margaret L

    2015-12-01

    Metastases that are resistant to conventional therapy are the major cause of death from cancer. In most patients, metastasis has already occurred by the time of diagnosis. Thus, the prevention of metastasis is unlikely to be of therapeutic benefit. The biological heterogeneity of metastases presents a major obstacle to treatment. However, the growth and survival of metastases depend on interactions between tumor cells and host homeostatic mechanisms. Targeting these interactions, in addition to the tumor cells, can produce synergistic therapeutic effects against existing metastases.

  13. Introduction to radar target recognition

    CERN Document Server

    Tait, P

    2006-01-01

    This new text provides an overview of the radar target recognition process and covers the key techniques being developed for operational systems. It is based on the fundamental scientific principles of high resolution radar, and explains how the techniques can be used in real systems, taking into account the characteristics of practical radar system designs and component limitations. It also addresses operational aspects, such as how high resolution modes would fit in with other functions such as detection and tracking. Mathematics is kept to a minimum and the complex techniques and issues are

  14. Targeting α-synuclein oligomers

    DEFF Research Database (Denmark)

    van Diggelen, Femke

    2017-01-01

    Parkinson’s Disease (PD) is a complex disease, characterised by degeneration of neocortical, limbic and nigrostriatal neurons. It is unknown what initiates neurodegeneration, but soluble oligomers of the protein α-synuclein (αSn) seem to be particularly toxic, compared to insoluble fibrils....... Although there is currently no cure for PD, αSn oligomers (αSOs) are a potential therapeutic target, but a major drawback it that little is known about the nature of PD-associated αSOs. The scientific literature describes a wide variety of protocols to generate αSOs in vitro, with a subsequent...

  15. LIFE Target Fabrication Research Plan Sept 2008

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  16. Targeting telomerase with radiolabeled inhibitors.

    Science.gov (United States)

    Waghorn, Philip A; Jackson, Mark R; Gouverneur, Veronique; Vallis, Katherine A

    2017-01-05

    The expression of telomerase in approximately 85% of cancers and its absence in the majority of normal cells makes it an attractive target for cancer therapy. However the lag period between initiation of telomerase inhibition and growth arrest makes direct inhibition alone an insufficient method of treatment. However, telomerase inhibition has been shown to enhance cancer cell radiosensitivity. To investigate the strategy of simultaneously inhibiting telomerase while delivering targeted radionuclide therapy to cancer cells, 123 I-radiolabeled inhibitors of telomerase were synthesized and their effects on cancer cell survival studied. An 123 I-labeled analogue of the telomerase inhibitor MST-312 inhibited telomerase with an IC 50 of 1.58 μM (MST-312 IC 50 : 0.23 μM). Clonogenic assays showed a dose dependant effect of 123 I-MST-312 on cell survival in a telomerase positive cell line, MDA-MB-435. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  17. Properties of Protein Drug Target Classes

    Science.gov (United States)

    Bull, Simon C.; Doig, Andrew J.

    2015-01-01

    Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID

  18. Neutron Protection Factor Determination and Validation for a Vehicle Surrogate Using a Californium Fission Source

    Science.gov (United States)

    2017-06-01

    a 4 mm x 4 mm (0.157" x 0.157") LiI(Eu) crystal with 96% enrichment of lithium -6. The crystal is connected to a photomultiplier tube (PMT) which...32 Figure 17. Lithium -6 Iodide, Europium Doped Scintillation Detector. Source: [27...Alamos National Laboratory LiI(Eu) Lithium Iodide Europium Doped LLD Low Level Discriminator LLNL Lawrence Livermore National Laboratory MASH Monte

  19. Bioengineering Strategies for Designing Targeted Cancer Therapies

    Science.gov (United States)

    Wen, Xuejun

    2014-01-01

    The goals of bioengineering strategies for targeted cancer therapies are (1) to deliver a high dose of an anticancer drug directly to a cancer tumor, (2) to enhance drug uptake by malignant cells, and (3) to minimize drug uptake by nonmalignant cells. Effective cancer-targeting therapies will require both passive- and active targeting strategies and a thorough understanding of physiologic barriers to targeted drug delivery. Designing a targeted therapy includes the selection and optimization of a nanoparticle delivery vehicle for passive accumulation in tumors, a targeting moiety for active receptor-mediated uptake, and stimuli-responsive polymers for control of drug release. The future direction of cancer targeting is a combinatorial approach, in which targeting therapies are designed to use multiple targeting strategies. The combinatorial approach will enable combination therapy for delivery of multiple drugs and dual ligand targeting to improve targeting specificity. Targeted cancer treatments in development and the new combinatorial approaches show promise for improving targeted anticancer drug delivery and improving treatment outcomes. PMID:23768509

  20. TARGET 2 and Settlement Finality

    Directory of Open Access Journals (Sweden)

    Ivan MANGATCHEV

    2011-03-01

    Full Text Available This article examines how TARGET 2 as system implements the idea of settlement finality regulated by Directive 98/26 EC of the European parliament and of the Council of 19 May 1998 on settlement finality in payment and securities settlement systems (Settlement Finality Directive and Directive 2009/44/EC of the European parliament and of the Council of 6 May 2009 amending Directive 98/26/EC on settlement finality in payment and securities settlement systems and Directive 2002/47/EC on financial collateral arrangements as regards linked systems and credit claims (Directive 2009/44/EC. As the title of the arti and finality of the settlement in this system.

  1. Terahertz-based target typing.

    Energy Technology Data Exchange (ETDEWEB)

    Lyo, Sungkwun Kenneth; Wanke, Michael Clement; Reno, John Louis; Shaner, Eric Arthur; Grine, Albert D.; Barrick, Todd A.

    2008-09-01

    The purpose of this work was to create a THz component set and understanding to aid in the rapid analysis of transient events. This includes the development of fast, tunable, THz detectors, along with filter components for use with standard detectors and accompanying models to simulate detonation signatures. The signature effort was crucial in order to know the spectral range to target for detection. Our approach for frequency agile detection was to utilize plasmons in the channel of a specially designed field-effect transistor called the grating-gate detector. Grating-gate detectors exhibit narrow-linewidth, broad spectral tunability through application of a gate bias, and no angular dependence in their photoresponse. As such, if suitable sensitivity can be attained, they are viable candidates for Terahertz multi-spectral focal plane arrays.

  2. Gene Therapy Targeting HIV Entry

    Directory of Open Access Journals (Sweden)

    Chuka Didigu

    2014-03-01

    Full Text Available Despite the unquestionable success of antiretroviral therapy (ART in the treatment of HIV infection, the cost, need for daily adherence, and HIV-associated morbidities that persist despite ART all underscore the need to develop a cure for HIV. The cure achieved following an allogeneic hematopoietic stem cell transplant (HSCT using HIV-resistant cells, and more recently, the report of short-term but sustained, ART-free control of HIV replication following allogeneic HSCT, using HIV susceptible cells, have served to both reignite interest in HIV cure research, and suggest potential mechanisms for a cure. In this review, we highlight some of the obstacles facing HIV cure research today, and explore the roles of gene therapy targeting HIV entry, and allogeneic stem cell transplantation in the development of strategies to cure HIV infection.

  3. Targeting Persistent Human Papillomavirus Infection.

    Science.gov (United States)

    Shanmugasundaram, Srinidhi; You, Jianxin

    2017-08-18

    While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.

  4. Targeting ECM Disrupts Cancer Progression

    DEFF Research Database (Denmark)

    Venning, Freja A; Wullkopf, Lena; Erler, Janine T

    2015-01-01

    Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings, the ex...... is summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression.......Metastatic complications are responsible for more than 90% of cancer-related deaths. The progression from an isolated tumor to disseminated metastatic disease is a multistep process, with each step involving intricate cross talk between the cancer cells and their non-cellular surroundings......, the extracellular matrix (ECM). Many ECM proteins are significantly deregulated during the progression of cancer, causing both biochemical and biomechanical changes that together promote the metastatic cascade. In this review, the influence of several ECM proteins on these multiple steps of cancer spread...

  5. Obesity treatment: novel peripheral targets.

    Science.gov (United States)

    Field, Benjamin C T; Chaudhri, Owais B; Bloom, Stephen R

    2009-12-01

    Our knowledge of the complex mechanisms underlying energy homeostasis has expanded enormously in recent years. Food intake and body weight are tightly regulated by the hypothalamus, brainstem and reward circuits, on the basis both of cognitive inputs and of diverse humoral and neuronal signals of nutritional status. Several gut hormones, including cholecystokinin, glucagon-like peptide-1, peptide YY, oxyntomodulin, amylin, pancreatic polypeptide and ghrelin, have been shown to play an important role in regulating short-term food intake. These hormones therefore represent potential targets in the development of novel anti-obesity drugs. This review focuses on the role of gut hormones in short- and long-term regulation of food intake, and on the current state of development of gut hormone-based obesity therapies.

  6. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  7. Target therapies in pancreatic carcinoma.

    Science.gov (United States)

    Silvestris, Nicola; Gnoni, Antonio; Brunetti, Anna Elisabetta; Vincenti, Leonardo; Santini, Daniele; Tonini, Giuseppe; Merchionne, Francesca; Maiello, Evaristo; Lorusso, Vito; Nardulli, Patrizia; Azzariti, Amalia; Reni, Michele

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early locoregional spread and distant metastases at diagnosis, leading to dismal prognosis and limited treatment options. Traditional cytotoxic chemotherapy provides only modest benefit to patients with PDAC. Identification of different molecular pathways, overexpressed in pancreatic cancer cells, has provided the opportunity to develop targeted therapies (monoclonal antibodies and small-molecule inhibitors) and peculiar new class of taxanes with a crucial therapeutic role in this cancer setting. A phase III trial has shown that erlotinib in combination with gemcitabine was clinically irrelevant and skin toxicity can be a positive prognostic factor. Moreover, the combination of cetuximab or erlotinib with radiotherapy in advanced pancreatic cancer has shown to be synergistic and a reversal of radio-resistance has been suggested by inhibition of VEGF/EGFR pathway. To overcome EGFR-inhibition therapy resistance several alternative pathways targets are under investigation (IGF- 1R, MMPs, Hedgehog proteins, m-TOR, MEK, COX-2) and provide the rationale for clinical use in phase II/III studies. Also nab-paclitaxel, a new taxanes class, uses high pancreatic albumin-binding protein SPARC levels to act in cancer cells with a less toxic and more effective dose with respect to classic taxanes. Understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. However, many promising data in preclinic and phase I/II trials did not yield promise in phase III trials, suggesting that identification of predictive biomarkers for these new agents is mandatory. The knowledge of biologic and molecular aspects of pancreatic cancer can be the basis for future therapeutic developments.

  8. Combinatorial microRNA target predictions

    DEFF Research Database (Denmark)

    Krek, Azra; Grün, Dominic; Poy, Matthew N.

    2005-01-01

    MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript1, 2, 3. Different combinations of microRNAs are expressed...... in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published micro......RNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results...

  9. Targets and processes for fabricating same

    Science.gov (United States)

    Cowna, Thomas; Malekos, Steven; Korgan, Grant; Adams, Jesse; Sentoku, Yasuhiko; LeGalloudec, Nathalie

    2014-06-10

    In particular embodiments, the present disclosure provides targets including a metal layer and defining a hollow inner surface. The hollow inner surface has an internal apex. The distance between at least two opposing points of the internal apex is less than about 15 .mu.m. In particular examples, the distance is less than about 1 .mu.m. Particular implementations of the targets are free standing. The targets have a number of disclosed shaped, including cones, pyramids, hemispheres, and capped structures. The present disclosure also provides arrays of such targets. Also provided are methods of forming targets, such as the disclosed targets, using lithographic techniques, such as photolithographic techniques. In particular examples, a target mold is formed from a silicon wafer and then one or more sides of the mold are coated with a target material, such as one or more metals.

  10. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  11. Study Identifies New Lymphoma Treatment Target

    Science.gov (United States)

    NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

  12. On the large COMPASS polarized deuteron target

    CERN Document Server

    Finger, M; Baum, G; Doshita, N; Finger, M Jr; Gautheron, F; Goertz, St; Hasegawa, T; Heckmann, J; Hess, Ch; Horikawa, N; Ishimoto, S; Iwata, T; Kisselev, Y; Koivuniemi, J; Kondo, K; Le Goff, J-M; Magnon, A; Marchand, C; Matsuda, T; Meyer, W; Reicherz, G; Srnka, A

    2006-01-01

    The spin structure of the nucleons is investigated in deep inelastic scattering of a polarized muon beam and a polarized nucleon target in the COMPASS experiment at CERN since 2001. To achieve high luminosities a large solid polarized target is used. The COMPASS polarized target consists of a high cooling power $^{3}$He/$^{4}$He dilution refrigerator capable to maintain working temperature of the target material at about 50mK, a superconducting solenoid and dipole magnet system for longitudinal and transversal magnetic field on the target material, respectively, target cells containing polarizable material, microwave cavities and high power microwave radiation systems for dynamic nuclear polarization and the nuclear magnetic resonance system for nuclear spin polarization measurements. During 2001–2004 experiments superconducting magnet system with opening angle $\\pm$69 mrad, polarized target holder with two target cells and corresponding microwave and NMR systems have been used. For the data taking from 200...

  13. Targeting Cancer with Antisense Oligomers

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, DJ

    2008-10-28

    With financial assistance from the Department of Energy, we have shown definitively that radiolabeled antisense DNAs and other oligomers will accumulate in target cancer cells in vitro and in vivo by an antisense mechanism. We have also shown that the number of mRNA targets for our antisense oligomers in the cancer cell types that we have investigated so far is sufficient to provide and antisense image and/or radiotherapy of cancer in mice. These studies have been reported in about 10 publications. However our observation over the past several years has shown that radiolabeled antisense oligomers administered intravenously in their native and naked form will accumulate and be retained in target xenografts by an antisense mechanism but will also accumulate at high levels in normal organs such as liver, spleen and kidneys. We have investigated unsuccessfully several commercially available vectors. Thus the use of radiolabeled antisense oligomers for the imaging of cancer must await novel approaches to delivery. This laboratory has therefore pursued two new paths, optical imaging of tumor and Auger radiotherapy. We are developing a novel method of optical imaging tumor using antisense oligomers with a fluorophore is administered while hybridized with a shorter complementary oligomer with an inhibitor. In culture and in tumored mice that the duplex remains intact and thus nonfluorescent until it encounters its target mRNA at which time it dissociates and the antisense oligomer binds along with its fluorophore to the target. Simultaneous with the above, we have also observed, as have others, that antisense oligomers migrate rapidly and quantitatively to the nucleus upon crossing cell membranes. The Auger electron radiotherapy path results from this observation since the nuclear migration properties could be used effectively to bring and to retain in the nucleus an Auger emitting radionuclide such as 111In or 125I bound to the antisense oligomer. Since the object becomes

  14. Targeted integration of genes in Xenopus tropicalis

    DEFF Research Database (Denmark)

    Shi, Zhaoying; Tian, Dandan; Xin, Huhu

    2017-01-01

    With the successful establishment of both targeted gene disruption and integration methods in the true diploid frog Xenopus tropicalis, this excellent vertebrate genetic model now is making a unique contribution to modelling human diseases. Here, we summarize our efforts on establishing homologous...... recombination-mediated targeted integration in Xenopus tropicalis, the usefulness, and limitation of targeted integration via the homology-independent strategy, and future directions on how to further improve targeted gene integration in Xenopus tropicalis....

  15. Capacitive Sensors And Targets Would Measure Alignments

    Science.gov (United States)

    Jenstrom, Del T.

    1994-01-01

    Multiple capacitive sensors and active targets used to measure distance between, and relative orientation of, two objects. Sensed target signals processed and used by control systems to align objects to be joined. Shapes, sizes, and layouts of sensors and targets optimized for specific application. Particular layout of targets and sensors enables determination of relative position and orientation of two objects in all six degrees of freedom.

  16. 40 CFR 35.9020 - Planning targets.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Planning targets. 35.9020 Section 35... STATE AND LOCAL ASSISTANCE Financial Assistance for the National Estuary Program § 35.9020 Planning targets. The EPA Assistant Administrator for Water develops planning targets each year to help each...

  17. Inflation Targeting and Business Cycle Synchronization

    OpenAIRE

    Flood, Robert P; Rose, Andrew K

    2009-01-01

    Inflation targeting seems to have a small but positive effect on the synchronization of business cycles; countries that target inflation seem to have cycles that move slightly more closely with foreign cycles. Thus the advent of inflation targeting does not explain the decoupling of global business cycles, for two reasons. Indeed business cycles have not in fact become less synchronized across countries.

  18. Starkweather Target Game for Preschool Children.

    Science.gov (United States)

    Starkweather, Elizabeth K.

    The Starkweather Target Game is designed to measure preschool children's willingness to try difficult tasks independent of ability. The game consists of a box-shaped target which responds, when the target is hit by a rolled ball, somewhat like a jack-in-a-box. When the bull's eye is hit, the lid opens and a surprise picture appears. After being…

  19. Vergence facility with stereoscopic and nonstereoscopic targets.

    Science.gov (United States)

    Momeni-Moghaddam, Hamed; Goss, David A; Dehvari, Abubakr

    2014-05-01

    To compare vergence facility with nonstereo and stereo targets in binocular symptomatic and asymptomatic subjects. Sixty-six students were divided into symptomatic and asymptomatic groups according to the Convergence Insufficiency Symptom Survey Questionnaire score. Vergence facility was tested at 40 cm by flipper prism 3Δ BI/12Δ BO (BI, base-in; BO, base-out). The targets used were a nonstereo target (a vertical column of small letter "E" of ~20/30 size), a stereo-local target (fifth set of circles of the Titmus test with stereoacuity of 100 arcsec), and a stereo-global target (page 6 of the TNO test with stereoacuity of 120 arcsec). Repeated-measures analysis of variance showed differences in the mean vergence facility with different targets in all subjects and separately in two symptom groups (p 0.05) but significant for the comparison of stereo-global targets with the other two targets. The receiver operating characteristic curve analysis showed the cutoff points 10.5, 10.5, and 9.75 cycles per minute with nonstereo, stereo-local, and stereo-global targets, respectively. The sensitivity of the three targets used was the same (97%). Specificity was 0.93 or higher with all three targets, with the highest specificity obtained with the stereo-global target (100%). The highest vergence facility was obtained with a nonstereo target and the lowest was obtained with a stereo-global target. High sensitivity with all three targets means that there are few false-negative results with them, and the high specificity is indicative of low false-positive results. Hence, the vergence facility predictive value would be high in diagnosing binocular symptomatic patients using a 3Δ BI/12Δ BO prism flipper at near and a response cutoff of about 10 cycles per minute or less.

  20. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  1. Attainment of low-density lipoprotein cholesterol target in the French general population according to levels of cardiovascular risk: Insights from the MONA LISA study.

    Science.gov (United States)

    Bongard, Vanina; Dallongeville, Jean; Arveiler, Dominique; Ruidavets, Jean-Bernard; Amouyel, Philippe; Wagner, Aline; Ferrières, Jean

    2013-02-01

    Controlling low-density lipoprotein (LDL)-cholesterol concentration is of tremendous importance to reduce cardiovascular risk. To investigate the attainment of LDL-cholesterol targets recommended in French and European guidelines on cardiovascular prevention, according to levels of cardiovascular risk. Participants aged 35 to 74 years (n=4609) were randomly selected from the general population of three French regions. A standardized data collection was performed to assess cardiovascular risk as described in the French and European guidelines. Overall, 17.5% of participants were considered to be at high risk and 25.4% at high or very high risk, according to the French and European guidelines, respectively. Only 1.2% of participants with no cardiovascular risk factors according to the French guidelines had an LDL-cholesterol concentration above the recommended target, whereas 82.5% of high-risk subjects did not attain their goal (70.8% among high-risk subjects receiving lipid-lowering therapy). Among untreated people, the median reduction in LDL-cholesterol needed to reach target ranged from 6.6% (lowest-risk groups) to 36.0% (highest-risk subjects). When risk was classified according to the European guidelines, the majority of participants did not reach the recommended LDL-cholesterol targets, irrespective of their level of risk or lipid-lowering therapy. In a majority of primary prevention candidates with multiple risk factors and in most high-risk subjects, LDL-cholesterol targets recommended by French guidelines are not being achieved, either because of insufficient treatment or because subjects are not recognized as being at risk. More stringent targets proposed by the European guidelines are not being achieved in most cases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Tantalum/Copper X-Ray Targets

    Science.gov (United States)

    Waters, William J.; Edmonds, Brian

    1993-01-01

    Lewis Research Center developed unique solution to subsidiary problem of fabrication of x-ray target. Plasma spraying enabled fabrication of lightweight, high-performance targets. Power settings, atmosphere-control settings, rate of deposition, and other spraying parameters developed. Thin coats of tantalum successfully deposited on copper targets. Targets performed successfully in tests and satisfied all criteria expressed in terms of critical parameters. Significantly reduces projected costs of fabrication of targets and contributes to development of improved, long-lived, lightweight x-ray system.

  3. Targeting nominal income growth or inflation?

    DEFF Research Database (Denmark)

    Jensen, Henrik

    2002-01-01

    Within a simple New Keynesian model emphasizing forward-looking behavior of private agents, I evaluate optimal nominal income growth targeting versus optimal inflation targeting. When the economy is mainly subject to shocks that do not involve monetary policy trade-offs for society, inflation...... targeting is preferable. Otherwise, nominal income growth targeting may be superior because it induces inertial policy making, which improves the inflation-output-gap trade-off. Somewhat paradoxically, inflation targeting may be relatively less favorable the more society dislikes inflation, and the more...

  4. Improved Targeting of Cancers with Nanotherapeutics

    DEFF Research Database (Denmark)

    Foster, Christian; Watson, Andre; Kaplinsky, Joseph John

    2017-01-01

    Targeted cancer nanotherapeutics offers numerous opportunities for the selective uptake of toxic chemotherapies within tumors and cancer cells. The unique properties of nanoparticles, such as their small size, large surface-to-volume ratios, and the ability to achieve multivalency of targeting...... ligands on their surface, provide superior advantages for nanoparticle-based drug delivery to a variety of cancers. This review highlights various key concepts in the design of targeted nanotherapeutics for cancer therapy, and discusses physicochemical parameters affecting nanoparticle targeting, along...... with recent developments for cancer-targeted nanomedicines....

  5. Graphite target for the spiral project

    Energy Technology Data Exchange (ETDEWEB)

    Putaux, J.C.; Ducourtieux, M.; Ferro, A.; Foury, P.; Kotfila, L.; Mueller, A.C.; Obert, J.; Pauwels, N.; Potier, J.C.; Proust, J. [Paris-11 Univ., 91 - Orsay (France). Inst. de Physique Nucleaire; Bertrand, P. [Grand Accelerateur National d`Ions Lourds (GANIL), 14 - Caen (France); Loiselet, M. [Universite Catholique de Louvain, Louvain-La-Neuve (Belgium)] [and others

    1996-12-31

    A study of the thermal and physical properties of graphite targets for the SPIRAL project is presented. The main objective is to develop an optimized set-up both mechanically and thermally resistant, presenting good release properties (hot targets with thin slices). The results of irradiation tests concerning the mechanical and thermal resistance of the first prototype of SPIRAL target with conical geometry are presented. The micro-structural properties of the graphite target is also studied, in order to check that the release properties are not deteriorated by the irradiation. Finally, the results concerning the latest pilot target internally heated by an electrical current are shown. (author). 5 refs.

  6. The trajectory of the target probability effect.

    Science.gov (United States)

    Hon, Nicholas; Yap, Melvin J; Jabar, Syaheed B

    2013-05-01

    The effect of target probability on detection times is well-established: Even when detection accuracy is high, lower probability targets are detected more slowly than higher probability ones. Although this target probability effect on detection times has been well-studied, one aspect of it has remained largely unexamined: How the effect develops over the span of an experiment. Here, we investigated this issue with two detection experiments that assessed different target probability ratios. Conventional block segment analysis and linear mixed-effects modeling converged on two key findings. First, we found that the magnitude of the target probability effect increases as one progresses through a block of trials. Second, we found, by examining the trajectories of the low- and high-probability targets, that this increase in effect magnitude was driven by the low-probability targets. Specifically, we found that low-probability targets were detected more slowly as a block of trials progressed. Performance to high-probability targets, on the other hand, was largely invariant across the block. The latter finding is of particular interest because it cannot be reconciled with accounts that propose that the target probability effect is driven by the high-probability targets.

  7. Secondary anchor targeted cell release.

    Science.gov (United States)

    Ansari, Ali; Lee-Montiel, Felipe T; Amos, Jennifer R; Imoukhuede, P I

    2015-11-01

    Personalized medicine offers the promise of tailoring therapy to patients, based on their cellular biomarkers. To achieve this goal, cellular profiling systems are needed that can quickly and efficiently isolate specific cell types without disrupting cellular biomarkers. Here we describe the development of a unique platform that facilitates gentle cell capture via a secondary, surface-anchoring moiety, and cell release. The cellular capture system consists of a glass surface functionalized with APTES, d-desthiobiotin, and streptavidin. Biotinylated mCD11b and hIgG antibodies are used to capture mouse macrophages (RAW 264.7) and human breast cancer (MCF7-GFP) cell lines, respectively. The surface functionalization is optimized by altering assay components, such as streptavidin, d-desthiobiotin, and APTES, to achieve cell capture on 80% of the functionalized surface and cell release upon biotin treatment. We also demonstrate an ability to capture 50% of target cells within a dual-cell mixture. This engineering advancement is a critical step towards achieving cell isolation platforms for personalized medicine. © 2015 Wiley Periodicals, Inc.

  8. Targeting ceramide metabolism in obesity.

    Science.gov (United States)

    Aburasayn, Hanin; Al Batran, Rami; Ussher, John R

    2016-08-01

    Obesity is a major health concern that increases the risk for insulin resistance, type 2 diabetes (T2D), and cardiovascular disease. Thus, an enormous research effort has been invested into understanding how obesity-associated dyslipidemia and obesity-induced alterations in lipid metabolism increase the risk for these diseases. Accordingly, it has been proposed that the accumulation of lipid metabolites in organs such as the liver, skeletal muscle, and heart is critical to these obesity-induced pathologies. Ceramide is one such lipid metabolite that accumulates in tissues in response to obesity, and both pharmacological and genetic strategies that reduce tissue ceramide levels yield salutary actions on overall metabolic health. We will review herein why ceramide accumulates in tissues during obesity and how an increase in intracellular ceramide impacts cellular signaling and function as well as potential mechanisms by which reducing intracellular ceramide levels improves insulin resistance, T2D, atherosclerosis, and heart failure. Because a reduction in skeletal muscle ceramide levels is frequently associated with improvements in insulin sensitivity in humans, the beneficial findings reported for reducing ceramides in preclinical studies may have clinical application in humans. Therefore, modulating ceramide metabolism may be a novel, exciting target for preventing and/or treating obesity-related diseases. Copyright © 2016 the American Physiological Society.

  9. Resource implications of a national health target

    DEFF Research Database (Denmark)

    Jones, Peter; Sopina, Liza Elizaveta; Ashton, Toni

    2014-01-01

    Background The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. Method A survey...... of clinical/service managers in ED throughout New Zealand determined the type and cost of resources used for the target. Responses to the target were classified according to their impact in ED, the hospital and the community. Quantifiable resource changes were assigned a financial value and grouped...... into categories: structure (facilities/beds), staff and processes. Simple statistics were used to describe the data, and the correlation between expenditure and target performance was determined. Results There was 100% response to the survey. Most DHBs reported some expenditure specifically on the target...

  10. Targeting dendritic cells--why bother?

    Science.gov (United States)

    Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

    2013-04-11

    Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

  11. Preliminary study of mercury target structure

    Energy Technology Data Exchange (ETDEWEB)

    Kaminaga, Masanori; Haga, Katsuhiro; Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Kumasaka, Katsuyuki; Uchida, Shoji; Nakagawa, Toshi; Mori, Seiji; Nishikawa, Akira

    1997-11-01

    Development of a proton accelerator based neutron source (1.5 GeV, 5.3 mA (for neutron source 3.3 mA), thermal power 8 MW) is currently conducted by the Special Task Force for Neutron Science Initiative, JAERI. Preliminary design studies and related R and D of a solid metal target for the first stage (1.5 GeV, 1 mA) and a liquid metal target for both the first and second stages (1.5 GeV, 3.3 mA) are conducted by the Target Group to develop both solid and liquid metal target systems. A few kinds of target structures have been investigated in FY 1996 and the preliminary results for the target structures are described in this paper. Investigation results of alternative materials for the target container are also described in this paper. (author)

  12. Governing by targets : Reductio ad unum and evolution of the two-degree climate target

    NARCIS (Netherlands)

    Morseletto, Piero; Biermann, Frank|info:eu-repo/dai/nl/176991662; Pattberg, Philipp

    2017-01-01

    Targets are widely employed in environmental governance. In this paper, we investigate the construction of the 2 °C climate target, one of the best known targets in global environmental governance. Our paper examines this target through a historical reconstruction that identifies four different

  13. Using the Dual-Target Cost to Explore the Nature of Search Target Representations

    Science.gov (United States)

    Stroud, Michael J.; Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

    2012-01-01

    Eye movements were monitored to examine search efficiency and infer how color is mentally represented to guide search for multiple targets. Observers located a single color target very efficiently by fixating colors similar to the target. However, simultaneous search for 2 colors produced a dual-target cost. In addition, as the similarity between…

  14. Target definition for shipwreck hunting

    Directory of Open Access Journals (Sweden)

    Kim Paul Kirsner

    2015-10-01

    Full Text Available The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or ‘mean’ just 2.7 NM (nautical miles from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor’s reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013. The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review.

  15. Target definition for shipwreck hunting.

    Science.gov (United States)

    Kirsner, Kim

    2015-01-01

    The research described in the present article was implemented to define the locations of two World War II shipwrecks, the German raider Kormoran, and the Australian light cruiser HMAS Sydney. The paper describes the long and complex trail that led through inefficient oceanographic prediction to ambiguous historical prediction involving a single report and on to precise cognitive prediction based on nine reports from more than 70 survivors, a process that yielded a single target position or "mean" just 2.7 NM (nautical miles) from the wreck of Kormoran. Prediction for the position of the wreck of Sydney opened with wishful thinking that she had somehow reached the coast more than 100 NM away when cognitive analysis of the survivor's reports actually provided the basis for accurate prediction in a position near to the wreck of Kormoran. In the account provided below, the focus on cognitive procedures emerged from, first, a review of a sample of the shipwreck hunts, and, second, growing awareness of the extraordinarily rich database available for this search, and the extent to which it was open to cognitive analysis. This review touches on both the trans-disciplinary and the cognitive or intra-disciplinary issues that so challenged the political entities responsible for supervising of the search for the wrecks of Kormoran and Sydney. One of the theoretical questions that emerged from these debate concerns the model of expertise advanced by Collins (2013). The decomposability of alleged forms of expertise is revealed as a fundamental problem for research projects that might or might not benefit from trans-disciplinary research. Where expertise can be decomposed for operational purposes, the traditional dividing lines between experts and novices, and fools for that matter, are much harder to discern, and require advanced and scientifically informed review.

  16. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  17. Target detection and tracking in infrared video

    Science.gov (United States)

    Deng, Zhihui; Zhu, Jihong

    2017-07-01

    In this paper, we propose a method for target detection and tracking in infrared video. The target is defined by its location and extent in a single frame. In the initialization process, we use an adaptive threshold to segment the target and then extract the fern feature and normalize it as a template. The detector uses the random forest and fern to detect the target in the infrared video. The random forest and fern is a random combination of 2bit Binary Pattern, which is robust to infrared targets with blurred and unknown contours. The tracker uses the gray-value weighted mean-Shift algorithm to track the infrared target which is always brighter than the background. And the tracker can track the deformed target efficiently and quickly. When the target disappears, the detector will redetect the target in the coming infrared image. Finally, we verify the algorithm on the real-time infrared target detection and tracking platform. The result shows that our algorithm performs better than TLD in terms of recall and runtime in infrared video.

  18. Fluid mechanics aspects of magnetic drug targeting.

    Science.gov (United States)

    Odenbach, Stefan

    2015-10-01

    Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.

  19. Recombinant expression and purification of a tumor-targeted toxin in Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Bachran, Christopher; Abdelazim, Suzanne; Fattah, Rasem J.; Liu, Shihui [National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Leppla, Stephen H., E-mail: sleppla@niaid.nih.gov [National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Non-infectious and protease-deficient Bacillus anthracis protein expression system. Black-Right-Pointing-Pointer Successful expression and purification of a tumor-targeted fusion protein drug. Black-Right-Pointing-Pointer Very low endotoxin contamination of purified protein. Black-Right-Pointing-Pointer Efficient protein secretion simplifies purification. Black-Right-Pointing-Pointer Functional anti-tumor fusion protein purified. -- Abstract: Many recombinant therapeutic proteins are purified from Escherichia coli. While expression in E. coli is easily achieved, some disadvantages such as protein aggregation, formation of inclusion bodies, and contamination of purified proteins with the lipopolysaccharides arise. Lipopolysaccharides have to be removed to prevent inflammatory responses in patients. Use of the Gram-positive Bacillus anthracis as an expression host offers a solution to circumvent these problems. Using the multiple protease-deficient strain BH460, we expressed a fusion of the N-terminal 254 amino acids of anthrax lethal factor (LFn), the N-terminal 389 amino acids of diphtheria toxin (DT389) and human transforming growth factor alpha (TGF{alpha}). The resulting fusion protein was constitutively expressed and successfully secreted by B. anthracis into the culture supernatant. Purification was achieved by anion exchange chromatography and proteolytic cleavage removed LFn from the desired fusion protein (DT389 fused to TGF{alpha}). The fusion protein showed the intended specific cytotoxicity to epidermal growth factor receptor-expressing human head and neck cancer cells. Final analyses showed low levels of lipopolysaccharides, originating most likely from contamination during the purification process. Thus, the fusion to LFn for protein secretion and expression in B. anthracis BH460 provides an elegant tool to obtain high levels of lipopolysaccharide-free recombinant protein.

  20. The effects of early versus delayed castration targeting androgen on prolonging survival in a mouse model of bladder cancer.

    Science.gov (United States)

    Zhang, Zaixian; Xu, Qingquan; Huang, Xiaobo; Yang, Jia; Xu, Yanhong; Zhang, Guixiang

    2015-01-01

    To compare the efficacy of early versus delayed surgical castration on prolonging survival and further to investigate the anticancer effect and potential value of targeting androgen in the therapeutic intervention of bladder cancer. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was used to induce bladder cancer in male mice. Mice were randomly divided into three groups: the early castration group (on which castration was perform at 4 weeks after first time of BBN administration), the delayed castration group (on which castration was perform at 20 weeks after first time of BBN administration), and the sham-castrated group. Mice were monitored daily throughout their lifespan until cancer-related death or the progress of an obviously moribund appearance, at which time the mice were killed. Androgen receptor expression and cell proliferation and apoptosis analysis were also evaluated. The average lifespan in early castration, delayed castration and sham-castrated groups were 315.8 days, 300.1 days and 254.6 days, respectively. Early castration conferred a statistically significant survival advantage when compared with the sham-castrated group (P cancer mice. This finding may enhance the feasibility of androgen ablation treatment in patients with bladder cancer.

  1. Resistance to Antibiotics Mediated by Target Alterations

    Science.gov (United States)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  2. High power target developments at ISAC

    CERN Document Server

    Bricault, P G; Dowling, A; Lane, M

    2003-01-01

    TRIUMF, Canada's national research facility for particle and nuclear physics is currently operating the ISAC facility. A high-energy proton beam from the H sup - TRIUMF cyclotron is used to generate short-lived radioactive species in a thick target. An ion source at the target creates a radioactive beam, which is then injected into the ISAC beam lines and accelerator system. The ISAC facility is designed to accept proton beam intensity up to 100 mu A at 500 MeV. At present our target design can only sustains 40 mu A at maximum. Beyond this point the target has to be cooled. A new target equipped with fins has been developed that may sustain proton beam up to 100 mu A. The fined target has been tested off-line and a thermal simulation using ANSYS[reg] has been conducted and the results are reported here.

  3. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano; David, Jean-Christophe; Leray, Sylvie; Letourneau, Alain; Michel-Sendis, Franco; Stankunas, Gediminas [CEA/IRFU, Gif-sur-Yvette (France); Berg, Klara; Filges, Uwe; Groeschel, Friedrich; Luethy, Markus; Scazzi, Selene; Tobler, Leonhard; Zanini, Luca [PSI, Villigen (Switzerland); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Gif-sur-Yvette (France); Guertin, Arnaud; Thiolliere, Nicolas [SUBATECH, Nantes (France); Konobeyev, Alexander Yu. [FZK/IRS, Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, St. Paul Lez Durance (France); Lemaire, Sebastien [CEA/DAM/DCSA/SCGA, Bruyeres-le-Chatel (France)

    2008-07-01

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). The project is an important step in the road-map towards the demonstration of the Accelerator Driven System (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment. (authors)

  4. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France)], E-mail: Stefano.panebianco@cea.fr; Berg, Klara [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); David, Jean-Christophe [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Centre de Saclay, F-91194 Gif-sur-Yvette (France); Filges, Uwe; Groeschel, Friedrich [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Guertin, Arnaud [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Konobeyev, Alexander Yu [Forschungszentrum Karlsruhe, IRS, D-76021 Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, Centre de Cadarache, F-13108 Saint-Paul-lez-Durance (France); Lemaire, Sebastien [CEA, DAM Ile de France, F-91297 Bruyeres le Chatel (France); Leray, Sylvie; Letourneau, Alain [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Luethy, Markus [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Michel-Sendis, Franco [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Scazzi, Selene [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Stankunas, Gediminas [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Thiolliere, Nicolas [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Tobler, Leonhard; Zanini, Luca [Paul Scherrer Institut, CH-5232 Villigen (Switzerland)

    2009-04-15

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of about 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). This project is an important step in the roadmap towards the demonstration of the accelerator driven system (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment.

  5. Polarized targets in high energy physics

    Energy Technology Data Exchange (ETDEWEB)

    Cates, G.D. Jr. [Princeton Univ., NJ (United States)

    1994-12-01

    Various approaches are discussed for producing polarized nuclear targets for high energy physics experiments. As a unifying theme, examples are drawn from experiments to measure spin dependent structure functions of nucleons in deep inelastic scattering. This single physics goal has, over roughly two decades, been a driving force in advances in target technology. Actual or planned approaches have included solid targets polarized by dynamic nuclear polarization (DNP), several types of internal targets for use in storage rings, and gaseous {sup 3}He targets polarized by spin-exchange optical pumping. This last approach is the type of target adopted for SLAC E-142, an experiment to measure the spin structure function of the neutron, and is described in detail.

  6. THERMAL OSCILLATIONS IN LIQUID HELIUM TARGETS.

    Energy Technology Data Exchange (ETDEWEB)

    WANG,L.; JIA,L.X.

    2001-07-16

    A liquid helium target for the high-energy physics was built and installed in the proton beam line at the Alternate Gradient Synchrotron of Brookhaven National Laboratory in 2001. The target flask has a liquid volume of 8.25 liters and is made of thin Mylar film. A G-M/J-T cryocooler of five-watts at 4.2K was used to produce liquid helium and refrigerate the target. A thermosyphon circuit for the target was connected to the J-T circuit by a liquid/gas separator. Because of the large heat load to the target and its long transfer lines, thermal oscillations were observed during the system tests. To eliminate the oscillation, a series of tests and analyses were carried out. This paper describes the phenomena and provides the understanding of the thermal oscillations in the target system.

  7. Protection Related to High-power Targets

    CERN Document Server

    Plum, M.A.

    2016-01-01

    Target protection is an important part of machine protection. The beam power in high-intensity accelerators is high enough that a single wayward pulse can cause serious damage. Today's high-power targets operate at the limit of available technology, and are designed for a very narrow range of beam parameters. If the beam pulse is too far off centre, or if the beam size is not correct, or if the beam density is too high, the target can be seriously damaged. We will start with a brief introduction to high-power targets and then move to a discussion of what can go wrong, and what are the risks. Next we will discuss how to control the beam-related risk, followed by examples from a few different accelerator facilities. We will finish with a detailed example of the Oak Ridge Spallation Neutron Source target tune up and target protection.

  8. Visualizing Energy on Target: Molecular Dynamics Simulations

    Science.gov (United States)

    2017-12-01

    ARL-TR-8234 ● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics Simulations by DeCarlos E...return it to the originator. ARL-TR-8234● DEC 2017 US Army Research Laboratory Visualizing Energy on Target: Molecular Dynamics...REPORT TYPE Technical Report 3. DATES COVERED (From - To) 1 October 2015–30 September 2016 4. TITLE AND SUBTITLE Visualizing Energy on Target

  9. ENTERPRISE RESOURCE STRATEGIC PLANNING: TARGET CHOICE TECHNIQUES

    Directory of Open Access Journals (Sweden)

    A. S. Lankin

    2011-01-01

    Full Text Available Choice of the targets is one of most important elements of the resource planning system. Particular feature of the strategic planning is development of future alternatives for the enterprise. Main resource strategic planning cycle elements: examination of principal external and internal environment components; forming the company mission; development of long-term targets; concretization of the long-term targets through short-term aims; examination of strategies and final choice.

  10. Targeting Malignant Brain Tumors with Antibodies

    OpenAIRE

    Rok Razpotnik; Neža Novak; Vladka Čurin Šerbec; Uros Rajcevic

    2017-01-01

    Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain deli...

  11. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Barnkob, Mike Stein

    2014-01-01

    therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...... and co-targets for single-epitope and multi-epitope strategies. We provide examples of application to the well-known tumor antigen HER2 and suggest bioinformatics methods to ameliorate therapy resistance and ensure efficient and lasting control of tumors....

  12. Promoting target models by potential measures

    OpenAIRE

    Dubiel, Joerg

    2010-01-01

    Direct marketers use target models in order to minimize the spreading loss of sales efforts. The application of target models has become more widespread with the increasing range of sales efforts. Target models are relevant for offline marketers sending printed mails as well as for online marketers who have to avoid intensity. However business has retained its evaluation since the late 1960s. Marketing decision-makers still prefer managerial performance measures of the economic benefit of a t...

  13. Design of the LBNF Beamline Target Station

    OpenAIRE

    Tariq, S.; Ammigan, K.; Anderson, K.; Buccellato, S. A.; Crowley, C. F.; Hartsell, B. D.; Hurh, P.; Hylen, J.; Kasper, P.; Krafczyk, G. E.; Lee, A.; Lundberg, B.; Marchionni, A; Mokhov, N. V.; Moore, C. D.

    2016-01-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-fil...

  14. Target R and D at JAERI

    Energy Technology Data Exchange (ETDEWEB)

    Hino, Ryutaro [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-03-01

    We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)

  15. Target Language Adaptation of Discriminative Transfer Parsers

    OpenAIRE

    Täckström, Oscar; McDonald, Ryan; Nivre, Joakim

    2013-01-01

    We study multi-source transfer parsing for resource-poor target languages; specifically methods for target language adaptation of delexicalized discriminative graph-based dependency parsers. We first show how recent insights on selective parameter sharing, based on typological and language-family features, can be applied to a discriminative parser by carefully decomposing its model features. We then show how the parser can be relexicalized and adapted using unlabeled target language data and ...

  16. Magnetic confinement system using charged ammonia targets

    Science.gov (United States)

    Porter, Gary D.; Bogdanoff, Anatoly

    1979-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  17. COST OF ADDRESSING TARGETS OF UNEQUAL VALUE

    Energy Technology Data Exchange (ETDEWEB)

    G.H. CANAVAN

    2001-08-01

    The formalism for evaluating first strike costs and incentives for military targeting generalize to include higher value targets. That introduces two new allocations to the usual allocation between missiles and military targets, but they can be performed analytically. As the number of weapons on each side decreases, the optimal fraction of second strike weapons allocated to military values falls. The shift to high value targets is more pronounced below about 1,000 weapons for nominal parameters. Below 500 weapons the first striker's cost of action drops below its cost of inaction. A strike would induce a second strike of about 250 weapons on high value targets. An increase in the first striker's preference for damage to the other's high value targets increases or a decrease in its preference for preventing damage to its own high value targets decreases first strike costs and stability margins. Including defenses complicates allocations slightly. The main effect is increased attrition of second strikes, particularly at larger defenses, which makes it possible to significantly reduce damage to high value targets. At 1,000 weapons, by 300 to 400 interceptors the first striker's costs are reduced to 30% below that of inaction and the number of weapons delivered on the first striker's high value targets is reduced to about 100.

  18. What makes a good drug target?

    Science.gov (United States)

    Gashaw, Isabella; Ellinghaus, Peter; Sommer, Anette; Asadullah, Khusru

    2012-02-01

    Novel therapeutics in areas with a high unmet medical need are based on innovative drug targets. Although 'biologicals' have enlarged the space of druggable molecules, the number of appropriate drug targets is still limited. Discovering and assessing the potential therapeutic benefit of a drug target is based not only on experimental, mechanistic and pharmacological studies but also on a theoretical molecular druggability assessment, an early evaluation of potential side effects and considerations regarding opportunities for commercialization. This article defines key properties of a good drug target from the perspective of a pharmaceutical company. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Uncertainty Prediction in Passive Target Motion Analysis

    Science.gov (United States)

    2016-05-12

    denote the bearing and range from observer 12B to target 10B at time t2 as indicated in FIG. 3. Between times t1 and t2, observer 12A has traveled over...Cartesian coordinates of the target with respect to time , and ?̇? and ?̇? are components of the target velocity. [0007] As is well known, a...as a time interval of constant platform velocity.) [0008] In addition to a point estimate of the current target state, a representation of the

  20. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

    Hansen, Allan; Friis, Ivar; Vámosi, Tamás S.

    In this paper we explore the processes of ‘bringing the market inside the firm’ to set performance targets and benchmark production workers productivity. We analyze attempts to use external suppliers’ bids in target setting in a Danish manufacturing company. The case study illustrates how...... the implementation of external market information in target setting – well known in transfer pricing, relative performance evaluation, beyond budgeting, target costing, piece rates systems and value based management – relate to challenging motivation and information problem. The analysis and discussion of those...

  1. An entropy model with variable target

    OpenAIRE

    K O Jörnsten; Larsson, T; J T Lundgren; Migdalas, A.

    1990-01-01

    In this paper an entropy model with variable target is presented, in which target values are assumed to belong to a specified convex set, so that multiple base-year information and forecasts of future trends can be handled without prior aggregation of such information into one fixed target. Three solution methods for such a model are presented -- one cutting-plane and two search methods -- all of which utilize the fact that entropy models with fixed targets can be solved efficiently. Some com...

  2. Tumour-targeted nanomedicines: principles and practice

    National Research Council Canada - National Science Library

    Lammers, T.G.G.M; Hennink, W.E; Storm, G

    2008-01-01

    .... Various different tumour-targeted nanomedicines have been evaluated over the years, and clear evidence is currently available for substantial improvement of the therapeutic index of anticancer agents...

  3. Selective targeting of epigenetic reader domains.

    Science.gov (United States)

    Greschik, Holger; Schüle, Roland; Günther, Thomas

    2017-05-01

    Epigenetic regulators including writers, erasers, and readers of chromatin marks have been implicated in numerous diseases and are therefore subject of intense academic and pharmaceutical research. While several small-molecule inhibitors targeting writers or erasers are either approved drugs or are currently being evaluated in clinical trials, the targeting of epigenetic readers has lagged behind. Proof-of-principle that epigenetic readers are also relevant drug targets was provided by landmark discoveries of selective inhibitors targeting the BET family of acetyl-lysine readers. More recently, high affinity chemical probes for non-BET acetyl- and methyl-lysine reader domains have also been developed. Areas covered: This article covers recent advances with the identification and validation of inhibitors and chemical probes targeting epigenetic reader domains. Issues related to epigenetic reader druggability, quality requirements for chemical probes, interpretation of cellular action, unexpected cross-talk, and future challenges are also discussed. Expert opinion: Chemical probes provide a powerful means to unravel biological functions of epigenetic readers and evaluate their potential as drug targets. To yield meaningful results, potency, selectivity, and cellular target engagement of chemical probes need to be stringently validated. Future chemical probes will probably need to fulfil additional criteria such as strict target specificity or the targeting of readers within protein complexes.

  4. Two target localization using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2016-02-19

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localization and tracking purposes. Many works focused on accurately localizing one or two targets laying within a narrow beam centered around the monopulse antenna boresight direction. In this work, however, a new approach uses the outputs of a four quadrant antenna receiver to rapidly localize two point targets present in the hemisphere. A second set of antennas can be required to localize two targets sharing the same elevation or azimuth angles. To combine the outputs of both antenna sets and enhance the estimation performance of the algorithm, two methods are presented and compared.

  5. Targeted advertising, platform competition and privacy

    NARCIS (Netherlands)

    Kox, Henk; Straathof, Bas; Zwart, Gijsbert

    2017-01-01

    Targeted advertising can benefit consumers through lower prices for access to web sites. Yet, if consumers dislike that web sites collect their personal information, their welfare may go down. We study competition for consumers between web sites that can show targeted advertisements. We find that

  6. A rotating target for Ra production

    NARCIS (Netherlands)

    Sohani, M.; Wilschut, H. W.

    2012-01-01

    A target wheel with pyrolytic graphite targets is designed and constructed at the TRI mu P facility to boost the production rate of Ra isotopes. Simulation, design properties and production results are discussed. (C) 2012 Elsevier B.V. All rights reserved.

  7. Technical Design Report, Second Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Galambos, John D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Anderson, David E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bechtol, D. [HDR, Inc., Chattanooga, TN (United States); Bethea, Katie L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Brown, N. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Carden, W. F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chae, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clark, A. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Counce, Deborah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Craft, K. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Crofford, Mark T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Collins, Richard M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cousineau, Sarah M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Curry, Douglas E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cutler, Roy I. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dayton, Michael J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dean, Robert A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Deibele, Craig E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Doleans, Marc [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Dye, T. [HDR, Inc., Chattanooga, TN (United States); Eason, Bob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eckroth, James A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Fincrock, C. [HDR, Inc., Chattanooga, TN (United States); Fritts, S. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Gallmeier, Franz X. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gawne, Ken R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hartman, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Herwig, Kenneth W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hess, S. [HDR, Inc., Chattanooga, TN (United States); Holmes, Jeffrey A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Horak, Charlie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Howell, Matthew P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Iverson, Erik B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jacobs, Lorelei L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jones, Larry C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Johnson, B. [HDR, Inc., Chattanooga, TN (United States); Johnson, S. [HDR, Inc., Chattanooga, TN (United States); Kasemir, Kay [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kim, Sang-Ho [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Laughon, Gregory J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lu, W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mahoney, Kelly L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Mammosser, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McManamy, T. [McManamy Consulting, Inc., Knoxville, TN (United States); Michilini, M. [HDR, Inc., Chattanooga, TN (United States); Middendorf, Mark E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); O' Neal, Ed [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nemec, B. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Peters, Roy Cecil [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Plum, Michael A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Reagan, G. [Barge Waggoner Sumner & Cannon, Inc., Nashville, TN (United States); Remec, Igor [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Rennich, Mark J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Riemer, Bernie [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Saethre, Robert B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Schubert, James Phillip [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shishlo, Andrei P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Smith, C. Craig [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Strong, William Herb [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tallant, Kathie M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tennant, David Alan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Thibadeau, Barbara M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Trumble, S. [HDR, Inc., Chattanooga, TN (United States); Trotter, Steven M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Z. [Institute of Modern Physics (IMP), Chinese Academy of Sciences (China); Webb, Steven B. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Williams, Derrick C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); White, Karen S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Zhao, Jinkui [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-01-01

    The Second Target Station (STS) is a proposed upgrade for SNS. It includes a doubling of the accelerator power and an additional instrument hall. The new instrument hall will receive a 467 kW 10 Hz beam. The parameters and preliminary design aspects of the STS are presented for the accelerator, target systems, instrument hall, instruments and civil construction aspects.

  8. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Green, Mark A.

    2000-03-22

    Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy.

  9. NIF Target Assembly Metrology Methodology and Results

    Energy Technology Data Exchange (ETDEWEB)

    Alger, E. T. [General Atomics, San Diego, CA (United States); Kroll, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Dzenitis, E. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Montesanti, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Hughes, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Swisher, M. [IAP, Livermore, CA (United States); Taylor, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Segraves, K. [IAP, Livermore, CA (United States); Lord, D. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Reynolds, J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Castro, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Edwards, G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2011-01-01

    During our inertial confinement fusion (ICF) experiments at the National Ignition Facility (NIF) we require cryogenic targets at the 1-cm scale to be fabricated, assembled, and metrologized to micron-level tolerances. During assembly of these ICF targets, there are physical dimensmetrology is completed using optical coordinate measurement machines that provide repeatable measurements with micron precision, while also allowing in-process data collection for absolute accuracy in assembly. To date, 51 targets have been assembled and metrologized, and 34 targets have been successfully fielded on NIF relying on these metrology data. In the near future, ignition experiments on NIF will require tighter tolerances and more demanding target assembly and metrology capability. Metrology methods, calculations, and uncertainty estimates will be discussed. Target diagnostic port alignment, target position, and capsule location results will be reviewed for the 2009 Energetics Campaign. The information is presented via control charts showing the effect of process improvements that were made during target production. Certain parameters, including capsule position, met the 2009 campaign specifications but will have much tighter requirements in the future. Finally, in order to meet these new requirements assembly process changes and metrology capability upgrades will be necessary.

  10. Inflation targeting and interest rate policy

    NARCIS (Netherlands)

    Verhagen, W.H.

    2001-01-01

    The thesis contains a collection of papers on issues in inflation targeting and its implications for the way interest rates are set. In this respect, the first part deals with two largely positive issues: the effect of inflation forecast targeting on the term structure of interest rates and the

  11. Population ageing and public finance targets

    OpenAIRE

    Heikki Oksanen

    2003-01-01

    The paper incorporates intergenerational fairness into a framework to analyse long-term sustainability of public finances under population ageing. It establishes a link between ageing-related public expenditure projections and public finance targets, thereby clarifying the connection between pension reforms and general government budget balance and debt targets.

  12. Thin Scintillating Polarized Targets for Spin Physics

    Science.gov (United States)

    van den Brandt, B.; Bunyatova, E. I.; Hautle, P.; Konter, J. A.

    2003-07-01

    At PSI polarized scintillating targets are available since 1996. Proton polarizations of more than 80%, and deuteron polarizations of 25% in polystyrene-based scintillators can be reached under optimum conditions in a vertical dilution refrigerator with optical access, suited for nuclear and particle physics experiments. New preparation procedures allow to provide very thin polarizable scintillating targets and widen the spectrum of conceivable experiments.

  13. Harmonic Phase Response of Nonlinear Radar Targets

    Science.gov (United States)

    2015-10-01

    ARL-TR-7513 ● OCT 2015 US Army Research Laboratory Harmonic Phase Response of Nonlinear Radar Targets by Sean F McGowan, Dr...Laboratory Harmonic Phase Response of Nonlinear Radar Targets by Sean F McGowan and Kelly D Sherbondy Sensors and Electron Devices Directorate...

  14. Function and targets of Fusarium oxysporum effectors

    NARCIS (Netherlands)

    Gawehns, F.K.K.

    2014-01-01

    A multi-layered immune system protects plants against pathogens. Adapted pathogens overcome or evade this immune system by secreting small proteins, called effectors. Often susceptibility genes encode host targets for these effectors, and loss-of-function mutations in such target genes can confer

  15. Security analysts' target prices and takeover premiums

    NARCIS (Netherlands)

    Gerritsen, Dirk F.

    2015-01-01

    Most existing studies conclude that the accuracy of analysts' target prices is questionable. In forecasting target prices, analysts estimate a future stock price under the constraint of a time frame of usually 12. months. We exclude this source of uncertainty by focusing on valuations in takeover

  16. ISOLDE target zone control room HD

    CERN Multimedia

    2016-01-01

    Operating the ISOLDE target handling robots from the dedicated control room in building 197. Monitors showing the movements of the robots (GPS in this case) in the target zone. The footage shows the actual operation by the operator as well as the different equipment such as camera electronics, camera motor controls, camera monitors and Kuka robot controls touch panel.

  17. Poverty Targeting Classifications and Distributional Effects

    OpenAIRE

    Elio H Londero

    2004-01-01

    This paper reviews two common definitions of poverty targeted projects, discusses the limitations of poverty targeting classifications, calls for a poverty focused cost-benefit analysis that looks at the main policy constraints affecting the distribution of project benefits, and argues for looking at the distribution of net benefits. Finally, it offers some conclusions for the distributionally-minded applied economists.

  18. The History of Target-Controlled Infusion

    NARCIS (Netherlands)

    Struys, Michel M. R. F.; De Smet, Tom; Glen, John (Iain) B.; Vereecke, Hugo E. M.; Absalom, Anthony R.; Schnider, Thomas W.

    Target-controlled infusion (TCI) is a technique of infusing IV drugs to achieve a user-defined predicted (target) drug concentration in a specific body compartment or tissue of interest. In this review, we describe the pharmacokinetic principles of TCI, the development of TCI systems, and technical

  19. Experimental identification of microRNA targets

    DEFF Research Database (Denmark)

    Ørom, Ulf Andersson; Lund, Anders H

    2009-01-01

    microRNAs are small RNAs that regulate protein synthesis post-transcriptionally. Animal microRNAs recognize their targets by incomplete base pairing to sequence motifs most often present in the 3' untranslated region of their target mRNAs. This partial complementarity vastly expands the repertoire...

  20. Targeted toxins in brain tumor therapy.

    Science.gov (United States)

    Li, Yan Michael; Hall, Walter A

    2010-11-01

    Targeted toxins, also known as immunotoxins or cytotoxins, are recombinant molecules that specifically bind to cell surface receptors that are overexpressed in cancer and the toxin component kills the cell. These recombinant proteins consist of a specific antibody or ligand coupled to a protein toxin. The targeted toxins bind to a surface antigen or receptor overexpressed in tumors, such as the epidermal growth factor receptor or interleukin-13 receptor. The toxin part of the molecule in all clinically used toxins is modified from bacterial or plant toxins, fused to an antibody or carrier ligand. Targeted toxins are very effective against cancer cells resistant to radiation and chemotherapy. They are far more potent than any known chemotherapy drug. Targeted toxins have shown an acceptable profile of toxicity and safety in early clinical studies and have demonstrated evidence of a tumor response. Currently, clinical trials with some targeted toxins are complete and the final results are pending. This review summarizes the characteristics of targeted toxins and the key findings of the important clinical studies with targeted toxins in malignant brain tumor patients. Obstacles to successful treatment of malignant brain tumors include poor penetration into tumor masses, the immune response to the toxin component and cancer heterogeneity. Strategies to overcome these limitations are being pursued in the current generation of targeted toxins.

  1. Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

    Science.gov (United States)

    Brown, K; Gordon, E; Williams, L; Bahramali, H; Harris, A; Gray, J; Gonsalvez, C; Meares, R

    2000-11-01

    While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

  2. Setting conservation targets for sandy beach ecosystems

    Science.gov (United States)

    Harris, Linda; Nel, Ronel; Holness, Stephen; Sink, Kerry; Schoeman, David

    2014-10-01

    Representative and adequate reserve networks are key to conserving biodiversity. This begs the question, how much of which features need to be placed in protected areas? Setting specifically-derived conservation targets for most ecosystems is common practice; however, this has never been done for sandy beaches. The aims of this paper, therefore, are to propose a methodology for setting conservation targets for sandy beach ecosystems; and to pilot the proposed method using data describing biodiversity patterns and processes from microtidal beaches in South Africa. First, a classification scheme of valued features of beaches is constructed, including: biodiversity features; unique features; and important processes. Second, methodologies for setting targets for each feature under different data-availability scenarios are described. From this framework, targets are set for features characteristic of microtidal beaches in South Africa, as follows. 1) Targets for dune vegetation types were adopted from a previous assessment, and ranged 19-100%. 2) Targets for beach morphodynamic types (habitats) were set using species-area relationships (SARs). These SARs were derived from species richness data from 142 sampling events around the South African coast (extrapolated to total theoretical species richness estimates using previously-established species-accumulation curve relationships), plotted against the area of the beach (calculated from Google Earth imagery). The species-accumulation factor (z) was 0.22, suggesting a baseline habitat target of 27% is required to protect 75% of the species. This baseline target was modified by heuristic principles, based on habitat rarity and threat status, with final values ranging 27-40%. 3) Species targets were fixed at 20%, modified using heuristic principles based on endemism, threat status, and whether or not beaches play an important role in the species' life history, with targets ranging 20-100%. 4) Targets for processes and 5

  3. Radiochemical aspects of liquid mercury spallation targets

    CERN Document Server

    Neuhausen, Joerg; Eichler, Bernd; Eller, Martin; Horn, Susanne; Schumann, Dorothea; Stora, Thierry

    2012-01-01

    Liquid metal spallation targets using mercury as target material are used in state-of-the-art high power pulsed neutron sources that have been constructed in the USA and Japan within the last decade. Similar target concepts were also proposed for next generation ISOL, beta-beam and neutrino facilities. A large amount of radioactivity will be induced in the liquid metal during operation caused by the interaction of the target material with the intense proton beam. This radioactivity - carried by a wide range of radioisotopes of all the elements of the periodic table from hydrogen up to thallium - must be considered for the assessment of safe operation and maintenance procedures as well as for a final disposal of the used target material and components. This report presents an overview on chemical investigations performed in our laboratory that deal with the behavior of radionuclides in proton irradiated mercury samples. The solubility of elements in mercury was calculated using thermodynamical data obtained by...

  4. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

    Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Dattolo, E; Galmiche, D; Gauthier, P; Giorla, J; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

    2009-12-15

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  5. Hydrogen isotope recycling at a tungsten target

    Energy Technology Data Exchange (ETDEWEB)

    Sakamoto, M., E-mail: sakamoto@prc.tsukuba.ac.jp [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Nakashima, Y. [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Higashizono, Y. [Research Institute for Applied Mechanics, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Ogawa, K. [Interdisciplinary Graduate School for Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Hosoi, K. [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan); Rusinov, A. [Interdisciplinary Graduate School for Engineering Sciences, Kyushu University, Kasuga, Fukuoka 816-8580 (Japan); Takeda, H.; Akabane, Y.; Kohagura, J.; Yoshikawa, M.; Ichimura, M.; Imai, T. [Plasma Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8577 (Japan)

    2013-07-15

    Hydrogen recycling has been studied focusing on the neutral behavior in front of tungsten target in the plasma–wall interaction simulator APSEDAS and the tandem mirror GAMMA 10. The line intensity of hydrogen Balmer series decreased toward the target corresponding to a decrease in the electron density in APSEDAS. The relative population of n = 3 and n = 4 increased and that of n = 5 and n = 6 decreased just in front of the target (Z < 5 mm). This might be attributed to the reflected atom or reemitted molecule from the target. In GAMMA 10, the intensity of hydrogen Balmer (H{sub α}) line decreased exponentially with distance from the target with two decay lengths: ∼16 mm and ∼53 mm. These two short decay lengths are attributed to the fact that a fraction of the reflected atoms and atoms dissociated from molecules are at excited energy states.

  6. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  7. Delayed neutrons measurement at the MEGAPIE target

    CERN Document Server

    Panebianco, Stefano; Dore, Diane; Ledoux, Xavier; Letourneau, Alain; Prevost, Aurelien; Ridikas, Danas

    2007-01-01

    In the framework of the Neutronic and Nuclear Assessment Task Group of the MEGAPIE experiment we measured the delayed neutron (DN) flux at the top of the target. The measurement was proposed mainly for radioprotection purposes since the DN flux at the top of the target has been estimated to be of the same order of magnitude as the prompt neutron flux. Given the strong model-dependence of DN predictions, the measurement of DN contribution to the total neutron activity at the top of the target was thus desired. Moreover, this measurement is complementary to the DN experiments performed at PNPI (Gatchina) on solid lead and bismuth targets. The DN measurement at MEGAPIE was performed during the start-up phase of the target. In this paper we present a detailed description of the experimental setup and some preliminary results on decay spectra.

  8. Launch window definition for sky target experiments.

    Science.gov (United States)

    Michaud, N. H.

    1973-01-01

    This paper is a brief report on the computer program developed for the Extraterrestrial Physics Barium Ion Cloud (BIC) Project. The mathematical analysis developed for the program along with its programing characteristics are pointed out to show that this program is adaptable to similar sky target projects. Definite viewing constraints are specified so that the chosen ground tracking stations can photograph the behavior of the sky target after its release. Viewing factors include the illumination of the target by the sun, the relative elevation look angle to the target from each tracking station, the solar and lunar depression angles at each tracking station, and the total sky background brightness of the target relative to each tracking station. Numeric values are assigned to each factor through program input. The program output is flexible so that the results of the window calculations can be studied to the depth required.

  9. Target Identification Strategies in Plant Chemical Biology

    Directory of Open Access Journals (Sweden)

    Wim eDejonghe

    2014-07-01

    Full Text Available The current needs to understand gene function in plant biology increasingly require more dynamic and conditional approaches opposed to classic genetic strategies. Gene redundancy and lethality can substantially complicate research, which might be solved by applying a chemical genetics approach. Now understood as the study of small molecules and their effect on biological systems with subsequent target identification, chemical genetics is a fast developing field with a strong history in pharmaceutical research and drug discovery. In plant biology however, chemical genetics is still largely in the starter blocks, with most studies relying on forward genetics and phenotypic analysis for target identification, while studies including direct target identification are limited. Here, we provide an overview of recent advances in chemical genetics in plant biology with a focus on target identification. Furthermore, we discuss different strategies for direct target identification and the possibilities and challenges for plant biology

  10. Radar target identification using multifractal geometry

    Science.gov (United States)

    Quach, Ban; Leung, Henry; Lo, Titus K. Y.; Litva, John

    1996-06-01

    The design of a system to distinguish objects from measurements of their radar backscatter signals has been a topic of considerable investigation. In the identification of a particular target out of a library of possible targets, the difficulty is that the radar signals cannot be fed rawly into a classifier. Some signal processing has to be done to generate the signal features for target identification. In this paper, multifractal geometry is applied to address the practical issue of discrimination between fishing boat, growlers (small pieces of glacial ice) and sea scattered signals, which is important for search-and-rescue operation. An efficient box-counting method is used to compute the generalized dimension and the multifractal spectrum of different targets and sea scattered signals. In an effort to support our study, X-band radar measurements were collected and analyzed to determine the separability of sea surface targets and sea scattered signals using the multifractal geometry.

  11. The Jefferson Lab Frozen Spin Target

    Energy Technology Data Exchange (ETDEWEB)

    Christopher Keith, James Brock, Christopher Carlin, Sara Comer, David Kashy, Josephine McAndrew, David Meekins, Eugene Pasyuk, Joshua Pierce, Mikell Seely

    2012-08-01

    A frozen spin polarized target, constructed at Jefferson Lab for use inside a large acceptance spectrometer, is described. The target has been utilized for photoproduction measurements with polarized tagged photons of both longitudinal and circular polarization. Protons in TEMPO-doped butanol were dynamically polarized to approximately 90% outside the spectrometer at 5 T and 200-300 mK. Photoproduction data were acquired with the target inside the spectrometer at a frozen-spin temperature of approximately 30 mK with the polarization maintained by a thin, superconducting coil installed inside the target cryostat. A 0.56 T solenoid was used for longitudinal target polarization and a 0.50 T dipole for transverse polarization. Spin relaxation times as high as 4000 hours were observed. We also report polarization results for deuterated propanediol doped with the trityl radical OX063.

  12. Peptide Selection for Targeted Protein Quantitation.

    Science.gov (United States)

    Chiva, Cristina; Sabidó, Eduard

    2017-03-03

    Targeted proteomics methods in their different flavors rely on the use of a few peptides as proxies for protein quantitation, which need to be specified either prior to or after data acquisition. However, in contrast with discovery methods that use all identified peptides for a given protein to estimate its abundance, targeted proteomics methods are limited in the number of peptides that are used for protein quantitation. Because only a few peptides per protein are acquired or extracted in targeted experiments, the selection of peptides that are used for targeted protein quantitation becomes crucial. Several rules have been proposed to guide peptide selection for targeted proteomics studies, which have generally been based on the amino acidic composition of the peptide sequences. However, the compliance of these rules does not imply that not-conformed peptides are not reproducibly generated nor do they guarantee that the selected peptides correctly represent the behavior of the protein abundance under different conditions.

  13. Behavioral and neurophysiological aspects of target interception.

    Science.gov (United States)

    Merchant, Hugo; Zarco, Wilbert; Prado, Luis; Pérez, Oswaldo

    2009-01-01

    This chapter focuses on the behavioral and neurophysiological aspects of manual interception. We review the most important elements of an interceptive action from the sensory and cognitive stage to the motor side of this behavior. We describe different spatial and temporal target parameters that can be used to control the interception movement, as well as the different strategies used by the subject to intercept a moving target. We review the neurophysiological properties of the parietofrontal system during target motion processing and during a particular experiment of target interception. Finally, we describe the neural responses associated with the temporal and spatial parameters of a moving target and the possible neurophysiological mechanisms used to integrate this information in order to trigger an interception movement.

  14. Production and characterization of a novel long-acting Herceptin-targeted nanobubble contrast agent specific for Her-2-positive breast cancers.

    Science.gov (United States)

    Jiang, Qiongchao; Hao, Shaoyun; Xiao, Xiaoyun; Yao, Jiyi; Ou, Bing; Zhao, Zizhuo; Liu, Fengtao; Pan, Xin; Luo, Baoming; Zhi, Hui

    2016-05-01

    There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors. Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model. The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells (p Herceptin-conjugated nanobubble had many properties that made it useful for in vivo imaging, including longer circulation time and better tumor selectivity. This platform may be able to provide targeted delivery of therapeutic drugs or genes.

  15. Exploration of allosteric agonism structure-activity relationships within an acetylene series of metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulators (PAMs): discovery of 5-((3-fluorophenyl)ethynyl)-N-(3-methyloxetan-3-yl)picolinamide (ML254).

    Science.gov (United States)

    Turlington, Mark; Noetzel, Meredith J; Chun, Aspen; Zhou, Ya; Gogliotti, Rocco D; Nguyen, Elizabeth D; Gregory, Karen J; Vinson, Paige N; Rook, Jerri M; Gogi, Kiran K; Xiang, Zixiu; Bridges, Thomas M; Daniels, J Scott; Jones, Carrie; Niswender, Colleen M; Meiler, Jens; Conn, P Jeffrey; Lindsley, Craig W; Stauffer, Shaun R

    2013-10-24

    Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) represent a promising therapeutic strategy for the treatment of schizophrenia. Both allosteric agonism and high glutamate fold-shift have been implicated in the neurotoxic profile of some mGlu5 PAMs; however, these hypotheses remain to be adequately addressed. To develop tool compounds to probe these hypotheses, the structure-activity relationship of allosteric agonism was examined within an acetylenic series of mGlu5 PAMs exhibiting allosteric agonism in addition to positive allosteric modulation (ago-PAMs). PAM 38t, a low glutamate fold-shift allosteric ligand (maximum fold-shift ~ 3.0), was selected as a potent PAM with no agonism in the in vitro system used for compound characterization and in two native electrophysiological systems using rat hippocampal slices. PAM 38t (ML254) will be useful to probe the relative contribution of cooperativity and allosteric agonism to the adverse effect liability and neurotoxicity associated with this class of mGlu5 PAMs.

  16. Ecosystem Targets - Defining target levels for ecosystem components: a socio-ecological approach

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Ecological indicators can facilitate Ecosystem-based Management, but only if targets for indicators exist. Because targets are an expression of the desired state of...

  17. Multiple Model Adaptive Estimator Target Tracker for Maneuvering Targets in Clutter

    National Research Council Canada - National Science Library

    Smith, Brian D

    2005-01-01

    ...) to be implemented directly. Poorly known or varying target dynamics complicate the design of any tracking filter, and filters using only a single dynamics model can rarely handle anything beyond the most benign target maneuvers...

  18. Search for Two Categories of Target Produces Fewer Fixations to Target-Color Items

    Science.gov (United States)

    Menneer, Tamaryn; Stroud, Michael J.; Cave, Kyle R.; Li, Xingshan; Godwin, Hayward J.; Liversedge, Simon P.; Donnelly, Nick

    2012-01-01

    Searching simultaneously for metal threats (guns and knives) and improvised explosive devices (IEDs) in X-ray images is less effective than 2 independent single-target searches, 1 for metal threats and 1 for IEDs. The goals of this study were to (a) replicate this dual-target cost for categorical targets and to determine whether the cost remains…

  19. Hitting moving targets : A dissociation between the use of the target's speed and direction of motion

    NARCIS (Netherlands)

    Brouwer, Anne Marie; Middelburg, Tom; Smeets, Jeroen B J; Brenner, Eli

    2003-01-01

    Previous work has indicated that people do not use their judgment of a target's speed to determine where to hit it. Instead, they use their judgment of the target's changing position and an expected speed (based on the speed of previous targets). In the present study we investigate whether people

  20. Subcellular drug targeting, pharmacokinetics and bioavailability.

    Science.gov (United States)

    Leucuta, Sorin Emilian

    2014-02-01

    Effective treatment of diseases at the molecular level is possible by directing the drug substance (micromolecular, protein or peptide drugs, DNA, oligonucleotides, siRNA) with the aid of a specialized nanoparticulate carrier, for safe and effective transport to the specific site of action in the cytosol and its organelles including nuclear targeting. To achieve efficient cytosolic delivery of therapeutics or nuclear targeting, different drug delivery systems (DDS) have been developed (macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers) capable of subcellular internalization overcoming the biological barriers, by passive targeting and especially by active targeting (receptor-targeted delivery). The success depends on the physicochemical nature of DDS, intracellular barriers that these systems need to overcome, the bioavailability of the bioactive drug, biodistribution, the intracellular pharmacokinetics and its influence on the pharmacodynamic effect. Models necessary for this purpose exist but they need to be more developed especially with quantitative treatments, after the development of the means of highlighting the evolution of the drug substance in biophase or at the level of the target cellular organelle by quantitative assays. It is expected that intracellularly targeted drug delivery approaches will be clinically useful using specialized DDSs belonging to the pharmaceutical nanotechnologies.

  1. Hypersonic sliding target tracking in near space

    Directory of Open Access Journals (Sweden)

    Xiang-yu Zhang

    2015-12-01

    Full Text Available To improve the tracking accuracy of hypersonic sliding target in near space, the influence of target hypersonic movement on radar detection and tracking is analyzed, and an IMM tracking algorithm is proposed based on radial velocity compensating and cancellation processing of high dynamic biases under the earth centered earth fixed (ECEF coordinate. Based on the analysis of effect of target hypersonic movement, a measurement model is constructed to reduce the filter divergence which is caused by the model mismatch. The high dynamic biases due to the target hypersonic movement are approximately compensated through radial velocity estimation to achieve the hypersonic target tracking at low systematic biases in near space. The high dynamic biases are further eliminated by the cancellation processing of different radars, in which the track association problem can be solved when the dynamic biases are low. An IMM algorithm based on constant acceleration (CA, constant turning (CT and Singer models is used to achieve the hypersonic sliding target tracking in near space. Simulation results show that the target tracking in near space can be achieved more effectively by using the proposed algorithm.

  2. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, S. [Fermilab; Ammigan, K. [Fermilab; Anderson, K.; ; Buccellato, S. A. [Fermilab; Crowley, C. F. [Fermilab; Hartsell, B. D. [Fermilab; Hurh, P. [Fermilab; Hylen, J. [Fermilab; Kasper, P. [Fermilab; Krafczyk, G. E. [Fermilab; Lee, A. [Fermilab; Lundberg, B. [Fermilab; Reitzner, S. D. [Fermilab; Sidorov, V. [Fermilab; Stefanik, A. M. [Fermilab; Tropin, I. S. [Fermilab; Vaziri, K. [Fermilab; Williams, K. [Fermilab; Zwaska, R. M. [Fermilab; Densham, C. [RAL, Didcot

    2016-10-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding in a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.

  3. Improving pharmacological targeting of AKT in melanoma.

    Science.gov (United States)

    Kuzu, Omer F; Gowda, Raghavendra; Sharma, Arati; Noory, Mohammad A; Dinavahi, Saketh S; Kardos, Gregory; Drabick, Joseph J; Robertson, Gavin P

    2017-09-28

    Targeting AKT with pharmacological agents inhibiting this protein in the melanoma clinic is ineffective. This is a major contradiction considering the substantial preclinical data suggesting AKT as an effective target. Various approaches have been undertaken to unravel this contradiction and drug combinations sought that could resolve this concern. We have shown that genetic targeting AKT3 or WEE1 can be effective for inhibiting tumor growth in preclinical animal models. However, no one has examined whether combining pharmacological agents targeting each of these enzymes could be more effective than inhibiting each alone and enhance the efficacy of targeting AKT in melanoma. This report shows that combining the AKT inhibitors (AZD5363 or MK1775) with the WEE1 inhibitor, AZD5363, can synergistically kill cultured melanoma cells and decrease melanoma tumor growth by greater than 90%. Co-targeting AKT and WEE1 led to enhanced deregulation of the cell cycle and DNA damage repair pathways by modulating the transcription factors p53 and FOXM1, as well as the proteins whose expression is regulated by these two proteins. Thus, this study identifies a unique combination of pharmacological agents and the ratio needed for efficacy that could be used to potentially improve the therapeutic effectiveness of targeting AKT in the clinic. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. COMPASS polarized target for Drell-Yan

    CERN Document Server

    Pešek, M

    2014-01-01

    In the COMPASS Drell–Yan experiment the pion beam with momen tum of 190 GeV/ c and in- tensity up to 10 8 pions/s will interact with transversely polarized proton t arget producing muon pair via Drell–Yan process. The solid-state NH 3 will be polarized by dynamic nuclear polar- ization. Maximum polarization reached during data taking i s expected to be up to 90%. The non-interacting beam and other particles produced inside t he target will be stopped in the hadron absorber after the target. Two target cells, sepparated by a 20 cm gap in between, each 55 cm long and 4 cm in diameter give the target material volume about 691 cm 3 . The target platform needs to be moved by 2.3 m in upstream dire ction from the position used in previous experiments in order to accomodate the absorber. D uring the beam time higher radiation is expected in the area of the control room. Thus a new target r emote control system is needed. The target magnet is undergoing a substantial upgrade. Drell–Yan data taking is expected t...

  5. Systemic Targeted Alpha Radiotherapy for Cancer

    Directory of Open Access Journals (Sweden)

    Allan B. J.

    2013-09-01

    Full Text Available Background: The fundamental principles of internal targeted alpha therapy for cancer were established many decades ago.The high linear energy transfer (LET of alpha radiation to the targeted cancer cellscauses double strand breaks in DNA. At the same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g.glioblastoma multiformeand to inhibit the development of lethal metastatic cancer after successful treatment of the primary cancer. Objective: This review charts the developing role of systemic high LET, internal radiation therapy. Method: Targeted alpha therapy is a rapidly advancing experimental therapy that holds promise to deliver high cytotoxicity to targeted cancer cells. Initially thought to be indicated for leukemia and micrometastases, there is now evidence that solid tumors can also be regressed. Results: Alpha therapy may be molecular or physiological in its targeting. Alpha emitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to label monoclonal antibodies or proteins that target specifc cancer cells. Alternatively, Radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. Conclusion: Preclinical studies and clinical trials of alpha therapy are discussed for leukemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers.

  6. Gene Therapy and Targeted Toxins for Glioma

    Science.gov (United States)

    Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

    2011-01-01

    The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

  7. Folate targeted polymeric 'green' nanotherapy for cancer

    Science.gov (United States)

    Narayanan, Sreeja; Binulal, N. S.; Mony, Ullas; Manzoor, Koyakutty; Nair, Shantikumar; Menon, Deepthy

    2010-07-01

    The concept of 'green' chemotherapy by employing targeted nanoparticle mediated delivery to enhance the efficacy of phytomedicines is reported. Poly (lactide-co-glycolide) (PLGA) nanoparticles encapsulating a well known nutraceutical namely, grape seed extract (GSE)—'NanoGSE'—was prepared by a nanoprecipitation technique. The drug-loaded nanoparticles of size ~ 100 nm exhibited high colloidal stability at physiological pH. Molecular receptor targeting of this nanophytomedicine against folate receptor over-expressing cancers was demonstrated in vitro by conjugation with a potential cancer targeting ligand, folic acid (FA). Fluorescence microscopy and flow cytometry data showed highly specific cellular uptake of FA conjugated NanoGSE on folate receptor positive cancer cells. Studies were also conducted to investigate the efficiency of targeted (FA conjugated) versus non-targeted (non-FA conjugated) nanoformulations in causing cancer cell death. The IC50 values were lowered by a factor of ~ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

  8. Targeting tumor suppressor genes for cancer therapy.

    Science.gov (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. © 2015 WILEY Periodicals, Inc.

  9. Preliminary investigation of solid target geometry

    Energy Technology Data Exchange (ETDEWEB)

    Haga, Katsuhiro; Kaminaga, Masanori; Hino, Ryutaro; Takada, Hiroshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Shafiqul, I.M.; Tsuji, Nobumasa; Okamoto, Hutoshi; Kumasaka, Katsuyuki; Hayashi, Katsumi

    1997-11-01

    In this report, we introduce the developing plan for a solid metal target structure. Supposing tantalum as the target material, the temperature distribution and the maximum thermal stress in a tantalum plate of a solid metal target was evaluated under a water cooling condition, using the heat generation rate calculated with the JAERI`s neutron transport code. The calculation results showed that the water velocity was higher than 10 m/s in order to cool the 3mm-thick target plate down to 200degC when the target surface was smooth and heat transfer rate was calculated with the Dittus-Boelter equation. In this case, the maximum thermal stress is 50 MPa at the target plate surface. The coolant water flow distribution in a target vessel was also evaluated for ISIS-type flow channels and the parallel flow channels. In the ISIS-type flow channels, at least 25mm height of the coolant plenum is needed for a uniform flow distribution. The maximum flow velocity difference between the flow gaps in the parallel flow channels was 30%. A heat transfer augmentation experiment was conducted using ribbed-surface flow channel. The heat transfer rate was confirmed to increase up to twice the value of that for a smooth surface. (author)

  10. Degradable Polymersomes for Targeted Drug Delivery

    Science.gov (United States)

    Petersen, Matthew Alan

    Chemotherapy today is often accompanied by major side effects due to delivery of toxic drugs to healthy tissue in addition to diseased cells. Targeted drug delivery offers the possibility of minimizing these side effects by specific delivery to cancer cells using targeted nanocarriers that enhance drug accumulation in tumors and facilitate target-specific cellular uptake. Polymersomes, vesicles self-assembled from polymeric amphiphiles, are an attractive targeted vehicle, as they are capable of encapsulating both hydrophobic and hydrophilic drugs, have lengthy circulation times in vivo, and can employ degradable functionality for triggered release of payload and clearance from the body. This thesis reports on efforts to enhance the capabilities of degradable polymersomes for targeted delivery. First, targeting functionality is incorporated into polymersomes of the block copolymer poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) by incorporating the reactive vinyl sulfone group into the amphiphile's hydrophilic terminus, allowing site-selective reaction with cysteine-functionalized targeting peptides following self-assembly. The performance of targeted delivery using this polymersome is then evaluated in vitro. Binding and delivery to model cell lines for targeted and bystander cells is tracked using nontargeted polymersomes and compared to that for polymersomes using a high- or low-affinity ligand. Polymer degradation is also tracked both in simple media and during cellular delivery. Finally, a new monomer is developed incorporating acid-labile acetal functionality into a cyclic polyester. The polymerization of this monomer to two distinct polymers is also characterized and the degradation behavior of both polymers evaluated.

  11. Protein search for multiple targets on DNA

    Energy Technology Data Exchange (ETDEWEB)

    Lange, Martin [Johannes Gutenberg University, Mainz 55122 (Germany); Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Kochugaeva, Maria [Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Kolomeisky, Anatoly B., E-mail: tolya@rice.edu [Department of Chemistry, Rice University, Houston, Texas 77005 (United States); Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005 (United States)

    2015-09-14

    Protein-DNA interactions are crucial for all biological processes. One of the most important fundamental aspects of these interactions is the process of protein searching and recognizing specific binding sites on DNA. A large number of experimental and theoretical investigations have been devoted to uncovering the molecular description of these phenomena, but many aspects of the mechanisms of protein search for the targets on DNA remain not well understood. One of the most intriguing problems is the role of multiple targets in protein search dynamics. Using a recently developed theoretical framework we analyze this question in detail. Our method is based on a discrete-state stochastic approach that takes into account most relevant physical-chemical processes and leads to fully analytical description of all dynamic properties. Specifically, systems with two and three targets have been explicitly investigated. It is found that multiple targets in most cases accelerate the search in comparison with a single target situation. However, the acceleration is not always proportional to the number of targets. Surprisingly, there are even situations when it takes longer to find one of the multiple targets in comparison with the single target. It depends on the spatial position of the targets, distances between them, average scanning lengths of protein molecules on DNA, and the total DNA lengths. Physical-chemical explanations of observed results are presented. Our predictions are compared with experimental observations as well as with results from a continuum theory for the protein search. Extensive Monte Carlo computer simulations fully support our theoretical calculations.

  12. Dicty_cDB: VFM254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available (All Frames) Frame A: ---xxxxxxxxxxxxxxxxvxxxxxxxrxxxxxxxxxxxxxxxkvxxxxxkxxfxxvxnx xmvvlxxittfkrnplsi*ssd*ev...vckflskpslvrllhxklkvlitlrmlkpksktkk vfhqinnvsfspvnnwrmvvlslittfkrnplsi*fsd*evvckfl*klslvkplhsklk vvttlrm*kqkfktkkvshq Frame B: ---xxx...xxxxxxxxxxxxwxxxxxxsxgxxxxxxcxxxxxxxxryxxxxxxxxfxw*xix x

  13. Dicty_cDB: VSK254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available |BQ633139.1 PfESToab38c04.y1 Plasmodium falciparum 3D7 asexual cDNA Plasmodium falciparum cDNA 5', mRNA sequence...|BU496524.1 PfESToab51c12.y1 Plasmodium falciparum 3D7 asexual cDNA Plasmodium falciparum cDNA 5', mRNA sequence...|BU496772.1 PfESToab58f06.y1 Plasmodium falciparum 3D7 asexual cDNA Plasmodium falciparum cDNA 5', mRNA sequence

  14. Dicty_cDB: VFA254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available *ktcqny*fycyyhwllqsfqlhwmimsmlltiptsgh*iiqlnmkllqvtf*s*h hkhgwlknqigqfgnigfqfvyqkvlqlqlhlymlmvvqmitgkyqvqwik...ic*kfnr**iys*ihf*schctkyftirfmlli*cmgxesrxsa sstat Translated Amino Acid sequence (All Frames) Frame A: ikdw

  15. 36 CFR 254.23 - Studies, assessments, and approval.

    Science.gov (United States)

    2010-07-01

    ... applied for would serve indigenous community objectives that outweigh other public objectives and values... rights and uses; and (6) Determine if zoning ordinances, covenants, or standards are needed to protect adjacent National Forest land and to protect or mitigate valid existing rights and uses. (b) Upon approval...

  16. 40 CFR 264.254 - Monitoring and inspection.

    Science.gov (United States)

    2010-07-01

    ... liners and covers must be inspected to ensure tight seams and joints and the absence of tears, punctures... detection system under § 264.251(c) must record the amount of liquids removed from each leak detection...

  17. 24 CFR 221.254 - Mortgage insurance premiums.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Mortgage insurance premiums. 221... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES LOW COST AND MODERATE INCOME MORTGAGE INSURANCE-SAVINGS CLAUSE Contract Rights and Obligations-Low...

  18. 24 CFR 236.254 - Termination of mortgage insurance.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Termination of mortgage insurance... HOUSING AND URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES MORTGAGE INSURANCE AND INTEREST REDUCTION PAYMENT FOR RENTAL PROJECTS Contract Rights and...

  19. Dicty_cDB: SSC254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available BH339179 |BH339179.1 CH230-41C3.TV CHORI-230 Segment 1 Rattus norvegicus genomic ...clone CH230-41C3, DNA sequence. 48 0.12 1 BH261451 |BH261451.1 CH230-90I24.TV CHORI-230 Segment 1 Rattus nor

  20. 36 CFR 254.8 - Notice of exchange proposal.

    Science.gov (United States)

    2010-07-01

    ... users, the jurisdictional State and local governments, and the congressional delegation and shall make... lands being considered for exchange; (3) A statement as to the effect of segregation from appropriation... writing any comments on or concerns about the exchange proposal, including advising the agency as to any...

  1. Dicty_cDB: VHE254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available lnqfqwtqqfilkvqflingq niiiilkkptqevmlkplew*kqn*tqqqkfqnflqmilklhqih*vlcniqsylnitl...*fyh*fwv*v**lqslnqfqwtqqfilkvqflingq niiiilkkptqevmlkplew*kqn*tqqqkfqnflqmilklhqih*vlcniqsylnitlh qmlmhqhpkt

  2. Dicty_cDB: SHD254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available -16-2_G01_sjs2-16-2G01-T3 SJS Schistosoma japonicum cDNA, mRNA sequence. 56 0.001 1 CV682907 |CV682907.1 service...43_H06_sjs2-16-2B11-T3 SJS Schistosoma japonicum cDNA, mRNA sequence. 56 0.001 1 CV682854 |CV682854.1 service

  3. Dicty_cDB: SHI254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available eppox virus strain TU-V02127, complete genome. 46 1.0 1 AY077833 |AY077833.1 Shee...ppox virus A, complete genome. 46 1.0 1 AY077834 |AY077834.1 Sheeppox virus NISKHI,...3120 |AC173120.2 Bos taurus clone CH240-493D3, *** SEQUENCING IN PROGRESS ***, 41 unordered pieces. 46 1.0 1 AY077832 |AY077832.1 She

  4. Dicty_cDB: SSI254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 2_F NXLV (Nsf Xylem Late wood Vertical) Pinus taeda cDNA clone NXLV130_B02 5', mRNA sequence. 36 1.2 2 CD018...464 |CD018464.1 NXLV_028_H10_F NXLV (Nsf Xylem Late wood Vertical) Pinus taeda cD

  5. 7 CFR 2018.254 - Requests for records.

    Science.gov (United States)

    2010-01-01

    ... Development Manager, and each Community Development Manager are delegated authority to act respectively at the... records are to be submitted in accordance with 7 CFR 1.3 and may be made to the appropriate Community Development Manager, Rural Development Manager, State Administrative Management Program Director (formerly...

  6. Dicty_cDB: CHM254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available cds. 62 3e-05 2 CK808839 |CK808839.1 Rasgsc1686 Salivary Gland 4th instar 3rd period (spinning cocoon)...sequence. 34 3e-05 4 CK808739 |CK808739.1 Rasgsc1529 Salivary Gland 4th instar 3rd period (spinning cocoon)...cds. 58 4e-04 2 CK808037 |CK808037.1 Rasgsc0316 Salivary Gland 4th instar 3rd period (spinning cocoon)

  7. 24 CFR 92.254 - Qualification as affordable housing: Homeownership.

    Science.gov (United States)

    2010-04-01

    ... revitalization strategy under § 91.215(e)(2) of its consolidated plan or Empowerment Zone or Enterprise Community... a reasonable administrative cost of its HOME program, so that the additional HOME funds for the housing are not subject to the maximum per-unit subsidy amount. To the extent administrative funds are...

  8. Dicty_cDB: SSG254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ssykilpaygfvstiaail iaiatmylryhyfvdflaalpvtifcllyggfytpsdfknvfvncfysiksifqnilskf nnk**iylknkkkkkk Translated...aiglssykilpaygfvstiaail iaiatmylryhyfvdflaalpvtifcllyggfytpsdfknvfvncfysiksifqnilskf nnk**iylknkkkkkk Frame

  9. Dicty_cDB: AHA254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available LVQHXHELEVSHQLGSPXY FMPHVGQFFQGITLTISMELKYPMTKEQVVERYQKFYQNEPLIKIDXDGIPEVKSNSGKH Translated Amino Acid...LVQHXHELEVSHQLGSPXY FMPHVGQFFQGITLTISMELKYPMTKEQVVERYQKFYQNEPLIKIDXDGIPEVKSNSGKH Frame C: ---wriqvnh

  10. 36 CFR 254.22 - Designation and public notice.

    Science.gov (United States)

    2010-07-01

    ... the lands from other forms of entry as long as the application remains in force. (c) The designation... aside. (d) A Forest Service official must prepare a public notice of the proposed townsite sale to be... information on the proposed townsite sale and identify the applicant and responsible Forest Service official...

  11. Dicty_cDB: VHF254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available EIIL--- ---TSSTITSSSSTTAAATATTTNNSGQQSPPLKEIITVKTANKKVSVKIRAIPLPKNIT NLIEQRSQQLRDLFLGGKNTNKELSDNKITK...rdhs--- ---TSSTITSSSSTTAAATATTTNNSGQQSPPLKEIITVKTANKKVSVKIRAIPLPKNIT NLIEQRSQQLRDLFLGGKNTNKELSDNKITK

  12. Dicty_cDB: SHK254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available instar 3rd period (spinning cocoon) Rhynchosciara americana cDNA, mRNA sequence. 34 4e-05 3 CK808739 |CK808739...instar 3rd period (spinning cocoon) Rhynchosciara americana cDNA, mRNA sequence. 32 6e-04 3 AF066072 |AF066072...instar 3rd period (spinning cocoon) Rhynchosciara americana cDNA, mRNA sequence. 34 0.002 3 DT775356 |DT775356

  13. Dicty_cDB: VSI254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available :VS... 515 e-142 1 ( EC825581 ) SME00002373 esmbsro2 Sawyeria marylandensis cDNA,... carnea cDNA 5'... 66 1e-12 3 ( EC821344 ) SME00006756 esmbsro2 Sawyeria marylandensis cDNA,... 86 2e-12 1 d

  14. 16 CFR 254.0 - Scope and application.

    Science.gov (United States)

    2010-01-01

    ..., social aptitude, personality, or other attributes. These Guides do not apply to resident primary or... guidance of the public in conducting its affairs in conformity with legal requirements. These Guides...

  15. All projects related to | Page 254 | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2012-02-10

    Violent conflict related to drug trafficking in Mexico has had a profound impact on the quality of life and health of affected communities. Start Date: February 10, 2012. End Date: May 10, 2014. Topic: NARCOTICS, VICTIMS, VIOLENCE, DRUG TRAFFIC, VULNERABLE GROUPS, JUDICIAL SYSTEM. Region: Mexico, North ...

  16. Dicty_cDB: VHL254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available AAAAAAA sequence update 2002.10.25 Translated Amino Acid sequence fkriyfegrsgegfhnngihlwvsrs*glg*lslirllghwieseggfntsdfig...mgapvrvm*pikhxiixkrkkk Frame C: fkriyfegrsgegfhnngihlwvsrs*glg*lslirllghwieseggfntsdfigrkgsg lkflhhrmgy*gnrs

  17. Dicty_cDB: SFK254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available mology vs Protein Score E Sequences producing significant alignments: (bits) Value AB126005_1( AB126005 |pid:none) Orthetrum triangul...are melania mito... 32 8.5 protein update 2009. 1.13 PSO

  18. Dicty_cDB: VHA254 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available sequence. 44 0.004 7 CV301445 |CV301445.1 MM8_F01 Young roots probed with 3 week old root enriched transcripts...sequence. 54 0.011 1 CV301444 |CV301444.1 MM8_E01 Young roots probed with 3 week old root enriched transcripts

  19. 7 CFR 254.4 - Application by an ITO.

    Science.gov (United States)

    2010-01-01

    ... government programs, as well as its management and fiscal capabilities. Other factors for evaluation include... Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION ADMINISTRATION OF THE FOOD DISTRIBUTION PROGRAM FOR...

  20. 7 CFR 1710.254 - Alternative sources of power.

    Science.gov (United States)

    2010-01-01

    ... facilities bears a significant relationship to the amount of the proposed loan. (2) If a borrower already... service, the short-term and long-term financial viability of the supplier, and the financial risk to the... effective alternative. (f) RUS may make independent inquiries with potential power suppliers as to the...

  1. Proton bombarded reactions of Calcium target nuclei

    Directory of Open Access Journals (Sweden)

    Tel Eyyup

    2017-01-01

    Full Text Available In this study, proton bombarded nuclear reactions calculations of Calcium target nuclei have been investigated in the incident proton energy range of 1–50 MeV. The excitation functions for 40Ca target nuclei reactions have been calculated by using PCROSS nuclear reaction calculation code. Weisskopf-Ewing and the full exciton models were used for equilibrium and for pre-equilibrium calculations, respectively. The excitation functions for 40Ca target nuclei reactions (p,α, (p,n, (p,p have been calculated using the semi-empirical formula Tel et al. [5].

  2. Fixed target issues for the Tevatron Upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Stefanski, R.

    1988-08-29

    The Tevatron Upgrade poses some interesting prospects for the Fixed-Target program if an option to extract the high energy proton beam is preserved. This paper presents a summary of the advantages of increased energy for fixed target experiments, and evaluates some of the more challenging technical issues. In particular, Bottom production, muon and neutrino interactions, and polarized /bar p/ experiments would benefit substantially from a higher energy primary beam. The new Main Injector will also be important for fixed target experiments as a source for test beams and intense kaon and neutrino beams. 4 refs., 2 tabs.

  3. Reduce proton energy spread by target ablation

    CERN Document Server

    Zhao, Shuan; Chen, Jiaer; Yan, Xueqing

    2015-01-01

    It's shown that, with strong target ablation monoenergetic protons along the laser direction is available during the laser aluminum foil interaction, which is different from the classic TNSA theory. When the laser pre-pulse is too strong that the whole target is vaporized, the energetic electrons generated in the gas preplasma will play an important role for the ion acceleration because the sheath field will not be available. These electrons beam, which is highly directional, will setup triangle envelope acceleration field along the laser direction at the target rear, reducing the ion energy spread.

  4. Targets for a Neutral Kaon Beam

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Christopher [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

    2016-04-01

    A secondary beam of neutral Kaons is under consideration for Hall D at Jefferson Lab to perform spectroscopic studies of hyperons produced by K 0 L particles scattering from proton and deuteron targets. The proposed physics program would utilize the GlueX detector package currently installed in Hall D. This contribution looks at potential targets for use in the new facility, paying close attention to the existing infrastructure of GlueX and Hall D. Unpolarized cryotargets of liquid hydrogen and deuerium, as well as polarized solid targets of protons and deuterons are examined.

  5. Antiproton production target of the AA

    CERN Multimedia

    Photographic Service; CERN PhotoLab

    1980-01-01

    The target rods were initially of tungsten, later of iridium. Diameters were around 3 mm and the lengths 60-110 mm. The rod is embedded in graphite, pressed into an aluminium body with cooling fins for forced air cooling. The 26 GeV proton beam from the PS was focused to the dimension of the rod. To aim precisely at its centre, the target was fitted with a scintillator screen, with circles at every 5 mm radius. Both scintillator and target had to stand pulses of 1.4E13 protons every 4.8 s, without interruption for many months.

  6. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael

    2010-01-01

    Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug...... further newly identified drug-induced differential regulation of Lanosterol 14-alpha demethylase, Endoplasmin, DNA topoisomerase 2-alpha and Calmodulin 1. The feedback regulation in these and other targets is likely to be relevant for the success or failure of the molecular intervention....

  7. 29 mm Diameter Target Test Report

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Olivas, Eric Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Naranjo, Angela Carol [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Frank Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chemerisov, Sergey [Argonne National Lab. (ANL), Argonne, IL (United States); Gromov, Roman [Argonne National Lab. (ANL), Argonne, IL (United States)

    2017-10-23

    After numerous delays, the test of the 29 mm diameter target was conducted on 8/18/2017. The complete target design report, dated 8/15/2016, is reproduced below for completeness. This describes in detail the 10 disk target with varying thickness disks. The report presents and discusses the test results. In brief summary, there appears to have been multiple instrumentation errors. Measured temperatures, pressures and IR camera window temperature measurement are all suspect. All tests were done at 35 MeV, with 171 μA current, or 6 kW of beam power.

  8. Performance Simulations of Moving Target Search Algorithms

    Directory of Open Access Journals (Sweden)

    Peter K. K. Loh

    2009-01-01

    Full Text Available The design of appropriate moving target search (MTS algorithms for computer-generated bots poses serious challenges as they have to satisfy stringent requirements that include computation and execution efficiency. In this paper, we investigate the performance and behaviour of existing moving target search algorithms when applied to search-and-capture gaming scenarios. As part of the investigation, we also introduce a novel algorithm known as abstraction MTS. We conduct performance simulations with a game bot and moving target within randomly generated mazes of increasing sizes and reveal that abstraction MTS exhibits competitive performance even with large problem spaces.

  9. Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

    CERN Document Server

    Blacknell, David

    2013-01-01

    The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

  10. TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

    Directory of Open Access Journals (Sweden)

    Yi-An Chen

    Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

  11. New Cholesterol Fighting Meds Target Key Gene

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_165942.html New Cholesterol Fighting Meds Target Key Gene Two trials show ... New gene-based therapies appear to significantly decrease cholesterol levels in people, and could even cut down ...

  12. Is telomerase a viable target in cancer?

    Science.gov (United States)

    Buseman, C.M.; Wright, W.E.; Shay, J.W.

    2012-01-01

    The ideal cancer treatment would specifically target cancer cells yet have minimal or no adverse effects on normal somatic cells. Telomerase, the ribonucleoprotein reverse transcriptase that maintains the ends of human chromosome, is an attractive cancer therapeutic target for exactly this reason [1]. Telomerase is expressed in more than 85% of cancer cells, making it a nearly universal cancer marker, while the majority of normal somatic cells are telomerase negative. Telomerase activity confers limitless replicative potential to cancer cells, a hallmark of cancer which must be attained for the continued growth that characterizes almost all advanced neoplasms [2]. In this review we will summarize the role of telomeres and telomerase in cancer cells, and how properties of telomerase are being exploited to create targeted cancer therapies including telomerase inhibitors, telomerase-targeted immunotherapies and telomerase-driven virotherapies. A frank and balanced assessment of the current state of telomerase inhibitors with caveats and potential limitations will be included. PMID:21802433

  13. Logarithm laws and shrinking target properties

    Indian Academy of Sciences (India)

    Abstract. We survey some of the recent developments in the study of logarithm laws and shrinking target properties for various families of dynamical systems. We discuss connections to geometry, diophantine approximation and probability theory.

  14. EURISOL Multi-MW Target: Preliminary Study

    CERN Document Server

    A.Herrera-Martínez and Y.Kadi

    This technical note summarises the design calculations performed within Task #2 of the EURopean Isotope Separation On-Line Radioactive Ion Beam Facility Design Study (EURISOL DS).A preliminary study was carried out in order to determine the optimum value of relevant parameters in the target design. Different scenarios were simulated using the Monte Carlo code FLUKA. Namely, sensitivity studies were performed to assess the impact of the projectile particle energy on the neutronics and energy deposition in the spallation target. The optimum target dimension was also studied for every case as well as the proper target material for the liquid metal proton-to-neutron converter, since mercury and lead-bismuth eutectic are reasonable options. The effect of the beam width on the power densities was also evaluated, taking into account the geometrical limitations of the facility. Finally, a comparison between protons and deuterons as primary particles was performed, acknowledging the limitations of using FLUKA for thes...

  15. Nuclear Targeting Terms for Engineers and Scientists

    Energy Technology Data Exchange (ETDEWEB)

    St Ledger, John W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-01

    The Department of Defense has a methodology for targeting nuclear weapons, and a jargon that is used to communicate between the analysts, planners, aircrews, and missile crews. The typical engineer or scientist in the Department of Energy may not have been exposed to the nuclear weapons targeting terms and methods. This report provides an introduction to the terms and methodologies used for nuclear targeting. Its purpose is to prepare engineers and scientists to participate in wargames, exercises, and discussions with the Department of Defense. Terms such as Circular Error Probable, probability of hit and damage, damage expectancy, and the physical vulnerability system are discussed. Methods for compounding damage from multiple weapons applied to one target are presented.

  16. Therapeutic Approaches to Target Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, Arlhee, E-mail: arlhee@cim.sld.cu; Leon, Kalet [Department of Systems Biology, Center of Molecular Immunology, 216 Street, PO Box 16040, Atabey, Havana 11600 (Cuba)

    2011-08-15

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC.

  17. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  18. Tumor-targeted nanomedicines for cancer theranostics.

    Science.gov (United States)

    Arranja, Alexandra G; Pathak, Vertika; Lammers, Twan; Shi, Yang

    2017-01-01

    Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. IMS Mitigation Target Areas - 2010 [ds673

    Data.gov (United States)

    California Department of Resources — Mitigation Target Areas (MTA) were developed by the California Department of Fish and Game for the Interim Mitigation Strategy (IMS). The MTAs are an identification...

  20. Novel molecular multilevel targeted antitumor agents

    Directory of Open Access Journals (Sweden)

    Poonam Sonawane

    2017-01-01

    Conclusion: We believe that our receptor-directed intracellular organelle-targeted proteins can be employed for numerous specific and safer treatment applications when drugs have specific intracellular sites of their action.

  1. Targeting the tumor microenvironment for cancer therapy

    National Research Council Canada - National Science Library

    Sounni, Nor Eddine; Noel, Agnès

    With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic...

  2. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

    Magneto-resistive sensors in combination with magnetic beads provide sensing platforms, which are small in size and highly sensitive. These platforms can be fully integrated with microchannels and electronics to enable devices capable of performing complex tasks. Commonly, a sandwich method is used that requires a specific coating of the sensor\\'s surface to immobilize magnetic beads and biological targets on top of the sensor. This paper concerns a micro device to detect biological targets using magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer and reduces the number of steps required to run an experiment. © 2012 IEEE.

  3. Enhancing proton acceleration by using composite targets

    Energy Technology Data Exchange (ETDEWEB)

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; Bulanov, S. V.; Esirkepov, T. Zh.; Kando, M.; Pegoraro, F.; Leemans, W. P.

    2015-07-10

    Efficient laser ion acceleration requires high laser intensities, which can only be obtained by tightly focusing laser radiation. In the radiation pressure acceleration regime, where the tightly focused laser driver leads to the appearance of the fundamental limit for the maximum attainable ion energy, this limit corresponds to the laser pulse group velocity as well as to another limit connected with the transverse expansion of the accelerated foil and consequent onset of the foil transparency. These limits can be relaxed by using composite targets, consisting of a thin foil followed by a near critical density slab. Such targets provide guiding of a laser pulse inside a self-generated channel and background electrons, being snowplowed by the pulse, compensate for the transverse expansion. The use of composite targets results in a significant increase in maximum ion energy, compared to a single foil target case.

  4. Computing the apparent centroid of radar targets

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.E.

    1996-12-31

    A high-frequency multibounce radar scattering code was used as a simulation platform for demonstrating an algorithm to compute the ARC of specific radar targets. To illustrate this simulation process, several targets models were used. Simulation results for a sphere model were used to determine the errors of approximation associated with the simulation; verifying the process. The severity of glint induced tracking errors was also illustrated using a model of an F-15 aircraft. It was shown, in a deterministic manner, that the ARC of a target can fall well outside its physical extent. Finally, the apparent radar centroid simulation based on a ray casting procedure is well suited for use on most massively parallel computing platforms and could lead to the development of a near real-time radar tracking simulation for applications such as endgame fuzing, survivability, and vulnerability analyses using specific radar targets and fuze algorithms.

  5. Target Visualization at the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Potter, Daniel Abraham [Univ. of California, Davis, CA (United States)

    2011-01-01

    As the National Ignition Facility continues its campaign to achieve ignition, new methods and tools will be required to measure the quality of the targets used to achieve this goal. Techniques have been developed to measure target surface features using a phase-shifting diffraction interferometer and Leica Microsystems confocal microscope. Using these techniques we are able to produce a detailed view of the shell surface, which in turn allows us to refine target manufacturing and cleaning processes. However, the volume of data produced limits the methods by which this data can be effectively viewed by a user. This paper introduces an image-based visualization system for data exploration of target shells at the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. It aims to combine multiple image sets into a single visualization to provide a method of navigating the data in ways that are not possible with existing tools.

  6. Characterizing Health Information for Different Target Audiences.

    Science.gov (United States)

    Sun, Yueping; Hou, Zhen; Hou, Li; Li, Jiao

    2015-01-01

    Different groups of audiences in health care: health professionals and health consumers, each have different information needs. Health monographs targeting different audiences are created by leveraging readers' background knowledge. The NCI's Physician Data Query (PDQ®) Cancer Information Summaries provide parallel cancer information and education resources with different target audiences. In this paper, we used targeted audience-specific cancer information PDQs to measure characteristic differences on the element level between audiences. In addition, we compared vocabulary coverage. Results show a significant difference between the professional and patient version of cancer monographs in both content organization and vocabulary. This study provides a new view to assess targeted audience-specific health information, and helps editors to improve the quality and readability of health information.

  7. Kansas Water Quality Action Targeting System (KATS)

    Data.gov (United States)

    Kansas Data Access and Support Center — This system is a revision of the original KATS system developed in 1990 as a tool to aid resource managers target Kansas valuable and vulnerable water resources for...

  8. WTS - Risk Based Resource Targeting (RBRT) -

    Data.gov (United States)

    Department of Transportation — The Risk Based Resource Targeting (RBRT) application supports a new SMS-structured process designed to focus on safety oversight of systems and processes rather than...

  9. RNA as a small molecule druggable target.

    Science.gov (United States)

    Rizvi, Noreen F; Smith, Graham F

    2017-12-01

    Small molecule drugs have readily been developed against many proteins in the human proteome, but RNA has remained an elusive target for drug discovery. Increasingly, we see that RNA, and to a lesser extent DNA elements, show a persistent tertiary structure responsible for many diverse and complex cellular functions. In this digest, we have summarized recent advances in screening approaches for RNA targets and outlined the discovery of novel, drug-like small molecules against RNA targets from various classes and therapeutic areas. The link of structure, function, and small-molecule Druggability validates now for the first time that RNA can be the targets of therapeutic agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Targeted ocean sampling guidance for tropical cyclones

    Science.gov (United States)

    Chen, Sue; Cummings, James A.; Schmidt, Jerome M.; Sanabia, Elizabeth R.; Jayne, Steven R.

    2017-05-01

    A 3-D variational ocean data assimilation adjoint approach is used to examine the impact of ocean observations on coupled tropical cyclone (TC) model forecast error for three recent hurricanes: Isaac (2012), Hilda (2015), and Matthew (2016). In addition, this methodology is applied to develop an innovative ocean observation targeting tool validated using TC model simulations that assimilate ocean temperature observed by Airborne eXpendable Bathy Thermographs and Air-Launched Autonomous Micro-Observer floats. Comparison between the simulated targeted and real observation data assimilation impacts reveals a positive maximum mean linear correlation of 0.53 at 400-500 m, which implies some skill in the targeting application. Targeted ocean observation regions from these three hurricanes, however, show that the largest positive impacts in reducing the TC model forecast errors are sensitive to the initial prestorm ocean conditions such as the location and magnitude of preexisting ocean eddies, storm-induced ocean cold wake, and model track errors.

  11. Targeting Prostate Cancer with Multifunctional Nanoparticles

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0487 TITLE: Targeting Prostate Cancer with Multifunctional Nanoparticles PRINCIPAL INVESTIGATOR: Darryl Martin...Targeting Prostate Cancer with Multifunctional Nanoparticles 5b. GRANT NUMBER W81XWH-14-1-0487 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Darryl...claudin-3 and claudin-4 are expressed in subsets of aggressive prostate cancer. Finally, we produced our first two batches of nanoparticles during year

  12. Targeting the Neural Microenvironment in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-14-1-0505 TITLE: Targeting the Neural Microenvironment in Prostate Cancer PRINCIPAL INVESTIGATOR: Michael Ittmann MD PhD...CONTRACT NUMBER Targeting the Neural Microenvironment in Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0505 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...ABSTRACT Prostate cancer (PCa) remains the most common malignancy and the second leading cause of cancer -related death for men in the United States. Recent

  13. Targeting Discoidin Domain Receptors in Prostate Cancer

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...AND SUBTITLE 5a. CONTRACT NUMBER Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0226 5c. PROGRAM ELEMENT...response to collagen in prostate cancer . The project’s goal is to define the expression and therapeutic potential of DDRs in prostate cancer . During

  14. Design of the Target Fabrication Tritium Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Sherohman, J.W.; Roberts, D.H.; Levine, B.H.

    1982-05-05

    The design of the Target Fabrication Tritium Laboratory for deuterium-tritium fuel processing for laser fusion targets has been accomplished with the intent of providing redundant safeguard systems. The design of the tritium laboratory is based on a combination of tritium handling techniques that are currently used by experienced laboratories. A description of the laboratory in terms of its interrelated processing systems is presented to provide an understanding of the design features for safe operation.

  15. Gas Production in the MEGAPIE Spallation Target

    OpenAIRE

    Thiollière, Nicolas; Zanini, Luca; David, Jean-Christophe; Eikenberg, Jost; Guertin, Arnaud; Konobeyev, Alexander Yu.; Lemaire, Sébastien; Panebianco, Stefano

    2011-01-01

    International audience; The MEGAwatt PIlot Experiment (MEGAPIE) project was started in 2000 to design, build, and operate a liquid lead-bismuth eutectic (LBE) spallation neutron target at the power level of 1 MW. The target was irradiated for 4 months in 2006 at the Paul Scherrer Institute in Switzerland. Gas samples wereextracted in various phases of operation and analyzed by g spectroscopy, leading to the determination of the main radioactive isotopes released from the LBE. Comparison with ...

  16. Simple scaling model for exploding pusher targets

    Energy Technology Data Exchange (ETDEWEB)

    Storm, E.K.; Larsen, J.T.; Nuckolls, J.H.; Ahlstrom, H.G.; Manes, K.R.

    1977-11-04

    A simple model has been developed which when normalized by experiment or Lasnex calculations can be used to scale neutron yields for variations in laser input power and pulse length and target radius and wall thickness. The model also illucidates some of the physical processes occurring in this regime of laser fusion experiments. Within certain limitations on incident intensity and target geometry, the model scales with experiments and calculations to within a factor of two over six decades in neutron yield.

  17. Novel targeted therapies for inflammatory bowel disease

    DEFF Research Database (Denmark)

    Coskun, Mehmet; Vermeire, Severine; Nielsen, Ole Haagen

    2017-01-01

    Our growing understanding of the immunopathogenesis of inflammatory bowel disease (IBD) has opened new avenues for developing targeted therapies. These advances in treatment options targeting different mechanisms of action offer new hope for personalized management. In this review we highlight...... to intestinal sites of inflammation (e.g., sphingosine 1-phosphate receptor modulators). We also provide an update on the current status in clinical development of these new classes of therapeutics....

  18. Test of a High Power Target Design

    CERN Multimedia

    2002-01-01

    %IS343 :\\\\ \\\\ A high power tantalum disc-foil target (RIST) has been developed for the proposed radioactive beam facility, SIRIUS, at the Rutherford Appleton Laboratory. The yield and release characteristics of the RIST target design have been measured at ISOLDE. The results indicate that the yields are at least as good as the best ISOLDE roll-foil targets and that the release curves are significantly faster in most cases. Both targets use 20 -25 $\\mu$m thick foils, but in a different internal geometry.\\\\ \\\\Investigations have continued at ISOLDE with targets having different foil thickness and internal geometries in an attempt to understand the release mechanisms and in particular to maximise the yield of short lived isotopes. A theoretical model has been developed which fits the release curves and gives physical values of the diffusion constants.\\\\ \\\\The latest target is constructed from 2 $\\mu$m thick tantalum foils (mass only 10 mg) and shows very short release times. The yield of $^{11}$Li (half-life of ...

  19. The SPES High Power ISOL production target

    Science.gov (United States)

    Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

    2016-11-01

    SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

  20. Targeting Signaling Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Johannes Haybaeck

    2013-05-01

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies. Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR inhibitors, poly-ADP-ribose polymerase (PARP inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy. Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

  1. Caffeine and performance in clay target shooting.

    Science.gov (United States)

    Share, Bianca; Sanders, Nick; Kemp, Justin

    2009-04-01

    Controversy surrounds the influence that caffeine has on accuracy and cognitive performance in precision activities such as shooting and archery. The aim of this study was to assess the effects of two doses of caffeine on shooting performance, reaction time, and target tracking times in the sport of clay target shooting. A randomized, double-blind, placebo-controlled design was undertaken by seven elite male shooters from the double-trap discipline. Three intervention trials (2 mg caffeine . kg(-1) body mass (BM); 4 mg caffeine . kg(-1) BM; placebo) were undertaken, in which shooters completed four rounds per trial of 50 targets per round. Performance accuracy (score) and digital video footage (for determination of reaction time and target tracking times) were gathered during competition. Data were analysed using repeated-measures analysis of variance. No differences in shooting accuracy, reaction time or target tracking times among the three intervention trials or across the four rounds within each intervention were observed (P > 0.05). The results indicate that ingestion of caffeine . kg(-1) BM does not provide performance benefits to elite performers of clay target shooting in the double-trap discipline.

  2. NDCX-II target experiments and simulations

    Energy Technology Data Exchange (ETDEWEB)

    Barnard, J.J., E-mail: jjbarnard@llnl.gov [Lawrence Livermore National Laboratory, Livermore, CA (United States); More, R.M. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Terry, M.; Friedman, A. [Lawrence Livermore National Laboratory, Livermore, CA (United States); Henestroza, E.; Koniges, A.; Kwan, J.W. [Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Ng, A. [University of British Columbia, BC (Canada); Ni, P.A.; Liu, W.; Logan, B.G. [Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Startsev, E. [Princeton Plasma Physics Laboratory, Princeton, NJ (United States); Yuen, A. [Lawrence Berkeley National Laboratory, Berkeley, CA (United States)

    2014-01-01

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

  3. Achieving target refraction after cataract surgery.

    Science.gov (United States)

    Simon, Shira S; Chee, Yewlin E; Haddadin, Ramez I; Veldman, Peter B; Borboli-Gerogiannis, Sheila; Brauner, Stacey C; Chang, Kenneth K; Chen, Sherleen H; Gardiner, Matthew F; Greenstein, Scott H; Kloek, Carolyn E; Chen, Teresa C

    2014-02-01

    To evaluate the difference between target and actual refraction after phacoemulsification and intraocular lens implantation at an academic teaching institution's Comprehensive Ophthalmology Service. Retrospective study. We examined 1275 eye surgeries for this study. All consecutive cataract surgeries were included if they were performed by an attending or resident surgeon from January through December 2010. Postoperative refractions were compared with preoperative target refractions. Patients were excluded if they did not have a preoperative target refraction documented or if they did not have a recorded postoperative manifest refraction within 90 days. The main outcome measure was percentage of cases achieving a postoperative spherical equivalent ± 1.0 diopter (D) of target spherical equivalent. We performed 1368 cataract surgeries from January through December of 2010. Of these, 1275 (93%) had sufficient information for analysis. Of the included cases, 94% (1196 of 1275) achieved ± 1.0 D of target refraction by 90 days after cataract surgery. This paper establishes a new benchmark for a teaching hospital, where 94% of patients achieved within 1.0 D of target refraction after cataract surgery. The refractive outcomes after cataract surgery at this academic teaching institution were higher than average international benchmarks. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  4. Achieving the Renewable Energy Target for Jamaica

    Directory of Open Access Journals (Sweden)

    Abdullahi Olabode ABDULKADRI

    2014-05-01

    Full Text Available ieving the Renewable Energy Target for Jamaica Abstract: The high cost of energy in Jamaica, one of the highest in the Caribbean region, is usually cited as a hindrance to industrial development and efficiency, especially in the manufacturing sector. High energy cost is also considered to be a national energy security issue and the government is taking steps to ensure adequate supply of energy at affordable prices. In the current National Development Plan, the government has set a target for renewable energy sources to supply 20% of the country's energy need by the year 2030. Using a linear programing model of energy planning, we examine how realistically this target could be achieved. Our findings indicate that the 20% renewable energy target is technically achievable with the optimal plan showing a mixture of wind power, hydropower and bagasse power but no solar power. However, when the timeline for investment in new generating capacities that will ensure the attainment of the target is considered, it becomes highly improbable that the target will be met. This study fills the gap that exists in evidence-based analysis of energy policy in Jamaica.

  5. Protein tyrosine phosphatases as potential therapeutic targets.

    Science.gov (United States)

    He, Rong-Jun; Yu, Zhi-Hong; Zhang, Ruo-Yu; Zhang, Zhong-Yin

    2014-10-01

    Protein tyrosine phosphorylation is a key regulatory process in virtually all aspects of cellular functions. Dysregulation of protein tyrosine phosphorylation is a major cause of human diseases, such as cancers, diabetes, autoimmune disorders, and neurological diseases. Indeed, protein tyrosine phosphorylation-mediated signaling events offer ample therapeutic targets, and drug discovery efforts to date have brought over two dozen kinase inhibitors to the clinic. Accordingly, protein tyrosine phosphatases (PTPs) are considered next-generation drug targets. For instance, PTP1B is a well-known targets of type 2 diabetes and obesity, and recent studies indicate that it is also a promising target for breast cancer. SHP2 is a bona-fide oncoprotein, mutations of which cause juvenile myelomonocytic leukemia, acute myeloid leukemia, and solid tumors. In addition, LYP is strongly associated with type 1 diabetes and many other autoimmune diseases. This review summarizes recent findings on several highly recognized PTP family drug targets, including PTP1B, Src homology phosphotyrosyl phosphatase 2(SHP2), lymphoid-specific tyrosine phosphatase (LYP), CD45, Fas associated phosphatase-1 (FAP-1), striatal enriched tyrosine phosphatases (STEP), mitogen-activated protein kinase/dual-specificity phosphatase 1 (MKP-1), phosphatases of regenerating liver-1 (PRL), low molecular weight PTPs (LMWPTP), and CDC25. Given that there are over 100 family members, we hope this review will serve as a road map for innovative drug discovery targeting PTPs.

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

    Science.gov (United States)

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

    2016-05-01

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

  7. Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

    Science.gov (United States)

    Yang, Ye; Zhang, Jianyun; Yao, Yijun

    2017-01-01

    Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

  8. Affinity Propagation Clustering of Measurements for Multiple Extended Target Tracking

    OpenAIRE

    Tao Zhang; Renbiao Wu

    2015-01-01

    More measurements are generated by the target per observation interval, when the target is detected by a high resolution sensor, or there are more measurement sources on the target surface. Such a target is referred to as an extended target. The probability hypothesis density filter is considered an efficient method for tracking multiple extended targets. However, the crucial problem of how to accurately and effectively partition the measurements of multiple extended targets remains unsolved....

  9. Modeling target erosion during reactive sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Strijckmans, K., E-mail: Koen.Strijckmans@ugent.be; Depla, D.

    2015-03-15

    Highlights: • The erosion of a target is simulated with the RSD2013 software during reactive magnetron sputtering. • The influence of redeposition on the target state and on the hysteresis is explained. • The racetrack formation along the hysteresis and as function of the redeposition is quantified. • Comparison of the racetrack and the sputter profile shows clear differences. - Abstract: The influence of the reactive sputter conditions on the racetrack and the sputter profile for an Al/O{sub 2} DC reactive sputter system is studied by modeling. The role of redeposition, i.e. the deposition of sputtered material back on the target, is therefore taken into account. The used model RSD2013 is capable of simulating the effect of redeposition on the target condition in a spatial resolved way. Comparison between including and excluding redeposition in the RSD2013 model shows that the in-depth oxidation profile of the target differs. Modeling shows that it is important to distinguish between the formed racetrack, i.e. the erosion depth profile, and the sputter profile. The latter defines the distribution of the sputtered atoms in the vacuum chamber. As the target condition defines the sputter yield, it does determine the racetrack and the sputter profile of the planar circular target. Both the shape of the racetrack and the sputter profile change as function of the redeposition fraction as well as function of the oxygen flow change. Clear asymmetries and narrowing are observed for the racetrack shape. Similar effects are noticed for the sputter profile but to a different extent. Based on this study, the often heard misconception that the racetrack shape defines the distribution of the sputtered atoms during reactive sputtering is proven to be wrong.

  10. Temperature targets revisited under climate sensitivity uncertainty

    Science.gov (United States)

    Neubersch, Delf; Roth, Robert; Held, Hermann

    2015-04-01

    While the 2° target has become an official goal of the COP (Conference of the Parties) process recent work has shown that it requires re-interpretation if climate sensitivity uncertainty in combination with anticipated future learning is considered (Schmidt et al., 2011). A strict probabilistic limit as suggested by the Copenhagen diagnosis may lead to conceptual flaws in view of future learning such a negative expected value of information or even ill-posed policy recommendations. Instead Schmidt et al. suggest trading off the probabilistic transgression of a temperature target against mitigation-induced welfare losses and call this procedure cost risk analysis (CRA). Here we spell out CRA for the integrated assessment model MIND and derive necessary conditions for the exact nature of that trade-off. With CRA at hand it is for the first time that the expected value of climate information, for a given temperature target, can meaningfully be assessed. When focusing on a linear risk function as the most conservative of all possible risk functions, we find that 2° target-induced mitigation costs could be reduced by up to 1/3 if the climate response to carbon dioxide emissions were known with certainty, amounting to hundreds of billions of Euros per year (Neubersch et al., 2014). Further benefits of CRA over strictly formulated temperature targets are discussed. References: D. Neubersch, H. Held, A. Otto, Operationalizing climate targets under learning: An application of cost-risk analysis, Climatic Change, 126 (3), 305-318, DOI 10.1007/s10584-014-1223-z (2014). M. G. W. Schmidt, A. Lorenz, H. Held, E. Kriegler, Climate Targets under Uncertainty: Challenges and Remedies, Climatic Change Letters, 104 (3-4), 783-791, DOI 10.1007/s10584-010-9985-4 (2011).

  11. Optimized Parameters for a Mercury Jet Target

    Energy Technology Data Exchange (ETDEWEB)

    Ding, X.; Kirk, H.

    2010-12-01

    A study of target parameters for a high-power, liquid mercury jet target system for a neutrino factory or muon collider is presented. Using the MARS code, we simulate particle production initiated by incoming protons with kinetic energies between 2 and 100 GeV. For each proton beam energy, we maximize production by varying the geometric parameters of the target: the mercury jet radius, the incoming proton beam angle, and the crossing angle between the mercury jet and the proton beam. The number of muons surviving through an ionization cooling channel is determined as a function of the proton beam energy. We optimize the mercury jet target parameters: the mercury jet radius, the incoming proton beam angle and the crossing angle between the mercury jet and the proton beam for each proton beam energy. The optimized target radius varies from about 0.4 cm to 0.6 cm as the proton beam energy increases. The optimized beam angle varies from 75 mrad to 120 mrad. The optimized crossing angle is near 20 mrad for energies above 5 GeV. These values differ from earlier choices of 67 mrad for the beam angle and 33 mrad for the crossing angle. These new choices for the beam parameters increase the meson production by about 20% compared to the earlier parameters. Our study demonstrates that the maximum meson production efficiency per unit proton beam power occurs when the proton kinetic energy is in the range of 5-15 GeV. Finally, the dependence on energy of the number of muons at the end of the cooling channel is nearly identical to the dependence on energy of the meson production 50 m from the target. This demonstrates that the target parameters can be optimized without the additional step of running the distribution through a code such as ICOOL that simulates the bunching, phase rotation, and cooling.

  12. Protein Targeting to the Plastid of Euglena.

    Science.gov (United States)

    Durnford, Dion G; Schwartzbach, Steven D

    2017-01-01

    The lateral transfer of photosynthesis between kingdoms through endosymbiosis is among the most spectacular examples of evolutionary innovation. Euglena, which acquired a chloroplast indirectly through an endosymbiosis with a green alga, represents such an example. As with other endosymbiont-derived plastids from eukaryotes, there are additional membranes that surround the organelle, of which Euglena has three. Thus, photosynthetic genes that were transferred from the endosymbiont to the host nucleus and whose proteins are required in the new plastid, are now faced with targeting and plastid import challenges. Early immunoelectron microscopy data suggested that the light-harvesting complexes, photosynthetic proteins in the thylakoid membrane, are post-translationally targeted to the plastid via the Golgi apparatus, an unexpected discovery at the time. Proteins targeted to the Euglena plastid have complex, bipartite presequences that direct them into the endomembrane system, through the Golgi apparatus and ultimately on to the plastid, presumably via transport vesicles. From transcriptome sequencing, dozens of plastid-targeted proteins were identified, leading to the identification of two different presequence structures. Both have an amino terminal signal peptide followed by a transit peptide for plastid import, but only one of the two classes of presequences has a third domain-the stop transfer sequence. This discovery implied two different transport mechanisms; one where the protein was fully inserted into the lumen of the ER and another where the protein remains attached to, but effectively outside, the endomembrane system. In this review, we will discuss the biochemical and bioinformatic evidence for plastid targeting, discuss the evolution of the targeting system, and ultimately provide a working model for the targeting and import of proteins into the plastid of Euglena.

  13. Normalization for triple-target microarray experiments

    Directory of Open Access Journals (Sweden)

    Magniette Frederic

    2008-04-01

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

  14. Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects?

    Directory of Open Access Journals (Sweden)

    Hugues de Thé

    2011-06-01

    Full Text Available Adult T cell leukemia/lymphoma (ATL represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT and interferon-alpha (IFN has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT and Tax degradation (arsenic/IFN are needed to cure ATL.

  15. TBC2target: A Resource of Predicted Target Genes of Tea Bioactive Compounds

    Directory of Open Access Journals (Sweden)

    Shihua Zhang

    2018-02-01

    Full Text Available Tea is one of the most popular non-alcoholic beverages consumed worldwide. Numerous bioactive constituents of tea were confirmed to possess healthy benefits via the mechanisms of regulating gene expressions or protein activities. However, a complete interacting profile between tea bioactive compounds (TBCs and their target genes is lacking, which put an obstacle in the study of healthy function of tea. To fill this gap, we developed a database of target genes of TBCs (TBC2target, http://camellia.ahau.edu.cn/TBC2target based on a pharmacophore mapping approach. In TBC2target, 6,226 interactions between 240 TBCs and 673 target genes were documented. TBC2target contains detailed information about each interacting entry, such as TBC, CAS number, PubChem CID, source of compound (e.g., green, black, compound type, target gene(s of TBC, gene symbol, gene ID, ENSEMBL ID, PDB ID, TBC bioactivity and the reference. Using the TBC-target associations, we constructed a bipartite network and provided users the global network and local sub-network visualization and topological analyses. The entire database is free for online browsing, searching and downloading. In addition, TBC2target provides a BLAST search function to facilitate use of the database. The particular strengths of TBC2target are the inclusion of the comprehensive TBC-target interactions, and the capacity to visualize and analyze the interacting networks, which may help uncovering the beneficial effects of tea on human health as a central resource in tea health community.

  16. Targeted therapy using nanotechnology: focus on cancer.

    Science.gov (United States)

    Sanna, Vanna; Pala, Nicolino; Sechi, Mario

    2014-01-01

    Recent advances in nanotechnology and biotechnology have contributed to the development of engineered nanoscale materials as innovative prototypes to be used for biomedical applications and optimized therapy. Due to their unique features, including a large surface area, structural properties, and a long circulation time in blood compared with small molecules, a plethora of nanomaterials has been developed, with the potential to revolutionize the diagnosis and treatment of several diseases, in particular by improving the sensitivity and recognition ability of imaging contrast agents and by selectively directing bioactive agents to biological targets. Focusing on cancer, promising nanoprototypes have been designed to overcome the lack of specificity of conventional chemotherapeutic agents, as well as for early detection of precancerous and malignant lesions. However, several obstacles, including difficulty in achieving the optimal combination of physicochemical parameters for tumor targeting, evading particle clearance mechanisms, and controlling drug release, prevent the translation of nanomedicines into therapy. In spite of this, recent efforts have been focused on developing functionalized nanoparticles for delivery of therapeutic agents to specific molecular targets overexpressed on different cancer cells. In particular, the combination of targeted and controlled-release polymer nanotechnologies has resulted in a new programmable nanotherapeutic formulation of docetaxel, namely BIND-014, which recently entered Phase II clinical testing for patients with solid tumors. BIND-014 has been developed to overcome the limitations facing delivery of nanoparticles to many neoplasms, and represents a validated example of targeted nanosystems with the optimal biophysicochemical properties needed for successful tumor eradication.

  17. Molecular Therapeutic Targets for Glioma Angiogenesis

    Directory of Open Access Journals (Sweden)

    Shingo Takano

    2010-01-01

    Full Text Available Due to the prominent angiogenesis that occurs in malignant glioma, antiangiogenic therapy has been attempted. There have been several molecular targets that are specific to malignant gliomas, as well as more broadly in systemic cancers. In this review, I will focus on some topics related to molecular therapeutic targets for glioma angiogenesis. First, important angiogenic factors that could be considered molecular targets are VEGF, VEGF-induced proteins on endothelial cells, tissue factor, osteopontin, v3 integrin, and thymidine phosphorylase as well as endogenous inhibitors, soluble Flt1, and thrombospondin 1. Second, hypoxic areas are also decreased by metronomic CPT11 treatment as well as temozolomide. Third, glioma-derived endothelial cells that are genetically and functionally distinct from normal endothelial cells should be targeted, for example, with SDF-1 and CXCR7 chemokine. Fourth, endothelial progenitor cells (EPCs likely contribute towards glioma angiogenesis in the brain and could be useful as a drug delivery tool. Finally, blockade of delta-like 4 (Dll4 results in a nonfunctioning vasculature and could be another important target distinct from VEGF.

  18. Multi-Agent Cooperative Target Search

    Directory of Open Access Journals (Sweden)

    Jinwen Hu

    2014-05-01

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

  19. Cisplatin Targeting of Bacterial Ribosomal RNA Hairpins

    Directory of Open Access Journals (Sweden)

    Gayani N. P. Dedduwa-Mudalige

    2015-09-01

    Full Text Available Cisplatin is a clinically important chemotherapeutic agent known to target purine bases in nucleic acids. In addition to major deoxyribonucleic acid (DNA intrastrand cross-links, cisplatin also forms stable adducts with many types of ribonucleic acid (RNA including siRNA, spliceosomal RNAs, tRNA, and rRNA. All of these RNAs play vital roles in the cell, such as catalysis of protein synthesis by rRNA, and therefore serve as potential drug targets. This work focused on platination of two highly conserved RNA hairpins from E. coli ribosomes, namely pseudouridine-modified helix 69 from 23S rRNA and the 790 loop of helix 24 from 16S rRNA. RNase T1 probing, MALDI mass spectrometry, and dimethyl sulfate mapping revealed platination at GpG sites. Chemical probing results also showed platination-induced RNA structural changes. These findings reveal solvent and structural accessibility of sites within bacterial RNA secondary structures that are functionally significant and therefore viable targets for cisplatin as well as other classes of small molecules. Identifying target preferences at the nucleotide level, as well as determining cisplatin-induced RNA conformational changes, is important for the design of more potent drug molecules. Furthermore, the knowledge gained through studies of RNA-targeting by cisplatin is applicable to a broad range of organisms from bacteria to human.

  20. Target Response Adaptation for Correlation Filter Tracking

    KAUST Repository

    Bibi, Adel Aamer

    2016-09-16

    Most correlation filter (CF) based trackers utilize the circulant structure of the training data to learn a linear filter that best regresses this data to a hand-crafted target response. These circularly shifted patches are only approximations to actual translations in the image, which become unreliable in many realistic tracking scenarios including fast motion, occlusion, etc. In these cases, the traditional use of a single centered Gaussian as the target response impedes tracker performance and can lead to unrecoverable drift. To circumvent this major drawback, we propose a generic framework that can adaptively change the target response from frame to frame, so that the tracker is less sensitive to the cases where circular shifts do not reliably approximate translations. To do that, we reformulate the underlying optimization to solve for both the filter and target response jointly, where the latter is regularized by measurements made using actual translations. This joint problem has a closed form solution and thus allows for multiple templates, kernels, and multi-dimensional features. Extensive experiments on the popular OTB100 benchmark show that our target adaptive framework can be combined with many CF trackers to realize significant overall performance improvement (ranging from 3 %-13.5% in precision and 3.2 %-13% in accuracy), especially in categories where this adaptation is necessary (e.g. fast motion, motion blur, etc.). © Springer International Publishing AG 2016.

  1. Novel targeted agents for gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Lian

    2012-06-01

    Full Text Available Abstract Contemporary advancements have had little impact on the treatment of gastric cancer (GC, the world’s second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs and receptor tyrosine kinase inhibitors (TKIs. Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2 gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF, mammalian target of rapamycin (mTOR, and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers.

  2. Staufen2 Regulates Neuronal Target RNAs

    Directory of Open Access Journals (Sweden)

    Jacki E. Heraud-Farlow

    2013-12-01

    Full Text Available RNA-binding proteins play crucial roles in directing RNA translation to neuronal synapses. Staufen2 (Stau2 has been implicated in both dendritic RNA localization and synaptic plasticity in mammalian neurons. Here, we report the identification of functionally relevant Stau2 target mRNAs in neurons. The majority of Stau2-copurifying mRNAs expressed in the hippocampus are present in neuronal processes, further implicating Stau2 in dendritic mRNA regulation. Stau2 targets are enriched for secondary structures similar to those identified in the 3′ UTRs of Drosophila Staufen targets. Next, we show that Stau2 regulates steady-state levels of many neuronal RNAs and that its targets are predominantly downregulated in Stau2-deficient neurons. Detailed analysis confirms that Stau2 stabilizes the expression of one synaptic signaling component, the regulator of G protein signaling 4 (Rgs4 mRNA, via its 3′ UTR. This study defines the global impact of Stau2 on mRNAs in neurons, revealing a role in stabilization of the levels of synaptic targets.

  3. Engineering liposomal nanoparticles for targeted gene therapy.

    Science.gov (United States)

    Zylberberg, C; Gaskill, K; Pasley, S; Matosevic, S

    2017-08-01

    Recent mechanistic studies have attempted to deepen our understanding of the process by which liposome-mediated delivery of genetic material occurs. Understanding the interactions between lipid nanoparticles and cells is still largely elusive. Liposome-mediated delivery of genetic material faces systemic obstacles alongside entry into the cell, endosomal escape, lysosomal degradation and nuclear uptake. Rational design approaches for targeted delivery have been developed to reduce off-target effects and enhance transfection. These strategies, which have included the modification of lipid nanoparticles with target-specific ligands to enhance intracellular uptake, have shown significant promise at the proof-of-concept stage. Control of physical and chemical specifications of liposome composition, which includes lipid-to-DNA charge, size, presence of ester bonds, chain length and nature of ligand complexation, is integral to the performance of targeted liposomes as genetic delivery agents. Clinical advances are expected to rely on such systems in the therapeutic application of liposome nanoparticle-based gene therapy. Here, we discuss the latest breakthroughs in the development of targeted liposome-based agents for the delivery of genetic material, paying particular attention to new ligand and cationic lipid design as well as recent in vivo advances.

  4. Biopolymer based nanosystem for doxorubicin targeted delivery.

    Science.gov (United States)

    Csikós, Zsuzsanna; Kerekes, Krisztina; Fazekas, Erika; Kun, Sándor; Borbély, János

    2017-01-01

    This study describes formation of an actively and passively targeted, water-soluble drug delivery system (DDS) which contains doxorubicin (DOX). The system comprises two biocompatible and biodegradable polymers: poly-γ-glutamic acid (PGA) and chitosan (CH). Self-assembly of these biopolymers in aqueous medium results stable nanoparticles (NPs) with a hydrodynamic size of 80-150 nm and slightly negative surface charge. Folic acid (FA) was used as targeting agent bonded to the polyanion (PA) and also to the surface of the NPs. The NP's physical stability, active targeting effect, cellular toxicity, release profile and in vivo anti-tumor efficacy were investigated. It was found that the targeted, self-assembled nanoparticles are stable at 4°C for several months, cause better in vitro toxicity effect on folate receptor (FR) positive cell lines than the doxorubicin or the non-targeted nanosystem and based on its release profile it is expected, that the nanosystem will remain stable during the circulation in the body. Pharmacodynamic studies demonstrated that the DOX-loaded nanoparticles can deliver greater tumor growth inhibition than the free drug molecules and the liposomal compound, with less general toxicity. It was observed that the overall survival is the main benefit of the biopolymer based drug delivery system.

  5. 29 mm Diameter Test Target Design Report

    Energy Technology Data Exchange (ETDEWEB)

    Woloshun, Keith Albert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dale, Gregory E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Olivas, Eric Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Naranjo, Angela Carol [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Romero, Frank Patrick [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-08-15

    The Northstar target for Mo99 production is made up of Mo100 disks in a stack separated by coolant gaps for helium flow. A number of targets have been tested at ANL for both production of Mo99 and for thermal-hydraulic performance. These have all been with a 12 mm diameter target, even while the production goals have increased the diameter to now 29 mm. A 29 mm diameter target has been designed that is consistent with the ANL beam capabilities and the capabilities of the helium circulation system currently in use at ANL. This target is designed for 500 μA at 35 MeV electrons. While the plant design calls for 42 MeV, the chosen design point is more favorable and higher power given the limits of the ANL accelerator. The intended beam spot size is 12 mm FWHM, but the thermal analysis presented herein conservatively assumed a 10 mm FWHM beam, which results in a 44% higher beam current density at beam center.

  6. PAK1 AS A THERAPEUTIC TARGET

    Science.gov (United States)

    Kichina, Julia V; Goc, Anna; Al-Husein, Belal; Somanath, Payaningal R; Kandel, Eugene S

    2011-01-01

    Importance of the field P21-activated kinases (PAKs) are involved in multiple signal transduction pathways in mammalian cells. PAKs, and PAK1 in particular, play a role in such disorders as cancer, mental retardation and allergy. Cell motility, survival and proliferation, the organization and function of cytoskeleton and extracellular matrix, transcription and translation are among the processes affected by PAK1. Areas covered in this review We discuss the mechanisms that control PAK1 activity; its involvement in physiological and pathophysiological processes; the benefits and the drawbacks of the current tools to regulate PAK1 activity; the evidences that point to PAK1 as a therapeutic target; and the likely directions of future research. What the reader will gain The reader will gain a better knowledge and understanding of the areas covered in this review. Take-home message PAK1 is a promising therapeutic target in cancer and allergen-induced disorders. Its suitability as a target in vascular, neurological and infectious diseases remains ambiguous. Further advancement of this field requires progress on such issues as the development of specific and clinically acceptable inhibitors, the choice between targeting one or multiple PAK isoforms, elucidation of the individual roles of PAK1 targets and the mechanisms that may circumvent inhibition of PAK1. PMID:20507214

  7. Cooperative Robots to Observe Moving Targets: Review.

    Science.gov (United States)

    Khan, Asif; Rinner, Bernhard; Cavallaro, Andrea

    2018-01-01

    The deployment of multiple robots for achieving a common goal helps to improve the performance, efficiency, and/or robustness in a variety of tasks. In particular, the observation of moving targets is an important multirobot application that still exhibits numerous open challenges, including the effective coordination of the robots. This paper reviews control techniques for cooperative mobile robots monitoring multiple targets. The simultaneous movement of robots and targets makes this problem particularly interesting, and our review systematically addresses this cooperative multirobot problem for the first time. We classify and critically discuss the control techniques: cooperative multirobot observation of multiple moving targets, cooperative search, acquisition, and track, cooperative tracking, and multirobot pursuit evasion. We also identify the five major elements that characterize this problem, namely, the coordination method, the environment, the target, the robot and its sensor(s). These elements are used to systematically analyze the control techniques. The majority of the studied work is based on simulation and laboratory studies, which may not accurately reflect real-world operational conditions. Importantly, while our systematic analysis is focused on multitarget observation, our proposed classification is useful also for related multirobot applications.

  8. Thick-target yields of radioactive targets deduced from inverse kinematics

    Energy Technology Data Exchange (ETDEWEB)

    Aikawa, M., E-mail: aikawa@sci.hokudai.ac.jp [Faculty of Science, Hokkaido University, Sapporo 060-0810 (Japan); Ebata, S.; Imai, S. [Meme Media Laboratory, Hokkaido University, Sapporo 060-8628 (Japan)

    2015-06-15

    The thick-target yield (TTY) is a macroscopic quantity reflected by nuclear reactions and matter properties of targets. In order to evaluate TTYs on radioactive targets, we suggest a conversion method from inverse kinematics corresponding to the reaction of radioactive beams on stable targets. The method to deduce the TTY is theoretically derived from inverse kinematics. We apply the method to the {sup nat}Cu({sup 12}C,X){sup 24}Na reaction to confirm availability. In addition, it is applied to the {sup 137}Cs + {sup 12}C reaction as an example of a radioactive system and discussed a conversion coefficient of a TTY measurement.

  9. ANALYSIS OF PULSE OPTICAL TARGET SEEKER STATIC CHARACTERISTICS AT TARGET AIRCRAFTS EXPOSURE

    Directory of Open Access Journals (Sweden)

    K. V. Trifonov,

    2016-01-01

    Full Text Available Subject of Research.The paper deals with operating principles of optical pulse target seekers based on quadrant photodiode when targets are located in short-range field region. Method. Target image shape and light intensity distribution can affect static characteristics and cause appearance of image energy maximums when targets are located in short-range field region. Physical modeling of static characteristics plotting process was carried out. The main idea of the proposed method lies in counting sums of image pixels intensities in every virtual area of the sensor while virtual frame of the whole photodetector is moving over the target image. Main Results. Most probable target illumination directions were analyzed. Critical distances when the first extra image energy maximum appears were calculated for every target illumination directions. Time of missile uncontrollable flight at a near miss distance was also estimated. Practical Relevance. Research results point out that using of control loop proper logic is required to provide reliable target shot down for active and semi-active laser homing systems. Also disabling of such systems should be carried out when targets are located in short-range field region.

  10. Targeting mutant NRAS signaling pathways in melanoma.

    Science.gov (United States)

    Vu, Ha Linh; Aplin, Andrew E

    2016-05-01

    Cutaneous melanoma is a devastating form of skin cancer and its incidence is increasing faster than any other preventable cancer in the United States. The mutant NRAS subset of melanoma is more aggressive and associated with poorer outcomes compared to non-NRAS mutant melanoma. The aggressive nature and complex molecular signaling conferred by this transformation has evaded clinically effective treatment options. This review examines the major downstream effectors of NRAS relevant in melanoma and the associated advances made in targeted therapies that focus on these effector pathways. We outline the history of MEK inhibition in mutant NRAS melanoma and recent advances with newer MEK inhibitors. Since MEK inhibitors will likely be optimized when combined with other targeted therapies, we focus on recently identified targets that can be used in combination with MEK inhibitors. Published by Elsevier Ltd.

  11. Targeted Delivery of Protein Drugs by Nanocarriers

    Directory of Open Access Journals (Sweden)

    Antonella Battisti

    2010-03-01

    Full Text Available Recent advances in biotechnology demonstrate that peptides and proteins are the basis of a new generation of drugs. However, the transportation of protein drugs in the body is limited by their high molecular weight, which prevents the crossing of tissue barriers, and by their short lifetime due to immuno response and enzymatic degradation. Moreover, the ability to selectively deliver drugs to target organs, tissues or cells is a major challenge in the treatment of several human diseases, including cancer. Indeed, targeted delivery can be much more efficient than systemic application, while improving bioavailability and limiting undesirable side effects. This review describes how the use of targeted nanocarriers such as nanoparticles and liposomes can improve the pharmacokinetic properties of protein drugs, thus increasing their safety and maximizing the therapeutic effect.

  12. A ligand's view of target similarity

    DEFF Research Database (Denmark)

    Garland, Stephen L; Gloriam, David E

    2011-01-01

    shows with several examples how focusing on the binding site(s) has a clear advantage when it comes to establishing sequence-correlated pharmacological profiles. By organizing and comparing sequence and structural data it is possible to "borrow" SAR from similar targets to increase the speed of lead......-finding and, potentially, to produce ligands for previously intractable receptors. Sequence motifs correlated with ligands can be applied in the design of target-specific focused libraries that are both efficient and cost-effective and should provide increased hit-rates over diversity screening. Furthermore......, in the optimization phase, the binding motif approach offers the possibility to identify quickly the most likely off-target candidates to be chosen for selectivity screening, as well as potentially characterizing those pockets which may best be exploited for improved selectivity....

  13. Small target detection using objectness and saliency

    Science.gov (United States)

    Zhang, Naiwen; Xiao, Yang; Fang, Zhiwen; Yang, Jian; Wang, Li; Li, Tao

    2017-10-01

    We are motived by the need for generic object detection algorithm which achieves high recall for small targets in complex scenes with acceptable computational efficiency. We propose a novel object detection algorithm, which has high localization quality with acceptable computational cost. Firstly, we obtain the objectness map as in BING[1] and use NMS to get the top N points. Then, k-means algorithm is used to cluster them into K classes according to their location. We set the center points of the K classes as seed points. For each seed point, an object potential region is extracted. Finally, a fast salient object detection algorithm[2] is applied to the object potential regions to highlight objectlike pixels, and a series of efficient post-processing operations are proposed to locate the targets. Our method runs at 5 FPS on 1000*1000 images, and significantly outperforms previous methods on small targets in cluttered background.

  14. Target materials for exotic ISOL beams

    CERN Document Server

    Gottberg, A

    2016-01-01

    The demand for intensity, purity, reliability and availability of short-lived isotopes far from stability is steadily high, and considerably exceeding the supply. In many cases the ISOL (Isotope Separation On-Line) method can provide beams of high intensity and purity. Limitations in terms of accessible chemical species and minimum half-life are driven mainly by chemical reactions and physical processes inside of the thick target. A wide range of materials are in use, ranging from thin metallic foils and liquids to refractory ceramics, while poly-phasic mixed uranium carbides have become the reference target material for most ISOL facilities world-wide. Target material research and development is often complex and especially important post-irradiation analyses are hindered by the high intrinsic radiotoxicity of these materials. However, recent achievements have proven that these investigations are possible if the effort of different facilities is combined, leading to the development of new material matrices t...

  15. Stable Targets for Spaceborne Microwave Radiometer Calibration

    Science.gov (United States)

    Njoku, Eni G.; Chan, S. K.; Armstrong, R. L.; Brodzik, M. J.; Savoie, M. H.; Knowles, K.

    2006-01-01

    Beginning in the 1970s, continuous observations of the Earth have been made by spaceborne microwave radiometers. Since these instruments have different observational characteristics, care must be taken in combining their data to form consistent long term records of brightness temperatures and derived geophysical quantities. To be useful for climate studies, data from different instruments must be calibrated relative to each other and to reference targets on the ground whose characteristics are stable and can be monitored continuously. Identifying such targets over land is not straightforward due to the heterogeneity and complexity of the land surface and cover. In this work, we provide an analysis of multi-sensor brightness temperature statistics over ocean, tropical forest, and ice sheet locations, spanning the period from 1978 to the present, and indicate the potential of these sites as continuous calibration monitoring targets.

  16. Targeting Specific Immunologic Pathways in Crohn's Disease.

    Science.gov (United States)

    Ramos, Guilherme Piovezani; Faubion, William A; Papadakis, Konstantinos A

    2017-09-01

    Understanding the immunologic pathways in intestinal inflammation is crucial for the development of new therapies that can maximize patient response and minimize toxicity. Targeting integrins and cytokines is intended to control leukocyte migration to effector sites or inhibit the action of proinflammatory cytokines. New approaches to preventing leukocyte migration may target integrin receptors expressed on the intestinal vascular endothelium. The interleukin (IL)-12/IL-23 pathway has been a therapeutic target of interest in controlling active Crohn's disease (CD). New therapeutic approaches in CD may involve the enhancement of anti-inflammatory cytokine pathways and modulation of cellular responses and intranuclear signals associated with intestinal inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Progress on LMJ targets for ignition

    Energy Technology Data Exchange (ETDEWEB)

    Cherfils-Clerouin, C; Boniface, C; Bonnefille, M; Fremerye, P; Galmiche, D; Gauthier, P; Giorla, J; Lambert, F; Laffite, S; Liberatore, S; Loiseau, P; Malinie, G; Masse, L; Masson-Laborde, P E; Monteil, M C; Poggi, F; Seytor, P; Wagon, F; Willien, J L, E-mail: catherine.cherfils@cea.f [CEA, DAM, DIF, F-91297 Arpajon (France)

    2010-08-01

    Targets designed to produce ignition on the Laser MegaJoule are presented. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-shaped cocktail hohlraum. 1D and 2D robustness evaluations of these different targets shed light on critical points for ignition, that can be traded off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  18. Targeting the Met pathway in lung cancer.

    Science.gov (United States)

    Belalcazar, Astrid; Azaña, Daisy; Perez, Cesar A; Raez, Luis E; Santos, Edgardo S

    2012-04-01

    Dysregulation of Met signaling has been implicated in the initiation, progression and metastasis of human cancers, and therefore represents an attractive target for anticancer drug development. Met is overexpressed in non-small-cell lung cancer and its lack of staining in normal lung tissue makes it an attractive target. To date, erlotinib and gefitinib have established themselves as first-line therapy for non-small-cell lung cancer patients whose tumors harbor an EGF receptor gene mutation, and hence, it is crucial that we identify mechanisms of resistance that could be targeted by novel agents, while keeping an acceptable toxicity profile at the same time; something very important when we develop these new drugs. Inhibitors of the Met pathway represent a therapeutic alternative in this setting. In this review, we discuss the early clinical studies reported using two Met inhibitors, a monoclonal antibody (MetMAb) and a small molecule tyrosine kinase inhibitor (MGCD265).

  19. Will nanotechnology influence targeted cancer therapy?

    Science.gov (United States)

    Grimm, Jan; Scheinberg, David A

    2011-04-01

    The rapid development of techniques that enable synthesis (and manipulation) of matter on the nanometer scale and the development of new nanomaterials will play a large role in disease diagnosis and treatment, specifically in targeted cancer therapy. Targeted nanocarriers are an intriguing means to selectively deliver high concentrations of cytotoxic agents or imaging labels directly to the cancer site. Often, solubility issues and an unfavorable biodistribution can result in a suboptimal response of novel agents even though they are very potent. New nanoparticulate formulations allow simultaneous imaging and therapy ("theranostics"), which can provide a realistic means for the clinical implementation of such otherwise suboptimal formulations. In this review, we did not attempt to provide a complete overview of the rapidly enlarging field of nanotechnology in cancer; rather, we presented properties specific to nanoparticles and examples of their uses, which show their importance for targeted cancer therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Targeted radionuclide therapy: frontiers in theranostics.

    Science.gov (United States)

    Gallivanone, Francesca; Valente, Mauro; Savi, Annarita; Canevari, Carla; Castiglioni, Isabella

    2017-06-01

    The concept of targeted radionuclide therapy (TRT) relies on the use of injected nuclear medicine as treating agents, targeted at the cellular or molecular level. The growth of the interest in TRT was stimulated by the advances in radionuclide production and labeling as well as by the improvement in the knowledge of appropriate and specific molecular targets. In recent years, different studies on TRT were focused on the evaluation of radionuclide compounds able to combine imaging of the disease with TRT, in a theranostic approach. This approach is of particular interest towards the personalization of treatments, allowing both the baseline characterization of oncological pathologies and treatment optimization by correct dosimetric calculation as well as therapy monitoring. This paper presents a review of recent literature on TRT, with a particular focus on clinical applications promoting such a theranostic approach, showing the impact of the synergy of diagnostic imaging and therapeutics.