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Sample records for cdk1 targets srs2

  1. Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair.

    Directory of Open Access Journals (Sweden)

    Marco Saponaro

    2010-02-01

    Full Text Available Cdk1 kinase phosphorylates budding yeast Srs2, a member of UvrD protein family, displays both DNA translocation and DNA unwinding activities in vitro. Srs2 prevents homologous recombination by dismantling Rad51 filaments and is also required for double-strand break (DSB repair. Here we examine the biological significance of Cdk1-dependent phosphorylation of Srs2, using mutants that constitutively express the phosphorylated or unphosphorylated protein isoforms. We found that Cdk1 targets Srs2 to repair DSB and, in particular, to complete synthesis-dependent strand annealing, likely controlling the disassembly of a D-loop intermediate. Cdk1-dependent phosphorylation controls turnover of Srs2 at the invading strand; and, in absence of this modification, the turnover of Rad51 is not affected. Further analysis of the recombination phenotypes of the srs2 phospho-mutants showed that Srs2 phosphorylation is not required for the removal of toxic Rad51 nucleofilaments, although it is essential for cell survival, when DNA breaks are channeled into homologous recombinational repair. Cdk1-targeted Srs2 displays a PCNA-independent role and appears to have an attenuated ability to inhibit recombination. Finally, the recombination defects of unphosphorylatable Srs2 are primarily due to unscheduled accumulation of the Srs2 protein in a sumoylated form. Thus, the Srs2 anti-recombination function in removing toxic Rad51 filaments is genetically separable from its role in promoting recombinational repair, which depends exclusively on Cdk1-dependent phosphorylation. We suggest that Cdk1 kinase counteracts unscheduled sumoylation of Srs2 and targets Srs2 to dismantle specific DNA structures, such as the D-loops, in a helicase-dependent manner during homologous recombinational repair.

  2. Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair.

    Science.gov (United States)

    Saponaro, Marco; Callahan, Devon; Zheng, Xiuzhong; Krejci, Lumir; Haber, James E; Klein, Hannah L; Liberi, Giordano

    2010-02-01

    Cdk1 kinase phosphorylates budding yeast Srs2, a member of UvrD protein family, displays both DNA translocation and DNA unwinding activities in vitro. Srs2 prevents homologous recombination by dismantling Rad51 filaments and is also required for double-strand break (DSB) repair. Here we examine the biological significance of Cdk1-dependent phosphorylation of Srs2, using mutants that constitutively express the phosphorylated or unphosphorylated protein isoforms. We found that Cdk1 targets Srs2 to repair DSB and, in particular, to complete synthesis-dependent strand annealing, likely controlling the disassembly of a D-loop intermediate. Cdk1-dependent phosphorylation controls turnover of Srs2 at the invading strand; and, in absence of this modification, the turnover of Rad51 is not affected. Further analysis of the recombination phenotypes of the srs2 phospho-mutants showed that Srs2 phosphorylation is not required for the removal of toxic Rad51 nucleofilaments, although it is essential for cell survival, when DNA breaks are channeled into homologous recombinational repair. Cdk1-targeted Srs2 displays a PCNA-independent role and appears to have an attenuated ability to inhibit recombination. Finally, the recombination defects of unphosphorylatable Srs2 are primarily due to unscheduled accumulation of the Srs2 protein in a sumoylated form. Thus, the Srs2 anti-recombination function in removing toxic Rad51 filaments is genetically separable from its role in promoting recombinational repair, which depends exclusively on Cdk1-dependent phosphorylation. We suggest that Cdk1 kinase counteracts unscheduled sumoylation of Srs2 and targets Srs2 to dismantle specific DNA structures, such as the D-loops, in a helicase-dependent manner during homologous recombinational repair. PMID:20195513

  3. Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer cells

    International Nuclear Information System (INIS)

    Although MYC is an attractive therapeutic target for breast cancer treatment, it has proven challenging to inhibit MYC directly, and clinically effective pharmaceutical agents targeting MYC are not yet available. An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. Recent studies have identified several cell cycle kinases as MYC synthetic-lethal genes. We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast cancer. Using small interfering RNA (siRNA), MYC expression was depleted in 26 human breast cancer cell lines and cell proliferation evaluated by BrdU incorporation. MYC-dependent and MYC-independent cell lines were classified based on their sensitivity to siRNA-mediated MYC knockdown. We then inhibited CDKs including CDK4/6, CDK2 and CDK1 individually using either RNAi or small molecule inhibitors, and compared sensitivity to CDK inhibition with MYC dependence in breast cancer cells. Breast cancer cells displayed a wide range of sensitivity to siRNA-mediated MYC knockdown. The sensitivity was correlated with MYC protein expression and MYC phosphorylation level. Sensitivity to siRNA-mediated MYC knockdown did not parallel sensitivity to the CDK4/6 inhibitor PD0332991; instead MYC-independent cell lines were generally sensitive to PD0332991. Cell cycle arrest induced by MYC knockdown was accompanied by a decrease in CDK2 activity, but inactivation of CDK2 did not selectively affect the viability of MYC-dependent breast cancer cells. In contrast, CDK1 inactivation significantly induced apoptosis and reduced viability of MYC-dependent cells but not MYC- independent cells. This selective induction of apoptosis by CDK1 inhibitors was associated with up-regulation of the pro-apoptotic molecule BIM and was p53-independent. Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast cancer

  4. CDK1 Inhibition Targets the p53-NOXA-MCL1 Axis, Selectively Kills Embryonic Stem Cells, and Prevents Teratoma Formation

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    Noelle E. Huskey

    2015-03-01

    Full Text Available Embryonic stem cells (ESCs have adopted an accelerated cell-cycle program with shortened gap phases and precocious expression of cell-cycle regulatory proteins, including cyclins and cyclin-dependent kinases (CDKs. We examined the effect of CDK inhibition on the pathways regulating proliferation and survival of ESCs. We found that inhibiting cyclin-dependent kinase 1 (CDK1 leads to activation of the DNA damage response, nuclear p53 stabilization, activation of a subset of p53 target genes including NOXA, and negative regulation of the anti-apoptotic protein MCL1 in human and mouse ESCs, but not differentiated cells. We demonstrate that MCL1 is highly expressed in ESCs and loss of MCL1 leads to ESC death. Finally, we show that clinically relevant CDK1 inhibitors prevent formation of ESC-derived tumors and induce necrosis in established ESC-derived tumors. Our data demonstrate that ES cells are uniquely sensitive to CDK1 inhibition via a p53/NOXA/MCL1 pathway.

  5. CDK1 structures reveal conserved and unique features of the essential cell cycle CDK

    Science.gov (United States)

    Brown, Nicholas R.; Korolchuk, Svitlana; Martin, Mathew P.; Stanley, Will A.; Moukhametzianov, Rouslan; Noble, Martin E. M.; Endicott, Jane A.

    2015-04-01

    CDK1 is the only essential cell cycle CDK in human cells and is required for successful completion of M-phase. It is the founding member of the CDK family and is conserved across all eukaryotes. Here we report the crystal structures of complexes of CDK1-Cks1 and CDK1-cyclin B-Cks2. These structures confirm the conserved nature of the inactive monomeric CDK fold and its ability to be remodelled by cyclin binding. Relative to CDK2-cyclin A, CDK1-cyclin B is less thermally stable, has a smaller interfacial surface, is more susceptible to activation segment dephosphorylation and shows differences in the substrate sequence features that determine activity. Both CDK1 and CDK2 are potential cancer targets for which selective compounds are required. We also describe the first structure of CDK1 bound to a potent ATP-competitive inhibitor and identify aspects of CDK1 structure and plasticity that might be exploited to develop CDK1-selective inhibitors.

  6. Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1.

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    Candas, Demet; Qin, Lili; Fan, Ming; Li, Jian-Jian

    2016-01-01

    Although mitochondria possess their own transcriptional machinery, merely 1% of mitochondrial proteins are synthesized inside the organelle. The nuclear-encoded proteins are transported into mitochondria guided by their mitochondria targeting sequences (MTS); however, a majority of mitochondrial localized proteins lack an identifiable MTS. Nevertheless, the fact that MTS can instruct proteins to go into the mitochondria provides a valuable tool for studying mitochondrial functions of normally nuclear and/or cytoplasmic proteins. We have recently identified the cell cycle kinase CyclinB1/Cdk1 complex in the mitochondria. To specifically study the mitochondrial functions of this complex, mitochondrial overexpression and knock-down of this complex without interfering with its nuclear or cytoplasmic functions were essential. By tagging CyclinB1/Cdk1 with MTS, we were able to achieve mitochondrial overexpression of this complex to study its mitochondrial targets as well as functions. Via tagging dominant-negative Cdk1 with MTS, inhibition of Cdk1 activity was accomplished particularly in the mitochondria. Potential mitochondrial targets of CyclinB1/Cdk1 complex were identified using a gel-based proteomics approach. Unlike traditional 2D gel analysis, we employed 2-dimensional difference gel electrophoresis (2D-DIGE) technology followed by phosphoprotein staining to fluorescently label differentially phosphorylated proteins in mitochondrial Cdk1 expressing cells. Identification of phosphoprotein spots that were altered in wild type versus dominant negative Cdk1 bearing mitochondria revealed the identity of mitochondrial targets of Cdk1. Finally, to determine the effect of CyclinB1/Cdk1 mitochondrial localization in cell cycle progression, a cell proliferation assay using a synthetic thymidine analogue EdU (5-ethynyl-2'-deoxyuridine) was used to monitor the cells as they go through the cell cycle and replicate their DNA. Altogether, we demonstrated a variety of approaches

  7. Functional specialization of chordate CDK1 paralogs during oogenic meiosis.

    Science.gov (United States)

    Øvrebø, Jan Inge; Campsteijn, Coen; Kourtesis, Ioannis; Hausen, Harald; Raasholm, Martina; Thompson, Eric M

    2015-01-01

    Cyclin-dependent kinases (CDKs) are central regulators of eukaryotic cell cycle progression. In contrast to interphase CDKs, the mitotic phase CDK1 is the only CDK capable of driving the entire cell cycle and it can do so from yeast to mammals. Interestingly, plants and the marine chordate, Oikopleura dioica, possess paralogs of the highly conserved CDK1 regulator. However, whereas in plants the 2 CDK1 paralogs replace interphase CDK functions, O. dioica has a full complement of interphase CDKs in addition to its 5 odCDK1 paralogs. Here we show specific sub-functionalization of odCDK1 paralogs during oogenesis. Differential spatiotemporal dynamics of the odCDK1a, d and e paralogs and the meiotic polo-like kinase 1 (Plk1) and aurora kinase determine the subset of meiotic nuclei in prophase I arrest that will seed growing oocytes and complete meiosis. Whereas we find odCDK1e to be non-essential, knockdown of the odCDK1a paralog resulted in the spawning of non-viable oocytes of reduced size. Knockdown of odCDK1d also resulted in the spawning of non-viable oocytes. In this case, the oocytes were of normal size, but were unable to extrude polar bodies upon exposure to sperm, because they were unable to resume meiosis from prophase I arrest, a classical function of the sole CDK1 during meiosis in other organisms. Thus, we reveal specific sub-functionalization of CDK1 paralogs, during the meiotic oogenic program. PMID:25714331

  8. Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity.

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    Yee-Fun Su

    Full Text Available Increasing evidence has pointed to an important role of SUMOylation in cell cycle regulation, especially for M phase. In the current studies, we have obtained evidence through in vitro studies that the master M phase regulator CDK1/cyclin B kinase phosphorylates the SUMOylation machinery component Ubc9, leading to its enhanced SUMOylation activity. First, we show that CDK1/cyclin B, but not many other cell cycle kinases such as CDK2/cyclin E, ERK1, ERK2, PKA and JNK2/SAPK1, specifically enhances SUMOylation activity. Second, CDK1/cyclin B phosphorylates the SUMOylation machinery component Ubc9, but not SAE1/SAE2 or SUMO1. Third, CDK1/cyclin B-phosphorylated Ubc9 exhibits increased SUMOylation activity and elevated accumulation of the Ubc9-SUMO1 thioester conjugate. Fourth, CDK1/cyclin B enhances SUMOylation activity through phosphorylation of Ubc9 at serine 71. These studies demonstrate for the first time that the cell cycle-specific kinase CDK1/cyclin B phosphorylates a SUMOylation machinery component to increase its overall SUMOylation activity, suggesting that SUMOylation is part of the cell cycle program orchestrated by CDK1 through Ubc9.

  9. Synthesis and Biological Evaluation of Scutellaria Flavone Cyclaneaminol Mannich Base Derivatives as Novel CDK1 Inhibitors.

    Science.gov (United States)

    Ha, Lisha; Qian, Yuan; Zhang, Shixuan; Ju, Xiulan; Sun, Shiyou; Guo, Hongmin; Wang, Qianru; Li, Kangjian; Fan, Qingyu; Zheng, Yang; Li, Hailiang

    2016-01-01

    Cyclin-dependent kinase 1 (CDK1) is the only necessary CDK in the cell proliferation process and a new target in the research and development of anti-cancer drugs. Natural flavones are selective CDK1 inhibitors which can suppress the proliferation of cancer cells. However, their bioavailability is poor. To solve these problems, 6 Scutellaria flavones were isolated from hydrolyzed products of Scutellaria baicalensis and used as lead compounds, 18 Scutellaria flavones cyclane-aminol Mannich base derivatives were semi-synthesized and their biological activity as novel CDK1 inhibitors was evaluated. Results indicated that the biological activity of 8-Hydroxypiperidinemethyl-baicalein (BA-j) is the highest among these compounds. BA-j is a selective CDK1 inhibitor, and has broad-spectrum anti-proliferative activity in human cancer cells (IC50 12.3μM). BA-j can capture oxygen free radicals (.O2(-)) and selectively increase intracellular H2O2 level in cancer cells and activated lymphocytes, thus inducing their apoptosis rather than in normal cells. These findings suggest that BA-j selectively induces apoptosis in cancer and activated lymphocyte by controlling intracellular H2O2 level, and can be developed into a novel anti-proliferative agent for the treatment of cancer, AIDS, and some immune diseases. PMID:26411959

  10. Influence of CDK1 and CDK2 siRNA interference on tumor cell cycle and cell apoptosis%CDK1、CDK2 siRNA干扰对肿瘤细胞凋亡和细胞周期的影响

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    Hui Xiao; Wanjun Gong; Jingpeng Cao; Xiaolan Li; Deding Tao; Junbo Hu; Jianping Gong

    2009-01-01

    Objective: We investigated the influence of CDK1 and CDK2 expression inhibited by cotransfection of CDK1 and CDK2 siRNA on cell cycle and apoptosis, explored the exact role of cell cycle master regulator in tumor cell apoptosis process. Methods: The siRNA targeting the CDK1 and CDK2 genes were synthesized and simultaneously cotransfected into Hela cells by lipofectamine 2000.48 or 60 h after the cotransfection, CDK1 and CDK2 protein expressions were examined by Western blot. Cell cycle distribution was analyzed by flow cytometry. Cell apoptosis was detected by the Annexin V/PI method. The changes of the transfected cell morphological under a microscope after Wright-Giemsa Staining were studied. Results: CDK1 and CDK2 protein expression was decreased at 48 or 60 h after cotransfection. The accumulation of the G2/M and S phase population in cell cycle of the cotrensfected cells at 48 or 60 h after transfection was enhanced obviously compared with control. The ratio of apoptotic cell of cotransfected cells at 48 or 60 h after transfection was increased significantly compared with control. More binucleate or multinucleate cells among cotransfected cells were observed under the microscope. Conclu- sion: The decreased expression of CDK1 and CDK2 by cotransfection of CDK1 and CDK2 siRNA not only leads to tumor cell cycle arrest in S phase and G2/M phase, but also induces tumor cell apoptosis.

  11. Cyclin-dependent kinase CDK1/CDC28 and checkpoints

    International Nuclear Information System (INIS)

    The genetic instability induced by defects in the cell cycle progression contributes to different human diseases, particularly neoplastic transformation. The control mechanisms of correct cell cycle progression are the most studied in the yeast Saccharomyces cerevisiae, in which checkpoint was first discovered. Many components of these processes have been identified by now. Here, the role of the central kinase of cell cycle CDK1/CDC28 is considered in checkpoint in different phases.

  12. Evidence that phosphorylation by the mitotic kinase Cdk1 promotes ICER monoubiquitination and nuclear delocalization

    Energy Technology Data Exchange (ETDEWEB)

    Memin, Elisabeth, E-mail: molinac@mail.montclair.edu [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103 (United States); Genzale, Megan [Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103 (United States); Crow, Marni; Molina, Carlos A. [Department of Biology and Molecular Biology, Montclair State University, Montclair, NJ, 07043 (United States)

    2011-10-15

    In contrast to normal prostatic cells, the transcriptional repressor Inducible cAMP Early Repressor (ICER) is undetected in the nuclei of prostate cancer cells. The molecular mechanisms for ICER abnormal expression in prostate cancer cells remained largely unknown. In this report data is presented demonstrating that ICER is phosphorylated by the mitotic kinase cdk1. Phosphorylation of ICER on a discrete residue targeted ICER to be monoubiquitinated. Different from unphosphorylated, phosphorylated and polyubiquitinated ICER, monoubiquitinated ICER was found to be cytosolic. Taken together, these results hinted on a mechanism for the observed abnormal subcellular localization of ICER in human prostate tumors.

  13. Evidence that phosphorylation by the mitotic kinase Cdk1 promotes ICER monoubiquitination and nuclear delocalization

    International Nuclear Information System (INIS)

    In contrast to normal prostatic cells, the transcriptional repressor Inducible cAMP Early Repressor (ICER) is undetected in the nuclei of prostate cancer cells. The molecular mechanisms for ICER abnormal expression in prostate cancer cells remained largely unknown. In this report data is presented demonstrating that ICER is phosphorylated by the mitotic kinase cdk1. Phosphorylation of ICER on a discrete residue targeted ICER to be monoubiquitinated. Different from unphosphorylated, phosphorylated and polyubiquitinated ICER, monoubiquitinated ICER was found to be cytosolic. Taken together, these results hinted on a mechanism for the observed abnormal subcellular localization of ICER in human prostate tumors.

  14. Identification of Candidate Cyclin-dependent kinase 1 (Cdk1) Substrates in Mitosis by Quantitative Phosphoproteomics.

    Science.gov (United States)

    Petrone, Adam; Adamo, Mark E; Cheng, Chao; Kettenbach, Arminja N

    2016-07-01

    Cyclin-dependent kinase 1 (Cdk1) is an essential regulator of many mitotic processes including the reorganization of the cytoskeleton, chromosome segregation, and formation and separation of daughter cells. Deregulation of Cdk1 activity results in severe defects in these processes. Although the role of Cdk1 in mitosis is well established, only a limited number of Cdk1 substrates have been identified in mammalian cells. To increase our understanding of Cdk1-dependent phosphorylation pathways in mitosis, we conducted a quantitative phosphoproteomics analysis in mitotic HeLa cells using two small molecule inhibitors of Cdk1, Flavopiridol and RO-3306. In these analyses, we identified a total of 24,840 phosphopeptides on 4,273 proteins, of which 1,215 phosphopeptides on 551 proteins were significantly reduced by 2.5-fold or more upon Cdk1 inhibitor addition. Comparison of phosphopeptide quantification upon either inhibitor treatment revealed a high degree of correlation (R(2) value of 0.87) between the different datasets. Motif enrichment analysis of significantly regulated phosphopeptides revealed enrichment of canonical Cdk1 kinase motifs. Interestingly, the majority of proteins identified in this analysis contained two or more Cdk1 inhibitor-sensitive phosphorylation sites, were highly connected with other candidate Cdk1 substrates, were enriched at specific subcellular structures, or were part of protein complexes as identified by the CORUM database. Furthermore, candidate Cdk1 substrates were enriched in G2 and M phase-specific genes. Finally, we validated a subset of candidate Cdk1 substrates by in vitro kinase assays. Our findings provide a valuable resource for the cell signaling and mitosis research communities and greatly increase our knowledge of Cdk1 substrates and Cdk1-dependent signaling pathways. PMID:27134283

  15. Waves of Cdk1 Activity in S Phase Synchronize the Cell Cycle in Drosophila Embryos.

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    Deneke, Victoria E; Melbinger, Anna; Vergassola, Massimo; Di Talia, Stefano

    2016-08-22

    Embryos of most metazoans undergo rapid and synchronous cell cycles following fertilization. While diffusion is too slow for synchronization of mitosis across large spatial scales, waves of Cdk1 activity represent a possible process of synchronization. However, the mechanisms regulating Cdk1 waves during embryonic development remain poorly understood. Using biosensors of Cdk1 and Chk1 activities, we dissect the regulation of Cdk1 waves in the Drosophila syncytial blastoderm. We show that Cdk1 waves are not controlled by the mitotic switch but by a double-negative feedback between Cdk1 and Chk1. Using mathematical modeling and surgical ligations, we demonstrate a fundamental distinction between S phase Cdk1 waves, which propagate as active trigger waves in an excitable medium, and mitotic Cdk1 waves, which propagate as passive phase waves. Our findings show that in Drosophila embryos, Cdk1 positive feedback serves primarily to ensure the rapid onset of mitosis, while wave propagation is regulated by S phase events. PMID:27554859

  16. Long non-coding RNA ZFAS1 interacts with CDK1 and is involved in p53-dependent cell cycle control and apoptosis in colorectal cancer

    Science.gov (United States)

    Thorenoor, Nithyananda; Faltejskova-Vychytilova, Petra; Hombach, Sonja; Mlcochova, Jitka; Kretz, Markus; Svoboda, Marek; Slaby, Ondrej

    2016-01-01

    We determined expression of 83 long non-coding RNAs (lncRNAs) and identified ZFAS1 to be significantly up-regulated in colorectal cancer (CRC) tissue. In cohort of 119 CRC patients we observed that 111 cases displayed at least two-times higher expression of ZFAS1 in CRC compared to paired normal colorectal tissue (P HCT116+/+, HCT116−/− and DLD-1) we showed, that ZFAS1 silencing decreases proliferation through G1-arrest of cell cycle, and also tumorigenicity of CRC cells. We identified Cyclin-dependent kinase 1 (CDK1) as interacting partner of ZFAS1 by pull-down experiment and RNA immunoprecipitation. Further, we have predicted by bioinformatics approach ZFAS1 to sponge miR-590-3p, which was proved to target CDK1. Levels of CDK1 were not affected by ZFAS1 silencing, but cyclin B1 was decreased in both cell lines. We observed significant increase in p53 levels and PARP cleavage in CRC cell lines after ZFAS1 silencing indicating increase in apoptosis. Our data suggest that ZFAS1 may function as oncogene in CRC by two main actions: (i) via destabilization of p53 and through (ii) interaction with CDK1/cyclin B1 complex leading to cell cycle progression and inhibition of apoptosis. However, molecular mechanisms behind these interactions have to be further clarified. PMID:26506418

  17. Srs2 and Mus81-Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates.

    Directory of Open Access Journals (Sweden)

    Kenji Keyamura

    2016-07-01

    Full Text Available Homologous recombination is an evolutionally conserved mechanism that promotes genome stability through the faithful repair of double-strand breaks and single-strand gaps in DNA, and the recovery of stalled or collapsed replication forks. Saccharomyces cerevisiae ATP-dependent DNA helicase Srs2 (a member of the highly conserved UvrD family of helicases has multiple roles in regulating homologous recombination. A mutation (srs2K41A resulting in a helicase-dead mutant of Srs2 was found to be lethal in diploid, but not in haploid, cells. In diploid cells, Srs2K41A caused the accumulation of inter-homolog joint molecule intermediates, increased the levels of spontaneous Rad52 foci, and induced gross chromosomal rearrangements. Srs2K41A lethality and accumulation of joint molecules were suppressed by inactivating Rad51 or deleting the Rad51-interaction domain of Srs2, whereas phosphorylation and sumoylation of Srs2 and its interaction with sumoylated proliferating cell nuclear antigen (PCNA were not required for lethality. The structure-specific complex of crossover junction endonucleases Mus81 and Mms4 was also required for viability of diploid, but not haploid, SRS2 deletion mutants (srs2Δ, and diploid srs2Δ mus81Δ mutants accumulated joint molecule intermediates. Our data suggest that Srs2 and Mus81-Mms4 have critical roles in preventing the formation of (or in resolving toxic inter-homolog joint molecules, which could otherwise interfere with chromosome segregation and lead to genetic instability.

  18. Srs2 and Mus81-Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates.

    Science.gov (United States)

    Keyamura, Kenji; Arai, Kota; Hishida, Takashi

    2016-07-01

    Homologous recombination is an evolutionally conserved mechanism that promotes genome stability through the faithful repair of double-strand breaks and single-strand gaps in DNA, and the recovery of stalled or collapsed replication forks. Saccharomyces cerevisiae ATP-dependent DNA helicase Srs2 (a member of the highly conserved UvrD family of helicases) has multiple roles in regulating homologous recombination. A mutation (srs2K41A) resulting in a helicase-dead mutant of Srs2 was found to be lethal in diploid, but not in haploid, cells. In diploid cells, Srs2K41A caused the accumulation of inter-homolog joint molecule intermediates, increased the levels of spontaneous Rad52 foci, and induced gross chromosomal rearrangements. Srs2K41A lethality and accumulation of joint molecules were suppressed by inactivating Rad51 or deleting the Rad51-interaction domain of Srs2, whereas phosphorylation and sumoylation of Srs2 and its interaction with sumoylated proliferating cell nuclear antigen (PCNA) were not required for lethality. The structure-specific complex of crossover junction endonucleases Mus81 and Mms4 was also required for viability of diploid, but not haploid, SRS2 deletion mutants (srs2Δ), and diploid srs2Δ mus81Δ mutants accumulated joint molecule intermediates. Our data suggest that Srs2 and Mus81-Mms4 have critical roles in preventing the formation of (or in resolving) toxic inter-homolog joint molecules, which could otherwise interfere with chromosome segregation and lead to genetic instability. PMID:27390022

  19. Phosphorylation by Cdk1 induces Plk1-mediated vimentin phosphorylation during mitosis

    NARCIS (Netherlands)

    Yamaguchi, Tomoya; Goto, Hidemasa; Yokoyama, Tomoya; Silljé, Herman; Hanisch, Anja; Uldschmid, Andreas; Takai, Yasushi; Oguri, Takashi; Nigg, Erich A; Inagaki, Masaki

    2005-01-01

    Several kinases phosphorylate vimentin, the most common intermediate filament protein, in mitosis. Aurora-B and Rho-kinase regulate vimentin filament separation through the cleavage furrow-specific vimentin phosphorylation. Cdk1 also phosphorylates vimentin from prometaphase to metaphase, but its si

  20. Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

    International Nuclear Information System (INIS)

    Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Polδ and Polη from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability. (authors)

  1. The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1

    NARCIS (Netherlands)

    E. Voets (Erik); J. Marsman (Judith); J.A.A. Demmers (Jeroen); R.L. Beijersbergen (Roderick); R. Wolthuis (Rob)

    2015-01-01

    textabstractCyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cd

  2. Prediction of paclitaxel sensitivity by CDK1 and CDK2 activity in human breast cancer cells

    OpenAIRE

    Nakayama, Satoshi; Torikoshi, Yasuhiro; Takahashi, Takeshi; Yoshida, Tomokazu; Sudo, Tamotsu; Matsushima, Tomoko; Kawasaki, Yuko; Katayama, Aya; Gohda, Keigo; Hortobagyi, Gabriel N.; Noguchi, Shinzaburo; Sakai, Toshiyuki; Ishihara, Hideki; Ueno, Naoto T.

    2009-01-01

    Introduction Paclitaxel is used widely in the treatment of breast cancer. Not all tumors respond to this drug, however, and the characteristics that distinguish resistant tumors from sensitive tumors are not well defined. Activation of the spindle assembly checkpoint is required for paclitaxel-induced cell death. We hypothesized that cyclin-dependent kinase (CDK) 1 activity and CDK2 activity in cancer cells, which reflect the activation state of the spindle assembly checkpoint and the growth ...

  3. Stereospecific phosphorylation by the central mitotic kinase Cdk1-cyclin B.

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    Etzkorn, Felicia A; Zhao, Song

    2015-04-17

    The cis vs trans conformation, or shape, of phosphoserine-proline (pSer-Pro), a prevalent motif in cell cycle proteins, may play a significant role in regulating mitosis. We demonstrate that Cdk1-cyclin B, the central mitotic kinase, is specific for the trans conformation, not cis, of synthetic, locked Ser-Pro 11-residue peptide substrates, using LC-MSMS detection and sequencing of phosphorylated products. This substrate stereospecificity may contribute an additional level of mitotic regulation. PMID:25603287

  4. Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity

    OpenAIRE

    Nabti, Ibtissem; Marangos, Petros; Bormann, Jenny; Kudo, Nobuaki R; Carroll, John

    2014-01-01

    Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates...

  5. Cooperative Action of Cdk1/cyclin B and SIRT1 Is Required for Mitotic Repression of rRNA Synthesis

    OpenAIRE

    Voit, Renate; Seiler, Jeanette; Grummt, Ingrid

    2015-01-01

    Author Summary In metazoans, transcription is arrested during mitosis. Previous studies have established that mitotic repression of cellular transcription is mediated by Cdk1/cyclin B-dependent phosphorylation of basal transcription factors that nucleate transcription complex formation. Repression of rDNA transcription at the onset of mitosis is brought about by inactivation of the TBP-containing transcription factor SL1 by Cdk1/cyclin B-dependent phosphorylation of the TAFI110 subunit, which...

  6. Securin and not CDK1/cyclin B1 regulates sister chromatid disjunction during meiosis II in mouse eggs.

    Science.gov (United States)

    Nabti, Ibtissem; Reis, Alexandra; Levasseur, Mark; Stemmann, Olaf; Jones, Keith T

    2008-09-15

    Mammalian eggs remain arrested at metaphase of the second meiotic division (metII) for an indeterminate time before fertilization. During this period, which can last several hours, the continued attachment of sister chromatids is thought to be achieved by inhibition of the protease separase. Separase is known to be inhibited by binding either securin or Maturation (M-Phase)-Promoting Factor, a heterodimer of CDK1/cyclin B1. However, the relative contribution of securin and CDK/cyclin B1 to sister chromatid attachment during metII arrest has not been assessed. Although there are conditions in which either CDK1/cyclinB1 activity or securin can prevent sister chromatid disjunction, principally by overexpression of non-degradable cyclin B1 or securin, we find here that separase activity is primarily regulated by securin and not CDK1/cyclin B1. Thus the CDK1 inhibitor roscovitine and an antibody we designed to block the interaction of CDK1/cyclin B1 with separase, both failed to induce sister disjunction. In contrast, securin morpholino knockdown specifically induced loss of sister attachment, that could be restored by securin cRNA rescue. During metII arrest separase appears primarily regulated by securin binding, not CDK1/cyclin B1. PMID:18639540

  7. Srs2 and Mus81–Mms4 Prevent Accumulation of Toxic Inter-Homolog Recombination Intermediates

    Science.gov (United States)

    Keyamura, Kenji; Arai, Kota

    2016-01-01

    Homologous recombination is an evolutionally conserved mechanism that promotes genome stability through the faithful repair of double-strand breaks and single-strand gaps in DNA, and the recovery of stalled or collapsed replication forks. Saccharomyces cerevisiae ATP-dependent DNA helicase Srs2 (a member of the highly conserved UvrD family of helicases) has multiple roles in regulating homologous recombination. A mutation (srs2K41A) resulting in a helicase-dead mutant of Srs2 was found to be lethal in diploid, but not in haploid, cells. In diploid cells, Srs2K41A caused the accumulation of inter-homolog joint molecule intermediates, increased the levels of spontaneous Rad52 foci, and induced gross chromosomal rearrangements. Srs2K41A lethality and accumulation of joint molecules were suppressed by inactivating Rad51 or deleting the Rad51-interaction domain of Srs2, whereas phosphorylation and sumoylation of Srs2 and its interaction with sumoylated proliferating cell nuclear antigen (PCNA) were not required for lethality. The structure-specific complex of crossover junction endonucleases Mus81 and Mms4 was also required for viability of diploid, but not haploid, SRS2 deletion mutants (srs2Δ), and diploid srs2Δ mus81Δ mutants accumulated joint molecule intermediates. Our data suggest that Srs2 and Mus81–Mms4 have critical roles in preventing the formation of (or in resolving) toxic inter-homolog joint molecules, which could otherwise interfere with chromosome segregation and lead to genetic instability. PMID:27390022

  8. Semidominant mutations in the yeast Rad51 protein and their relationships with the Srs2 helicase.

    Science.gov (United States)

    Chanet, R; Heude, M; Adjiri, A; Maloisel, L; Fabre, F

    1996-09-01

    Suppressors of the methyl methanesulfonate sensitivity of Saccharomyces cerevisiae diploids lacking the Srs2 helicase turned out to contain semidominant mutations in Rad5l, a homolog of the bacterial RecA protein. The nature of these mutations was determined by direct sequencing. The 26 mutations characterized were single base substitutions leading to amino acid replacements at 18 different sites. The great majority of these sites (75%) are conserved in the family of RecA-like proteins, and 10 of them affect sites corresponding to amino acids in RecA that are probably directly involved in ATP reactions, binding, and/or hydrolysis. Six mutations are in domains thought to be involved in interaction between monomers; they may also affect ATP reactions. By themselves, all the alleles confer a rad5l null phenotype. When heterozygous, however, they are, to varying degrees, negative semidominant for radiation sensitivity; presumably the mutant proteins are coassembled with wild-type Rad51 and poison the resulting nucleofilaments or recombination complexes. This negative effect is partially suppressed by an SRS2 deletion, which supports the hypothesis that Srs2 reverses recombination structures that contain either mutated proteins or numerous DNA lesions. PMID:8756636

  9. Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Anthony A.; Mohideen, Firaz; Lima, Christopher D. (SKI)

    2013-04-08

    Ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers such as SUMO (also known as Smt3 in Saccharomyces cerevisiae) mediate signal transduction through post-translational modification of substrate proteins in pathways that control differentiation, apoptosis and the cell cycle, and responses to stress such as the DNA damage response. In yeast, the proliferating cell nuclear antigen PCNA (also known as Pol30) is modified by ubiquitin in response to DNA damage and by SUMO during S phase. Whereas Ub-PCNA can signal for recruitment of translesion DNA polymerases, SUMO-PCNA signals for recruitment of the anti-recombinogenic DNA helicase Srs2. It remains unclear how receptors such as Srs2 specifically recognize substrates after conjugation to Ub and Ubls. Here we show, through structural, biochemical and functional studies, that the Srs2 carboxy-terminal domain harbors tandem receptor motifs that interact independently with PCNA and SUMO and that both motifs are required to recognize SUMO-PCNA specifically. The mechanism presented is pertinent to understanding how other receptors specifically recognize Ub- and Ubl-modified substrates to facilitate signal transduction.

  10. Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation.

    Science.gov (United States)

    Velásquez, Celestino; Cheng, Erdong; Shuda, Masahiro; Lee-Oesterreich, Paula J; Pogge von Strandmann, Lisa; Gritsenko, Marina A; Jacobs, Jon M; Moore, Patrick S; Chang, Yuan

    2016-07-26

    Mammalian target of rapamycin (mTOR)-directed eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) phosphorylation promotes cap-dependent translation and tumorigenesis. During mitosis, cyclin-dependent kinase 1 (CDK1) substitutes for mTOR and fully phosphorylates 4E-BP1 at canonical sites (T37, T46, S65, and T70) and the noncanonical S83 site, resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. Although S83 phosphorylation of 4E-BP1 does not affect general cap-dependent translation, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus small T antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain of function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function. PMID:27402756

  11. EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling.

    Science.gov (United States)

    Pan, Xiu-Wu; Chen, Lu; Hong, Yi; Xu, Dan-Feng; Liu, Xi; Li, Lin; Huang, Yi; Cui, Li-Ming; Gan, Si-Shun; Yang, Qi-Wei; Huang, Hai; Qu, Fa-Jun; Ye, Jian-Qing; Wang, Lin-Hui; Cui, Xin-Gang

    2016-06-01

    There are no effective therapies for advanced renal cell carcinoma (RCC), except for VEGFR inhibitors with only ~50% response rate. To identify novel targets and biomarkers for RCC is of great importance in treating RCC. In this study, we observed that eukaryotic initiation factor 3d (EIF3D) expression was significantly increased in RCC compared with paracarcinoma tissue using immunohistochemistry staining and western blot analysis. Furthermore, bioinformatics meta-analysis using ONCOMINE microarray datasets showed that EIF3D mRNA expressions in CCRCC tissue specimens were significantly higher than that in normal tissue specimens. In addition, RCC tissue microarray demonstrated that elevated EIF3D expression was positively correlated with TNM stage and tumor size. EIF3D silencing in human 786-O and ACHN CCRCC cell lines by RNA interference demonstrated that EIF3D knockdown obviously inhibited cell proliferation and colony formation, caused G2/M arrest through downregulation of Cyclin B1 and Cdk1 and upregulation of p21, and induced apoptosis shown by sub-G1 accumulation and RARP cleavage. Moreover, correlation analysis using ONCOMINE microarray datasets indicated that increased EIF3D mRNA expression was positively correlated to PCNA, Cyclin B1 and CDK1 mRNA expression in RCC. Collectively, these results provide reasonable evidences that EIF3D may function as a potential proto-oncogene that participates in the occurrence and progression of RCC. PMID:27035563

  12. Mitotic Exit Function of Polo-like Kinase Cdc5 Is Dependent on Sequential Activation by Cdk1.

    Science.gov (United States)

    Rodriguez-Rodriguez, Jose-Antonio; Moyano, Yolanda; Játiva, Soraya; Queralt, Ethel

    2016-05-31

    To complete mitosis, Saccharomyces cerevisiae needs to activate the mitotic phosphatase Cdc14. Two pathways contribute to Cdc14 regulation: FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network). Cdc5 polo-like kinase was found to be an important mitotic exit component. However, its specific role in mitotic exit regulation and its involvement in Cdc14 release remain unclear. Here, we provide insight into the mechanism by which Cdc5 contributes to the timely release of Cdc14. Our genetic and biochemical data indicate that Cdc5 acts in parallel with MEN during anaphase. This MEN-independent Cdc5 function requires active separase and activation by Cdk1-dependent phosphorylation. Cdk1 first phosphorylates Cdc5 to activate it in early anaphase, and then, in late anaphase, further phosphorylation of Cdc5 by Cdk1 is needed to promote its MEN-related functions. PMID:27210759

  13. Genetic labelling and application of the isoproturon-mineralizing Sphingomonas sp. strain SRS2 in soil and rhizosphere

    DEFF Research Database (Denmark)

    Kristensen, K.E.; Jacobsen, C.S.; Hansen, L.H.;

    2006-01-01

    AIMS: To construct a luxAB-labelled Sphingomonas sp. strain SRS2 maintaining the ability to mineralize the herbicide isoproturon and usable for monitoring the survival and distribution of strain SRS2 on plant roots in laboratory systems. METHODS AND RESULTS: We inserted the mini-Tn5-luxAB marker...... for monitoring colonization of barley roots. CONCLUSIONS: We successfully constructed a genetically labelled isoproturon-mineralizing-strain SRS2 and demonstrated its ability to survive in soil and its colonization of rhizosphere. SIGNIFICANCE AND IMPACT OF THE STUDY: The construction of a lux...... into strain SRS2 using conjugational mating. In the transconjugant mutants luciferase was produced in varying levels. The mutants showed significant differences in their ability to degrade isoproturon. One luxAB-labelled mutant maintained the ability to mineralize isoproturon and was therefore selected...

  14. Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity.

    Science.gov (United States)

    Nabti, Ibtissem; Marangos, Petros; Bormann, Jenny; Kudo, Nobuaki R; Carroll, John

    2014-03-17

    Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes. PMID:24637322

  15. The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1.

    Science.gov (United States)

    Voets, Erik; Marsman, Judith; Demmers, Jeroen; Beijersbergen, Roderick; Wolthuis, Rob

    2015-01-01

    Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. Here, we used a large-scale RNAi screen to identify the human genes that critically determine the cellular toxicity of Cdk1 inhibition. We show that Cdk1 inhibition leads to fatal sister chromatid alignment errors and mitotic arrest in the spindle checkpoint. These problems start early in mitosis and are alleviated by depletion of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or by abrogation of KIF4 motor activity. Our results show that, normally, Cdk1 activity must rise above the level required for mitotic entry. This prevents KIF4-dependent PRC1-1 translocation to astral microtubule tips and safeguards proper chromosome congression. We conclude that cell death in response to Cdk1 inhibitors directly relates to chromosome alignment defects generated by insufficient repression of PRC1-1 and KIF4 during prometaphase. PMID:26423135

  16. Cell proliferation and migration are modulated by Cdk-1-phosphorylated endothelial-monocyte activating polypeptide II.

    Directory of Open Access Journals (Sweden)

    Margaret A Schwarz

    Full Text Available BACKGROUND: Endothelial-Monocyte Activating Polypeptide (EMAP II is a secreted protein with well-established anti-angiogenic activities. Intracellular EMAP II expression is increased during fetal development at epithelial/mesenchymal boundaries and in pathophysiologic fibroproliferative cells of bronchopulmonary dysplasia, emphysema, and scar fibroblast tissue following myocardial ischemia. Precise function and regulation of intracellular EMAP II, however, has not been explored to date. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that high intracellular EMAP II suppresses cellular proliferation by slowing progression through the G2M cell cycle transition in epithelium and fibroblast. Furthermore, EMAP II binds to and is phosphorylated by Cdk1, and exhibits nuclear/cytoplasmic partitioning, with only nuclear EMAP II being phosphorylated. We observed that extracellular secreted EMAP II induces endothelial cell apoptosis, where as excess intracellular EMAP II facilitates epithelial and fibroblast cells migration. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that EMAP II has specific intracellular effects, and that this intracellular function appears to antagonize its extracellular anti-angiogenic effects during fetal development and pulmonary disease progression.

  17. Exploratory Factor Analysis of SRS-2 Teacher Ratings for Youth with ASD.

    Science.gov (United States)

    Nelson, Andrew T; Lopata, Christopher; Volker, Martin A; Thomeer, Marcus L; Toomey, Jennifer A; Dua, Elissa

    2016-09-01

    This study examined the factor structure and internal consistency of special education teaching staff ratings on the Social Responsiveness Scale-2 (SRS-2; Constantino and Gruber 2012), as well as the percentage of ratings falling above pre-established cut scores, for a sample of lower-functioning youth with autism spectrum disorder (ASD; n = 264). Results of the exploratory factor analysis yielded a four-factor correlated solution. The individual factors and total score demonstrated satisfactory internal consistency reliability for screening purposes. When applying the lowest pre-established cut score (T ≥ 60; minimum indication of clinically significant symptoms/impairments), 85 % of the sample had ratings in that range or higher (more severe). Implications for assessment and future research are provided. PMID:27334872

  18. Cdk1 Phosphorylates Drosophila Sas-4 to Recruit Polo to Daughter Centrioles and Convert Them to Centrosomes.

    Science.gov (United States)

    Novak, Zsofia A; Wainman, Alan; Gartenmann, Lisa; Raff, Jordan W

    2016-06-20

    Centrosomes and cilia are organized by a centriole pair comprising an older mother and a younger daughter. Centriole numbers are tightly regulated, and daughter centrioles (which assemble in S phase) cannot themselves duplicate or organize centrosomes until they have passed through mitosis. It is unclear how this mitotic "centriole conversion" is regulated, but it requires Plk1/Polo kinase. Here we show that in flies, Cdk1 phosphorylates the conserved centriole protein Sas-4 during mitosis. This creates a Polo-docking site that helps recruit Polo to daughter centrioles and is required for the subsequent recruitment of Asterless (Asl), a protein essential for centriole duplication and mitotic centrosome assembly. Point mutations in Sas-4 that prevent Cdk1 phosphorylation or Polo docking do not block centriole disengagement during mitosis, but block efficient centriole conversion and lead to embryonic lethality. These observations can explain why daughter centrioles have to pass through mitosis before they can duplicate and organize a centrosome. PMID:27326932

  19. Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission-induced cardiomyocyte death

    Energy Technology Data Exchange (ETDEWEB)

    Zaja, Ivan [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Bai, Xiaowen, E-mail: xibai@mcw.edu [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Liu, Yanan; Kikuchi, Chika; Dosenovic, Svjetlana; Yan, Yasheng; Canfield, Scott G. [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Bosnjak, Zeljko J. [Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

    2014-10-31

    Highlights: • Drp1-mediated increased mitochondrial fission but not fusion is involved the cardiomyocyte death during anoxia-reoxygenation injury. • Reactive oxygen species are upstream initiators of mitochondrial fission. • Increased mitochondrial fission is resulted from Cdk1-, PKCδ-, and calcineurin-mediated Drp1 pathways. - Abstract: Myocardial ischemia–reperfusion (I/R) injury is one of the leading causes of death and disability worldwide. Mitochondrial fission has been shown to be involved in cardiomyocyte death. However, molecular machinery involved in mitochondrial fission during I/R injury has not yet been completely understood. In this study we aimed to investigate molecular mechanisms of controlling activation of dynamin-related protein 1 (Drp1, a key protein in mitochondrial fission) during anoxia-reoxygenation (A/R) injury of HL1 cardiomyocytes. A/R injury induced cardiomyocyte death accompanied by the increases of mitochondrial fission, reactive oxygen species (ROS) production and activated Drp1 (pSer616 Drp1), and decrease of inactivated Drp1 (pSer637 Drp1) while mitochondrial fusion protein levels were not significantly changed. Blocking Drp1 activity with mitochondrial division inhibitor mdivi1 attenuated cell death, mitochondrial fission, and Drp1 activation after A/R. Trolox, a ROS scavenger, decreased pSer616 Drp1 level and mitochondrial fission after A/R. Immunoprecipitation assay further indicates that cyclin dependent kinase 1 (Cdk1) and protein kinase C isoform delta (PKCδ) bind Drp1, thus increasing mitochondrial fission. Inhibiting Cdk1 and PKCδ attenuated the increases in pSer616 Drp1, mitochondrial fission, and cardiomyocyte death. FK506, a calcineurin inhibitor, blocked the decrease in expression of inactivated pSer637 Drp1 and mitochondrial fission. Our findings reveal the following novel molecular mechanisms controlling mitochondrial fission during A/R injury of cardiomyocytes: (1) ROS are upstream initiators of

  20. Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission-induced cardiomyocyte death

    International Nuclear Information System (INIS)

    Highlights: • Drp1-mediated increased mitochondrial fission but not fusion is involved the cardiomyocyte death during anoxia-reoxygenation injury. • Reactive oxygen species are upstream initiators of mitochondrial fission. • Increased mitochondrial fission is resulted from Cdk1-, PKCδ-, and calcineurin-mediated Drp1 pathways. - Abstract: Myocardial ischemia–reperfusion (I/R) injury is one of the leading causes of death and disability worldwide. Mitochondrial fission has been shown to be involved in cardiomyocyte death. However, molecular machinery involved in mitochondrial fission during I/R injury has not yet been completely understood. In this study we aimed to investigate molecular mechanisms of controlling activation of dynamin-related protein 1 (Drp1, a key protein in mitochondrial fission) during anoxia-reoxygenation (A/R) injury of HL1 cardiomyocytes. A/R injury induced cardiomyocyte death accompanied by the increases of mitochondrial fission, reactive oxygen species (ROS) production and activated Drp1 (pSer616 Drp1), and decrease of inactivated Drp1 (pSer637 Drp1) while mitochondrial fusion protein levels were not significantly changed. Blocking Drp1 activity with mitochondrial division inhibitor mdivi1 attenuated cell death, mitochondrial fission, and Drp1 activation after A/R. Trolox, a ROS scavenger, decreased pSer616 Drp1 level and mitochondrial fission after A/R. Immunoprecipitation assay further indicates that cyclin dependent kinase 1 (Cdk1) and protein kinase C isoform delta (PKCδ) bind Drp1, thus increasing mitochondrial fission. Inhibiting Cdk1 and PKCδ attenuated the increases in pSer616 Drp1, mitochondrial fission, and cardiomyocyte death. FK506, a calcineurin inhibitor, blocked the decrease in expression of inactivated pSer637 Drp1 and mitochondrial fission. Our findings reveal the following novel molecular mechanisms controlling mitochondrial fission during A/R injury of cardiomyocytes: (1) ROS are upstream initiators of

  1. NANOG Is Multiply Phosphorylated and Directly Modified by ERK2 and CDK1 In Vitro

    Directory of Open Access Journals (Sweden)

    Justin Brumbaugh

    2014-01-01

    Full Text Available NANOG is a divergent homeobox protein and a core component of the transcriptional circuitry that sustains pluripotency and self-renewal. Although NANOG has been extensively studied on the transcriptional level, little is known regarding its posttranslational regulation, likely due to its low abundance and challenging physical properties. Here, we identify eleven phosphorylation sites on endogenous human NANOG, nine of which mapped to single amino acids. To screen for the signaling molecules that impart these modifications, we developed the multiplexed assay for kinase specificity (MAKS. MAKS simultaneously tests activity for up to ten kinases while directly identifying the substrate and exact site of phosphorylation. Using MAKS, we discovered site-specific phosphorylation by ERK2 and CDK1/CyclinA2, providing a putative link between key signaling pathways and NANOG.

  2. Effect of CDK1/CDK2 interference on cell cycle by lentivirus vector in cancer cells%慢病毒介导 CDK1/CDK2干扰对肿瘤细胞周期的影响❉

    Institute of Scientific and Technical Information of China (English)

    江文娇; 李慧萍; 齐庆远

    2015-01-01

    In order to investigate the influence of CDK1 and CDK2 interference on cell cycle in CBRH-7919 cell, the CDK1, CDK2 specific shRNA lentiviral expression vectors were structured, then three plasmids were contransfected into 293 FT cells to produce viral particles, which infected the CBRH-7919 cells after collecting and concentrating the virals.The morphological changes of cells were observed by fluorescence microscope, Real-time PCR and Western Blotting demonstrated the level changes of CDK1 , CDK2 mRNA and protein ex-pression in CBRH-7919 cells.It was analyzed the changes of cell proliferation and cycle effect by MTT and flow cytometry.The results showed that it was successful to construct the CDK1 and CDK2 specific shRNA lentiviral expression vector;silencing of CDK1 led to arrest of cells in G2/M phase, cell proliferation rate de-creased obviously, and increased cell debris, while silencing CDK2 cells remained growth as normal.%为了检测细胞周期性蛋白激酶CDK1与CDK2干扰对CBRH-7919细胞周期的影响,构建了CDK1和CDK2特异性shRNA慢病毒沉默表达载体,三质粒共转染293 FT细胞产生病毒颗粒,收集浓缩后感染CBRH-7919细胞,荧光显微镜下观察了细胞形态,实时定量荧光PCR和聚丙烯酰胺凝胶电泳检测了细胞中CDK1和CDK2 mRNA和蛋白质表达水平的变化,MTT法和流式细胞仪分别检测了细胞增殖和细胞周期的变化情况。结果表明:成功构建了CDK1与CDK2特异性shRNA慢病毒表达载体,干扰CDK1导致细胞G2/M期的阻滞,细胞增殖明显降低,细胞碎片增多;而干扰CDK2后细胞仍正常生长。

  3. Evaluation and comparison of 3D-QSAR CoMSIA models for CDK1, CDK5, and GSK-3 inhibition by paullones

    DEFF Research Database (Denmark)

    Kunick, Conrad; Lauenroth, Kathrin; Wieking, Karen; Xie, Xu; Schultz, Christiane; Gussio, Rick; Zaharevitz, Daniel; Leost, Maryse; Meijer, Laurent; Weber, Alexander; Jørgensen, Flemming Steen; Lemcke, Thomas

    2004-01-01

    data of 52 paullone entities, which were aligned by a docking routine into the ATP-binding cleft of a CDK1/cyclin B homology model. Variation of grid spacing and column filtering were used during the optimization of the models. The predictive ability of the models was shown by a leave-one-out cross...

  4. Pin1-mediated Sp1 phosphorylation by CDK1 increases Sp1 stability and decreases its DNA-binding activity during mitosis.

    Science.gov (United States)

    Yang, Hang-Che; Chuang, Jian-Ying; Jeng, Wen-Yih; Liu, Chia-I; Wang, Andrew H-J; Lu, Pei-Jung; Chang, Wen-Chang; Hung, Jan-Jong

    2014-12-16

    We have shown that Sp1 phosphorylation at Thr739 decreases its DNA-binding activity. In this study, we found that phosphorylation of Sp1 at Thr739 alone is necessary, but not sufficient for the inhibition of its DNA-binding activity during mitosis. We demonstrated that Pin1 could be recruited to the Thr739(p)-Pro motif of Sp1 to modulate the interaction between phospho-Sp1 and CDK1, thereby facilitating CDK1-mediated phosphorylation of Sp1 at Ser720, Thr723 and Thr737 during mitosis. Loss of the C-terminal end of Sp1 (amino acids 741-785) significantly increased Sp1 phosphorylation, implying that the C-terminus inhibits CDK1-mediated Sp1 phosphorylation. Binding analysis of Sp1 peptides to Pin1 by isothermal titration calorimetry indicated that Pin1 interacts with Thr739(p)-Sp1 peptide but not with Thr739-Sp1 peptide. X-ray crystallography data showed that the Thr739(p)-Sp1 peptide occupies the active site of Pin1. Increased Sp1 phosphorylation by CDK1 during mitosis not only stabilized Sp1 levels by decreasing interaction with ubiquitin E3-ligase RNF4 but also caused Sp1 to move out of the chromosomes completely by decreasing its DNA-binding activity, thereby facilitating cell cycle progression. Thus, Pin1-mediated conformational changes in the C-terminal region of Sp1 are critical for increased CDK1-mediated Sp1 phosphorylation to facilitate cell cycle progression during mitosis. PMID:25398907

  5. Jumping the nuclear envelop barrier: Improving polyplex-mediated gene transfection efficiency by a selective CDK1 inhibitor RO-3306.

    Science.gov (United States)

    Zhou, Xuefei; Liu, Xiangrui; Zhao, Bingxiang; Liu, Xin; Zhu, Dingcheng; Qiu, Nasha; Zhou, Quan; Piao, Ying; Zhou, Zhuxian; Tang, Jianbin; Shen, Youqing

    2016-07-28

    Successful transfection of plasmid DNA (pDNA) requires intranuclear internalization of pDNA effectively and the nuclear envelope appears to be one of the critical intracellular barriers for polymer mediated pDNA delivery. Polyethylenimine (PEI), as the classic cationic polymer, compact the negatively charged pDNA tightly and make up stable polyplexes. The polyplexes are too large to enter the nuclear through nuclear pores and it is believed that the nuclear envelope breakdown in mitosis could facilitate the nuclear entry of polyplexes. To jump the nuclear envelope barrier, we used a selective and reversible CDK1 inhibitor RO-3306 to control the G2/M transition of the cell cycle and increased the proportion of mitotic cells which have disappeared nuclear envelope during transfection. Herein, we show that RO-3306 remarkably increases the transfection efficiency of PEI polyplexes through enhanced nuclear localization of PEI and pDNA. However, RO-3306 is less effective to the charge-reversal polymer poly[(2-acryloyl)ethyl(p-boronic acid benzyl)diethylammonium bromide] (B-PDEAEA) which responses to cellular stimuli and releases free pDNA in cytoplasm. Our findings not only offer new opportunities for improving non-viral based gene delivery but also provide theoretical support for the rational design of novel functional polymers for gene delivery. We also report current data showing that RO-3306 synergizes TRAIL gene induced apoptosis in cancer cells. PMID:27212103

  6. Regulation of the G1/S Transition in Hepatocytes: Involvement of the Cyclin-Dependent Kinase Cdk1 in the DNA Replication

    Directory of Open Access Journals (Sweden)

    Anne Corlu

    2012-01-01

    Full Text Available A singular feature of adult differentiated hepatocytes is their capacity to proliferate allowing liver regeneration. This review emphasizes the literature published over the last 20 years that established the most important pathways regulating the hepatocyte cell cycle. Our article also aimed at illustrating that many discoveries in this field benefited from the combined use of in vivo models of liver regeneration and in vitro models of primary cultures of human and rodent hepatocytes. Using these models, our laboratory has contributed to decipher the different steps of the progression into the G1 phase and the commitment to S phase of proliferating hepatocytes. We identified the mitogen dependent restriction point located at the two-thirds of the G1 phase and the concomitant expression and activation of both Cdk1 and Cdk2 at the G1/S transition. Furthermore, we demonstrated that these two Cdks contribute to the DNA replication. Finally, we provided strong evidences that Cdk1 expression and activation is correlated to extracellular matrix degradation upon stimulation by the pro-inflammatory cytokine TNFα leading to the identification of a new signaling pathway regulating Cdk1 expression at the G1/S transition. It also further confirms the well-orchestrated regulation of liver regeneration via multiple extracellular signals and pathways.

  7. Test Review: Constantino, J. N., & Gruber, C. P. (2012). "Social Responsiveness Scale-Second Edition" ("SRS-2"). Torrance, CA: Western Psychological Services

    Science.gov (United States)

    Bruni, Teryn P.

    2014-01-01

    This article reviews the Social Responsiveness Scale-Second Edition (SRS-2), a 65-item rating scale measuring deficits in social behavior associated with Autism Spectrum Disorder (ASD), as outlined by the "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.; "DSM-IV-TR"; American Psychiatric Association,…

  8. Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction

    DEFF Research Database (Denmark)

    Kolesar, Peter; Altmannova, Veronika; Silva, Sonia;

    2016-01-01

    -interacting motif (SIM) of Srs2 is important for the interaction with several recombination factors. Lack of SIM, but not proliferating cell nuclear antigen (PCNA)-interacting motif (PIM), leads to increased cell death under circumstances requiring homologous recombination for DNA repair. Simultaneous mutation of...

  9. The SRS2 suppressor of rad6 mutations of Saccharomyces cerevisiae acts by channeling DNA lesions into the RAD52 DNA repair pathway

    International Nuclear Information System (INIS)

    rad6 mutants of Saccharomyces cerevisiae are defective in the repair of damaged DNA, DNA damage induced mutagenesis, and sporulation. In order to identify genes that can substitute for RAD6 function, the authors have isolated genomic suppressors of the UV sensitivity of rad6 deletion (rad6Δ) mutations and show that they also suppress the γ-ray sensitivity but not the UV mutagenesis or sporulation defects of rad6. The suppressors show semidominance for suppression of UV sensitivity and dominance for suppression of γ-ray sensitivity. The six suppressor mutations they isolated are all alleles of the same locus and are also allelic to a previously described suppressor of the rad6-1 nonsense mutation, SRS2. They show that suppression of rad6Δ is dependent on the RAD52 recombinational repair pathway since suppression is not observed in the rad6Δ SRS2 strain containing an additional mutation in either the RAD51, RAD52, RAD54, RAD55 or RAD57 genes. Possible mechanisms by which SRS2 may channel unrepaired DNA lesions into the RAD52 DNA repair pathway are discussed

  10. Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

    Energy Technology Data Exchange (ETDEWEB)

    Velasquez, Celestino; Cheng, Erdong; Shuda, Masahiro; Lee-Oesterreich, Paula J.; Pogge von Strandmann, Lisa; Gritsenko, Marina A.; Jacobs, Jon M.; Moore, Patrick S.; Chang, Yuan

    2016-07-26

    mTOR-directed 4E-BP1 phosphorylation promotes cap-dependent translation and tumorigen-esis. During mitosis, CDK1 substitutes for mTOR and fully phosphorylates 4E-BP1 at canoni-cal as well a non-canonical S83 site resulting in a mitosis-specific hyperphosphorylated δ isoform. Colocalization studies with a phospho-S83 specific antibody indicate that 4E-BP1 S83 phosphorylation accumulates at centrosomes during prophase, peaks at metaphase, and decreases through telophase. While S83 phosphorylation of 4E-BP1 does not affect in vitro cap-dependent translation, nor eIF4G/4E-BP1 cap-binding, expression of an alanine substitution mutant 4E-BP1.S83A partially reverses rodent cell transformation induced by Merkel cell polyomavirus (MCV) small T (sT) antigen viral oncoprotein. In contrast to inhibitory mTOR 4E-BP1 phosphorylation, these findings suggest that mitotic CDK1-directed phosphorylation of δ-4E-BP1 may yield a gain-of-function, distinct from translation regulation, that may be important in tumorigenesis and mitotic centrosome function.

  11. Two new competing pathways establish the threshold for cyclin-B-Cdk1 activation at the meiotic G2/M transition.

    Science.gov (United States)

    Hiraoka, Daisaku; Aono, Ryota; Hanada, Shin-Ichiro; Okumura, Eiichi; Kishimoto, Takeo

    2016-08-15

    Extracellular ligands control biological phenomena. Cells distinguish physiological stimuli from weak noise stimuli by establishing a ligand-concentration threshold. Hormonal control of the meiotic G2/M transition in oocytes is essential for reproduction. However, the mechanism for threshold establishment is unclear. In starfish oocytes, maturation-inducing hormones activate the PI3K-Akt pathway through the Gβγ complex of heterotrimeric G-proteins. Akt directly phosphorylates both Cdc25 phosphatase and Myt1 kinase, resulting in activation of cyclin-B-Cdk1, which then induces meiotic G2/M transition. Here, we show that cyclin-B-Cdk1 is partially activated after subthreshold hormonal stimuli, but this triggers negative feedback, resulting in dephosphorylation of Akt sites on Cdc25 and Myt1, thereby canceling the signal. We also identified phosphatase activity towards Akt substrates that exists independent of stimuli. In contrast to these negative regulatory activities, an atypical Gβγ-dependent pathway enhances PI3K-Akt-dependent phosphorylation. Based on these findings, we propose a model for threshold establishment in which hormonal dose-dependent competition between these new pathways establishes a threshold; the atypical Gβγ-pathway becomes predominant over Cdk-dependent negative feedback when the stimulus exceeds this threshold. Our findings provide a regulatory connection between cell cycle and signal transduction machineries. PMID:27390173

  12. Germinal vesicle materials are requisite for male pronucleus formation but not for change in the activities of CDK1 and MAP kinase during maturation and fertilization of pig oocytes.

    Science.gov (United States)

    Ogushi, Sugako; Fulka, Josef; Miyano, Takashi

    2005-10-01

    In amphibian oocytes, it is known that germinal vesicle (GV) materials are essential for sperm head decondensation but not for activation of MPF (CDK1 and cyclin B). However, in large animals, the role of GV materials in maturation and fertilization is not defined. In this study, we prepared enucleated pig oocytes at the GV stage and cultured them to examine the activation and inactivation of CDK1 and MAP kinase during maturation and after electro-activation. Moreover, enucleated GV-oocytes after maturation culture were inseminated or injected intracytoplasmically with spermatozoa to examine their ability to decondense the sperm chromatin. Enucleated oocytes showed similar activation/inactivation patterns of CDK1 and MAP kinase as sham-operated oocytes during maturation and after electro-stimulation or intracytoplasmic sperm injection. During the time corresponding to MI/MII transition of sham-operated oocytes, enucleated oocytes inactivated CDK1. However, penetrating sperm heads in enucleated oocytes did not decondense enough to form male pronuclei. To determine whether the factor(s) involved in sperm head decondensation remains associated with the chromatin after GV breakdown (GVBD), we did enucleation soon after GVBD (corresponding to pro-metaphase I, pMI) to remove only chromosomes. The injected sperm heads in pMI-enucleated oocytes decondensed and formed the male pronuclei. These results suggest that in pig oocytes, GV materials are not required for activation/inactivation of CDK1 and MAP kinase, but they are essential for male pronucleus formation. PMID:16153631

  13. AZD5438, an Inhibitor of Cdk1, 2, and 9, Enhances the Radiosensitivity of Non-Small Cell Lung Carcinoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan, Pavithra; Tumati, Vasu; Yu Lan [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Chan, Norman [Departments of Medical Biophysics and Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario (Canada); Tomimatsu, Nozomi [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Burma, Sandeep [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Comprehensive Cancer Center, Dallas, Texas (United States); Bristow, Robert G. [Departments of Medical Biophysics and Radiation Oncology, Princess Margaret Hospital, University Health Network, University of Toronto, Ontario (Canada); Saha, Debabrata, E-mail: debabrata.saha@utsouthwestern.edu [Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas (United States); Simmons Comprehensive Cancer Center, Dallas, Texas (United States)

    2012-11-15

    Purpose: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT. Methods and Materials: The combined effect of ionizing radiation and AZD5438, a highly specific inhibitor of Cdk1, 2, and 9, was determined in vitro by surviving fraction, cell cycle distribution, apoptosis, DNA double-strand break (DSB) repair, and homologous recombination (HR) assays in 3 NSCLC cell lines (A549, H1299, and H460). For in vivo studies, human xenograft animal models in athymic nude mice were used. Results: Treatment of NSCLC cells with AZD5438 significantly augmented cellular radiosensitivity (dose enhancement ratio rangeing from 1.4 to 1.75). The degree of radiosensitization by AZD5438 was greater in radioresistant cell lines (A549 and H1299). Radiosensitivity was enhanced specifically through inhibition of Cdk1, prolonged G{sub 2}-M arrest, inhibition of HR, delayed DNA DSB repair, and increased apoptosis. Combined treatment with AZD5438 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7. Conclusions: This study supports the evaluation of newer generation Cdk inhibitors, such as AZD5438, as potent radiosensitizers in NSCLC models, especially in tumors that demonstrate variable intrinsic radiation responses.

  14. AZD5438, an Inhibitor of Cdk1, 2, and 9, Enhances the Radiosensitivity of Non-Small Cell Lung Carcinoma Cells

    International Nuclear Information System (INIS)

    Purpose: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT. Methods and Materials: The combined effect of ionizing radiation and AZD5438, a highly specific inhibitor of Cdk1, 2, and 9, was determined in vitro by surviving fraction, cell cycle distribution, apoptosis, DNA double-strand break (DSB) repair, and homologous recombination (HR) assays in 3 NSCLC cell lines (A549, H1299, and H460). For in vivo studies, human xenograft animal models in athymic nude mice were used. Results: Treatment of NSCLC cells with AZD5438 significantly augmented cellular radiosensitivity (dose enhancement ratio rangeing from 1.4 to 1.75). The degree of radiosensitization by AZD5438 was greater in radioresistant cell lines (A549 and H1299). Radiosensitivity was enhanced specifically through inhibition of Cdk1, prolonged G2-M arrest, inhibition of HR, delayed DNA DSB repair, and increased apoptosis. Combined treatment with AZD5438 and irradiation also enhanced tumor growth delay, with an enhancement factor ranging from 1.2-1.7. Conclusions: This study supports the evaluation of newer generation Cdk inhibitors, such as AZD5438, as potent radiosensitizers in NSCLC models, especially in tumors that demonstrate variable intrinsic radiation responses.

  15. Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma.

    Science.gov (United States)

    Lescarbeau, Rebecca S; Lei, Liang; Bakken, Katrina K; Sims, Peter A; Sarkaria, Jann N; Canoll, Peter; White, Forest M

    2016-06-01

    Glioblastoma (GBM) is the most common malignant primary brain cancer. With a median survival of about a year, new approaches to treating this disease are necessary. To identify signaling molecules regulating GBM progression in a genetically engineered murine model of proneural GBM, we quantified phosphotyrosine-mediated signaling using mass spectrometry. Oncogenic signals, including phosphorylated ERK MAPK, PI3K, and PDGFR, were found to be increased in the murine tumors relative to brain. Phosphorylation of CDK1 pY15, associated with the G2 arrest checkpoint, was identified as the most differentially phosphorylated site, with a 14-fold increase in phosphorylation in the tumors. To assess the role of this checkpoint as a potential therapeutic target, syngeneic primary cell lines derived from these tumors were treated with MK-1775, an inhibitor of Wee1, the kinase responsible for CDK1 Y15 phosphorylation. MK-1775 treatment led to mitotic catastrophe, as defined by increased DNA damage and cell death by apoptosis. To assess the extensibility of targeting Wee1/CDK1 in GBM, patient-derived xenograft (PDX) cell lines were also treated with MK-1775. Although the response was more heterogeneous, on-target Wee1 inhibition led to decreased CDK1 Y15 phosphorylation and increased DNA damage and apoptosis in each line. These results were also validated in vivo, where single-agent MK-1775 demonstrated an antitumor effect on a flank PDX tumor model, increasing mouse survival by 1.74-fold. This study highlights the ability of unbiased quantitative phosphoproteomics to reveal therapeutic targets in tumor models, and the potential for Wee1 inhibition as a treatment approach in preclinical models of GBM. Mol Cancer Ther; 15(6); 1332-43. ©2016 AACR. PMID:27196784

  16. In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Antony M Latham

    Full Text Available Protein kinases play a central role in tumor progression, regulating fundamental processes such as angiogenesis, proliferation and metastasis. Such enzymes are an increasingly important class of drug target with small molecule kinase inhibitors being a major focus in drug development. However, balancing drug specificity and efficacy is problematic with off-target effects and toxicity issues.We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2 and cyclin-dependent kinase 1 (CDK1. This compound acts by simultaneously inhibiting pro-angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A-mediated signaling response and CDK1-mediated mitotic entry elicits anti-angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis.We deduce that JK-31 reduces the growth of both human endothelial cells and human breast cancer cells in vitro. This novel synthetic molecule has broad implications for development of similar multi-kinase inhibitors with anti-angiogenic and anti-cancer properties. In silico design is an attractive and innovative method to aid such drug discovery.

  17. In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

    Science.gov (United States)

    van Dam, Peter A.; van Dam, Pieter-Jan H. H.; Rolfo, Christian; Giallombardo, Marco; van Berckelaer, Christophe; Trinh, Xuan Bich; Altintas, Sevilay; Huizing, Manon; Papadimitriou, Kostas; Tjalma, Wiebren A. A.; van Laere, Steven

    2016-01-01

    An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability. PMID:26701206

  18. CERN: Fixed target targets

    International Nuclear Information System (INIS)

    Full text: While the immediate priority of CERN's research programme is to exploit to the full the world's largest accelerator, the LEP electron-positron collider and its concomitant LEP200 energy upgrade (January, page 1), CERN is also mindful of its long tradition of diversified research. Away from LEP and preparations for the LHC proton-proton collider to be built above LEP in the same 27-kilometre tunnel, CERN is also preparing for a new generation of heavy ion experiments using a new source, providing heavier ions (April 1992, page 8), with first physics expected next year. CERN's smallest accelerator, the LEAR Low Energy Antiproton Ring continues to cover a wide range of research topics, and saw a record number of hours of operation in 1992. The new ISOLDE on-line isotope separator was inaugurated last year (July, page 5) and physics is already underway. The remaining effort concentrates around fixed target experiments at the SPS synchrotron, which formed the main thrust of CERN's research during the late 1970s. With the SPS and LEAR now approaching middle age, their research future was extensively studied last year. Broadly, a vigorous SPS programme looks assured until at least the end of 1995. Decisions for the longer term future of the West Experimental Area of the SPS will have to take into account the heavy demand for test beams from work towards experiments at big colliders, both at CERN and elsewhere. The North Experimental Area is the scene of larger experiments with longer lead times. Several more years of LEAR exploitation are already in the pipeline, but for the longer term, the ambitious Superlear project for a superconducting ring (January 1992, page 7) did not catch on. Neutrino physics has a long tradition at CERN, and this continues with the preparations for two major projects, the Chorus and Nomad experiments (November 1991, page 7), to start next year in the West Area. Delicate neutrino oscillation effects could become

  19. Sputter target

    Science.gov (United States)

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

  20. Target capture and target ghosts

    Science.gov (United States)

    Auerbach, Steven P.

    1996-05-01

    Optimal detection methods for small targets rely on whitened matched filters, which convolve the measured data with the signal model, and whiten the result with the noise covariance. In real-world implementations of such filters, the noise covariance must be estimated from the data, and the resulting covariance estimate may be corrupted by presence of the target. The resulting loss in SNR is called 'target capture'. Target capture is often thought to be a problem only for bright targets. This presentation shows that target capture also arises for dim targets, leading to an SNR loss which is independent of target strength and depends on the averaging method used to estimate the noise covariance. This loss is due to a 'coherent beat' between the true noise and that portion of the estimated noise covariance due to the target. This beat leads to 'ghost targets', which diminish the target SNR by producing a negative target ghost at the target's position. A quantitative estimate of this effect will be given, and shown to agree with numerical results. The effect of averaging on SNR is also discussed for data scenes with synthetic injected targets, in cases where the noise covariance is estimated using 'no target' data. For these cases, it is shown that the so-called 'optimal' filter, which uses the true noise covariance, is actually worse than a 'sub-optimal' filter which estimates the noise from scene. This apparent contradiction is resolved by showing that the optimal filter is best if the same filter is used for many scenes, but is outperformed by a filter adapted to a specific scene.

  1. The high-risk HPV E6 oncoprotein preferentially targets phosphorylated nuclear forms of hDlg

    International Nuclear Information System (INIS)

    High-risk mucosal HPV E6 oncoproteins target a number of PDZ domain-containing substrates for proteasome mediated degradation. One of these, Discs Large (Dlg), is involved in the regulation of cell polarity and proliferation control. Previous studies had suggested that Dlg when hyperphosphorylated by osmotic shock, or when present in the nucleus could be preferentially targeted by E6. In this study we use phospho-specific antibodies directed against Dlg phosphorylated at residues S158 and S442 to show that these two observations are, in fact, linked. Dlg, when phosphorylated on S158 and S442 by CDK1 or CDK2, shows a preferential nuclear accumulation. However, these forms of Dlg are absent in cells derived from HPV-induced cervical cancers. Upon either proteasome inhibition or siRNA ablation of E6 expression, we see specific rescue of these phosphorylated forms of Dlg. These results demonstrate that nuclear forms of Dlg phosphorylated on its CDK phospho-acceptor sites has enhanced susceptibility to E6-induced degradation and place previous studies on the stress-induced phosphorylation of Dlg into a relevant biological context.

  2. 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...

  3. Anomalous centriole configurations are detected in Drosophila wing disc cells upon Cdk1 inactivation

    OpenAIRE

    Vidwans, Smruti J.; Wong, Mei Lie; O'Farrell, Patrick H.

    2003-01-01

    The centriole, organizer of the centrosome, duplicates by assembling a unique daughter identical to itself in overall organization and length. The centriole is a cylindrical structure composed of nine sets of microtubules and is thus predicted to have nine-fold symmetry. During duplication, a daughter lacking discrete microtubular organization first appears off the wall of the mother centriole. It increases in length perpendicularly away from the mother and terminates growth when it matches t...

  4. Disjunction of conjoined twins: Cdk1, Cdh1 and separation of centrosomes

    Directory of Open Access Journals (Sweden)

    Surana Uttam

    2006-06-01

    Full Text Available Abstract Accurate transmission of chromosomes from parent to progeny cell requires assembly of a bipolar spindle. Centrosomes (spindle pole body in yeast are critical for the biogenesis of this complex mitotic apparatus since they confer bipolarity on the spindle and serve as the site of microtubule polymerization. In each division cycle, the centrosome is duplicated and the sister-centrosomes move away from each other, forming the two poles of the spindle. While the structure and the duplication of centrosomes have been investigated extensively, the understanding of the control of their segregation remains scant. Recent findings are beginning to yield insights into the regulation of centrosome segregation in yeast and its link to the mitotic kinase.

  5. 2,6,8,9-Tetrasubstituted Purines as New CDK1 Inhibitors

    Czech Academy of Sciences Publication Activity Database

    Moravec, Jiří; Kryštof, Vladimír; Hanuš, Jan; Havlíček, Libor; Moravcová, Daniela; Fuksová, K.; Kuzma, Marek; Lenobel, René; Otyepka, M.; Strnad, Miroslav

    2003-01-01

    Roč. 13, č. 18 (2003), s. 2993ů2996. ISSN 0960-894X R&D Projects: GA ČR GA301/02/0475; GA AV ČR KJB6137301 Institutional research plan: CEZ:AV0Z5020903; CEZ:AV0Z5038910 Keywords : Purine inhibitors * cyclin-dependent kinases * roscovitine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.182, year: 2003

  6. Phosphorylation-Dependent Targeting of Tetrahymena HP1 to Condensed Chromatin.

    Science.gov (United States)

    Yale, Katerina; Tackett, Alan J; Neuman, Monica; Bulley, Emily; Chait, Brian T; Wiley, Emily

    2016-01-01

    The evolutionarily conserved proteins related to heterochromatin protein 1 (HP1), originally described in Drosophila, are well known for their roles in heterochromatin assembly and gene silencing. Targeting of HP1 proteins to specific chromatin locales is mediated, at least in part, by the HP1 chromodomain, which binds to histone H3 methylated at lysine 9 that marks condensed regions of the genome. Mechanisms that regulate HP1 targeting are emerging from studies with yeast and metazoans and point to roles for posttranslational modifications. Here, we report that modifications of an HP1 homolog (Hhp1) in the ciliate model Tetrahymena thermophila correlated with the physiological state and with nuclear differentiation events involving the restructuring of chromatin. Results support the model in which Hhp1 chromodomain binds lysine 27-methylated histone H3, and we show that colocalization with this histone mark depends on phosphorylation at a single Cdc2/Cdk1 kinase site in the "hinge region" adjacent to the chromodomain. These findings help elucidate important functional roles of reversible posttranslational modifications of proteins in the HP1 family, in this case, regulating the targeting of a ciliate HP1 to chromatin regions marked with methylated H3 lysine 27. IMPORTANCE Compacting the genome to various degrees influences processes that use DNA as a template, such as gene transcription and replication. This project was aimed at learning more about the cellular mechanisms that control genome compaction. Posttranslational modifications of proteins involved in genome condensation are emerging as potentially important points of regulation. To help elucidate protein modifications and how they affect the function of condensation proteins, we investigated the phosphorylation of the chromatin protein called Hhp1 in the ciliated protozoan Tetrahymena thermophila. This is one of the first functional investigations of these modifications of a nonhistone chromatin

  7. 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

  8. Accelerator target

    Energy Technology Data Exchange (ETDEWEB)

    Schlyer, David J. (Bellport, NY); Ferrieri, Richard A. (Patchogue, NY); Koehler, Conrad (Miller Place, NY)

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  9. Analysis of Gene Targeting & Nonhomologous End-joining. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Haber, J. E.

    2002-11-30

    Overall, we identified a number of new proteins that participate in nonhomologous end-joining and also in telomere addition to the ends of broken chromosomes. We showed that NHEJ is severely reduced in cells expressing both yeast mating-type genes and then went on to identify the NEJ1 gene that was under this control. We showed the epistasis relations among a set of mutations that impair telomere addition and we showed that there are in fact two pathways to repair broken chromosomes in the absence of telomerase. We characterized the DNA damage checkpoint pathway in response to a single broken chromosome and characterized especially the adaptation of cells arrested by an unrepaired DSB. We demonstrated that the DNA damage response is nuclear-limited. We showed adaptation defects for Tid1and Srs2 proteins and showed that Srs2 was also recovery-defective, even when DNA was repaired.

  10. α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

    Science.gov (United States)

    Santha, Sreevidya; Dwivedi, Chandradhar

    2013-01-01

    This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis. PMID:23480292

  11. Target Awareness: Lupus

    Science.gov (United States)

    ... Target Awareness: Lupus Jan. 15, 2009 Target Awareness: Lupus Target Awareness: Lupus provides a brief overview of ... Email Print Tags for this Story treatments symptoms Lupus FAQ What is lupus? What are the common ...

  12. Target Awareness: Lupus

    Medline Plus

    Full Text Available ... Target Awareness: Lupus Jan. 15, 2009 Target Awareness: Lupus Target Awareness: Lupus provides a brief overview of ... Email Print Tags for this Story treatments symptoms Lupus FAQ What is lupus? What are the common ...

  13. Target factory in perspective

    International Nuclear Information System (INIS)

    A target factory diagram has been constructed for an analysis of the shell coating process system in relation to target production. The number of deposition units needed to achieve the coating requirements will be a major target production operating cost

  14. Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis

    International Nuclear Information System (INIS)

    Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin α and β subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin α and β subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer

  15. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

    OpenAIRE

    Jiang, Yindi; Hsieh, Jenny

    2014-01-01

    Cell cycle regulation is one of the most fundamental mechanisms to control various biological processes, including the proliferation of neural stem/progenitor cells (NSPCs) in adult mouse brain. This study shows that histone deacetylase 3 (HDAC3), a well-studied epigenetic factor, is required for the proliferation of neural stem cells. We also demonstrate that HDAC3 controls gap 2 and mitosis phase of cell cycle through stabilization of cell cycle protein cyclin-dependent kinase 1. These find...

  16. Effective neutron targets

    International Nuclear Information System (INIS)

    Because of the lack of a free neutron target, deuterium targets have been used extensively in studying the neutron structure. The unique spin structure of the 3He ground state wave function and the recent developments in laser technologies made polarized 3He targets widely used in many experiments from neutron electromagnetic form factor studies to nucleon spin structure function measurements at all major electron accelerator facilities. In this talk, the current status of the polarized 3He targets will be reviewed. The author will focus on neutron electromagnetic form factor studies using polarized 3He targets. The polarized nucleon spin structure function measurements using polarized 3He targets will also be discussed

  17. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

  18. Price level targeting

    OpenAIRE

    Shukayev, Malik; Ueberfeldt, Alexander

    2010-01-01

    Various papers have suggested that Price-Level targeting is a welfare improving policy relative to Inflation targeting. From a practical standpoint, this raises an important yet unanswered question: What is the optimal price index to target? This paper derives the optimal price level targeting index defined over the eight main components of the Consumer Price Index. It finds that such an index places a heavier weight, relative to the expenditure weight, on sectors with slow price adjustments....

  19. Multilayer polymer microspot targets

    International Nuclear Information System (INIS)

    Last year the authors reported on the development of a seeded microspot x-ray diagnostic target. This target consisted of a 300-μm-diam, 2-μm-thick disk of silicon or sulfur-seeded hydrocarbon polymer nested tightly in a hole in a 2-μm-thick film of pure hydrocarbon polymer. This year they extended our work on the microspot target, fully encapsulating the microspot in what they call the multilayer polymer microspot target

  20. Target Price Accuracy

    OpenAIRE

    Alexander G. Kerl

    2011-01-01

    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 positive...

  1. The Targeting of Advertising

    OpenAIRE

    Ganesh Iyer; David Soberman; J. Miguel Villas-Boas

    2005-01-01

    An important question that firms face in advertising is developing effective media strategy. Major improvements in the quality of consumer information and the growth of targeted media vehicles allow firms to precisely target advertising to consumer segments within a market. This paper examines advertising strategy when competing firms can target advertising to different groups of consumers within a market. With targeted advertising, we find that firms advertise more to consumers who have a st...

  2. TARGET COSTING FUNCTIONS

    OpenAIRE

    Dimi OFILEANU

    2015-01-01

    This article aims to highlight the concept of Target Costing. Based on the characteristics of Target Costing, identified in specialized literature, the article presents its main advantages and disadvantages. Also, a comparison is being made between Target Cost and Traditional Cost (in its traditional form, the cost represents an independent variable on the basis of which the sell price is established; and in the Target Cost form the cost represents a dependent variable which is determined on ...

  3. An actionable climate target

    Science.gov (United States)

    Geden, Oliver

    2016-05-01

    The Paris Agreement introduced three mitigation targets. In the future, the main focus should not be on temperature targets such as 2 or 1.5 °C, but on the target with the greatest potential to effectively guide policy: net zero emissions.

  4. Targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Neal Rosen; Carlos Arteaga

    2011-01-01

    With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted Cancer Therapies serias that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of Cancer.

  5. Polarized targets and beams

    International Nuclear Information System (INIS)

    First the experimental situation of the single-pion photoproduction and the photodisintegration of the deuteron is briefly discussed. Then a description of the Bonn polarization facilities is given. The point of main effort is put on the polarized target which plays a vital role in the program. A facility for photon induced double polarization experiments at ELSA will be presented in section 4. Properties of a tensor polarized deuteron target are discussed in section 5. The development in the field of polarized targets, especially on new target materials, enables a new generation of polarized target experiments with (polarized) electrons. Some comments on the use of a polarized target in combination with electron beams will be discussed in section 6. Electron deuteron scattering from a tensor polarized deuteron target is considered and compared with other experimental possibilities. (orig./HSI)

  6. GWAS and drug targets

    OpenAIRE

    Cao, Chen; Moult, John

    2014-01-01

    Background Genome wide association studies (GWAS) have revealed a large number of links between genome variation and complex disease. Among other benefits, it is expected that these insights will lead to new therapeutic strategies, particularly the identification of new drug targets. In this paper, we evaluate the power of GWAS studies to find drug targets by examining how many existing drug targets have been directly 'rediscovered' by this technique, and the extent to which GWAS results may ...

  7. Deuterium high pressure target

    International Nuclear Information System (INIS)

    The design of the deuterium high-pressure target is presented. The target having volume of 76 cm3 serves to provide the experimental research of muon catalyzed fusion reactions in ultra-pure deuterium in the temperature range 80-800 K under pressures of up to 150 MPa. The operation of the main systems of the target is described: generation and purification of deuterium gas, refrigeration, heating, evacuation, automated control system and data collection system

  8. 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.

  9. Deuterium High Pressure Target

    CERN Document Server

    Perevozchikov, V; Vinogradov, Yu I; Vikharev, M D; Ganchuk, N S; Golubkov, A N; Grishenchkin, S K; Demin, A M; Demin, D L; Zinov, V G; Kononenko, A A; Lobanov, V N; Malkov, I L; Yukhimchuk, S A

    2001-01-01

    The design of the deuterium high-pressure target is presented. The target having volume of 76 cm^3 serves to provide the experimental research of muon catalyzed fusion reactions in ultra-pure deuterium in the temperature range 80-800 K under pressures of up to 150 MPa. The operation of the main systems of the target is described: generation and purification of deuterium gas, refrigeration, heating, evacuation, automated control system and data collection system.

  10. 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.

  11. Moving Target Defense

    CERN Document Server

    Jajodia, Sushil; Swarup, Vipin; Wang, Cliff; Wang, X Sean

    2011-01-01

    Moving Target Defense: Creating Asymmetric Uncertainty for Cyber Threats was developed by a group of leading researchers. It describes the fundamental challenges facing the research community and identifies new promising solution paths. Moving Target Defense which is motivated by the asymmetric costs borne by cyber defenders takes an advantage afforded to attackers and reverses it to advantage defenders. Moving Target Defense is enabled by technical trends in recent years, including virtualization and workload migration on commodity systems, widespread and redundant network connectivity, instr

  12. 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.

  13. 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...

  14. 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.

  15. Bayesian multiple target tracking

    CERN Document Server

    Streit, Roy L

    2013-01-01

    This second edition has undergone substantial revision from the 1999 first edition, recognizing that a lot has changed in the multiple target tracking field. One of the most dramatic changes is in the widespread use of particle filters to implement nonlinear, non-Gaussian Bayesian trackers. This book views multiple target tracking as a Bayesian inference problem. Within this framework it develops the theory of single target tracking, multiple target tracking, and likelihood ratio detection and tracking. In addition to providing a detailed description of a basic particle filter that implements

  16. The Target Visitation Problem

    OpenAIRE

    Hildenbrandt, Achim

    2015-01-01

    The thesis considers the target visitation problem, a combinatorial optimization problem, which merges the classical traveling salesman problem with the linear ordering problem. In more detail, we are looking for a tour which visits a set of targets and which is optimal with respect to two different aspects: On the one hand, we have given a travel cost from each target to every other. On the other hand, we have preference values which tell us how much we would like to visit one target before ...

  17. 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 rand

  18. Pure HD polarized targets

    International Nuclear Information System (INIS)

    The HD polarized target project is now ready to use a target in a physics experiment. This must be done in early 1998 at LEGS (BNL). The IPN cryogenic group takes its part in this venture by doing the transfer and in-beam cryostats. (authors)

  19. 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.

  20. 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.

  1. AA antiproton production target

    CERN Multimedia

    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.

  2. Targeted therapies for cancer

    Science.gov (United States)

    ... to be untrue. Possible side effects from targeted therapies include: Diarrhea Liver problems Skin problems such as rash, dry skin, and nail changes Problems with blood clotting and wound healing High blood pressure As with any treatment, you ...

  3. SETI target selection.

    Science.gov (United States)

    Latham, D. W.; Soderblom, D. R.

    1995-06-01

    The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. The authors propose strategies for target selection with two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites.

  4. High pressure gas target

    Science.gov (United States)

    Gelbart, W.; Johnson, R. R.; Abeysekera, B.

    2012-12-01

    Compact, high pressure, high current gas target features all metal construction and semi-automatic window assembly change. The unique aspect of this target is the domed-shaped window. The Havar alloy window is electron beam welded to a metal ring, thus forming one, interchangeable assembly. The window assembly is sealed by knife-edges locked by a pneumatic toggle allowing a quick, in situ window change.

  5. 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.

  6. Radar target detection simulation

    Directory of Open Access Journals (Sweden)

    Tarig Ibrahim Osman

    2014-12-01

    Full Text Available Standard radar detection process requires that the sensor output is compared to a predetermined threshold. The threshold is selected based on a-priori knowledge available and/or certain assumptions. However, any knowledge and/or assumptions become in adequate due to the presence of multiple targets with varying signal return and usually non stationary background. Thus, any predetermined threshold may result in either increased false alarm rate or increased track loss. Even approaches where the threshold is adaptively varied will not perform well in situations when the signal return from the target of interest is too low compared to the average level of the background .Track-before-detect techniques eliminate the need for a detection threshold and provide detecting and tracking targets with lower signal-to-noise ratios than standard methods. However, although trackbefore-detect techniques eliminate the need for detection threshold at sensor's signal processing stage, they often use tuning thresholds at the output of the filtering stage .This paper presents a computerized simulation model for target detection process. Moreover, the proposed model method is based on the target motion models, the output of the detection process can easily be employed for maneuvering target tracking.

  7. 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.

  8. Targeted assets risk analysis.

    Science.gov (United States)

    Bouwsema, Barry

    2013-01-01

    Risk assessments utilising the consolidated risk assessment process as described by Public Safety Canada and the Centre for Security Science utilise the five threat categories of natural, human accidental, technological, human intentional and chemical, biological, radiological, nuclear or explosive (CBRNE). The categories of human intentional and CBRNE indicate intended actions against specific targets. It is therefore necessary to be able to identify which pieces of critical infrastructure represent the likely targets of individuals with malicious intent. Using the consolidated risk assessment process and the target capabilities list, coupled with the CARVER methodology and a security vulnerability analysis, it is possible to identify these targeted assets and their weaknesses. This process can help emergency managers to identify where resources should be allocated and funding spent. Targeted Assets Risk Analysis (TARA) presents a new opportunity to improve how risk is measured, monitored, managed and minimised through the four phases of emergency management, namely, prevention, preparation, response and recovery. To reduce risk throughout Canada, Defence Research and Development Canada is interested in researching the potential benefits of a comprehensive approach to risk assessment and management. The TARA provides a framework against which potential human intentional threats can be measured and quantified, thereby improving safety for all Canadians. PMID:23615063

  9. Production 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)

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  10. Inflation Forecast Targeting: Implementing and Monitoring Inflation Targets

    OpenAIRE

    Lars E.O. Svensson

    1996-01-01

    Inflation targeting is shown to imply inflation forecast targeting: the central bank's inflation forecast becomes an intermediate target. Inflation forecast targeting simplifies both implementing and monitoring of monetary policy. The inflation forecast is actually an ideal intermediate target: it is most correlated with the goal, easier to control than the goal, more observable than the goal, and very transparent. Money growth targeting generally leads to higher inflation variability than in...

  11. Setting reference targets

    International Nuclear Information System (INIS)

    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

  12. 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...

  13. Targeted Phototherapy (newer phototherapy

    Directory of Open Access Journals (Sweden)

    Zonunsanga

    2015-04-01

    Full Text Available Conventional phototherapy uses a whole body cabinet or body part machine such as hand, foot or scalp machines. They have many disadvantages due to which new phototherapy technique was then developed to overcome this situation. This new technique is called targeted phototherapy which includes excimer laser, intense pulse light system (IPL, photodynamic therapy and ultraviolet (UV light source with a sophisticated delivery system which is easy to be operated by hands. The mechanisms of action of targeted phototherapy systems are similar to those in conventional UVB/UVA therapy. They have many advantages like less chances of side effects, avoidance of exposure of unnecessary sites, faster response, shortening of the duration of treatments. But they have disadvantages like high costs and inability to use for extensive areas. This review article discusses targeted phototherapy in considerable to the mechanism of actions and advantages and disadvantages in comparison to the conventional phototherapy.

  14. Phoenix Color Targets

    Science.gov (United States)

    2008-01-01

    These images of three Phoenix color targets were taken on sols 1 and 2 by the Surface Stereo Imager (SSI) on board the Phoenix lander. The bottom target was imaged in approximate color (SSI's red, green, and blue filters: 600, 530, and 480 nanometers), while the others were imaged with an infrared filter (750 nanometers). All of them will be imaged many times over the mission to monitor the color calibration of the camera. The two at the top show grains 2 to 3 millimeters in size that were likely lifted to the Phoenix deck during landing. Each of the large color chips on each target contains a strong magnet to protect the interior material from Mars' magnetic dust. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  15. Targeted polypeptide degradation

    Science.gov (United States)

    Church, George M.; Janse, Daniel M.

    2008-05-13

    This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

  16. Fine target of deuterium

    International Nuclear Information System (INIS)

    A fine target of deuterium on a tantalum plate by the absorption method is obtained. In order to obtain the de gasification temperature an induction generator of high frequency is used and the deuterium pass is regulated by means of a palladium valve. Two vacuum measures are available, one to measure the high vacuum in the de gasification process of the tantalum plate and the other, for low vacuum, to measure the deuterium inlet in the installation and the deuterium pressure change in the installation after the absorption in the tantalum plate. A target of 48 μ gr/cm2 thick is obtained. (Author) 1 refs

  17. AA antiproton production target

    CERN Multimedia

    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.

  18. Major Targets for 2010

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ This year, the main targets we have set for economic and social development are: increasing GDP by approximately 8 percent, creating jobs for more than 9 million people, keeping the urban registered unemployment rate no higher than 4.6 percent, holding the rise in consumer prices to around 3 percent, and improving the balance of payments.

  19. 12. Target fabrication

    International Nuclear Information System (INIS)

    This series of papers presents the requirements and critical issues for IFE (inertial fusion energy) target fabrication and injection. The critical issues for target fabrication are: -) ability to fabricate target capsules and hohlraums, -) ability to fabricate them economically, and -) ability to fabricate, assemble, fill and layer at the required rate. Potential fabrication processes or methodologies include: micro-encapsulation (for foam shells and thick ablators), phase-inversion technique (for CH foams), super-fast cooling techniques, emulsion technique, injection molding (for higher density foam shells), sputter coating (for density high-Z coating), permeation (for DT filling) and cryogenic fluidized beds (for layering of individual capsules). The cooling-induced deformation (CID) of polystyrene shells is characterized in detail (2 papers). Another paper deals with the fabrication of hollow pellets with high Z metal oxide coating of the inner surface. In order to achieve high density compression in laser experiments, the non-contact suspension of pellets is required, Japanese teams propose 2 ways to get it: magnetic suspension and the use of electromagnetic force. The last paper summarizes the major steps in cost reduction that will be taken to economically supply targets for IFE power plants. (A.C.)

  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. 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...

  2. Enhanced target factor analysis.

    Science.gov (United States)

    Rostami, Akram; Abdollahi, Hamid; Maeder, Marcel

    2016-03-10

    Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets. PMID:26893084

  3. The targets of curcumin.

    Science.gov (United States)

    Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

    2011-03-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  4. Polarization discrimination between repeater false-target and radar target

    Institute of Scientific and Technical Information of China (English)

    SHI LongFei; WANG XueSong; XIAO ShunPing

    2009-01-01

    High fidelity repeater false-target badly affects a radar system's detecting, tracking, and data processing. It is an available approach of confronting false-target for radar that discriminates firstly and then eliminates. Whereas for the technique progress about the repeater false-target jam, it is more and more difficult to discriminate this jam in the time-domain, frequency-domain, or space-domain. The technique using polarization information to discriminate the target and false-target is discussed in this paper. With the difference that false-target signal vector's polarization ratio is fixed and target echo signal vector's polarization ratio is variational along with radar transmission signal's polarization, we transform the discrimination problem to beeline distinguish problem in the 2-dim complex space. The distributing characteristic expression of the false-target discrimination statistic is constructed, with which the discrimination ratio of false-target is analyzed. For the target case, the decomposed model of target scattering matrix and the concept of distinguish quantity are proposed. Then, the discrimination ratio of target can be forecasted according to target distinguish quantity. Thus, the performance of discrimination method has been analyzed integrally. The simulation results demonstrate the method in this paper is effective on the discrimination of target and false-target.

  5. Evolution with Drifting Targets

    CERN Document Server

    Kanade, Varun; Vaughan, Jennifer Wortman

    2010-01-01

    We consider the question of the stability of evolutionary algorithms to gradual changes, or drift, in the target concept. We define an algorithm to be resistant to drift if, for some inverse polynomial drift rate in the target function, it converges to accuracy 1 -- \\epsilon , with polynomial resources, and then stays within that accuracy indefinitely, except with probability \\epsilon , at any one time. We show that every evolution algorithm, in the sense of Valiant (2007; 2009), can be converted using the Correlational Query technique of Feldman (2008), into such a drift resistant algorithm. For certain evolutionary algorithms, such as for Boolean conjunctions, we give bounds on the rates of drift that they can resist. We develop some new evolution algorithms that are resistant to significant drift. In particular, we give an algorithm for evolving linear separators over the spherically symmetric distribution that is resistant to a drift rate of O(\\epsilon /n), and another algorithm over the more general prod...

  6. 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...

  7. Autonomous Target Ranging Techniques

    DEFF Research Database (Denmark)

    Jørgensen, Peter Siegbjørn; Jørgensen, John Leif; Denver, Troelz;

    2003-01-01

    determination two ranging strategies are presented. One is an improved laser ranger with an effective range with non-cooperative targets of at least 10,000 km, demonstrated in ground tests. The accuracy of the laser ranging will be approximately 1 m. The laser ranger may furthermore be used for trajectory...... determination of nano-gravity probes, which will perform direct mass measurements of selected targets. The other is triangulation from two spacecraft. For this method it is important to distinguish between detection and tracking range, which will be different for Bering since different instruments are used for......For the deep space asteroid mission, Bering, the main goal is the detection and tracking of near Earth objects (NEOs) and asteroids. One of the key science instruments is the 0.3-m telescope used for imaging and tracking of the detected asteroidal objects. For efficient use of the observation time...

  8. Careful price level targeting

    OpenAIRE

    Waters , George A.

    2012-01-01

    This paper examines a class of interest rate rules that respond to public expectations and to lagged variables. Varying levels of commitment correspond to varying degrees of response to lagged output and targeting of the price level. If the response rises (unintentionally) above the optimal level, the outcome deteriorates severely. Hence, the optimal level of commitment is sensitive to the method of expectations formation and partial commitment is the robust, optimal policy.

  9. Targeting fragile X

    OpenAIRE

    Gantois, Ilse; Kooy, R. Frank

    2002-01-01

    Ten years after the identification of the gene responsible for fragile X syndrome, recent studies have revealed a list of mRNAs bound by the fragile X gene product and have identified specific sequences required for the interaction between the fragile X protein and its targets. These results are a breakthrough in understanding why absence of the fragile X protein leads to mental retardation.

  10. 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...

  11. 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

  12. Low intensity beam target unit

    CERN Multimedia

    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.

  13. 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.

  14. Some Issues in Inflation Targeting

    OpenAIRE

    Andrew Haldane

    1997-01-01

    This paper discusses some of the operational issues relevant to the implementation of an inflation-targeting regime. In particular it focuses on: whether inflation targeting is 'new'; whether (and how) the forward-looking nature of inflation-targeting helps to prevent instabilities in inflation; whether inflation-targeting potentially destabilises output; and whether it requires too much knowledge on the part of the authorities. The paper argues that none of these propositions is in general c...

  15. Targeting of Antibodies using Aptamers

    OpenAIRE

    Missailidis, Sotiris

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  16. STRATEGIES (LEVELS) OF TARGET MARKET

    OpenAIRE

    Ramakrishna Mohan Rao Munaga

    2015-01-01

    Generally target marketing can be carried out in several different levels. They are Target-Market Strategies or Mass (Undifferentiated) Marketing: Choosing the Number of Markets to Target, Multi segment (Differentiated) Marketing, Concentrated Marketing or Niche Marketing, Micro Marketing or Single or Individual Marketing. Firms that compete in the global marketplace can use any combination of the segmenting strategies or none at all.

  17. After treat-to-target

    DEFF Research Database (Denmark)

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

    2012-01-01

    rheumatologists who 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...

  18. After treat-to-target

    DEFF Research Database (Denmark)

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

    2012-01-01

    rheumatologists who 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...

  19. Targets for heavy ion fusion

    International Nuclear Information System (INIS)

    This paper describes some of the basic principles of fusion target implosions, using some simple targets designed for irradiation by ion beams. Present estimates are that ion beams with 1-5 MJ, and 100-500 TW will be required to ignite high gain targets. (orig.)

  20. ORION laser target diagnostics

    International Nuclear Information System (INIS)

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  1. ORION laser target diagnosticsa)

    Science.gov (United States)

    Bentley, C. D.; Edwards, R. D.; Andrew, J. E.; James, S. F.; Gardner, M. D.; Comley, A. J.; Vaughan, K.; Horsfield, C. J.; Rubery, M. S.; Rothman, S. D.; Daykin, S.; Masoero, S. J.; Palmer, J. B.; Meadowcroft, A. L.; Williams, B. M.; Gumbrell, E. T.; Fyrth, J. D.; Brown, C. R. D.; Hill, M. P.; Oades, K.; Wright, M. J.; Hood, B. A.; Kemshall, P.

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics.

  2. ORION laser target diagnostics.

    Science.gov (United States)

    Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P

    2012-10-01

    The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics. PMID:23126904

  3. Hypoxia targeting copper complexes

    International Nuclear Information System (INIS)

    The importance and incidence of tumour hypoxia, its measurement and current treatments available, including pharmacological and radiopharmacological methods of targeting hypoxia, are discussed. A variety of in vitro and in vivo methods for imposing hypoxia have been developed and are reviewed. Copper, its chemistry, biochemistry and radiochemistry, the potential for use of copper radionuclides and its use to date in this field is considered with particular reference to the thiosemicarbazones. Their biological activity, metal chelation, in vitro and in vivo studies of their radiocopper complexes and the potential for their use as hypoxia targeting radiopharmaceuticals is described. The reduction of the copper(II) complex to copper(l), its pivotal importance in their biological behaviour, and the potential for manipulation of this to effect hypoxia selectivity are described. An in vitro method for assessing the hypoxia selectivity of radiopharmaceuticals is reported. The rapid deoxygenation and high viability of a mammalian cell culture in this system is discussed and factors which may affect the cellular uptake of a radiopharmaceutical are described. The design, synthesis and complexation with copper and radiocopper of a range of bis(thiosemicarbazones) is reported. Synthesis of these compounds is simple giving high yields of pure products. The characteristics of the radiocopper complexes (64Cu) including lipophilicity and redox activity are reported (reduction potentials in the range -0.314 - -0.590 V). High cellular uptakes of the radiocopper complexes of the ligands, in hypoxic and normoxic EMT6 and CHO320 cells, were observed. Extremes of selectivity are shown ranging from the hypoxia selective 64Cu(II)ATSM to normoxic cell selective 64Cu(II)GTS. The selectivities observed are compared with the physico chemical characteristics of the complexes. A good correlation exists between selectivity of the complex and its Cu(II)/Cu(I) reduction potential, with hypoxia

  4. Hypoxia targeting copper complexes

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, J.L

    1998-11-01

    The importance and incidence of tumour hypoxia, its measurement and current treatments available, including pharmacological and radiopharmacological methods of targeting hypoxia, are discussed. A variety of in vitro and in vivo methods for imposing hypoxia have been developed and are reviewed. Copper, its chemistry, biochemistry and radiochemistry, the potential for use of copper radionuclides and its use to date in this field is considered with particular reference to the thiosemicarbazones. Their biological activity, metal chelation, in vitro and in vivo studies of their radiocopper complexes and the potential for their use as hypoxia targeting radiopharmaceuticals is described. The reduction of the copper(II) complex to copper(l), its pivotal importance in their biological behaviour, and the potential for manipulation of this to effect hypoxia selectivity are described. An in vitro method for assessing the hypoxia selectivity of radiopharmaceuticals is reported. The rapid deoxygenation and high viability of a mammalian cell culture in this system is discussed and factors which may affect the cellular uptake of a radiopharmaceutical are described. The design, synthesis and complexation with copper and radiocopper of a range of bis(thiosemicarbazones) is reported. Synthesis of these compounds is simple giving high yields of pure products. The characteristics of the radiocopper complexes ({sup 64}Cu) including lipophilicity and redox activity are reported (reduction potentials in the range -0.314 - -0.590 V). High cellular uptakes of the radiocopper complexes of the ligands, in hypoxic and normoxic EMT6 and CHO320 cells, were observed. Extremes of selectivity are shown ranging from the hypoxia selective {sup 64}Cu(II)ATSM to normoxic cell selective {sup 64}Cu(II)GTS. The selectivities observed are compared with the physico chemical characteristics of the complexes. A good correlation exists between selectivity of the complex and its Cu(II)/Cu(I) reduction potential

  5. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  6. Magnetic targeted drug delivery

    Directory of Open Access Journals (Sweden)

    Timothy Wiedmann

    2009-10-01

    Full Text Available Lung cancer is the most common cause of death from cancer in both men and women. Treatment by intravenous or oral administration of chemotherapy agents results in serious and often treatment-limiting side effects. Delivery of drugs directly to the lung by inhalation of an aerosol holds the promise of achieving a higher concentration in the lung with lower blood levels. To further enhance the selective lung deposition, it may be possible to target deposition by using external magnetic fields to direct the delivery of drug coupled to magnetic particles. Moreover, alternating magnetic fields can be used to induce particle heating, which in turn controls the drug release rate with the appropriate thermal sensitive material.With this goal, superparamagetic nanoparticles (SPNP were prepared and characterized, and enhanced magnetic deposition was demonstrated in vitro and in vivo. SPNPs were also incorporated into a lipid-based/SPNP aerosol formulation, and drug release was shown to be controlled by thermal activation. Because of the inherent imaging potential of SPNPs, this use of nanotechnology offers the possibility of coupling the diagnosis of lung cancer to drug release, which perhaps will ultimately provide the “magic bullet” that Paul Ehrlich originally sought.

  7. ICF target positioning robot system

    International Nuclear Information System (INIS)

    Based on the function analysis of target positioner for inertial confinement fusion, a kind of ICF target positioning robot system is designed to realize the adjustment and the alignment of a target. The robot system includes a target storage sub-system, a target exchange subsystem, a target transport subsystem and a 6-degree of freedom precision parallel robot subsystem, the structure and principle of every subsystem are dissertated. The system realizes micro scale position by parallel structure which is in the front of the system, and has the advantages of low mass, high stiffness, small cone angle, small volume and high precision. The robot system can position a target into a very small micro scale scope around the center of the target chamber whose diameter is several meters, the precision of the position reaches micro scale. Motion parameter of the positioning robot system has been tested. Experiment proves that the robot system has realized precision target position and target exchange on the condition of vacuum. (authors)

  8. Windowless target: Design of the XT-ADS spallation target

    International Nuclear Information System (INIS)

    The design of the XT-ADS spallation target is performed within the European integrated project EUROTRANS (FP6 Contract FI6W-516520) that has started in April 2005. At the current status of the spallation target design process, the boundary conditions for the spallation target loop with respect to the XT-ADS performance requirements and the design of the subcritical core and primary system have been established. The next steps will concentrate on further development of the spallation target nozzle, the vacuum and spallation product confinement system and the pumping, LIDAR (LIght Detection And Ranging) and cooling system

  9. Facility target insert shielding assessment

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michal [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  10. 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...

  11. The OLYMPUS Internal Hydrogen Target

    CERN Document Server

    Bernauer, J C; Ciullo, G; Henderson, B S; Ihloff, E; Kelsey, J; Lenisa, P; Milner, R; Schmidt, A; Statera, M

    2014-01-01

    An internal hydrogen target system was developed for the OLYMPUS experiment at DESY, in Hamburg, Germany. The target consisted of a long, thin-walled, tubular cell within an aluminum scattering chamber. Hydrogen entered at the center of the cell and exited through the ends, where it was removed from the beamline by a multistage pumping system. A cryogenic coldhead cooled the target cell to counteract heating from the beam and increase the density of hydrogen in the target. A fixed collimator protected the cell from synchrotron radiation and the beam halo. A series of wakefield suppressors reduced heating from beam wakefields. The target system was installed within the DORIS storage ring and was successfully operated during the course of the OLYMPUS experiment in 2012. Information on the design, fabrication, and performance of the target system is reported.

  12. Target support for inertial confinement fusion

    International Nuclear Information System (INIS)

    General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF)

  13. Target properties and nuclear data

    International Nuclear Information System (INIS)

    The influence of the properties of the target on nuclear data was shown. In the case of targets consisting of fissionable material, this influence was demonstrated in experiments involving fission cross-section, average number of neutrons, and prompt fission neutron spectrum. The experimental methods for determining certain corrections were analysed. The method of tritium density determination for a solid target used as neutron source was likewise demonstrated. (author). 10 refs, 4 figs

  14. 'Inflation Targeting and Inflation Persistence'

    OpenAIRE

    George J. Bratsiotis; Jakob Madsen; Christopher Martin

    2015-01-01

    This paper argues that the adoption of an inflation target reduces the persistence of inflation. We develop the theoretical literature on inflation persistence by introducing a Taylor rule for monetary policy into a model of persistence and showing that inflation targets reduce inflation persistence. We investigate changes in the time series properties of inflation in seven countries that introduced inflation targets in the late 1980s or early 1990s. We find that the persistenc...

  15. Learning About Intervention Target Zones

    OpenAIRE

    Michael W. Klein; Karen K. Lewis

    1991-01-01

    This paper provides a framework for evaluating how market participants' beliefs about foreign exchange target zones change as they learn about central bank intervention policy. In order to examine this behavior, we first generalize the standard target zone model to allow for intra-marginal intervention. Intra-marginal intervention implies that the position of market participants' beliefs about the target zone can be determined from their beliefs about the likelihood of intervention. As an app...

  16. Target repurposing for neglected diseases

    OpenAIRE

    Pollastri, Michael P.; Campbell, Robert K.

    2011-01-01

    Infectious diseases are an enormous burden to global health and since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug-discovery efforts. Therefore, pragmatic means by which new therapeutics can be discovered are needed. One such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. In many cases, the medicinal...

  17. Targeting Nominal Income: A Note

    OpenAIRE

    Kenneth D. West

    1986-01-01

    This paper compares nominal income and monetary targets in a standard aggregate demand - aggregate supply framework. If the desirability of policies is measured by their effect on the unconditional variance of output, nominal income targeting is preferable if and only if the aggregate elasticity of demand for real balances is greater than one. This is precisely the opposite of the condition that in Bean (1984) is sufficient to make nominal income targeting preferable.This points out the impor...

  18. Nominal Income and Inflation Targeting

    OpenAIRE

    Arayssi, Mahmoud

    2014-01-01

    In this paper a macro- economic model in the area of monetary policy game theory is extended to one-sided dismissal rules concerning observed nominal output and inflation targets for the central banker. These rules specify firing the central banker if some observed policy targets have been exceeded. Such rules are shown to reduce inflationary bias if the central banker perceives her reappointment chances as being strong and is preferred to discretionary monetary policy. Various policy targets...

  19. The Bering Target Tracking Instrumentation

    OpenAIRE

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

    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...

  20. Inertial-confinement-fusion targets

    International Nuclear Information System (INIS)

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques have been 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

  1. Limits of Inflation Targeting Strategy

    Directory of Open Access Journals (Sweden)

    Aura Niculescu

    2006-03-01

    Full Text Available This paper evaluates the trade-off between output volatility and the variability of the inflation rate around its target (Romanian case. The optimal choice for National Bank of Romania (NBR, in our opinion, is the flexible inflation targeting. For this purpose, NBR must explain the loss function and the optimal monetary policy rule. We then argued that this Romanian authority – NBR – can substantially improve its credibility under inflation targeting policy regime by becoming more accountable and transparent. Is the direct inflation targeting the best choice for the monetary policy regime in Romanian economy?

  2. Targeted Therapies for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  3. The Bering Target Tracking Instrumentation

    DEFF Research Database (Denmark)

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

    2003-01-01

    '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 is...... inside the telescope FOV. During the telescope observation time, the ASC will constantly control the folding mirror to correctly position the target at the center of the telescope, basically performing a standard telescope tracking service. The telescope will alter the initial target acquisition track...

  4. Therapeutic Targeting of Telomerase.

    Science.gov (United States)

    Jäger, Kathrin; Walter, Michael

    2016-01-01

    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 methods, and

  5. Therapeutic Targeting of Telomerase

    Science.gov (United States)

    Jäger, Kathrin; Walter, Michael

    2016-01-01

    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 methods, and

  6. 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

  7. A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint

    DEFF Research Database (Denmark)

    van Vugt, Marcel A T M; Gardino, Alexandra K; Linding, Rune; Ostheimer, Gerard J; Reinhardt, H Christian; Ong, Shao-En; Tan, Chris S; Miao, Hua; Keezer, Susan M; Li, Jeijin; Pawson, Tony; Lewis, Timothy A; Carr, Steven A; Smerdon, Stephen J; Brummelkamp, Thijn R; Yaffe, Michael B

    2010-01-01

    DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair. The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance. While activation of DNA damage checkpoints has been studied extensively, molecular...

  8. Radiopharmaceuticals targeting melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Pham, T.Q.; Berghofer, P.; Liu, X.; Greguric, I.; Dikic, B.; Ballantyne, P.; Mattner, F.; Nguyen, V.; Loc' h, C.; Katsifis, A. [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Menai, N.S.W., Sydney (Australia)

    2008-02-15

    Melanoma is one of the most aggressive cancers known with a high rate of mortality and increasing global incidence. So, the development of radiopharmaceuticals for either diagnostic or therapeutic purposes could make enormous contributions to melanoma patient health care. We have been studying melanoma tumours through several targeting mechanisms including melanin or specific receptor based radiopharmaceuticals Structure activity studies indicate that the substitution patterns on radioiodinated benzamides significantly influence the uptake mechanism from melanin to sigma-receptor binding. Furthermore, the position of the iodine as well as the presence of key functional groups and substituents has resulted in compounds with varying degrees of activity uptake and retention in tumours. From these results, a novel molecule 2-(2-(4-(4-iodo benzyl)piperazin-1-yl)-2-oxo-ethyl)isoindoline- 1,3-dione (M.E.L.037) was synthesized, labelled with iodine-123 and evaluated for application in melanoma tumour scintigraphy and radiotherapy. The tumour imaging potential of {sup 123}IM.E.L.037 was studied in vivo in C.57 B.L./ 6 J female mice bearing the B.16 F.0. murine melanoma tumour and in BALB/c nude mice bearing the A.375 human amelanotic melanoma tumour by biodistribution, competition studies and by SPECT imaging. {sup 123}I-M.E.L.037 exhibited high and rapid uptake in the B.16 F.0 melanoma tumour at 1 h (13 % I.D./g) increasing with time to reach 25 % I.D./g at 6 h. A significant uptake was also observed in the eyes (2% I.D., at 3-6 h p.i.) of black mice. No uptake was observed in the tumour or in the eyes of nude mice bearing the A.375 tumour. Due to high uptake and long retention in the tumour and rapid body clearance, standardized uptake values(S.U.V.) of {sup 123}I-M.E.L.037 were 30 and 60, at 24 and 48 h p.i.,respectively. SPECT imaging of mice bearing the B.16 melanoma indicated the radioactivity was predominately located in the tumour followed by the eyes, while no

  9. LAMPF polarized 13C targets

    International Nuclear Information System (INIS)

    Ethylene glycol, 1-butanol, and toluene highly enriched in 13C have been used at LAMPF to produce dynamically polarized 13C targets for scattering experiments with protons and pions. Preparation of the materials and characteristic properties of these targets are described. 17 refs., 1 fig

  10. High performance inertial fusion targets

    International Nuclear Information System (INIS)

    Inertial confinement fusion (ICF) target designs are considered which may have very high gains (approximately 1000) and low power requirements (< 100 TW) for input energies of approximately one megajoule. These include targets having very low density shells, ultra thin shells, central ignitors, magnetic insulation, and non-ablative acceleration

  11. 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...

  12. 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...

  13. Targeted anti-cancerous therapies

    International Nuclear Information System (INIS)

    Crowning decades of efforts in fundamental and applied research, the first generation of targeted anti cancerous drugs is now on the market. Drugs coming from a new approach, conceived from molecular knowledge of cancer and directed against beforehand identified targets. In theory: a miracle of precision and technical success. In practice: a new sources of questions and new problems. (N.C.)

  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. High-Purity Chromium Targets

    OpenAIRE

    Rudoy, A.; Milman, Yu.; Korzhova, N.

    1995-01-01

    A procedure for producing large-scale chromium ingots by means of induction-arc melting was developed. From the high-purity, low-alloyed chromium ingots obtained, chromium targets were produced by of thermoplastic treatment techniques. The method of electron-beam evaporation of high-purity chromium was also used for production of targets.

  16. Nominal GDP: Target or Benchmark?

    OpenAIRE

    Hetzel, Robert L.

    2015-01-01

    Some observers have argued that the Federal Reserve would best fulfill its mandate by adopting a target for nominal gross domestic product (GDP). Insights from the monetarist tradition suggest that nominal GDP targeting could be destabilizing. However, adopting benchmarks for both nominal and real GDP could offer useful information about when monetary policy is too tight or too loose.

  17. Target recognition by wavelet transform

    International Nuclear Information System (INIS)

    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

  18. 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.

  19. The proteome targets of intracellular targeting antimicrobial peptides.

    Science.gov (United States)

    Shah, Pramod; Hsiao, Felix Shih-Hsiang; Ho, Yu-Hsuan; Chen, Chien-Sheng

    2016-04-01

    Antimicrobial peptides have been considered well-deserving candidates to fight the battle against microorganisms due to their broad-spectrum antimicrobial activities. Several studies have suggested that membrane disruption is the basic mechanism of AMPs that leads to killing or inhibiting microorganisms. Also, AMPs have been reported to interact with macromolecules inside the microbial cells such as nucleic acids (DNA/RNA), protein synthesis, essential enzymes, membrane septum formation and cell wall synthesis. Proteins are associated with many intracellular mechanisms of cells, thus protein targets may be specifically involved in mechanisms of action of AMPs. AMPs like pyrrhocoricin, drosocin, apidecin and Bac 7 are documented to have protein targets, DnaK and GroEL. Moreover, the intracellular targeting AMPs are reported to influence more than one protein targets inside the cell, suggesting for the multiple modes of actions. This complex mechanism of intracellular targeting AMPs makes them more difficult for the development of resistance. Herein, we have summarized the current status of AMPs in terms of their mode of actions, entry to cytoplasm and inhibition of macromolecules. To reveal the mechanism of action, we have focused on AMPs with intracellular protein targets. We have also included the use of high-throughput proteome microarray to determine the unidentified AMP protein targets in this review. PMID:26648572

  20. Oxide fiber targets at ISOLDE

    DEFF Research Database (Denmark)

    Köster, U.; Bergmann, U.C.; Carminati, D.; Catherall, R.; Cederkäll, J.; Correia, J.G.; Crepieux, B.; Dietrich, M.; Elder, K.; Fedoseyev, V.N.; Fraile, L.; Franchoo, S.; Fynbo, Hans Otto Uldall; Georg, U.; Giles, T.; Joinet, A.; Jonsson, Olle; Lau, Ch.; Lettry, J.; Oinonen, M.; Peräjärvi, K.; Ravn, H.L.; Rinaldi, T.; Santana-Leitner, M.; Weissman, L.; Mishin, V.I.; Kirchner, R.; Maier, H.J.; Wahl, U.; Rinaldi Barkat, Tania

    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...

  1. Target-Searching on Percolation

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    We study target-searching processes on a percolation, on which a hunter tracks a target by smelling odors it emits. The odor intensity is supposed to be inversely proportional to the distance it propagates. The Monte Carlo simulation is performed on a 2-dimensional bond-percolation above the threshold. Having no idea of the location of the target, the hunter determines its moves only by random attempts in each direction. For lager percolation connectivity p (>~) 0.90, it reveals a scaling law for the searching time versus the distance to the position of the target. The scaling exponent is dependent on the sensitivity of the hunter. For smaller p, the scaling law is broken and the probability of finding out the target significantly reduces. The hunter seems trapped in the cluster of the percolation and can hardly reach the goal.

  2. Target animacy influences gorilla handedness.

    Science.gov (United States)

    Forrester, Gillian S; Leavens, David A; Quaresmini, Caterina; Vallortigara, Giorgio

    2011-11-01

    We investigated the unimanual actions of a biological family group of twelve western lowland gorillas (Gorilla gorilla gorilla) using a methodological approach designed to assess behavior within social context from a bottom-up perspective. Measures of both the lateralization of unimanual actions (left, right) and the target of the action (animate, inanimate) were assessed during dual, synchronized video observations of naturalistic behavior. This paper demonstrates a corelationship between handedness and the animate quality of the target object. Analyses demonstrated a significant interaction between lateralized unimanual actions and target animacy and a right-hand bias for actions directed toward inanimate targets. We suggest that lateralized motor preference reflects the different processing capabilities of the left and right hemispheres, as influenced by the emotive (animate) and/or functional (inanimate) characteristics of the target, respectively. PMID:21562817

  3. Preparation of thin nuclear targets

    International Nuclear Information System (INIS)

    Thin film backings, sources and targets are needed for many applications in low energy nuclear physics and nuclear chemistry experiments. A survey of techniques used in the preparation of nuclear targets is first briefly discussed. These are classified as chemical, mechanical and physical preparations. Vacuum evaporation, being the most generally used technique, is discussed in detail. It is highly desirable to monitor the film thickness and control the deposition rate during evaporation and to measure the final target thickness after deposition has concluded. The relative merits of various thickness measuring techniques are described. Stages in the fabrication and mounting of self-supporting foils are described in detail, with emphasis given to the preparation of thin self-supporting carbon foils used as target backings and stripper foils. Various target backings, and the merits of the more generally used release agents are described in detail. The preparations of more difficult elemental targets are discussed, and a comprehensive list of the common targets is presented

  4. 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...

  5. Mycothiol: a promising antitubercular target.

    Science.gov (United States)

    Nilewar, S S; Kathiravan, M K

    2014-02-01

    Tuberculosis (TB) is the world's second commonest cause of death next to HIV/AIDS. The increasing emergence of multi drug resistance and the recalcitrant nature of persistent infections pose an additional challenge for the treatment of TB. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. One such target is Mycothiol (MSH), a major low molecular-mass thiol in mycobacteria, an important cellular anti-oxidant. MSH is present only in actinomycetes and hence is a good target. This review explores mycothiol as a potential target against tuberculosis and various research ongoing worldwide. PMID:24368170

  6. Development of targeted radiotherapy systems

    International Nuclear Information System (INIS)

    Conventional or external beam radiotherapy, has been a viable alternative for cancer treatment. Although this technique is effective, its use is limited if the patient has multiple malignant lesions (metastases). An alternative approach is based on the design of radiopharmaceuticals that, to be administered in the patient, are directed specifically toward the target cell producing a selective radiation delivery. This treatment is known as targeted radiotherapy. We have summarized and discussed some results related to our investigations on the development of targeted radiotherapy systems, including aspects of internal dosimetry

  7. Targeted therapy: tailoring cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Min Yan; Quentin Qiang Liu

    2013-01-01

    Targeted therapies include small-molecule inhibitors and monoclonal antibodies,have made treatment more tumor-specific and less toxic,and have opened new possibilities for tailoring cancer treatment.Nevertheless,there remain several challenges to targeted therapies,including molecular identification,drug resistance,and exploring reliable biomarkers.Here,we present several selected signaling pathways and molecular targets involved in human cancers including Aurora kinases,PI3K/mTOR signaling,FOXO-FOXM1 axis,and MDM2/MDM4-p53 interaction.Understanding the molecular mechanisms for tumorigenesis and development of drug resistance will provide new insights into drug discovery and design of therapeutic strategies for targeted therapies.

  8. Heavy flavors at fixed target

    International Nuclear Information System (INIS)

    The current situation of Heavy Flavor physics at fixed target experiments is reviewed. High statistics charm production and decay data are summarized and new results on beauty physics are presented. (author)

  9. 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...

  10. Special hydrogen target (Prop. 210)

    International Nuclear Information System (INIS)

    This guide contains a description of the electrical control and automatic vacuum systems for the Special Hydrogen Target (Prop. 210) together with the flow diagram and the mimic control panel layout for the system. (U.K.)

  11. Inertial-confinement-fusion targets

    International Nuclear Information System (INIS)

    Much of the research in laser fusion has been done using simple ball on-stalk targets filled with a deuterium-tritium mixture. The targets operated in the exploding pusher mode in which the laser energy was delivered in a very short time (approx. 100 ps or less) and was absorbed by the glass wall of the target. The high energy density in the glass literally exploded the shell with the inward moving glass compressing the DT fuel to high temperatures and moderate densities. Temperatures achieved were high enough to produce DT reactions and accompanying thermonuclear neutrons and alpha particles. The primary criteria imposed on the target builders were: (1) wall thickness, (2) sphere diameter, and (3) fuel in the sphere

  12. IUCF liquid hydrogen target system

    International Nuclear Information System (INIS)

    A liquid hydrogen or deuterium target system is described for use with intermediate energy light ion beams at IUCF. In its present use as a production target for polarized neutrons, the target cell is mounted within the beamline. Thus, certain safety features are required which prevent a possible hydrogen explosion inside the beamline or the cyclotron. These safety devices include an acoustical delay line which slows the hydrogen gas shock wave and a fast valve which closes before any large volume of escaping gas reaches it. Other safety interlocks to reduce the chances of target cell breakage and to quickly shut off ignition sources are discussed. A device involving a variable heat load which is coupled directly to the cryocondenser and is used to continually monitor and stabilize the pressure and temperature of the liquid hydrogen is described here

  13. 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

  14. National Ignition Facility Target Chamber

    International Nuclear Information System (INIS)

    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 was

  15. Targeting cancer with peptide aptamers

    OpenAIRE

    Seigneuric, Renaud; Gobbo, Jessica; Colas, Pierre; Garrido, Carmen

    2011-01-01

    A major endeavour in cancer chemotherapy is to develop agents that specifically target a biomolecule of interest. There are two main classes of targeting agents: small molecules and biologics. Among biologics (e.g.: antibodies), DNA, RNA but also peptide aptamers are relatively recent agents. Peptide aptamers are seldom described but represent attractive agents that can inhibit a growing panel of oncotargets including Heat Shock Proteins. Potential pitfalls and coming challenges towards succe...

  16. Proactive Steering Toward Oriented Targets

    OpenAIRE

    Boulic, R

    2005-01-01

    In this paper we introduce a real-time steering controller ensuring the reach of a (possible mobile) target position and orientation, without requiring to build/update the full trajectory to that target. We name it the funnelling control. The final orientation is achieved through the continuous adjustment of the heading direction. This control mode is proactive in the sense that it anticipates the success/failure of the reach and adjusts the desired speed accordingly. Both features rely on an...

  17. Plug Off: Target Group Perception

    OpenAIRE

    Kortbaek, Allan; Neubauer, Nathalie; Carreras, Barbara

    2012-01-01

    This project is a study of how a sample of defined target group of a campaign, build meaning through their introduction to such a campaign. With ethno-methodology as a focal point within the overlying context of discourse psychology and more importantly, social constructivism, the aim is to analyze how a defined target group make sense of a proto awareness raising campaign. Proto in this case denotes a planned communication effort in the form of a campaign encouraging responsible use of wirel...

  18. A Theory of Child Targeting

    OpenAIRE

    Donni, Olivier; Bargain, Olivier

    2007-01-01

    There is a large empirical literature on policy measures targeted at children but surprisingly very little theoretical foundation to ground the debate on the optimality of the different instruments. In the present paper, we examine the merit of targeting children through two general policies, namely selective commodity taxation and cash transfer to family with children. We consider a household that comprises an adult and a child. The household behavior is described by the ma...

  19. 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....

  20. Twenty years of inflation targeting

    OpenAIRE

    David Baqaee; Christie Smith

    2010-01-01

    In December 2009 the Reserve Bank of New Zealand, in conjunction with Northwestern University’s Centre for International Economics and Development (CIED), hosted a monetary policy conference to mark the 20th anniversary of the Reserve Bank of New Zealand Act. Passed in December 1989, the Act was one of the seminal events in the development of inflation targeting as a monetary policy regime. As of 2009, 26 countries have explicitly adopted inflation targeting, including Canada, the UK, Austral...

  1. Inflation Targeting in Latin America

    OpenAIRE

    Vittorio Corbo; Klaus Schmidt-Hebbel

    2002-01-01

    This paper analyzes Latin America’s recent experience with the use of inflation targeting (IT) while the region has made substantial progress toward eradicating high inflation. The paper assesses the implementation and results of inflation targeting in Latin America from a broad perspective. It starts by reviewing the issues relevant for the choice of exchange-rate regimes and monetary frameworks, documenting the evolution of exchange rate and monetary regimes in Latin America during the last...

  2. Polarized atomic beams for targets

    International Nuclear Information System (INIS)

    The basic principle of the production of polarized atomic hydrogen and deuterium beams are reviewed. The status of the present available polarization, density and intensity are presented. The improvement of atomic beam density by cooling the hydrogen atoms to low velocity is discussed. The possible use of polarized atomic beams as targets in storage rings is shown. It is proposed that polarized atomic beams can be used to produce polarized gas targets with high polarization and greatly improved density

  3. Symmetric solid target transport system

    OpenAIRE

    Tomov, D.; Lawrence, L; Gaehle, G.

    2015-01-01

    Introduction The expansion of our PET isotope production with a new TR-19 cyclotron necessitated a suitable solid target transport system. None of the known existing and proposed solid target transport systems (STTS) was able to meet the technical and budget requirements of the MIR cyclotron facility [5]. A unique carrier design allowed us to develop a fully automated 50.8 mm inner diameter pneumatic tube STTS with an in-hot-cell compact form factor receiving station. The cyclotron or v...

  4. Ion stopping in heated targets

    International Nuclear Information System (INIS)

    Ion stopping departs from classical, cold material values as the target material heats to appreciable ionization levels. The authors are investigating this phenomenon experimentally on the Proto I accelerator with a radial, Applied-B field ion diode. When the beam is focused to 0.5 TW/cm3 on thin aluminum foil targets the time-resolved departure from cold stopping is clear. Their observations and early interpretations will be presented. 9 references, 9 figures

  5. Target assignment for security officers to K targets (TASK)

    International Nuclear Information System (INIS)

    A probabilistic algorithm is developed to provide an optimal Target Assignment for Security officers to K targets (TASK) using a maximin criterion. Under the assumption of only a limited number (N) of security officers, the TASK computer model determines deployment assignments which maximize the system protection against sabotage by an adversary who may select any link in the system, including the weakest, for the point of attack. Applying the TASK model to a hypothetical nuclear facility containing a nine-level building reveals that aggregate targets covering multiple vital areas should be utilized to reduce the number of possible target assignments to a value equal to or only slightly larger than N. The increased probability that a given aggregate target is covered by one or more security officers offsets the slight decrease in interruption probability due to its occurring earlier in the adversary's path. In brief, the TASK model determines the optimal maximin deployment strategy for limited numbers of security officers and calculates a quantitative measure of the resulting system protection

  6. Unification of automatic target tracking and automatic target recognition

    Science.gov (United States)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  7. CPHD filter derivation for extended targets

    OpenAIRE

    Orguner, Umut

    2010-01-01

    This document derives the CPHD filter for extended targets. Only the update step is derived here. Target generated measurements, false alarms and prior are all assumed to be independent identically distributed cluster processes. We also prove here that the derived CPHD filter for extended targets reduce to PHD filter for extended targets and CPHD filter for standard targets under suitable assumptions.

  8. Monoclonal antibodies in targeted therapy

    Directory of Open Access Journals (Sweden)

    Beata Powroźnik

    2012-09-01

    Full Text Available Targeted therapy is a new therapeutic method consisting in the inhibition of specific molecular pathways. In modern therapy, the key role is played by monoclonal antibodies, included in the group of biological agents. The success of molecularly targeted therapy is to define the proper “molecular target”, selecting the right drug active against a specific “target” and selecting a group of patients who benefit from treatment. Introduction of targeted therapy resulted in improved results of the treatment of many serious and chronic diseases. In general, targeted molecular therapies have good toxicity profiles, but some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. Patient selection and proper monitoring significantly decrease the risk of life-threatening adverse events. Data concerning late side effects are still unavailable because of the short follow-up of molecularly targeted therapy. Currently in the U.S. and Europe there are approximately 31 registered therapeutic monoclonal antibodies, while 160 are subjected to clinical trials. This paper presents an overview of therapeutic monoclonal antibodies currently used in therapy and the present state of knowledge about them. 

  9. Infrared Targeting System (IRTS) demonstration

    Science.gov (United States)

    Ohair, Mark A.; Eucker, Shelly S.; Eucker, Brad A.; Lewis, Tim

    1992-02-01

    The objective of the Infrared Targeting System (IRTS) is to successfully demonstrate the mission performance that can be achieved in manned air-to-ground targeting applications utilizing a synergistic combination of state of the art active/passive infrared sensor and automatic target recognizer (ATR) technologies. The IRTS program is centered around a demonstration FLIR/Laser Radar/ATR (FLASHER). The FLASHER consists of a dual field of view (2 x 2 degree and 6 x 6 degree) second generation FLIR pixel mapped to a CO2 laser radar, with a FLIR ATR processor, a laser radar ATR processor, and a sensor fusion ATR processor. Following construction and laboratory testing of the IRTS, the system will be installed on a test aircraft and demonstrated in flight against realistic tactical, strategic, and special operations scenarios.

  10. 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...... reporting formats, along with a tested process that facilitates the production of a wide range of analytical products for civilian, military, and hybrid intelligence environments. Readers will learn how to perform the specific actions of problem definition modeling, target network modeling, 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...

  11. Ribosome Assembly as Antimicrobial Target.

    Science.gov (United States)

    Nikolay, Rainer; Schmidt, Sabine; Schlömer, Renate; Deuerling, Elke; Nierhaus, Knud H

    2016-01-01

    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. PMID:27240412

  12. Target identification by image analysis.

    Science.gov (United States)

    Fetz, V; Prochnow, H; Brönstrup, M; Sasse, F

    2016-05-01

    Covering: 1997 to the end of 2015Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches. PMID:26777141

  13. Integrin Targeted Delivery of Radiotherapeutics

    Directory of Open Access Journals (Sweden)

    Zhaofei Liu, Fan Wang, Xiaoyuan Chen

    2011-01-01

    Full Text Available Targeted radionuclide therapy, which is based on the selective delivery of a sufficient radiation dose to tumors without significantly affecting normal tissues, is a promising therapeutic approach for the treatment of a wide variety of malignancies. Integrins, a family of cell adhesion molecules, play key roles during tumor angiogenesis and metastasis. Among all the integrins, αvβ3 seems to be the most important in the process of tumor angiogenesis. Integrin αvβ3 is highly expressed on activated endothelial cells, new-born vessels as well as some tumor cells, but is not present in resting endothelial cells and most normal organ systems, making it a suitable target for anti-tumor therapy. In this review, we summarize the current development and applications of antibody-, peptide-, and other ligand-based integrin targeted radiotherapeutics for tumor radiation therapy.

  14. High-efficiency target-ion sources for RIB generation

    Energy Technology Data Exchange (ETDEWEB)

    Alton, G.D.

    1993-12-31

    A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory.

  15. Inflation Targeting at 20 - Achievements and Challenges

    OpenAIRE

    Scott Roger

    2009-01-01

    This paper provides an overview of inflation targeting frameworks and macroeconomic performance under inflation targeting. Inflation targeting frameworks are generally quite similar across countries, and a broad consensus has developed in favor of "flexible" inflation targeting. The evidence shows that, although inflation target ranges are missed frequently in most countries, the inflation and growth performance under inflation targeting compares very favorably with performance under alternat...

  16. USING OPTIMAL FEEDBACK CONTROL FOR CHAOS TARGETING

    Institute of Scientific and Technical Information of China (English)

    PENG ZHAO-WANG; ZHONG TING-XIU

    2000-01-01

    Since the conventional open-loop optimal targeting of chaos is very sensitive to noise, a close-loop optimal targeting method is proposed to improve the targeting performance under noise. The present optimal targeting model takes into consideration both precision and speed of the targeting procedure. The parameters, rather than the output, of the targeting controller, are directly optimized to obtain optimal chaos targeting. Analysis regarding the mechanism is given from physics aspect and numerical experiment on the Hénon map is carried out to compare the targeting performance under noise between the close-loop and the open-loop methods.

  17. 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.

  18. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

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

    2003-01-01

    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...

  19. 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 cus

  20. Particle physics using nuclear targets

    Energy Technology Data Exchange (ETDEWEB)

    Ferbel, T.

    1978-01-01

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references.

  1. Tumor targeting via integrin ligands

    Directory of Open Access Journals (Sweden)

    HorstKessler

    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.

  2. Target-point formation control

    NARCIS (Netherlands)

    Mou, Shaoshuai; Cao, Ming; Morse, A. Stephen

    2015-01-01

    In this paper a new distributed feedback strategy is proposed for controlling a rigid, acyclic formation of kinematic point-modeled mobile autonomous agents in the plane. The strategy makes use of a new concept called a "target point" and is applicable to any two-dimensional, acyclic formation whose

  3. Particle physics using nuclear targets

    International Nuclear Information System (INIS)

    The use of nuclear targets in particle physics is discussed and some recent results obtained in studies of hadronic interactions on nuclei summarized. In particular experimental findings on inclusive production and on coherent dissociation of mesons and baryons at high energies are presented. 41 references

  4. 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.

  5. Cooling of the ISIS target

    International Nuclear Information System (INIS)

    The paper describes the methods used to analyse and predict cooling of the uranium target of the ISIS facility at the Rutherford Appleton Laboratory by means of a combination of computer models (using the PHOENICS finite difference package) and practical tests. (author)

  6. Multi beam laser target illumination

    International Nuclear Information System (INIS)

    In order to compress matter to high densities by the application of intense pulses of laser energy it is necessary for the implosion of the target to be both stable and spherical. This imposes certain constraints on the uniformity of illumination of the target, and, this in turn places requirements on the illuminating optics and the laser beam quality. This report discusses the uniformity of illumination of a spherical target as provided by a variety of optical systems and for different numbers of laser beams and beam profiles. The results are compared with similar conclusions obtained by other workers. An alternative presentation of the calculations is given which is believed to be a more realistic estimate of the uniformity. Comments are made on the approximations that have been assumed and the results likely to be obtained from the full treatment are discussed. The effects of this non-uniform illumination on the target implosion are considered using the linear theory of the Rayleigh-Taylor instability. Finally, comments are made on other factors of a more practical nature which also govern the final choice of illumination system and the scope of experiments made possible by such a system. (author)

  7. 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)

  8. Toward targeted hypertension screening guidelines

    NARCIS (Netherlands)

    van Buuren, S; Boshuizen, HC; Reijneveld, SA

    2006-01-01

    Background. guidelines for screening and subsequent treatment of hypertension vary widely between countries. Part Of this variation can be attributed to systematic differences between Populations, but little is known about the way in which guidelines should be targeted to the population of interest.

  9. Polarized Sources, Targets and Polarimetry

    Science.gov (United States)

    Ciullo, Guiseppe; Contalbrigo, Marco; Lenisa, P.

    2011-01-01

    Remarks on the history of workshops on "spin tools" / E. Steffens -- Polarized proton beams in RHIC / A. Zelenski -- The COSY/Julich polarized H[symbol] and D[symbol] ion source / O. Felden -- The new source of polarized ions for the JINR accelerator complex / V. V. Fimushkin -- Resonance effects in nuclear dichroism - an inexpensive source of tensor-polarized deuterons / H. Seyfarth -- Polarized electrons and positrons at the MESA accelerator / K. Aulenbacher -- Status report of the Darmstadt polarized electron injector / Y. Poltoratska -- The Mott polarimeter at MAMI / V. Tioukine -- Proton polarimetry at the relativistic heavy ion collider / Y. Makdisi -- Polarisation and polarimetry at HERA / B. Sobloher -- Polarisation measurement at the ILC with a Compton polarimeter / C. Bartels -- Time evolution of ground motion-dependent depolarisation at linear colliders / A. Hartin -- Electron beam polarimetry at low energies and its applications / R. Barday -- Polarized solid targets: recent progress and future prospects / C. D. Keith -- HD gas distillation and analysis for HD frozen spin targets / A. D'Angelo -- Electron spin resonance study of hydrogen and alkyl free radicals trapped in solid hydrogen aimed for dynamic nuclear polarization of solid HD / T. Kumada -- Change of ultrafast nuclear-spin polarization upon photoionization by a short laser pulse / T. Nakajima -- Radiation damage and recovery in polarized [symbol]NH[symbol] ammonia targets at Jefferson lab / J. D. Maxwell.Polarized solid proton target in low magnetic field and at high temperature / T. Uesaka -- Pulse structure dependence of the proton spin polarization rate / T. Kawahara -- Proton NMR in the large COMPASS [symbol]NH[symbol] target / J. Koivuniemi -- DNP with TEMPO and trityl radicals in deuterated polystyrene / L. Wang -- The CLIC electron and positron polarized sources / L. Rinolfi -- Status of high intensity polarized electron gun at MIT-Bates / E. Tsentalovich -- Target section for spin

  10. Targeted multi-pinhole SPECT

    International Nuclear Information System (INIS)

    Small-animal single photon emission computed tomography (SPECT) with focused multi-pinhole collimation geometries allows scanning modes in which large amounts of photons can be collected from specific volumes of interest. Here we present new tools that improve targeted imaging of specific organs and tumours, and validate the effects of improved targeting of the pinhole focus. A SPECT system with 75 pinholes and stationary detectors was used (U-SPECT-II). An XYZ stage automatically translates the animal bed with a specific sequence in order to scan a selected volume of interest. Prior to stepping the animal through the collimator, integrated webcams acquire images of the animal. Using sliders, the user designates the desired volume to be scanned (e.g. a xenograft or specific organ) on these optical images. Optionally projections of an atlas are overlaid semiautomatically to locate specific organs. In order to assess the effects of more targeted imaging, scans of a resolution phantom and a mouse myocardial phantom, as well as in vivo mouse cardiac and tumour scans, were acquired with increased levels of targeting. Differences were evaluated in terms of count yield, hot rod visibility and contrast-to-noise ratio. By restricting focused SPECT scans to a 1.13-ml resolution phantom, count yield was increased by a factor 3.6, and visibility of small structures was significantly enhanced. At equal noise levels, the small-lesion contrast measured in the myocardial phantom was increased by 42%. Noise in in vivo images of a tumour and the mouse heart was significantly reduced. Targeted pinhole SPECT improves images and can be used to shorten scan times. Scan planning with optical cameras provides an effective tool to exploit this principle without the necessity for additional X-ray CT imaging. (orig.)

  11. Targeting targeted agents: open issues for clinical trial design

    Directory of Open Access Journals (Sweden)

    Giannarelli Diana

    2009-05-01

    Full Text Available Abstract Molecularly targeted agents for the treatment of solid tumors had entered the market in the last 5 years, with a great impact upon both the scientific community and the society. Many randomized phase III trials conducted in recent years with new targeted agents, despite previous data coming from preclinical research and from phase II trials were often promising, have produced disappointingly negative results. Some other trials have actually met their primary endpoint, demonstrating a statistically significant result favouring the experimental treatment. Unfortunately, with a few relevant exceptions, this advantage is often small, if not negligible, in absolute terms. The difference between statistical significance and clinical relevance should always be considered when translating clinical trials' results in the practice. The reason why this 'revolution' did not significantly impact on cancer treatment to displace chemotherapy from the patient' bedside is in part due to complicated, and in many cases, unknown, mechanisms of action of such drugs; indeed, the traditional way the clinical investigators were used to test the efficacy of 'older' chemotherapeutics, has become 'out of date' from the methodological perspective. As these drugs should be theoretically tailored upon featured bio-markers expressed by the patients, the clinical trial design should follow new rules based upon stronger hypotheses than those developed so far. Indeed, the early phases of basic and clinical drug development are crucial in the correct process which is able to correctly identify the target (when present. Targeted trial designs can result in easier studies, with less, better selected, and supported by stronger proofs of response evidences, patients, in order to not waste time and resources.

  12. Gated viewing for target detection and target recognition

    Science.gov (United States)

    Steinvall, Ove K.; Olsson, Hakan; Bolander, Goeran; Groenwall, Christina A.; Letalick, Dietmar

    1999-05-01

    Gated viewing using short pulse lasers and fast cameras offers many new possibilities in imaging compared with passive EO imaging. Among these we note ranging capability, large target-to-background contrast also in low visibility, good penetration capability trough obscurants and vegetation as well as through shadows in buildings, cars, etc. We also note that short wavelength laser systems have better angular resolution than long-wave infrared systems of the same aperture size. This gives an interesting potential of combined IR and laser systems for target detection and classification. Beside military applications civilian applications of gated viewing for search and rescue as well as vehicle enhanced vision and other applications are in progress. This presentation investigates the performance for gated viewing systems during different atmospheric conditions, including obscurants and gives examples of experimental data. The paper also deals with signal processing of gated viewing images for target detection. This is performed in two steps. First, image frames containing information of interest are found. In a second step those frames are investigated further to evaluate if man-made objects are present. In this step a sequence of images (video frames) are set up as a 3-D volume to incorporate spatial information. The object will then be detected using a set of quadrature filters operating on the volume.

  13. Progress of gene targeting in mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Gene targeting is a powerful approach of study- ing the genefunction in vivo. Specific genetic modifications, including simple gene disruption, point mutations, large chromosomal deletions and rearrangements, targeted incor- poration of foreign genes, could be introduced into the mouse genome by gene targeting. Recent studies make it possible to do the gene targeting with temporal and spatial control.

  14. Targeted Learning in Healthcare Research.

    Science.gov (United States)

    Gruber, Susan

    2015-12-01

    The increasing availability of Big Data in healthcare encourages investigators to seek answers to big questions. However, nonparametric approaches to analyzing these data can suffer from the curse of dimensionality, and traditional parametric modeling does not necessarily scale. Targeted learning (TL) combines semiparametric methodology with advanced machine learning techniques to provide a sound foundation for extracting information from data. Predictive models, variable importance measures, and treatment benefits and risks can all be addressed within this framework. TL has been applied in a broad range of healthcare settings, including genomics, precision medicine, health policy, and drug safety. This article provides an introduction to the two main components of TL, targeted minimum loss-based estimation and super learning, and gives examples of applications in predictive modeling, variable importance ranking, and comparative effectiveness research. PMID:27441404

  15. CNOOC Lifts 2011 Production Target

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ China National Offshore Oil Corporation (CNOOC), China's top offshore oil and gas producer, has lifted its 2011 production target by up to 11 percent as new projects at home and overseas come on stream.The offshore oil giant, with a market capitalization of about US$105 billion, said in a statement released in late January 2011 that it aimed to produce between 355 and 365 million barrels of oil equivalent (BOE).Oil prices climbed 15 percent in 2010 on the back of expectations that a global economic recovery will drive the demand.Analysts are similarly bullish for 2011, predicting crude prices to trade at around US$100 for the year.CNOOC, the smallest of China's triumvirate of energy companies that also includes CNPC and Sinopee, said it targeted US$8.8 billion in capital expenditure for 2011.

  16. 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.

  17. Geometric characterization of macroshell targets

    International Nuclear Information System (INIS)

    We are investigating methods of fabricating and characterizing large diameter, thin-walled glass capsules for Inertial Fusion (IF) experiments. Dimensional requirements for the capsules specify diameters of two to ten millimeters and a wide range of aspect ratios (diameter/wall). These shells are larger in diameter than shells made in drop towers. Because of their larger size, they have been given the designation, macroshell. Glass macroshell targets are transparent, seamless, fuel containers which are currently used in beta-heating experiments at KMSF. The capsules are also potentially useful for neutron production experiments with IF drivers like Nova. The technology developed to fabricate these fuel containers may be useful in the fabrication of polymer shells necessary for the proposed Laboratory Microfusion Facility (LMF); some work with polymers has started. Accurate target characterization is essential to ensure the accurate measurement of fuel layers produced by radioactively induced sublimation of cyrogenically cooled deuterium-tritium (DT) fuel. 3 refs., 4 figs

  18. Targeting vaccines to dendritic cells

    DEFF Research Database (Denmark)

    Foged, Camilla; Sundblad, Anne; Hovgaard, Lars

    2002-01-01

    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....

  19. Anticancer Agents Targeted to Sirtuins

    Directory of Open Access Journals (Sweden)

    Tomohiro Kozako

    2014-12-01

    Full Text Available Sirtuins are nicotinamide adenine dinucleotide+-dependent deacetylases of which there are seven isoforms (SIRT1–7. Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both antiaging and tumorigenesis, depending on its targets in specific signaling pathways or in specific cancers. Recent studies have identified small chemical compounds that modulate sirtuins, and these modulators have enabled a greater understanding of the biological function and molecular mechanisms of sirtuins. This review highlights the possibility of sirtuins, especially SIRT1 and SIRT2, for cancer therapy targets, and focuses on the therapeutic potential of sirtuin modulators both in cancer prevention and treatment.

  20. Nanodelivery System for Mitochondrial Targeting

    Science.gov (United States)

    Yoong, Sia Lee; Pastorin, Giorgia

    2014-02-01

    Mitochondria are indispensable in cellular functions such as energy production and death execution. They are emerging as intriguing therapeutic target as their dysregulation was found to be monumental in diseases such as neurodegenerative disease, obesity, and cancer etc. Despite tremendous interest being focused on therapeutically intervening mitochondrial function, few mito-active drugs were successfully developed, particularly due to challenges in delivering active compound to this organelle. In this review, effort in utilizing nanotechnology for targeted mitochondrial delivery of compound is expounded based on the nature of the nanomaterial used. The advantage and potential offered are discussed alongside the limitation. Finally the review is concluded with perspectives of the application of nanocarrier in mitochondrial medicine, given the unresolved concern on potential complications.

  1. Electronic warfare target location methods

    CERN Document Server

    Poisel, Richard

    2012-01-01

    Describing the mathematical development underlying current and classical methods of geolocating electronic systems that are emitting, this newly revised and greatly expanded edition of a classic Artech House book offers practical guidance in electronic warfare target location. The Second Edition features a wealth of additional material including new chapters on time delay estimation, direction finding techniques, and the MUSIC algorithm. This practical resource provides you with critical design information on geolocation algorithms, and establishes the fundamentals of existing algorithms as a

  2. Chemotherapy targeting cancer stem cells

    OpenAIRE

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cance...

  3. Aptamers and aptamer targeted delivery

    OpenAIRE

    Yan, Amy C.; Levy, Matthew

    2009-01-01

    When aptamers first emerged almost two decades ago, most were RNA species that bound and tagged or inhibited simple target ligands. Very soon after, the ‘selectionologists’ developing aptamer technology quickly realized more potential for the aptamer. In recent years, advances in aptamer techniques have enabled the use of aptamers as small molecule inhibitors, diagnostic tools and even therapeutics. Aptamers are now being employed in novel applications. We review, herein, some of the recent a...

  4. Therapeutic targeting of Janus kinases

    OpenAIRE

    Pesu, Marko; Laurence, Arian; Kishore, Nandini; Zwillich, Sam; Chan, Gary; O’Shea, John J.

    2008-01-01

    Cytokines play pivotal roles in immunity and inflammation, and targeting cytokines and their receptors is an effective means of treating such disorders. Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. These structurally unique protein kinases play essential and specific roles in immune cell development and function. One JAK, JAK3, has particularly selective functions. Mutations of this kinase underlie severe combined immunodeficie...

  5. Targeted advertising in magazine markets

    OpenAIRE

    Chandra, Ambarish; Kaiser, Ulrich

    2010-01-01

    We examine the scope and value of targeted advertising in the magazine industry. We use data on reader characteristics at individual media, in contrast to previous work that has needed to infer this information from aggregate data. Our results show a strong relationship between subscriber characteristics and advertising prices. Advertisers clearly value more homogenous groups of readers, measured according to income, gender and age. Our results explain recent trends of declining advertising e...

  6. Targeting ECM Disrupts Cancer Progression

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 is...... summarized. In addition, we highlight the promising (pre-)clinical data showing benefits of targeting these ECM macromolecules to prevent cancer progression....

  7. Target Advertising and Market Transparency

    OpenAIRE

    Stühmeier, Torben

    2012-01-01

    This paper examines the effects of increased transparency over online news sources, e.g. due to news aggregators, on online news outlets and the advertising industry. The role of news aggregators is controversially discussed, where the discussion widely points on user side effect. The present paper widens the discussion on the advertising side and shows that aggregators can help to better target advertising messages to a more homogenous group of users and, in turn, may both benefit advertiser...

  8. Philippines; Preparations for Inflation Targeting

    OpenAIRE

    Piyabha Kongsamut

    2001-01-01

    The Philippines is planning to shift toward adoption of an inflation targeting framework in 2001. This paper reviews key policy issues in this context, describes various operational and technical preparations, and presents an empirical analysis of the factors driving inflation. Among the key policy requirements, while central bank independence appears assured, the exchange rate has been allowed to fluctuate largely freely, and the authorities are embarking on a medium-term plan for fiscal con...

  9. 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. F...... interactive software is also part of a computer-assisted learning program on digital photogrammetry....

  10. Inflation Targeting in Latin America

    OpenAIRE

    Barajas, Adolfo; Steiner, Roberto; Villar, Leonardo; Pabon, Cesar

    2014-01-01

    Estimation of conventional Taylor rules for Brazil, Chile, Colombia and Peru shows that central banks increase their repo rate in response to increases in the output gap and, except in Peru, to deviations of inflation expectations from target. Using a Markov-Switching methodology, it is found that, in the presence of external shocks, Chile, Colombia and Peru temporarily abandoned their conventional reaction function. The Taylor Rule is expanded and variables are included related to exchange r...

  11. Inflation Targeting in Dollarized Economies

    OpenAIRE

    Leonardo Leiderman; Rodolfo Maino; Eric Parrado

    2006-01-01

    The shift to inflation targeting has contributed to the relatively low inflation observed in some emerging market economies although, as noted by many economists, the preconditions required for a successful implementation were not in place. The existence of managed exchange rate regimes, a narrow base of domestic nominal financial assets, the lack of market instruments to hedge exchange rate risks, together with fear of floating and dollarization, have been stressed as factors that might weak...

  12. Targeting the lysosome in cancer

    OpenAIRE

    Piao, Shengfu; Amaravadi, Ravi K.

    2015-01-01

    Lysosomes are membrane-bound intracellular organelles that receive macromolecules delivered by endocytosis, phagocytosis, and autophagy for degradation and recycling. Over the last decade, advances in lysosome research have established a broad role for the lysosome in the pathophysiology of disease. In this review, we highlight the recent discoveries in lysosome biology, with an emphasis on their implications for cancer therapy. We focus on targeting the lysosome in cancer by exploring lysoso...

  13. Toward targeted hypertension screening guidelines

    OpenAIRE

    Buuren, S. van; Boshuizen, HC; Reijneveld, SA

    2006-01-01

    Background. guidelines for screening and subsequent treatment of hypertension vary widely between countries. Part Of this variation can be attributed to systematic differences between Populations, but little is known about the way in which guidelines should be targeted to the population of interest. Optimal guidelines should have high yield and low complexity. The goal is to fit procedures for screening and subsequent treatment of hypertension optimally to a specific population. Methods. Simu...

  14. Anticancer Agents Targeted to Sirtuins

    OpenAIRE

    Tomohiro Kozako; Takayoshi Suzuki; Makoto Yoshimitsu; Naomichi Arima; Shin-ichiro Honda; Shinji Soeda

    2014-01-01

    Sirtuins are nicotinamide adenine dinucleotide+-dependent deacetylases of which there are seven isoforms (SIRT1–7). Sirtuin activity is linked to gene expression, lifespan extension, neurodegeneration, and age-related disorders. Numerous studies have suggested that sirtuins could be of great significance with regard to both antiaging and tumorigenesis, depending on its targets in specific signaling pathways or in specific cancers. Recent studies have identified small chemical compounds that m...

  15. Target fragmentation at intermediate energies

    International Nuclear Information System (INIS)

    We report the results of measurements of the average target fragment momenta and energies in the interaction of 12.0 and 18.4 MeV/u 160, and 45.4 and 83.8 MeV/u 12C with 197Au. We compare these data with previously published studies of the interaction of 380 MeV/u 20Ne and 400 and 2100 MeV/u 12C with 197Au

  16. Cancer Immunotherapy of Targeting Angiogenesis

    Institute of Scientific and Technical Information of China (English)

    JianmeiHou; LingTian; YuquanWei

    2004-01-01

    Tumor growth and metastasis are angiogenesis-dependent. Anti-angiogenic therapy may be a useful approach to cancer therapy. This review discussed tumor angiogenesis and immunotherapy of targeting tumor angiogenesis from two main aspects: (1) active vaccination to induce effective anti-angiogenesis immunity; (2) passive immunotherapy with anti-pro-angiogenic molecules relevant antibody. Evidence from the recent years suggested that anti-angiogenic therapy should be one of the most promising approaches to cancer therapy.

  17. Fixed target flammable gas upgrades

    International Nuclear Information System (INIS)

    In the past, fixed target flammable gas systems were not supported in an organized fashion. The Research Division, Mechanical Support Department began to support these gas systems for the 1995 run. This technical memo describes the new approach being used to supply chamber gasses to fixed target experiments at Fermilab. It describes the engineering design features, system safety, system documentation and performance results. Gas mixtures provide the medium for electron detection in proportional and drift chambers. Usually a mixture of a noble gas and a polyatomic quenching gas is used. Sometimes a small amount of electronegative gas is added as well. The mixture required is a function of the specific chamber design, including working voltage, gain requirements, high rate capability, aging and others. For the 1995 fixed target run all the experiments requested once through gas systems. We obtained a summary of problems from the 1990 fixed target run and made a summary of the operations logbook entries from the 1991 run. These summaries primarily include problems involving flammable gas alarms, but also include incidents where Operations was involved or informed. Usually contamination issues were dealt with by the experimenters. The summaries are attached. We discussed past operational issues with the experimenters involved. There were numerous incidents of drift chamber failure where contaminated gas was suspect. However analyses of the gas at the time usually did not show any particular problems. This could have been because the analysis did not look for the troublesome component, the contaminant was concentrated in the gas over the liquid and vented before the sample was taken, or that contaminants were drawn into the chambers directly through leaks or sub-atmospheric pressures. After some study we were unable to determine specific causes of past contamination problems, although in argon-ethane systems the problems were due to the ethane only

  18. Fixed-Target Electron Accelerators

    International Nuclear Information System (INIS)

    A tremendous amount of scientific insight has been garnered over the past half-century by using particle accelerators to study physical systems of sub-atomic dimensions. These giant instruments begin with particles at rest, then greatly increase their energy of motion, forming a narrow trajectory or beam of particles. In fixed-target accelerators, the particle beam impacts upon a stationary sample or target which contains or produces the sub-atomic system being studied. This is in distinction to colliders, where two beams are produced and are steered into each other so that their constituent particles can collide. The acceleration process always relies on the particle being accelerated having an electric charge; however, both the details of producing the beam and the classes of scientific investigations possible vary widely with the specific type of particle being accelerated. This article discusses fixed-target accelerators which produce beams of electrons, the lightest charged particle. As detailed in the report, the beam energy has a close connection with the size of the physical system studied. Here a useful unit of energy is a GeV, i.e., a giga electron-volt. (ne GeV, the energy an electron would have if accelerated through a billion volts, is equal to 1.6 x 10-10 joules.) To study systems on a distance scale much smaller than an atomic nucleus requires beam energies ranging from a few GeV up to hundreds of GeV and more

  19. Strategies for SETI target selection

    Science.gov (United States)

    Latham, David W.; Soderblom, David R.

    1993-08-01

    The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. In this paper we present a strategy for target selection and observing. The strategy has two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar- type stars, and to minimize the chances of missing signals from unexpected sites. For the main Targeted Search survey of approximately 1000 nearby solar-type stars, we argue that the selection criteria should be heavily biased by what we know about the origin and evolution of life here on earth. We propose that observations of stars with stellar companions orbiting near the habitable zone should be de-emphasized, because such companions would prevent the formation of habitable planets. We also propose that observations of stars younger than about three billion years should be de-emphasized in favor of older stars, because our own technical civilization took longer than three billion years to evolve here on earth.

  20. 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. PMID:26332195

  1. A Cryogenic Infrared Calibration Target

    CERN Document Server

    Wollack, Edward J; Rinehart, Stephan A

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, $R \\le 0.003$, from $800-4,800\\,{\\rm cm}^{-1}$ $(12-2\\,\\mu$m). Upon expanding the spectral range under consideration to $400-10,000\\,{\\rm cm}^{-1}$ $(25-1\\,\\mu$m) the observed performance gracefully degrades to $R \\le 0.02$ at the band edges. In the implementation described, a high-thermal-conductivity metallic substrate is textured with a pyramidal tiling and subsequently coated with a thin lossy dielectric coating that enables high absorption and thermal uniformity across the target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to $\\sim4\\,$K. Basic design considerations, governing equations, and test data for realizing the structure described are provided. The optical properties of selected absorptive materials -- Acktar Fractal Black, Aeroglaze Z306, and Stycast 2850 FT epoxy loaded with stainless steel powder -- are character...

  2. Drug targeting to the brain.

    Science.gov (United States)

    Pardridge, William M

    2007-09-01

    The goal of brain drug targeting technology is the delivery of therapeutics across the blood-brain barrier (BBB), including the human BBB. This is accomplished by re-engineering pharmaceuticals to cross the BBB via specific endogenous transporters localized within the brain capillary endothelium. Certain endogenous peptides, such as insulin or transferrin, undergo receptor-mediated transport (RMT) across the BBB in vivo. In addition, peptidomimetic monoclonal antibodies (MAb) may also cross the BBB via RMT on the endogenous transporters. The MAb may be used as a molecular Trojan horse to ferry across the BBB large molecule pharmaceuticals, including recombinant proteins, antibodies, RNA interference drugs, or non-viral gene medicines. Fusion proteins of the molecular Trojan horse and either neurotrophins or single chain Fv antibodies have been genetically engineered. The fusion proteins retain bi-functional properties, and both bind the BBB receptor, to trigger transport into brain, and bind the cognate receptor inside brain to induce the pharmacologic effect. Trojan horse liposome technology enables the brain targeting of non-viral plasmid DNA. Molecular Trojan horses may be formulated with fusion protein technology, avidin-biotin technology, or Trojan horse liposomes to target to brain virtually any large molecule pharmaceutical. PMID:17554607

  3. Aluminum-lithium target behavior

    Energy Technology Data Exchange (ETDEWEB)

    McDonell, W.R.

    1989-10-01

    Information on physical properties and irradiation behavior of aluminum-lithium target alloys employed for the production of tritium in Savannah River reactors has been reviewed to support development of technology for the New Production Reactor (NPR). Phase compositions and microstructures, thermal conductivity, mechanical properties, and constituent diffusion phenomena of the alloys, established in prior site studies, are presented. Irradiation behavior, including distributions of product tritium and helium and related exposure limits due to swelling and cracking of the target alloys is discussed, along with gas release processes occurring during subsequent product recovery operations. The property review supports designation of the aluminum-lithium alloys as ideally well-suited target materials for low-temperature, tritium-producing reactors, demonstrated over 35 years of Savannah River reactor operation. Low temperature irradiation and reaction with lithium in the alloy promotes tritium retention during reactor exposure, and the aluminum provides a matrix from which the product is readily recovered on heating following irradiation. 33 refs., 26 figs., 8 tabs.

  4. Therapeutic targets in liver fibrosis.

    Science.gov (United States)

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points. PMID:21233278

  5. Three Essays on Analyst Target Prices

    OpenAIRE

    Hashim, Noor

    2012-01-01

    This thesis presents three essays on analyst target prices. The essays contribute to the major debate on the value of analyst target prices in the capital market by addressing the following three questions: Does a bull-bear valuation analysis increase the accuracy of analysts’ target prices? Does analyst ranking affect how informative target prices are to institutional investors? And, do analysts use their cash flow forecasts when setting target prices?In the first essay, I explore whether co...

  6. X-ray diffraction indicates that active cross-bridges bind to actin target zones in insect flight muscle.

    OpenAIRE

    Tregear, R T; Edwards, R J; Irving, T C; Poole, K J; Reedy, M C; Schmitz, H.; Towns-Andrews, E; Reedy, M K

    1998-01-01

    We report the first time-resolved study of the two-dimensional x-ray diffraction pattern during active contraction in insect flight muscle (IFM). Activation of demembranated Lethocerus IFM was triggered by 1.5-2.5% step stretches (risetime 10 ms; held for 1.5 s) giving delayed active tension that peaked at 100-200 ms. Bundles of 8-12 fibers were stretch-activated on SRS synchrotron x-ray beamline 16.1, and time-resolved changes in diffraction were monitored with a SRS 2-D multiwire detector. ...

  7. Experimental identification of microRNA targets

    DEFF Research Database (Denmark)

    Ørom, Ulf Andersson; Lund, Anders H

    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...... of potential targets and constitutes a problem for computational target prediction. Although computational analyses have shed light on important aspects of microRNA target recognition, several questions remain regarding how microRNAs can recognize and regulate their targets. Forward experimental...... approaches allow for an unbiased study of microRNA target recognition and may unveil novel, rare or uncommon target binding patterns. In this review we focus on animal microRNAs and the experimental approaches that have been described for identification of their targets....

  8. 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.

  9. 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

  10. Conotoxins: Molecular and Therapeutic Targets

    Science.gov (United States)

    Lewis, Richard J.

    Marine molluscs known as cone snails produce beautiful shells and a complex array of over 50,000 venom peptides evolved for prey capture and defence. Many of these peptides selectively modulate ion channels and transporters, making them a valuable source of new ligands for studying the role these targets play in normal and disease physiology. A number of conopeptides reduce pain in animal models, and several are now in pre-clinical and clinical development for the treatment of severe pain often associated with diseases such as cancer. Less than 1% of cone snail venom peptides are pharmacologically characterised.

  11. Nova target chamber decontamination study

    International Nuclear Information System (INIS)

    An engineering study was performed to determine the most effective method for decontamination of the Nova target chamber. Manual and remote decontamination methods currently being used were surveyed. In addition, a concept that may not require in-situ decontamination was investigated. Based on the presently available information concerning material and system compatibility and particle penetration, it is recommended that a system of removable aluminum shields be considered. It is also recommended that a series of tests be performed to more precisely determine the vacuum compatibility and penetrability of other materials discussed in this report

  12. Antiviral targets of human noroviruses.

    Science.gov (United States)

    Prasad, Bv Venkataram; Shanker, Sreejesh; Muhaxhiri, Zana; Deng, Lisheng; Choi, Jae-Mun; Estes, Mary K; Song, Yongcheng; Palzkill, Timothy; Atmar, Robert L

    2016-06-01

    Human noroviruses are major causative agents of sporadic and epidemic gastroenteritis both in children and adults. Currently there are no licensed therapeutic intervention measures either in terms of vaccines or drugs available for these highly contagious human pathogens. Genetic and antigenic diversity of these viruses, rapid emergence of new strains, and their ability to infect a broad population by using polymorphic histo-blood group antigens for cell attachment, pose significant challenges for the development of effective antiviral agents. Despite these impediments, there is progress in the design and development of therapeutic agents. These include capsid-based candidate vaccines, and potential antivirals either in the form of glycomimetics or designer antibodies that block HBGA binding, as well as those that target essential non-structural proteins such as the viral protease and RNA-dependent RNA polymerase. In addition to these classical approaches, recent studies suggest the possibility of interferons and targeting host cell factors as viable approaches to counter norovirus infection. This review provides a brief overview of this progress. PMID:27318434

  13. Multifunction sensor for target recognition

    Science.gov (United States)

    James, William M.; Lindberg, Perry C.

    1993-09-01

    The U.S. Army has a critical need for the capability provided by a multifunction sensor. This is (in effect) a smart sensor system that can adapt to environmental conditions and adjust its mode of operation to effectively counter any threat it meets. It will have an intelligent signal processor which has all of the system's sensor signals to choose from. The processor chooses the appropriate signal information to rapidly detect, acquire, track, and automatically identify all targets in the vicinity of the sensor under a wide variety of battlefield scenarios and environmental conditions. The multiphenomenology signal information provides the flexibility to overcome the adverse effects of clutter, countermeasures (both active and passive), illumination, obscurants, target orientation, and weather. It should be noted, however, that the types of sensory information required is dependent on the mission and the operating environment. For instance, a strategic defense sensor operating in space can use (and will need) different types of sensor data than the multifunction sensor employed on an attack helicopter. In fact, the sensor configuration on a helicopter operating in Saudi Arabia may be quite different from one that is deployed to Vietnam. For the purpose of this paper we generalize about the technologies desired for an adaptable, `smart' sensor system. We do not specify a particular mission nor define a specific threat. However, in any case, we can assume the need to fuse sensor signal information in an intelligent processor to provide robust performance in the battlefield environment. 12

  14. Hypoxia-mediated tumour targeting.

    Science.gov (United States)

    Binley, K; Askham, Z; Martin, L; Spearman, H; Day, D; Kingsman, S; Naylor, S

    2003-04-01

    Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy. PMID:12646859

  15. Aquaporins as potential drug targets

    Institute of Scientific and Technical Information of China (English)

    Fang WANG; Xue-chao FENG; Yong-ming LI; Hong YANG; Tong-hui MA

    2006-01-01

    The aquaporins (AQP) are a family of integral membrane proteins that selectively transport water and,in some cases,small neutral solutes such as glycerol and urea.Thirteen mammalian AQP have been molecularly identified and localized to various epithelial,endothelial and other tissues.Phenotype studies of transgenic mouse models of AQP knockout,mutation,and in some cases humans with AQP mutations have demonstrated essential roles for AQP in mammalian physiology and pathophysiology,including urinary concentrating function,exocrine glandular fluid secretion,brain edema formation,regulation of intracranial and intraocular pressure,skin hydration,fat metabolism,tumor angiogenesis and cell migration.These studies suggest that AQP may be potential drug targets for not only new diuretic reagents for various forms of pathological water retention,but also targets for novel therapy of brain edema,inflammatory disease,glaucoma,obesity,and cancer.However,potent AQP modulators for in vivo application remain to be discovered.

  16. HIRFL–CSR internal cluster target

    International Nuclear Information System (INIS)

    Highlights: • An internal cluster target was built and installed at HIRFL–CSR. • The target thickness for H2 amounts up to 6.6 × 1012 atoms/cm2. • The feasibility and stability of the internal cluster target were verified by on-line experiments. -- Abstract: Since HIRFL–CSR internal cluster target was built, it has played a key role in in-ring experiments at HIRFL–CSR. So far it have been operated with five gas species as targets for scattering experiments, i.e. hydrogen, nitrogen, argon, neon, and krypton. The obtained highest thickness for hydrogen target amounts up to 1012 atoms/cm2, and those of other targets are larger than 1013 atoms/cm2 with the background pressure of 10−11 mbar in CSR. The target thickness can be varied by regulating the nozzle temperature and pressure of the inlet gas. The first online internal target experiment dedicated to investigate radioactive electron capture (REC) process with Xe54+ ions colliding with the nitrogen target demonstrated the stability and reliability of the internal target system. In addition, hydrogen and krypton were also tested online in recent experiments, which indicate the target system can meet experimental requirements for the thickness of target, pressure in scattering chamber, and long-term stability

  17. Progress on the SNS target station

    International Nuclear Information System (INIS)

    This review gives progress and modifications covering the last eighteen months, under the five broad areas of target, target assembly, control system, bulk shield and remote handling. Finally a discussion of additional facilities to the SNS is presented

  18. 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...

  19. Preparation of targets by ion implantation

    International Nuclear Information System (INIS)

    Various factors are described which are involved in target preparation by direct ion implantation and the limitations and pitfalls of the method are emphasized. Examples are given of experiments for which ion implanted targets are well suited. (author)

  20. Generating target probability sequences and events

    OpenAIRE

    Ella, Vaignana Spoorthy

    2013-01-01

    Cryptography and simulation of systems require that events of pre-defined probability be generated. This paper presents methods to generate target probability events based on the oblivious transfer protocol and target probabilistic sequences using probability distribution functions.

  1. Targets and processes for fabricating same

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Jesse D; Malekos, Steven; Le Galloudec, Nathalie; Korgan, Grant; Cowan, Thomas; Sentoku, Yasuhiko

    2016-05-17

    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.

  2. HIRFL-CSR internal target system

    International Nuclear Information System (INIS)

    The structure and the design of the HIRFL-CSR internal target system is reported. The HIRFL-CSR internal target can operate in two modes: cluster target mode and polarized target mode. The cluster target may provide the gas target of H2, N2, noble gases and small molecular gases with a density of ≥ 1013 atoms/cm2, and the polarized target may provide polarized H and D beams with a density of about 2 x 1011 atoms/cm2. The target polarization is expected to be +0.90/-0.90 for hydrogen beam, and the vector polarization is expected to +0.95/-0.95 for deuterium beam

  3. Targets and processes for fabricating same

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Target for optically activated seekers and trackers

    Science.gov (United States)

    Lakin, C. T.; Willett, N. F.

    1984-05-01

    This abstract discloses a target for optically activated seekers and trackers (TOAST) which provides for calibrated and variable target characteristics such as size, intensity, spatial position, color and interfering background. The TOAST has a first ilumination system providing a target light beam through an adjustable iris which controls image size. The target beam passes through a collimator lens which focuses the light at infinity. With the target beam focused at infinity, the motion of an elevation plate lengthens or shortens the distance from the collimator lens to a one motion mirror. The target beam is attenuated by a variable filter driven by a servo-motor, and a color selection process is provided by passing the beam through spectral filters. A background light beam with background imagery is provided to the beamsplitter mirror and mixed with the target image so as to simulate the target environment encountered by an operating optically activated seeker and tracker.

  5. A rotating target for Ra production

    International Nuclear Information System (INIS)

    A target wheel with pyrolytic graphite targets is designed and constructed at the TRIμP facility to boost the production rate of Ra isotopes. Simulation, design properties and production results are discussed.

  6. Does inflation targeting make a difference?

    OpenAIRE

    Frederic S. Mishkin; Schmidt-Hebbel, Klaus

    2006-01-01

    Yes, as inferred from panel evidence for inflation-targeting countries and a control group of high-achieving industrial countries that do not target inflation. Our evidence suggests that inflation targeting helps countries achieve lower inflation in the long run, have smaller inflation response to oil-price and exchange-rate shocks, strengthen monetary policy independence, improve monetary policy efficiency, and obtain inflation outcomes closer to target levels. Some benefits of inflation tar...

  7. Targeting Nominal Income Growth or Inflation?

    OpenAIRE

    Jensen, Henrik

    1999-01-01

    Within a simple New Keynesian model emphasizing forward-looking behaviour of private agents, I evaluate optimal nominal income growth targeting versus optimal inflation targeting. When the economy under consideration 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 interest rate behaviour that improves the inflation-output gap trade-o...

  8. 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.

  9. The Simplest Test of Inflation Target Credibility

    OpenAIRE

    Svensson, Lars E.O.

    1994-01-01

    A simple test of inflation target credibility is constructed by subtracting the maximum and minimum inflation rates consistent with the inflation targets from the yields to maturity on nominal bonds. This results in a target-consistent range of real yields on nominal bonds. If expected real yields, or market real interest rates on real bonds if such are available, fall outside the range of target- consistent real yields, credibility is rejected. Two concepts of credibility, called absolute cr...

  10. Evaluation and validation of drug targets

    Institute of Scientific and Technical Information of China (English)

    Guan-huaDU

    2004-01-01

    Drug target is one of the key factors for discovering and developing new drugs. To find and validate drug targets is a crucial technique required in drug discovery by the strategy of high throughput screening. Based on the knowledge of molecular biology, human genomics and proteomics, it has been predicted that 5000 to 10000 drug targets exist in human. So, it is important orocedure to evaluate and validate the drug targets.

  11. Targeting Radiotherapy to Cancer by Gene Transfer

    OpenAIRE

    R. J. Mairs; Boyd, M.

    2003-01-01

    Targeted radionuclide therapy is an alternative method of radiation treatment which uses a tumor-seeking agent carrying a radioactive atom to deposits of tumor, wherever in the body they may be located. Recent experimental data signifies promise for the amalgamation of gene transfer with radionuclide targeting. This review encompasses aspects of the integration of gene manipulation and targeted radiotherapy, highlighting the possibilities of gene transfer to assist the targeting of cancer ...

  12. Predicting new molecular targets for known drugs

    OpenAIRE

    Keiser, Michael J.; Setola, Vincent; Irwin, John J.; Laggner, Christian; Abbas, Atheir; Hufeisen, Sandra J.; Jensen, Niels H.; Kuijer, Michael B.; Matos, Roberto C.; Tran, Thuy B.; Whaley, Ryan; Glennon, Richard A.; Hert, Jérôme; THOMAS, KELAN L. H.; Edwards, Douglas D.

    2009-01-01

    Whereas drugs are intended to be selective, at least some bind to several physiologic targets, explaining both side effects and efficacy. As many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here, we compared 3,665 FDA-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested...

  13. Behavioral targeting: a European legal perspective

    NARCIS (Netherlands)

    F. Zuiderveen Borgesius

    2013-01-01

    Behavioral targeting, or online profiling, is a hotly debated topic. Much of the collection of personal information on the Internet is related to behavioral targeting, although research suggests that most people don't want to receive behaviorally targeted advertising. The World Wide Web Consortium i

  14. Research and development for the SPES target

    International Nuclear Information System (INIS)

    The target is one of the key issues of isotope separation on line (ISOL) facilities. SPES, now under development at LNL-INFN, is an innovative ISOL facility possessing a target characterized by seven separate uranium dicarbide thin disks. The research on the materials development and target prototyping is discussed in the following. (orig.)

  15. Automated laser fusion target production concept

    International Nuclear Information System (INIS)

    A target production concept is described for the production of multilayered cryogenic spherical inertial confinement fusion targets. The facility is to deliver targets to the reactor chamber at rates up to 10 per second and at costs consistent with economic production of power

  16. Communicating to heterogeneous target groups

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    people get out of the information provided in the pamphlet. The receivers that are subjected to the original pamphlet do not see the experimental version. Likewise the receivers that are subjected to the amended version do not see the original. I do so in order for the reception situations to be as......The paper proposal is part of a full-scale discourse analysis of a series of service information pamphlets published by the county of Ringkjøbing in Western Denmark. The project is an investigation of various aspects of the fact that government agencies as well as local and regional authorities...... 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. In the...

  17. 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 as a...... market mechanism that can be brought inside the firm to provide incentives for continuous improvement and the development of competitive advances. However, whereas extant research primarily has focused on the importance and effects of using external benchmarks, less attention has been directed towards...... the conditions upon which the market mechanism is performing within organizations. This paper aims to contribute to research by providing more insight to the conditions for the use of external benchmarking as an element in performance management in organizations. Our study explores a particular type...

  18. BAD: a good therapeutic target?

    International Nuclear Information System (INIS)

    The major goal in cancer treatment is the eradication of tumor cells. Under stress conditions, normal cells undergo apoptosis; this property is fortunately conserved in some tumor cells, leading to their death as a result of chemotherapeutic and/or radiation-induced stress. Many malignant cells, however, have developed ways to subvert apoptosis, a characteristic that constitutes a major clinical problem. Gilmore et al. recently described the ability of ZD1839, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR), to induce apoptosis of mammary cells that are dependent upon growth factors for survival. Furthermore, they showed that the major effector of the EGFR-targeted therapy is BAD, a widely expressed BCL-2 family member. These results are promising in light of the role of the EGFR in breast cancer development

  19. 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.

  20. Communicating to heterogeneous target groups

    DEFF Research Database (Denmark)

    Pedersen, Karsten

    The paper proposal is part of a full-scale discourse analysis of a series of service information pamphlets published by the county of Ringkjøbing in Western Denmark. The project is an investigation of various aspects of the fact that government agencies as well as local and regional authorities...... 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. In the...... identical as possible, thus creating fertile grounds for comparisons. The amendments will follow traditional advice for improving on professional communication, viz., direct address, active constructions, verbs rather than nominalizations etc., and it is my intention to refute or document the notion that...

  1. Target Points in Trastuzumab Resistance

    International Nuclear Information System (INIS)

    Epidermal growth factor (EGF) family of receptors is involved in cell growth and differentiation. The human EGF2 (HER2) lacks natural ligands, and correlation between HER2 levels and carcinogenesis makes the receptor an ideal candidate for targeted therapy in breast cancer. Trastuzumab is a humanized antibody applied against HER2-positive breast tumors in clinic. Metastatic tumors respond well to trastuzumab therapy for the first year, but development of antibody resistance helps the tumors to regrow allowing the disease to progress. Trastuzumab resistance is shaped via a range of intracellular signaling pathways that are interconnected and share in key effector molecules. Identification of a common node central to these resistance pathways could provide an ultimate solution for trastuzumab resistance in breast and other cancers

  2. Identification of Drosophila MicroRNA Targets

    Directory of Open Access Journals (Sweden)

    Stark Alexander

    2003-01-01

    Full Text Available MicroRNAs (miRNAs are short RNA molecules that regulate gene expression by binding to target messenger RNAs and by controlling protein production or causing RNA cleavage. To date, functions have been assigned to only a few of the hundreds of identified miRNAs, in part because of the difficulty in identifying their targets. The short length of miRNAs and the fact that their complementarity to target sequences is imperfect mean that target identification in animal genomes is not possible by standard sequence comparison methods. Here we screen conserved 3' UTR sequences from the Drosophila melanogaster genome for potential miRNA targets. The screening procedure combines a sequence search with an evaluation of the predicted miRNA-target heteroduplex structures and energies. We show that this approach successfully identifies the five previously validated let-7, lin-4, and bantam targets from a large database and predict new targets for Drosophila miRNAs. Our target predictions reveal striking clusters of functionally related targets among the top predictions for specific miRNAs. These include Notch target genes for miR-7, proapoptotic genes for the miR-2 family, and enzymes from a metabolic pathway for miR-277. We experimentally verified three predicted targets each for miR-7 and the miR-2 family, doubling the number of validated targets for animal miRNAs. Statistical analysis indicates that the best single predicted target sites are at the border of significance; thus, target predictions should be considered as tentative until experimentally validated. We identify features shared by all validated targets that can be used to evaluate target predictions for animal miRNAs. Our initial evaluation and experimental validation of target predictions suggest functions for two miRNAs. For others, the screen suggests plausible functions, such as a role for miR-277 as a metabolic switch controlling amino acid catabolism. Cross-genome comparison proved essential

  3. PLUTONIUM-238 PRODUCTION TARGET DESIGN STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Hurt, Christopher J [ORNL; Wham, Robert M [ORNL; Hobbs, Randall W [ORNL; Owens, R Steven [ORNL; Chandler, David [ORNL; Freels, James D [ORNL; Maldonado, G Ivan [ORNL

    2014-01-01

    A new supply chain is planned for plutonium-238 using existing reactors at the Oak Ridge National Laboratory (ORNL) and Idaho National Laboratory (INL) and existing chemical recovery facilities at ORNL. Validation and testing activities for new irradiation target designs have been conducted in three phases over a 2 year period to provide data for scale-up to production. Target design, qualification, target fabrication, and irradiation of fully-loaded targets have been accomplished. Data from post-irradiation examination (PIE) supports safety analysis and irradiation of future target designs.

  4. 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...

  5. Targeting of Carbon Ion-Induced G2 Checkpoint Activation in Lung Cancer Cells Using Wee-1 Inhibitor MK-1775.

    Science.gov (United States)

    Ma, Hongyu; Takahashi, Akihisa; Sejimo, Yukihiko; Adachi, Akiko; Kubo, Nobuteru; Isono, Mayu; Yoshida, Yukari; Kanai, Tatsuaki; Ohno, Tatsuya; Nakano, Takashi

    2015-12-01

    The potent inhibitor of the cell cycle checkpoint regulatory factor Wee-1, MK-1775, has been reported to enhance non-small cell lung cancer (NSCLC) cell sensitivity to photon radiation by abrogating radiation-induced G2 arrest. However, little is known about the effects of this sensitizer after exposure to carbon (C)-ion radiation. The purpose of this study was therefore to investigate the effects of C ions in combination with MK-1775 on the killing of NSCLC cells. Human NSCLC H1299 cells were exposed to X rays or C ions (290 MeV/n, 50 keV/μm at the center of a 6 cm spread-out Bragg peak) in the presence of MK-1775. The cell cycle was analyzed using flow cytometry and Western blotting. Radiosensitivity was determined using clonogenic survival assays. The mechanisms underlying MK-1775 radiosensitization were studied by observing H2AX phosphorylation and mitotic catastrophe. G2 checkpoint arrest was enhanced 2.3-fold by C-ion exposure compared with X-ray exposure. Radiation-induced G2 checkpoint arrest was abrogated by MK-1775. Exposure to radiation resulted in a significant reduction in the mitotic ratio and increased phosphorylation of cyclin-dependent kinase 1 (Cdk1), the primary downstream mediator of Wee-1-induced G2 arrest. The Wee-1 inhibitor, MK-1775 restored the mitotic ratio and suppressed Cdk1 phosphorylation. In addition, MK-1775 increased H1299 cell sensitivity to C ions and X rays independent of TP53 status. MK-1775 also significantly increased H2AX phosphorylation and mitotic catastrophe in irradiated cells. These results suggest that the G2 checkpoint inhibitor MK-1775 can enhance the sensitivity of human NSCLC cells to C ions as well as X rays. PMID:26645158

  6. Automatic target tracking in FLIR image sequences

    Science.gov (United States)

    Bal, Abdullah; Alam, Mohammad S.

    2004-09-01

    Moving target tracking is a challenging task and is increasingly becoming important for various applications. In this paper, we have presented target detection and tracking algorithm based on target intensity feature relative to surrounding background, and shape information of target. Proposed automatic target tracking algorithm includes two techniques: intensity variation function (IVF) and template modeling (TM). The intensity variation function is formulated by using target intensity feature while template modeling is based on target shape information. The IVF technique produces the maximum peak value whereas the reference target intensity variation is similar to the candidate target intensity variation. When IVF technique fails, due to background clutter, non-target object or other artifacts, the second technique, template modeling, is triggered by control module. By evaluating the outputs from the IVF and TM techniques, the tracker determines the real coordinates of the target. Performance of the proposed ATT is tested using real life forward-looking infrared (FLIR) image sequences taken from an airborne, moving platform.

  7. 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)

  8. Polarization of plastic targets by laser ablation

    Science.gov (United States)

    Giuffreda, E.; Delle Side, D.; Krasa, J.; Nassisi, V.

    2016-05-01

    Charge separation in plasmas produced on plastic targets by low laser irradiance, structure of the ion front, and the current of fast electrons expanding into the vacuum chamber ahead of ions are characterized. Of particular interest is the negative current flowing through the plastic targets to the grounded vacuum chamber during the period of laser-target interaction. The subsequent multi - peaked structure of positive target current is correlated with occurrence of double sheet layers. The late-time negative charging of targets provides evidence for production of very slow ions by ionization of neutrals ablated at the target crater by radiation from plasma produced by 23 ns excimer KrF laser. The experimental setting allowing the target current observation is discussed.

  9. Molecular imaging for cancer targeting

    International Nuclear Information System (INIS)

    Full text: Molecular-genetic imaging which has grown rapidly is currently been applied to studies of gene expression regulation, activity of signal transduction pathways, angiogenesis, tumor metastases, stem cell migration, and monitoring cells involved in different components of immune response. Our Molecular and Genetic Imaging Core (MAGIC), established in late 2002, has developed a platform of small animal functional, molecular, and morphologic quantitative imaging techniques which are providing data about biochemical, genetic or pharmacological processes in vivo, and repetitively in the same animal. We first established chimeric reporter and therapeutic gene systems for specific targeting on hepatoma of mouse model. In- vivo microPET and bioluminescence imaging demonstrated the usefulness of tissue specific chimeric tk and hNIS genes. For trafficking the stem cell and cancer cells, we also have established dual and triple reporter gene system and correspondent reporter probes for in vivo imaging by microPET or microSPECT. The second application of translational biomedical imaging of cancer targeting therapy is on the inhibitors of tyrosine kinase, the key enzyme of epidermal growth factor receptor (EGFR). Mutations in the kinase domain of EGFR have higher levels of basal receptor phosphorylation and that are associated with clinical responsiveness to Iressa in patients with non-small cell lung cancer (NSCLC). High mutation rate for EGFR in Taiwanese patients of adenocarcinoma of lung suggests an urgent requirement of a non-invasive imaging tool for pre-treatment and during therapy evaluation of lung cancer patients using EGFR signalling inhibitor. Our current work on radiosynthesis of the analogue of Iressa--morpholino-[124I]-IPQA and in vitro and in vivo studies of high basal EGFR-expressing H1299's derivatives (L858R and E746-A750 del cell lines) subcutaneous tumor xenografts in immunocompromised mice, has proven that [124I]-IPQA is a feasible in vivo imaging

  10. Targeted alpha therapy for cancer

    Science.gov (United States)

    Allen, Barry J.; Raja, Chand; Rizvi, Syed; Li, Yong; Tsui, Wendy; Zhang, David; Song, Emma; Qu, Chang Fa; Kearsley, John; Graham, Peter; Thompson, John

    2004-08-01

    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 213Bi-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 µCi in human

  11. 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…

  12. Effects of Participant Ethnicity, Target Physiognomy, and Target Gender on College Students' Judgments of Cheating.

    Science.gov (United States)

    O'Neal, Margaret F.; Medlin, Jennifer; Walker, Katrina L.; Jones, Lori R.

    2002-01-01

    Studied whether white and nonwhite males and females would judge cheating by target subjects differently based on the target's physiognomy and gender. Results from a sample of 146 undergraduates show that although whites' ratings did not differ according to target physiognomy, nonwhites favored more African targets. (SLD)

  13. The utility target market model

    International Nuclear Information System (INIS)

    A new model (the Utility Target Market Model) is used to evaluate the economic benefits of photovoltaic (PV) power systems located at the electrical utility customer site. These distributed PV demand-side generation systems can be evaluated in a similar manner to other demand-side management technologies. The energy and capacity values of an actual PV system located in the service area of the New England Electrical System (NEES) are the two utility benefits evaluated. The annual stream of energy and capacity benefits calculated for the utility are converted to the installed cost per watt that the utility should be willing to invest to receive this benefit stream. Different discount rates are used to show the sensitivity of the allowable installed cost of the PV systems to a utility's average cost of capital. Capturing both the energy and capacity benefits of these relatively environmentally friendly distributed generators, NEES should be willing to invest in this technology when the installed cost per watt declines to ca $2.40 using NEES' rated cost of capital (8.78%). If a social discount rate of 3% is used, installation should be considered when installed cost approaches $4.70/W. Since recent installations in the Sacramento Municipal Utility District have cost between $7-8/W, cost-effective utility applications of PV are close. 22 refs., 1 fig., 2 tabs

  14. Tensor Target Polarization at TRIUMF

    Energy Technology Data Exchange (ETDEWEB)

    Smith, G

    2014-10-27

    The first measurements of tensor observables in $\\pi \\vec{d}$ scattering experiments were performed in the mid-80's at TRIUMF, and later at SIN/PSI. The full suite of tensor observables accessible in $\\pi \\vec{d}$ elastic scattering were measured: $T_{20}$, $T_{21}$, and $T_{22}$. The vector analyzing power $iT_{11}$ was also measured. These results led to a better understanding of the three-body theory used to describe this reaction. %Some measurements were also made in the absorption and breakup channels. A direct measurement of the target tensor polarization was also made independent of the usual NMR techniques by exploiting the (nearly) model-independent result for the tensor analyzing power at 90$^\\circ _{cm}$ in the $\\pi \\vec{d} \\rightarrow 2p$ reaction. This method was also used to check efforts to enhance the tensor polarization by RF burning of the NMR spectrum. A brief description of the methods developed to measure and analyze these experiments is provided.

  15. Target for a spallation source

    International Nuclear Information System (INIS)

    This invention concerns a liquid metal target for a spallation source. It is composed of a flow channel in which liquid metal flows at a sufficiently high rate. The flow channel has an aperture to let in the proton beam; it is shaped in a way as to generate by appropriately diverting the liquid flow inertial forces which are designed so that they avoid liquid metal penetrating through the aperture. This is achieved by the fact that the combined effect of inertial forces and gravitational forces causes near the aperture the formation of a liquid surface of the channel sides that is more or less parallel the channel side having the aperture. According to the invention this effect can be obtained by using a bent channel piece with the aperture placed in the side pointing towards the centre of curvature or by constricting the flow of liquid before it gets to the aperture and subsequent expansion behind it. A combination of the two methods is possible according to the invention. (orig.)

  16. Terrorist targeting and energy security

    Energy Technology Data Exchange (ETDEWEB)

    Toft, Peter; Duero, Arash; Bieliauskas, Arunas [Institute of Energy, Joint Research Center of the European Commission, P.O. Box 2, 1755 ZG Petten (Netherlands)

    2010-08-15

    Sudden, short-term disruptions seriously endangering energy security can be triggered by a variety of events - among them attacks by terrorists. This study investigates terrorist attack practices against energy infrastructures and discusses how we may understand them. Our results indicate that attacks against energy infrastructures are comparatively few. Also, we find no strong connection between the ideologies of various terrorist groups and their proclivity to attack. In addition, the highly disproportionate number of attacks in a handful of countries highlights the strong geographic concentration of attacks. To explain these findings, we analyze terrorist targeting incentives including intimidation levels, symbolism, attack feasibility, and concerns for stakeholders. We argue that terrorists in general have comparatively few incentives to attack energy supply infrastructures based on our assessment of these factors. Moreover, higher levels of terrorist incidents in states more prone to internal violent conflict may suggest stronger incentives to attack energy infrastructures. When outlining energy security policies, the low frequency of worldwide attacks coupled with the high concentration of attacks in certain unstable countries should be taken into consideration. Energy importing countries could benefit from developing strategies to increase stability in key energy supply and/or transit countries facing risks of internal instability. (author)

  17. Terrorist targeting and energy security

    International Nuclear Information System (INIS)

    Sudden, short-term disruptions seriously endangering energy security can be triggered by a variety of events-among them attacks by terrorists. This study investigates terrorist attack practices against energy infrastructures and discusses how we may understand them. Our results indicate that attacks against energy infrastructures are comparatively few. Also, we find no strong connection between the ideologies of various terrorist groups and their proclivity to attack. In addition, the highly disproportionate number of attacks in a handful of countries highlights the strong geographic concentration of attacks. To explain these findings, we analyze terrorist targeting incentives including intimidation levels, symbolism, attack feasibility, and concerns for stakeholders. We argue that terrorists in general have comparatively few incentives to attack energy supply infrastructures based on our assessment of these factors. Moreover, higher levels of terrorist incidents in states more prone to internal violent conflict may suggest stronger incentives to attack energy infrastructures. When outlining energy security policies, the low frequency of worldwide attacks coupled with the high concentration of attacks in certain unstable countries should be taken into consideration. Energy importing countries could benefit from developing strategies to increase stability in key energy supply and/or transit countries facing risks of internal instability.

  18. Target for a spallation source

    International Nuclear Information System (INIS)

    This invention concerns a liquid metal target for a spallation source. It is composed of a flow channel in which liquid metal flows at a sufficiently high rate. The flow channel has an aperture to let in the proton beam; it is shaped in a way as to generate by appropriately diverting the liquid flow inertial forces which are designed so that they avoid liquid metal penetrating through the aperture. This is achieved by the fact that the combined effect of inertial forces and gravitational forces causes near the aperture the formation of a liquid surface of the channel sides that is more or less parallel to the channel side having the aperture. According to the invention this effect can be obtained by using a bent channel piece with the aperture placed in the side pointing towards the centre of curvature or by constricting the flow of liquid before it gets to the aperture and subsequent expansion behind it. A combination of the two methods is possible according to the invention. (orig./PW)

  19. Drug targeting through pilosebaceous route.

    Science.gov (United States)

    Chourasia, Rashmi; Jain, Sanjay K

    2009-10-01

    Local skin targeting is of interest for the pharmaceutical and the cosmetic industry. A topically applied substance has basically three possibilities to penetrate into the skin: transcellular, intercellular, and follicular. The transfollicular path has been largely ignored because hair follicles constitute only 0.1% of the total skin. The hair follicle is a skin appendage with a complex structure containing many cell types that produce highly specialised proteins. The hair follicle is in a continuous cycle: anagen is the hair growth phase, catagen the involution phase and telogen is the resting phase. Nonetheless, the hair follicle has great potential for skin treatment, owing to its deep extension into the dermis and thus provides much deeper penetration and absorption of compounds beneath the skin than seen with the transdermal route. In the case of skin diseases and of cosmetic products, delivery to sweat glands or to the pilosebaceous unit is essential for the effectiveness of the drug. Increased accumulation in the pilosebaceous unit could treat alopecia, acne and skin cancer more efficiently and improve the effect of cosmetic substances and nutrients. Therefore, we review herein various drug delivery systems, including liposomes, niosomes, microspheres, nanoparticles, nanoemulsions, lipid nanocarriers, gene therapy and discuss the results of recent researches. We also review the drugs which have been investigated for pilosebaceous delivery. PMID:19663765

  20. Target Therapy in Lung Cancer.

    Science.gov (United States)

    Cafarotti, Stefano; Lococo, Filippo; Froesh, Patrizia; Zappa, Francesco; Andrè, Dutly

    2016-01-01

    Lung cancer is an extremely heterogeneous disease, with well over 50 different histological variants recognized under the fourth revision of the World Health Organization (WHO) typing system. Because these variants have differing genetic and biological properties correct classification of lung cancer is necessary to assure that lung cancer patients receive optimum management. Due to the recent understanding that histologic typing and EGFR mutation status are important for target the therapy in lung adenocarcinoma patients there was a great need for a new classification that addresses diagnostic issues and strategic management to allow for molecular testing in small biopsy and cytology specimens. For this reason and in order to address advances in lung cancer treatment an international multidisciplinary classification was proposed by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), further increasing the histological heterogeneity and improving the existing WHO-classification. Is now the beginning of personalized therapy era that is ideally finalized to treat each individual case of lung cancer in different way. PMID:26667341

  1. Double-layered target and identification method of individual target correlated with evaporation residues

    International Nuclear Information System (INIS)

    A double-layered target system and an identification method (target ID) for individual targets mounted on a rotating wheel using correlation with evaporation residues were newly developed for the study of superheavy elements (SHE). The target system can be used in three modes: conventional single-layered mode, double-layered mode, and energy-degrader mode. The target ID method can be utilized for masking a target, measuring an excitation function without changing the beam energy from the accelerator, and searching for SHE nuclides using multiple targets during a single irradiation

  2. Target injection methods for inertial fusion energy

    Energy Technology Data Exchange (ETDEWEB)

    Petzoldt, R.W.; Moir, R.W.

    1994-06-01

    We have studied four methods to inject IFE targets: the gas gun, electrostatic accelerator, induction accelerator, and rail gun. We recommend a gas gun for indirect drive targets because they can support a gas pressure load on one end and can slide along the gun barrel without damage. With the gas gun, the amount of gas required for each target (about 10 to 100 mg) is acceptable; for other types of targets, a sabot would be necessary. A cam and poppet valve arrangement is recommended for gas flow control. An electrostatic accelerator is attractive for use with lightweight spherical direct drive targets. Since there is no physical contact between the target and the injector, there will be no wear of either component during the injection process. An induction accelerator has an advantage of no electrical contact between the target and the injector. Physical contact is not even necessary, so the wear should be minimal. It requires a cylindrical conductive target sleeve which is a substantial added mass. A rail gun is a simpler device than an electrostatic accelerator or induction accelerator. It requires electrical contact between the target and the rails and may have a significant wear rate. The wear in a vacuum could be reduced by use of a solid lubricant such as MoS{sub 2}. The total required accuracy of target injection, tracking and beam pointing of {plus_minus}0.4 mm appears achievable but will require development and experimental verification.

  3. Climate targets for all countries: the options

    International Nuclear Information System (INIS)

    This paper assesses five options for targets that could be taken by all countries to meet the ultimate objective of the Climate Change Convention: fixed, binding targets, dynamic targets; non-binding targets; sectoral targets, policies and measures. Each is evaluated according to criteria of environmental effectiveness, cost-effectiveness, contribution to economic growth and sustainable development, and equity. While fixed, binding targets continue to be viable for industrialized countries, they do not seem suitable for many developing countries in the near future. Dynamic targets could alleviate developing countries' concerns about constraining their development as well as broader concerns about possible introduction of 'hot air' in a world trading regime; they could also be considered for some or all industrialized countries. Non-binding targets could be politically appealing to developing counties, alleviate fears about development and/or hot air, but might only allow conditional participation in emissions trading by developing countries. Sectoral targets could offer a pragmatic first step - although their cost-effectiveness might be questioned. Finally, targets based on commitments to implement specific policies and measures might drive mitigation action and be part of negotiated packages including financial and technological cooperation. All these options may coexist in the future. (authors)

  4. HIRFL-CSR internal cluster target

    Science.gov (United States)

    Shao, Caojie; Lu, Rongchun; Cai, Xiaohong; Yu, Deyang; Ruan, Fangfang; Xue, Yingli; Zhang, Jianming; Torpokov, D. K.; Nikolenko, D.

    2013-12-01

    Since HIRFL-CSR internal cluster target was built, it has played a key role in in-ring experiments at HIRFL-CSR. So far it have been operated with five gas species as targets for scattering experiments, i.e. hydrogen, nitrogen, argon, neon, and krypton. The obtained highest thickness for hydrogen target amounts up to 1012 atoms/cm2, and those of other targets are larger than 1013 atoms/cm2 with the background pressure of 10-11 mbar in CSR. The target thickness can be varied by regulating the nozzle temperature and pressure of the inlet gas. The first online internal target experiment dedicated to investigate radioactive electron capture (REC) process with Xe54+ ions colliding with the nitrogen target demonstrated the stability and reliability of the internal target system. In addition, hydrogen and krypton were also tested online in recent experiments, which indicate the target system can meet experimental requirements for the thickness of target, pressure in scattering chamber, and long-term stability.

  5. 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. PMID:26415215

  6. Multipositional internal target at the Yerevan synchrotron

    International Nuclear Information System (INIS)

    Main characteristics of the inner targets of three gamma-ray beams from the Erevan synchrotron are given. The accelerated electron beam is dumped on the targets by the orbit local disturbance method. Oscillograms of the beam stretching with time during extraction are given for different target operation. Some drawbacks of the design of the operating targets are pointed out, the main being the large period of time (about 3 hours) required to replace the target radiator. The comparative analysis of other known target designs is presented. The investigation was aimed at the development of a new target design that may ensure the possibility of an operative radiator replacement without breaking the accelerator vacuum with minimum effort and time. The problem has been solved by the modification of the present target design. An additional electromotor has been installed on the target chamber; the shaft pf the electromotor passes through the vacuum seal inside the chamber. The shaft has a gear at the end and it can be engaged with a gear at the main rod end of the target. 8 various radiators may be placed simulltaniously on the gear. The accuracy of installing each radiator in the radial direction is +-0.2 mm, and the accuracy of fixing if in rotation is +-0.3 degree. The replacement of the radiator takes not more than 3 min. The target may be used as an inner or an outer target in experiments in interactions of various materials with a particle beam. The relay control system for the multi-position target is described

  7. Is it wise to protect false targets?

    International Nuclear Information System (INIS)

    The paper considers a system consisting of genuine elements and false targets that cannot be distinguished by the attacker's observation. The false targets can be destroyed with much less effort than the genuine elements. We show that even when an attacker cannot distinguish between the genuine elements and the false targets, in many cases it can enhance the attack efficiency using a double attack strategy in which it tries first to eliminate with minimal effort as many false targets as possible in the first attack and then distributes its entire remaining resource among all surviving targets in the second attack. The model for evaluating the system vulnerability in the double attack is suggested for a single genuine element, and multiple genuine elements configured in parallel or in series. This model assumes that in both attacks the attacking resource is distributed evenly among the attacked targets. The defender can optimize its limited resource distribution between deploying more false targets and protecting them better. The attacker can optimize its limited resource distribution between two attacks. The defense strategy is analyzed based on a two period minmax game. A numerical procedure is suggested that allows the defender to find the optimal resource distribution between deploying and protecting the false targets. The methodology of optimal attack and defense strategies analysis is demonstrated. It is shown that protecting the false targets may reduce the efficiency of the double attack strategy and make this strategy ineffective in situations with low contest intensity and few false targets. - Highlights: ► The efficiency of the double attack tactics against using false targets is analyzed. ► The role of the false target protection in system survivability enhancement is shown. ► The resource distribution between deploying more false targets and protecting them better is optimized. ► Both series and parallel systems are considered.

  8. Should inflation targeting be abandoned in favour of nominal income targeting?

    OpenAIRE

    Stan du Plessis; Malan Rietveld

    2013-01-01

    In the wake of the international financial crisis nominal income targeting has received renewed attention from a number of leading macroeconomists as alternative to inflation targeting. The case for nominal income targeting has been built on both positive and negative arguments. The negative case relates to perceived inadequacies of inflation targeting, including: the presumed lack of robustness of inflation targeting to aggregate supply shocks, inadequate concern with financial stability, as...

  9. Non-target Markets and Viewer Distinctiveness: The Impact of Target Marketing on Advertising Attitudes

    OpenAIRE

    Aaker, Jennifer L.; Brumbaugh, Anne M.; Grier, Sonya A.

    2000-01-01

    This research examines the effect of target marketing on members of the advertiser's intended audience as well as members not in the target market: the "non-target market." The results of three experiments show that unfavorable non-target market effects are stronger for members of non-distinctive groups (e.g., Causasian individuals, heterosexual individuals), and that favorable target market effects are stronger fro members of distinctive groups (e.g., Africian-American individuals, homosexua...

  10. Cytomegalovirus protease targeted prodrug development.

    Science.gov (United States)

    Sabit, Hairat; Dahan, Arik; Sun, Jing; Provoda, Chester J; Lee, Kyung-Dall; Hilfinger, John H; Amidon, Gordon L

    2013-04-01

    Human cytomegalovirus (HCMV) is a prevalent virus that infects up to 90% of the population. The goal of this research is to determine if small molecular prodrug substrates can be developed for a specific HCMV encoded protease and thus achieve site-specific activation. HCMV encodes a 256 amino acid serine protease that is responsible for capsid assembly, an essential process for herpes virus production. The esterase activity of the more stable HCMV A143T/A144T protease mutant was evaluated with model p-nitrophenol (ONp) esters, Boc-Xaa-ONp (Ala, Leu, Ile, Val, Gln, Phe at the Xaa position). We demonstrate that the A143T/A144T mutant has esterase activity toward specific small ester compounds, e.g., Boc-L-Ala-ONp. Mono amino acid and dipeptide prodrugs of ganciclovir (GCV) were also synthesized and evaluated for hydrolysis by the A143T/A144T protease mutant in solution. Hydrolysis of these prodrugs was also evaluated in Caco-2 cell homogenates, human liver microsomes (HLMs), and rat and human plasma. For the selectivity potential of the prodrugs, the hydrolysis ratio was evaluated as a percentage of prodrug hydrolyzed by the HCMV protease over the percentages of prodrug hydrolyses by Caco-2 cell homogenates, HLMs, and human/rat plasma. A dipeptide prodrug of ganciclovir, Ac-l-Gln-l-Ala-GCV, emerged as a potential selective prodrug candidate. The results of this research demonstrate that targeting prodrugs for activation by a specific protease encoded by the infectious HCMV pathogen may be achievable. PMID:23485093

  11. 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. PMID:25869441

  12. Quinoline: a promising antitubercular target.

    Science.gov (United States)

    Keri, Rangappa S; Patil, Siddappa A

    2014-10-01

    Tuberculosis (TB) remains a global public health problem in recent years. TB originated mainly from various strains of Mycobacterium tuberculosis, is a highly infectious and chronic disease with high infection rate since ancient times. Since the last 50 years, the same long-duration, multidrug treatment plan is being followed for the treatment of tuberculosis. Due to the development of resistance to conventional antibiotics there is a need for new therapeutic strategies to combat M. tuberculosis. Subsequently, there is an urgent need for the development of new drug molecules with newer targets and with an alternative mechanism of action. Among hetrocyclic compounds, quinoline compounds are important privileged structure in medicinal chemistry, are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain, quinoline-based compounds, also show effective anti-TB activity. This broad spectrum of biological and biochemical activities has been further facilitated by the synthetic versatility of quinoline, which allows the generation of a large number of structurally diverse derivatives. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review, we have collated published reports on this versatile core to provide an insight so that its full therapeutic potential can be utilized for the treatment tuberculosis. It is hoped that, this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic quinoline-based anti-TB drugs. PMID:25458785

  13. 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.

  14. CACAO facility. Radioactive targets at Orsay

    International Nuclear Information System (INIS)

    CACAO, Chimie des Actinides et Cibles radioActives a Orsay (actinide chemistry and radioactive targets at Orsay), is a new laboratory dedicated to the fabrication and characterization of radioactive targets. It is supported by the radiochemistry group and the stable target service of the IPNO. The recurring needs of physicists working in the nuclear fuel cycle physics and the growing difficulties to obtain radioactive targets elsewhere were the main motivating factors behind the construction of this new laboratory. The first targets of 235,238U and 232Th have already been prepared although the full operating licenses still need to be obtained. In this paper, the installation and the equipment of CACAO will be described. An extensive study of a U test target fabricated by the CACAO laboratory has been performed and results are reported here. The different techniques used to characterize the deposit are presented and the outcome is discussed. (author)

  15. 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.

  16. Target production for inertial fusion energy

    Energy Technology Data Exchange (ETDEWEB)

    Woodworth, J.G.; Meier, W.

    1995-03-01

    Inertial fusion energy (IFE) power plants will require the ignition and burn of 5-10 fusion fuel targets every second. The technology to economically mass produce high-quality, precision targets at this rate is beyond the current state of the art. Techniques that are scalable to high production rates, however, have been identified for all the necessary process steps, and many have been tested in laboratory experiments or are similar to current commercial manufacturing processes. In this paper, we describe a baseline target factory conceptual design and estimate its capital and operating costs. The result is a total production cost of {approximately}16{cents} per target. At this level, target production represents about 6% of the estimated cost of electricity from a 1-GW{sub e} IFE power plant. Cost scaling relationships are presented and used to show the variation in target cost with production rate and plant power level.

  17. Target production for inertial fusion energy

    International Nuclear Information System (INIS)

    Inertial fusion energy (IFE) power plants will require the ignition and burn of 5-10 fusion fuel targets every second. The technology to economically mass produce high-quality, precision targets at this rate is beyond the current state of the art. Techniques that are scalable to high production rates, however, have been identified for all the necessary process steps, and many have been tested in laboratory experiments or are similar to current commercial manufacturing processes. In this paper, we describe a baseline target factory conceptual design and estimate its capital and operating costs. The result is a total production cost of ∼16 cents per target. At this level, target production represents about 6% of the estimated cost of electricity from a 1-GWe IFE power plant. Cost scaling relationships are presented and used to show the variation in target cost with production rate and plant power level

  18. Micromachining applications for ICF target fabrication

    International Nuclear Information System (INIS)

    Micromachining techniques used in Inertial Confinement Fusion (ICF) target fabrication encompass laser drilling, single point diamond turning, and plasma as well as chemical etching. These techniques have been developed by several laboratories to produce target components with tolerances and surface finishes in the micron to submicron regime. Some of the spherical target components produced by micromachining techniques include free standing hemispherical shells (diameters 50--500 mm), micron-sized holes in thin glass shells, and plastic-coated glass microballons with surfaces which have been smoothly machined to remove a mounting stalk. Planar targets and components produced by these techniques include small disks and washers of thin brittle materials. Micromachining techniques are also used to fabricate diagnostic instruments such as x-ray mirrors and zone plates. This paper will examine micromachining techniques used to produce target components and diagnostic instruments. The relationship of each micromachining technique to presently used target configurations will also be discussed

  19. Aviation spectral camera infinity target simulation system

    Science.gov (United States)

    Liu, Xinyue; Ming, Xing; Liu, Jiu; Guo, Wenji; Lv, Gunbo

    2014-11-01

    With the development of science and technology, the applications of aviation spectral camera becoming more widely. Developing a test system of dynamic target is more important. Aviation spectral camera infinity target simulation system can be used to test the resolution and the modulation transfer function of camera. The construction and work principle of infinity target simulation system were introduced in detail. Dynamic target generator based digital micromirror device (DMD) and required performance of collimation System were analyzed and reported. The dynamic target generator based on DMD had the advantages of replacing image convenient, size small and flexible. According to the requirement of tested camera, by rotating and moving mirror, has completed a full field infinity dynamic target test plan.

  20. Isotope targets prepared by vapor deposition

    International Nuclear Information System (INIS)

    As the state of the art for producing thin films has developed, the parameters set by the experiments have in turn become more stringent. Often these targets must be of high purity, extremely thin, self-supporting, and of accurately determined thickness. In addition, the target material may be an expensive isotope which must be reduced to elemental form at the time of vapor deposition. Methods of producing some of these targets will be discussed with such examples as calcium, magnesium and boron

  1. Ion acceleration enhanced by target ablation

    International Nuclear Information System (INIS)

    Laser proton acceleration can be enhanced by using target ablation, due to the energetic electrons generated in the ablation preplasma. When the ablation pulse matches main pulse, the enhancement gets optimized because the electrons' energy density is highest. A scaling law between the ablation pulse and main pulse is confirmed by the simulation, showing that for given CPA pulse and target, proton energy improvement can be achieved several times by adjusting the target ablation

  2. FOMC Targets, Base Drift and Inflationary Expectations

    OpenAIRE

    Charles E. Hegji

    1989-01-01

    This paper uses a money supply-money demand model to study the effects on inflationary expectations of base drift and the Federal Open Market Committee's rebasing of its money supply targets. It is demonstrated that an averaging scheme for determining the Federal Open Market Committee's money stock target bases generates less inflationary uncertainty than no averaging. It is also shown that an alternative to target averaging is to accommodate long-run money supply strategy to changes in money...

  3. Design of liposomal formulations for cell targeting

    OpenAIRE

    Nogueira, E.; Gomes, Andreia C.; Preto, Ana; Cavaco-Paulo, Artur

    2015-01-01

    Liposomes have gained extensive attention as carriers for a wide range of drugs due to being both nontoxic and biodegradable as they are composed of substances naturally occurring in biological membranes. Active targeting for cells has explored specific modification of the liposome surface by functionalizing it with specific targeting ligands in order to increase accumulation and intracellular uptake into target cells. None of the Food and Drug Administration-licensed liposomes or lipid nanop...

  4. Advances in Targeting Signal Transduction Pathways

    OpenAIRE

    McCubrey, James A.; Steelman, Linda S.; Chappell, William H.; Sun, Lin; Davis, Nicole M.; Abrams, Stephen L.; Franklin, Richard A.; Cocco, Lucio; Evangelisti, Camilla; Chiarini, Francesca; Martelli, Alberto M.; Libra, Massimo; Candido, Saverio; Ligresti, Giovanni; Malaponte, Grazia

    2012-01-01

    Over the past few years, significant advances have occurred in both our understanding of the complexity of signal transduction pathways as well as the isolation of specific inhibitors which target key components in those pathways. Furthermore critical information is being accrued regarding how genetic mutations can affect the sensitivity of various types of patients to targeted therapy. Finally, genetic mechanisms responsible for the development of resistance after targeted therapy are being ...

  5. Target R and D at JAERI

    International Nuclear Information System (INIS)

    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)

  6. MicroRNA Targets - How to predict?

    OpenAIRE

    Das, Nabajit

    2012-01-01

    A number of web tools are available for the prediction and identification of target microRNAs (miRNAs). The choice, availability, validity and selection of an optimal yet appropriate tool are a challenge for the design of high throughput assays with promising miRNA targets. The current trends and challenges for target microRNAs (miRNAs) prediction, identification and selection is described in this review.

  7. From monetary to exchange rate targets

    Directory of Open Access Journals (Sweden)

    M.J. ARTIS

    2013-12-01

    Full Text Available This paper was presented at the Fourth International Seminar on European Economic and Monetary Union, held in Copenhagen in March of 1981. The author takes up the theoretical issues in the framework of both static and dynamic analysis. He argues, on the basis of the criterion of minimising the variance of prices around their target value, that an exchange-rate target outperforms a monetary target under most conceivable types of disturbances in a static analysis. 

  8. Applying target shadow models for SAR ATR

    Science.gov (United States)

    Papson, Scott; Narayanan, Ram M.

    2007-04-01

    Recent work has suggested that target shadows in synthetic aperture radar (SAR) images can be used effectively to aid in target classification. The method outlined in this paper has four steps - segmentation, representation, modeling, and selection. Segmentation is the process by which a smooth, background-free representation of the target's shadow is extracted from an image chip. A chain code technique is then used to represent the shadow boundary. Hidden Markov modeling is applied to sets of chain codes for multiple targets to create a suitable bank of target representations. Finally, an ensemble framework is proposed for classification. The proposed model selection process searches for an optimal ensemble of models based on various target model configurations. A five target subset of the MSTAR database is used for testing. Since the shadow is a back-projection of the target profile, some aspect angles will contain more discriminatory information then others. Therefore, performance is investigated as a function of aspect angle. Additionally, the case of multiple target looks is considered. The capability of the shadow-only classifier to enhance more traditional classification techniques is examined.

  9. Modeling and Filtering for Tracking Maneuvering Targets

    Directory of Open Access Journals (Sweden)

    Sadiq J. Abou-Loukh

    2009-01-01

    Full Text Available A new mathematical model describing the motion of manned maneuvering targets is presented. This model is simple to be implemented and closely represents the motion of maneuvering targets. The target maneuver or acceleration is correlated in time. Optimal Kalman filter is used as a tracking filter which results in effective tracker that prevents the loss of track or filter divergency that often occurs with conventional tracking filter when the target performs a moderate or heavy maneuver. Computer simulation studies show that the proposed tracker provides sufficient accuracy.

  10. Pyrographite water-cooled target analysis

    International Nuclear Information System (INIS)

    This report presents a study of two pyrographic water-cooled targets planned for use in the Clinton P. Anderson Meson Physics Facility. A steady-state thermal stress analysis was done that included a parameter study on the physical and numerical variables that affect the problem. The maximum target temperatures and stresses were calculated and compared for a variety of conditions. The comparisons show that the 0.6-cm half-width fin target proposed for the A-2 line is the most vulnerable of the targets analyzed

  11. Uncertainties in thick-target PIXE analysis

    International Nuclear Information System (INIS)

    Thick-target PIXE analysis insolves uncertainties arising from the calculation of thick-target X-ray production in addition to the usual PIXE uncertainties. The calculation demands knowledge of ionization cross-sections, stopping powers and photon attenuation coefficients. Information on these is reviewed critically and a computational method is used to estimate the uncertainties transmitted from this data base into results of thick-target PIXE analyses with reference to particular specimen types using beams of 2-3 MeV protons. A detailed assessment of the accuracy of thick-target PIXE is presented. (orig.)

  12. The potential therapeutic targets for cervical cancer

    Directory of Open Access Journals (Sweden)

    L Priyanka Dwarampudi

    2013-01-01

    Full Text Available In case of invasive cervical carcinoma several molecular events were reported and these molecular events resulting in multiple genetic abnormalities. In order to control these tumors multiple molecular therapeutic targets are needed with different molecular mechanisms. Unfortunately, these molecular targets were in early stages of development. Because of less degree of success of conventional therapeutics for late stages of cervical cancer and lowering of prognosis of patients there is an increase in interest for the development of potential therapeutic targets for cervical cancer. This review article emphasizes the current molecular targeted agents; with special attention to estrogen receptors for human papilloma virus infected cervical cancer.

  13. Target studies for surface muon production

    Science.gov (United States)

    Berg, F.; Desorgher, L.; Fuchs, A.; Hajdas, W.; Hodge, Z.; Kettle, P.-R.; Knecht, A.; Lüscher, R.; Papa, A.; Rutar, G.; Wohlmuther, M.

    2016-02-01

    Meson factories are powerful drivers of diverse physics programs. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90°. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30% and 60% over the standard "box-like" target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizing novel target materials such as, e.g., boron carbide.

  14. Physical measurements of inertial-fusion targets

    International Nuclear Information System (INIS)

    Measurement of inertial-fusion targets has stimulated the development of many new techniques and instruments. This paper reviews the basis for selected target measurement requirements and the development of optical interferometry, optical scattering, microradiography and scanning electron microscopy as applied to target measurement. We summarize the resolution and speed which have been achieved to date, and describe several systems in which these are traded off to fill specific measurement applications. We point out the extent to which present capabilities meet the requirements for target measurement and the key problems which remain to be solved

  15. Isomeric target for nuclear structure studies

    CERN Document Server

    Maunoury, L; Aubert, P; Aupiais, J; Baudin, M; Blier, G; Bonnereau, B; Boulin, Y; Pointurier, F; Sauvestre, J E; Sigaud, J; Szmigiel, M

    2002-01-01

    The experimental studies on nuclear structure and reactions dealing with nuclei in their isomeric state are, actually, mainly constrained by the difficulty of producing isomeric targets. The CEA/Bruyeres-le-Chatel laboratory has initiated the production of a sup 1 sup 7 sup 7 Lu sup m isomeric target. We plan to reach a 45% isomeric purity associated with a number of isomeric nuclei about 10 sup 1 sup 5. This target will be available for experiments at the end of the year 2000. The method performed to produce such targets will be discussed.

  16. Dual Target Design for CLAS12

    Science.gov (United States)

    Alam, Omair; Gilfoyle, Gerard; Christo, Steve

    2015-10-01

    An experiment to measure the neutron magnetic form factor (GnM) is planned for the new CLAS12 detector in Hall B at Jefferson Lab. This form factor will be extracted from the ratio of the quasielastic electron-neutron to electron-proton scattering off a liquid deuterium (LD2) target. A collinear liquid hydrogen (LH2) target will be used to measure efficiencies at the same time as production data is collected from the LD2 target. To test target designs we have simulated CLAS12 and the target geometry. Electron-nucleon events are produced first with the QUasiElastic Event Generator (QUEEG) which models the internal motion of the nucleons in deuterium.1 The results are used as input to the CLAS12 Monte Caro code gemc; a Geant4-based program that simulates the particle's interactions with each component of CLAS12 including the target material. The dual target geometry has been added to gemc including support structures and cryogenic transport systems. A Perl script was written to define the target materials and geometries. The output of the script is a set of database entries read by gemc at runtime. An initial study of the impact of this dual-target structure revealed limited effects on the electron momentum and angular resolutions. Work supported by the University of Richmond and the US Department of Energy.

  17. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Progress of molecular biology, genetic engineering, and polymer chemistry provide various tools to target molecules and cells in vivo. In this paper, recent achievements in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune, and stem cells using molecular nuclear imaging techniques are introduced

  18. How successful is nuclear targeting by nanocarriers?

    Science.gov (United States)

    Tammam, Salma N; Azzazy, Hassan M E; Lamprecht, Alf

    2016-05-10

    The nucleus is ultimately the final target for many therapeutics treating various disorders including cancers, heart dysfunction and brain disorders. Owing to their specialized cell uptake and trafficking mechanisms, nanoparticles (NPs) allow drug targeting where degradation sensitive therapeutics could be delivered to their target tissues and cell in active form and sufficient concentration. However, it has recently become increasingly obvious that cytosolic internalization of a drug molecule does not entail its interaction with its subcellular target and hence careful nanoparticle design and optimization is required to enable nuclear targeting. This review, discusses the barriers to NP nuclear delivery; crossing the cell membrane, endo/lysosomal escape, cytoplasmic trafficking and finally nuclear entry focusing on how NP synthesis and modification could allow for bypassing each of the aforementioned barriers and successfully reaching the nucleus. Examples of nuclear targeted NPs are also discussed, stressing on the critical aspects of nuclear targeting and pointing out how the disease state might change the normal NP path and how such change could be exploited to increase efficiency of nuclear targeting. Finally, the criteria set for the evaluation of nanocarriers for nuclear delivery are discussed highlighting that quantitative rather than qualitative evaluation is required to evaluate how successful nanocarriers for nuclear delivery are, particularly with regards to the amount of drug delivered and released in the nucleus. PMID:26995759

  19. Target asymmetry in inclusive photoproduction of pions

    International Nuclear Information System (INIS)

    We study the target asymmetry in inclusive pion photoproduction in the photon fragmentation region using a helicity dependent Mueller-Regge model, in which the Regge cut contributions are also included. We obtained predictions for the t-dependence and the magnitude of the target asymmetry. (orig.)

  20. Liquid hydrogen target cooled by circulating helium

    International Nuclear Information System (INIS)

    Structure and characteristics of a liquid hydrogen target, where hydrogen is liquefied with liquid helium flow using evaporation heat of liquid helium and vapour cold, are described. Good thermal insulation of liquid helium supply line permits to remove out of the target the most volumetric and heavy component - helium tank - and to supply liquid helium along spreaded pipeline from the Dewar helium flask. It results in considerable reduction of dimensions and weight, the structure simplification and work facilitation with the target. The target having a working volume of 400 mm length and 60 mm diameter was tested. Vacuum casing of the working volume was made of foam plastic, heat flow to the working volume is equal to 1.5 W. Achieving mode of operation including structure cooling and hydrogen liquefaction took approximately 3 h, liquid helium flow rate for liquefaction of 1 l hydrogen is 2.7 l. Liquid helium flow rate in the mode of operation was equal to 0.7 l/h, i.e. target operation period without adding liquid helium to the Dewar flask is 4-5 days. The target described is notable for simplicity in fabrication, reliability in operation and is very suitable for using in experiment as compared to existing targets with hydrogen liquefaction with liquid helium. Unit structure of the target enables to easily change its configuration relative to problems of concrete physical experiment

  1. Why cryogenic ICF [Inertial Confinement Fusion] targets?

    International Nuclear Information System (INIS)

    All advanced Inertial Confinement Fusion (ICF) targets will be built with cryogenic thermonuclear fuel configurations. This paper reviews the ICF concept with emphasis on the conditions required for efficient energy production, some details of the implosion process, along with a discussion of certain sources of potential inefficiencies, and estimates of target fabrication requirements. 4 refs., 8 figs

  2. Visual Search Asymmetry with Uncertain Targets

    Science.gov (United States)

    Saiki, Jun; Koike, Takahiko; Takahashi, Kohske; Inoue, Tomoko

    2005-01-01

    The underlying mechanism of search asymmetry is still unknown. Many computational models postulate top-down selection of target-defining features as a crucial factor. This feature selection account implies, and other theories implicitly assume, that predefined target identity is necessary for search asymmetry. The authors tested the validity of…

  3. Receptor-targeted metalloradiopharmaceuticals. Final technical report

    International Nuclear Information System (INIS)

    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

  4. The fabrication of 26Al targets

    International Nuclear Information System (INIS)

    Targets with up to 1.4x101626Al atoms have been fabricated. The artificial production of the 26Al nuclei via the reaction 26Mg(p, n)26Al was carried out at the cyclotrons in Juelich and Muenchen. The experimental procedures in the fabrication of these targets as well as some test measurements are described. (orig.)

  5. Mathematical modelling of magnetically targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Grief, Andrew D. [Theoretical Mechanics, School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)]. E-mail: andrew.grief@nottingham.ac.uk; Richardson, Giles [Theoretical Mechanics, School of Mathematical Sciences, University of Nottingham, University Park, Nottingham NG7 2RD (United Kingdom)]. E-mail: giles.richardson@nottingham.ac.uk

    2005-05-15

    A mathematical model for targeted drug delivery using magnetic particles is developed. This includes a diffusive flux of particles arising from interactions between erythrocytes in the microcirculation. The model is used to track particles in a vessel network. Magnetic field design is discussed and we show that it is impossible to specifically target internal regions using an externally applied field.

  6. Inflation Targeting in Emerging Market Countries

    OpenAIRE

    Mishkin, Frederic S.

    2000-01-01

    This paper outlines what inflation targeting involves for emerging market/transition countries and discusses the advantages and disadvantages of this monetary policy strategy. The discussion suggests that although inflation targeting is not a panacea and may not be appropriate for many emerging market countries, it can be a highly useful monetary policy strategy in a number of them.

  7. Polarized proton target-IV. Operations manual

    International Nuclear Information System (INIS)

    Standard operating procedures are presented for the vacuum, cryogenic, and electronic systems of a polarized proton target. The systems are comprised of (1) a target cryostat; (2) a 4He pumping system; (3) a 3He pumping system; (4) a microwave system; (5) a magnet and power supply; (6) a computerized polarization monitor; and (7) miscellaneous auxiliary equipment

  8. The spinning particle with curved target

    CERN Document Server

    Getzler, Ezra

    2016-01-01

    We extend our previous calculation [arXiv:1511.02135] of the BV cohomology of the spinning particle with a flat target to the general case, in which the target carries a non-trivial pseudo-Riemannian metric and a magnetic field.

  9. Active Targets For Capacitive Proximity Sensors

    Science.gov (United States)

    Jenstrom, Del T.; Mcconnell, Robert L.

    1994-01-01

    Lightweight, low-power active targets devised for use with improved capacitive proximity sensors described in "Capacitive Proximity Sensor Has Longer Range" (GSC-13377), and "Capacitive Proximity Sensors With Additional Driven Shields" (GSC-13475). Active targets are short-distance electrostatic beacons; they generate known alternating electro-static fields used for alignment and/or to measure distances.

  10. 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.

  11. Target Studies for Surface Muon Production

    CERN Document Server

    Berg, F; Fuchs, A; Hajdas, W; Hodge, Z; Kettle, P -R; Knecht, A; Lüscher, R; Papa, A; Rutar, G; Wohlmuther, M

    2015-01-01

    Meson factories are powerful drivers of diverse physics programmes. With beam powers already in the MW-regime attention has to be turned to target and beam line design to further significantly increase surface muon rates available for experiments. For this reason we have explored the possibility of using a neutron spallation target as a source of surface muons by performing detailed Geant4 simulations with pion production cross sections based on a parametrization of existing data. While the spallation target outperforms standard targets in the backward direction by more than a factor 7 it is not more efficient than standard targets viewed under 90{\\deg}. Not surprisingly, the geometry of the target plays a large role in the generation of surface muons. Through careful optimization, a gain in surface muon rate of between 30 - 60% over the standard "box-like" target used at the Paul Scherrer Institute could be achieved by employing a rotated slab target. An additional 10% gain could also be possible by utilizin...

  12. 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.

  13. Targeted Toxins in Brain Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Walter A. Hall

    2010-11-01

    Full Text Available 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.

  14. Target discrimination strategies in optics detection

    Science.gov (United States)

    Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

    2013-10-01

    Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

  15. Target system materials and engineering problems

    International Nuclear Information System (INIS)

    This paper discusses the common problems of target design. As a model for the discussion, the author considers a spallation source which is fed by a high power proton beam of the order of one megawatt. The materials used for the target station and particularly for the spallation target itself depend on whether the source is built for pulsed, modulated or continuous operation. The difference of materials used is mainly determined by the neutronics considerations. Depending on the choice of materials for the target systems, the characters of material problems met, are of somewhat different nature. It is recognized that for each target version quite specific difficulties have to be overcome. On the other hand, there is a whole set of problems which is common to all target versions. These are: heat load in region of proton beam interactions; thermal stress and cycling; and radiation damage. It is shown that solutions to the whole package of problems up to a beam power of 0 (1MW) have been found. The whole effort concentrates onto the region of the first few centimeters of beam penetration. Two solutions have been proposed: (1) Keep the power of proton beam limited and produce neutrons elsewhere in the target. and (2) Dilute the power by moving mechanically the target and the window. 8 refs., 11 figs

  16. INSTRUMENT CHOICE AND BUDGET-CONSTRAINED TARGETING

    OpenAIRE

    Horan, Richard D.; Claassen, Roger; Agapoff, Jean; Zhang, Wei

    2004-01-01

    We analyze how choosing to use a particular type of instrument for agri-environmental payments, when these payments are constrained by the regulatory authority's budget, implies an underlying targeting criterion with respect to costs, benefits, participation, and income, and the tradeoffs among these targeting criteria. The results provide insight into current policy debates.

  17. What "helps" tumors evade vascular targeting treatment?

    Institute of Scientific and Technical Information of China (English)

    SI Zhi-chao; LIU Jie

    2008-01-01

    Objective To throw a light on the possible factors which might induce resistance of vascular targeting treatment in tumors by reviewing the recent publications in the field of tumor angiogenesis and vascular targeting treatment.Data sources The data used in this review were mainly from Medline and PubMed for relevant English language articles published from 1971 to January 2008. The search terms were "angiogenesis", "vascular targeting treatment" and "endothelial progenitor cells".Study selection Articles involved in the possible influence factors during angiogenesis and vascular targeting treatment were selected, including angiogenic or anti-angiogenic mechanism, tumor vasculature, tumor cells, cancer stem cells and endothelial progenitor cells.Results As a promising strategy vascular targeting treatment still has experimental and clinical setbacks which may term tumor vasculature's resistance to anti-angiogenesis agents. There are several possible explanations for such a resistance that might account for clinical and preclinical failures of anti-angiogenic treatment against tumor.Proangiogenic effect of hypoxia, normal tumor vasculature, escape of tumor cells and tumor vasculogenesis are included.This review reveals some clues which might be helpful to direct future research in order to remove obstacles to vascular targeting treatment.Conclusions Generally and undoubtedly vascular targeting treatment remains a promising strategy. But we still have to realize the existence of a challenging future. Further research is required to enhance our knowledge of vascular targeting treatment strategy before it could make a more substantial success.

  18. Targeting hypoxia in head and neck cancer

    International Nuclear Information System (INIS)

    The idea of 'targeting' hypoxia stems from recognition of the fact that oxygen (or its lack) is central to the practice of radiation oncology. Targeting embraces the alternative goals of trying to overcome hypoxia on the one hand and trying to exploit it on the other. This presentation briefly reviews these two approaches with major emphasis on the latter

  19. Liner target interaction experiments on Pegasus II

    International Nuclear Information System (INIS)

    The Los Alamos High Energy Density Physics program uses capacitively driven low voltage, inductive-storage pulse power to implode cylindrical targets for hydrodynamics experiments. Once a precision driver liner was characterized an experimental series characterizing the aluminum target dynamics was performed. The target was developed for shock-induced quasi-particle ejecta experiments including holography. The concept for the Liner shock experiment is that the driver liner is used to impact the target liner which then accelerates toward a collimator with a slit in it. A shock wave is set up in the target liner and as the shock emerges from the back side of the target liner, ejecta are generated. By taking a laser hologram the particle distribution of the ejecta are hoped to be determined. The goal for the second experimental series was to characterize the target dynamics and not to measure and generate the ejecta. Only the results from the third shot, Pegasus II-26 fired April 26th, 1994, from the series is discussed in detail. The second experimental series successfully characterized the target dynamics necessary to move forward towards the planned quasi-ejecta experiments

  20. Targeting bactoprenol-coupled cell envelope precursors.

    Science.gov (United States)

    Ulm, Hannah; Schneider, Tanja

    2016-09-01

    Targeting the bactoprenol-coupled cell wall precursor lipid II is a validated antibacterial strategy. In this review, selected prototype lipid II-binding antibiotics of different chemical classes are discussed. Although these compounds attack the same molecular target, they trigger nuanced and diverse cellular effects. Consequently, the mechanisms of antibacterial resistance and the likelihood of resistance development may vary substantially. PMID:27495122

  1. PIE preparation of the MEGAPIE target

    Science.gov (United States)

    Wohlmuther, Michael; Wagner, Werner

    2012-12-01

    The MEGAPIE target, after successfully operating for 4 months at a beam power of 0.77 MW, is now being prepared for post irradiation examination PIE. The lead-bismuth eutectic (LBE) target was irradiated from August until December 2006, and in this period received a beam charge of 2.8 A h of 575 MeV protons. After that, the target was stored in the target storage facility of PSI, waiting for its post irradiation examination. In the meantime several campaigns of tests have been conducted by PSI and ZWILAG, the interim storage facility of Swiss nuclear power plants. In these tests the feasibility of the conditioning of the target and the extraction of sample material for the PIE has been proven. After transport to the hot cell facility at ZWILAG in June 2009, the dismantling of the MEGAPIE target started. It finally was cut into 21 pieces. Ten of these pieces will be shipped to the Hot Laboratory of PSI ('PSI hotlab') to extract samples from the structural materials as well as from the LBE. Currently it is foreseen that the sample extraction will start in the first half of 2011. The remaining parts of the MEGAPIE target were conditioned as radioactive waste. The present paper will mainly focus on the dismantling and first visual inspection of the MEGAPIE target. In addition an outlook on the PIE phase of MEGAPIE is given.

  2. Fabrication and Characterization of Fast Ignition Targets

    International Nuclear Information System (INIS)

    Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. We have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets

  3. FABRICATION AND CHARACTERIZATION OF FAST IGNITION TARGETS

    International Nuclear Information System (INIS)

    OAK-B135 Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. The authors have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets

  4. Targeted inhibition of tumor growth and angiogenesis

    NARCIS (Netherlands)

    van der Meel, R.

    2013-01-01

    Two main strategies have been pursued for the development of an effective and targeted anti-cancer treatment. The first strategy comprised the generation of a targeted nanomedicine for the inhibition of tumor cell proliferation by blocking growth factor receptor pathways. The epidermal growth factor

  5. 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

  6. SEQUENTIAL TARGETED THERAPY FOR DISSEMINATED KIDNEY CANCER

    Directory of Open Access Journals (Sweden)

    V. B. Matveev

    2014-07-01

    Full Text Available Targeted therapy is a standard treatment in advanced renal cell carcinoma. Stabilization is an expected response to targeted therapy. The main goal of targeted therapy is to improve progression-free survival. This purpose is served through the sequential use of targeted agents. First-line therapy agents in the good and intermediate MSKCC prognostic groups are antiangiogenic ones such as bevacizumab, sunitinib, sorafenib, pazopanib; in the poor MSKCC prognostic group treatment of choice is an mTOR inhibitor temsirolimus. The antiangiogenic agent axitinib and the mTOR inhibitor everolimus were proved to be effective as second-line therapy. Axitinib administration after anti-VEGF drugs is associated with cumulative toxicity. The efficacy of axitinib in sorafenib-refractory renal cell carcinoma has not been proven. So everolimus remains the agent of choice for second-line targeted therapy. The effect of repeated antiangiogenic therapy may be anticipated after everolimus therapy. 

  7. Targeted Radionuclide Therapy of Human Tumors

    Science.gov (United States)

    Gudkov, Sergey V.; Shilyagina, Natalya Yu.; Vodeneev, Vladimir A.; Zvyagin, Andrei V.

    2015-01-01

    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. PMID:26729091

  8. 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...... problems, in particular those related to accounting for the internal performance (that are going to be compared with the external target), calculating the ‘inside’ costs and defining controllability, contributes to the management accounting as well as the piece-rate literature....

  9. Thick backed carbon targets via mechanical rolling

    International Nuclear Information System (INIS)

    For targets requiring thick backing foils, the straight-forward and usual method is to deposit the target material directly on the backing by thermal evaporation. In some instances the reverse is more desirable, adding a backing to an already existing target foil, for example. A recent study involving measurement of the lifetime of the first 2+ excited state in 36Ar by the Doppler shift attenuation method required 0.5 mg/cm2 natural carbon targets on thick (18 mg/cm2) gold and lead backings. Problems of delamination had arisen after beam irradiation using thick gold backings for these experiments. Carbon target foils were then prepared by mechanical rolling in direct contact with a thick lead backing using an intermediate layer of indium to assure good adhesion of the layers. Details of the method will be discussed. (author)

  10. 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.

  11. Exploiting novel molecular targets in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

  12. 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.

  13. 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.

  14. Step brazing a multi-target TRAX

    International Nuclear Information System (INIS)

    Fabrication of a target holder for a multi-target transmission anode x-ray tube (TRAX) involved joining of five different materials. The TRAX will generate a nearly mono-energetic x-ray beam useful for instrument calibration and dosimetry studies. Each of three different targets will provide a different energy. The design will allow the experimenter to place a different target in front of the electron beam without breaking vacuum each time. The procedure is described for attaching three 12.7 mm (1/2 in.) diameter targets - made of tungsten, gold and uranium 238 (D-38) - to an OFHC copper support bar. The joining of the copper bar to a welded stainless steel bellows and flange is also described

  15. 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...

  16. Electrostatics, small particles, and laser fusion targets

    International Nuclear Information System (INIS)

    The success of any Inertial Confinement Fusion system for the production of useful power depends critically on the production of suitable targets. This is true whether the arrangement is that proposed by Nuckolls et al. or some other arrangement. The target must have characteristics such as material composition, structure, and surface finish which are tailored to the laser pulse length, energy, peak and average power and pulse shape. To provide useful power on a continuous basis, it is likely that the repetition rate will be 1.0 to 10 per second. Thus, in a 24 hour running period 864,000 targets may be necessary and one must be placed at the focal point of the laser every tenth of a second. For economic operation it is necessary that the targets be produced at costs of less than $1.00 per target

  17. Resource implications of a national health target

    DEFF Research Database (Denmark)

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

    2014-01-01

    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...... 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...... target, with estimated total expenditure of over NZ$52 m. The majority of expenditure occurred in ED (60.8%) and hospital (38.7%) with little spent in the community. New staff accounted for 76.5% of expenditure. Per capita expenditure in the ED was associated with improved target performance (r = 0.48, P...

  18. A method for comparing impacts with real targets to impacts onto the IAEA unyielding target

    International Nuclear Information System (INIS)

    The severity of the IAEA accident conditions test requirement (IAEA 1990) of an impact onto an essentially unyielding target from a drop height of 9 meters encompasses a large fraction of all real world impacts. This is true, in part, because of the unyielding nature of the impact target. Impacts onto the unyielding target have severities equivalent to higher velocity impacts onto real targets which are not unyielding. The severity of impacts with yielding targets is decreased by the amount of the impact energy absorbed in damaging the target. In demonstrating the severity of the regulatory impact event it is advantageous to be able to relate this impact onto an essentially unyielding target to impacts with yielding targets

  19. 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...

  20. Cooperative target convergence using multiple agents

    International Nuclear Information System (INIS)

    This work considers the problem of causing multiple (100''s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots

  1. Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Gitter, K., E-mail: kurt.gitter@tu-dresden.de [TU Dresden, Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, 01062 Dresden (Germany); Odenbach, S. [TU Dresden, Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, 01062 Dresden (Germany)

    2011-12-15

    Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted. - Highlights: > Quantitative targeting maps summarise a series of measurements. > Targeting maps combine quantitative data, magnetic volume forces and magnet position. > Here, up to 97% of injected particles were targeted towards the tumour region. > High concentration of injected ferrofluid brings the danger of accretion. > Low miscibility of ferrofluid by water modelling the blood flow is detected.

  2. High or Low Target Prevalence Increases the Dual-Target Cost in Visual Search

    Science.gov (United States)

    Menneer, Tamaryn; Donnelly, Nick; Godwin, Hayward J.; Cave, Kyle R.

    2010-01-01

    Previous studies have demonstrated a dual-target cost in visual search. In the current study, the relationship between search for one and search for two targets was investigated to examine the effects of target prevalence and practice. Color-shape conjunction stimuli were used with response time, accuracy and signal detection measures. Performance…

  3. 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…

  4. From monetary targeting to inflation targeting : lessons from the industrialized countries

    OpenAIRE

    Mishkin, Frederic S.

    2001-01-01

    The author examines changes in monetary policy in industrial countries by evaluating, and providing case studies of monetary targeting, and inflation targeting. Inflation targeting has successfully controlled inflation, with some qualifications. It weakens the effects of inflationary shocks, as examples from Canada, Sweden, and the United Kingdom show. It can promote growth, and does not l...

  5. The Cost of Search for Multiple Targets: Effects of Practice and Target Similarity

    Science.gov (United States)

    Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

    2009-01-01

    With the use of X-ray images, performance in the simultaneous search for two target categories was compared with performance in two independent searches, one for each category. In all cases, displays contained one target at most. Dual-target search, for both categories simultaneously, produced a cost in accuracy, although the magnitude of this…

  6. Molecular Targets of Cannabidiol in Neurological Disorders.

    Science.gov (United States)

    Ibeas Bih, Clementino; Chen, Tong; Nunn, Alistair V W; Bazelot, Michaël; Dallas, Mark; Whalley, Benjamin J

    2015-10-01

    Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases

  7. Non-targeted effects of ionising radiation

    International Nuclear Information System (INIS)

    The universality of the target theory of radiation-induced effects is challenged by observations on non-targeted effects such as bystander effects and genomic instability. Essential features of non-targeted effects are that they do not require direct nuclear exposure by radiation and they are particularly significant at low doses. This new evidence suggests a need for a new paradigm in radiation biology. The new paradigm would cover both the classical (targeted) and the non-targeted effects. New aspects include the role of cellular communication and tissue-level responses. A better understanding of non-targeted effects may have important consequences for health risk assessment and, consequently, on radiation protection. Non-targeted effects may contribute to the estimation of cancer risk from occupational, medical and environmental exposures. In particular, they may have implications for the applicability of the Linear-No-Threshold (LNT) model in extrapolating radiation risk data into the low-dose region. This also means that the adequacy of the concept of dose to estimate risk is challenged by these findings. Moreover, these effects may provide new mechanistic explanations for the development of non-cancer diseases. Further research is required to determine if these effects, typically measured in cell cultures, are applicable in tissue level, whole animals, and ultimately in humans. (orig.)

  8. 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)

  9. Detecting targets hidden in random forests

    Science.gov (United States)

    Kouritzin, Michael A.; Luo, Dandan; Newton, Fraser; Wu, Biao

    2009-05-01

    Military tanks, cargo or troop carriers, missile carriers or rocket launchers often hide themselves from detection in the forests. This plagues the detection problem of locating these hidden targets. An electro-optic camera mounted on a surveillance aircraft or unmanned aerial vehicle is used to capture the images of the forests with possible hidden targets, e.g., rocket launchers. We consider random forests of longitudinal and latitudinal correlations. Specifically, foliage coverage is encoded with a binary representation (i.e., foliage or no foliage), and is correlated in adjacent regions. We address the detection problem of camouflaged targets hidden in random forests by building memory into the observations. In particular, we propose an efficient algorithm to generate random forests, ground, and camouflage of hidden targets with two dimensional correlations. The observations are a sequence of snapshots consisting of foliage-obscured ground or target. Theoretically, detection is possible because there are subtle differences in the correlations of the ground and camouflage of the rocket launcher. However, these differences are well beyond human perception. To detect the presence of hidden targets automatically, we develop a Markov representation for these sequences and modify the classical filtering equations to allow the Markov chain observation. Particle filters are used to estimate the position of the targets in combination with a novel random weighting technique. Furthermore, we give positive proof-of-concept simulations.

  10. Triplex-mediated genome targeting and editing.

    Science.gov (United States)

    Reza, Faisal; Glazer, Peter M

    2014-01-01

    Genome targeting and editing in vitro and in vivo can be achieved through an interplay of exogenously introduced molecules and the induction of endogenous recombination machinery. The former includes a repertoire of sequence-specific binding molecules for targeted induction and appropriation of this machinery, such as by triplex-forming oligonucleotides (TFOs) or triplex-forming peptide nucleic acids (PNAs) and recombinagenic donor DNA, respectively. This versatile targeting and editing via recombination approach facilitates high-fidelity and low-off-target genome mutagenesis, repair, expression, and regulation. Herein, we describe the current state-of-the-art in triplex-mediated genome targeting and editing with a perspective towards potential translational and therapeutic applications. We detail several materials and methods for the design, delivery, and use of triplex-forming and recombinagenic molecules for mediating and introducing specific, heritable, and safe genomic modifications. Furthermore we denote some guidelines for endogenous genome targeting and editing site identification and techniques to test targeting and editing efficiency. PMID:24557900

  11. 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...

  12. Folate targeted polymeric 'green' nanotherapy for cancer

    International Nuclear Information System (INIS)

    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.

  13. 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.

  14. Target technology of high energy neutron source

    International Nuclear Information System (INIS)

    As a facility of high energy neutron source for materials research and development, Fusion Materials Irradiation Test Facility (FMIT) is a strong candidate. The FMIT is designed to study the irradiation effect of fusion neutron on a fusion reactor materials. The FMIT generates a high-flux, high-energy neutron, which is produced in a stripping reaction by impinging a 3.5 MeV-0.1A beam of deuterons on a flowing lithium target. Target technology obtained in the FMIT will be useful for Energy Selective Neutron Irradiation Test Facility (ESNIT) and IFMIF of D-Li stripping reaction facility. In the first report (I), the flowing lithium target of the FMIT was reviewed, and some technical considerations in design were pointed out. In the second report (II), the target assembly and target material were proposed as the option of the HEDEL reference design of FMIT in order to improve the hazard and economy for the Li system: Firstly, the exchangeable target back wall and the measures to minimize the outside device damage in case of back wall breaking, and secondly, the option of molten fluoride salt as target material were proposed. (M.T.)

  15. Adaptive collaborative tracking for multiple targets

    International Nuclear Information System (INIS)

    This paper presents a new method for tracking multiple targets in video sequences. A common dilemma that multiple target tracking methods have to face in practice is reducing computational cost and addressing occlusion to achieve efficient and robust long-duration tracking. Existing methods mainly focus on deriving the measurement-to-track assignment through probabilistic analysis, in which the motions of targets are considered to be independent of each other. These methods tend to be computationally expensive due to the complexity of implementation for the visual tracking task. In this paper, we propose a collaboration model in which the acceleration difference between two targets is used to calculate the motion correlation value based on the two-dimensional Gaussian function. By the collaboration model, the location of occluded target is estimated using the motion information from other targets. In order to sense the occurrence of an occlusion accurately before estimating the location of target, we also propose a border-based occlusion decision method which is integrated into our tracking framework. The proposed approach is computationally efficient and robust. Experimental results exhibit the performance of the tracker based on our approach. (paper)

  16. ZFN-Site searches genomes for zinc finger nuclease target sites and off-target sites

    Directory of Open Access Journals (Sweden)

    Iseli Christian

    2011-05-01

    Full Text Available Abstract Background Zinc Finger Nucleases (ZFNs are man-made restriction enzymes useful for manipulating genomes by cleaving target DNA sequences. ZFNs allow therapeutic gene correction or creation of genetically modified model organisms. ZFN specificity is not absolute; therefore, it is essential to select ZFN target sites without similar genomic off-target sites. It is important to assay for off-target cleavage events at sites similar to the target sequence. Results ZFN-Site is a web interface that searches multiple genomes for ZFN off-target sites. Queries can be based on the target sequence or can be expanded using degenerate specificity to account for known ZFN binding preferences. ZFN off-target sites are outputted with links to genome browsers, facilitating off-target cleavage site screening. We verified ZFN-Site using previously published ZFN half-sites and located their target sites and their previously described off-target sites. While we have tailored this tool to ZFNs, ZFN-Site can also be used to find potential off-target sites for other nucleases, such as TALE nucleases. Conclusions ZFN-Site facilitates genome searches for possible ZFN cleavage sites based on user-defined stringency limits. ZFN-Site is an improvement over other methods because the FetchGWI search engine uses an indexed search of genome sequences for all ZFN target sites and possible off-target sites matching the half-sites and stringency limits. Therefore, ZFN-Site does not miss potential off-target sites.

  17. Protein search for multiple targets on DNA

    International Nuclear Information System (INIS)

    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

  18. Protein search for multiple targets on DNA

    Science.gov (United States)

    Lange, Martin; Kochugaeva, Maria; Kolomeisky, Anatoly B.

    2015-09-01

    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.

  19. 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.

  20. 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.

  1. Self-assessing target with automatic feedback

    Science.gov (United States)

    Larkin, Stephen W.; Kramer, Robert L.

    2004-03-02

    A self assessing target with four quadrants and a method of use thereof. Each quadrant containing possible causes for why shots are going into that particular quadrant rather than the center mass of the target. Each possible cause is followed by a solution intended to help the marksman correct the problem causing the marksman to shoot in that particular area. In addition, the self assessing target contains possible causes for general shooting errors and solutions to the causes of the general shooting error. The automatic feedback with instant suggestions and corrections enables the shooter to improve their marksmanship.

  2. Characterisation of thin solid Xe targets

    International Nuclear Information System (INIS)

    A series of frozen xenon targets of thicknesses ranging between 1 and 15 mg/cm2 were characterised by elastic backscattering technique using a 3 MeV proton beam. Xenon was kept solid on a gold substrate having a thickness of 1 g/cm2 which was mounted on a cold copper finger. The temperature of targets during the experiment was maintained at 55 K by a compact solid nitrogen sublimation system under pressure of 10-5 mbar. Targets were used in series of experiments for populating samarium and gadolinium isotopes in the 136Xe (18O, Xn) and 136Xe (22Ne, Xn) nuclear reactions. (author)

  3. Polarized gas targets in electron rings

    International Nuclear Information System (INIS)

    The feasibility of performing electron scattering experiments with polarized targets in electron storage rings is discussed. Three examples of the physics which would be accessible with this novel method are given. It is noted that this new method is compatible with recent proposals for linac-stretcher-ring accelerator designs. A new method of producing a polarized hydrogen or deuterium target is proposed and some preliminary results are described. A brief summary of laser-driven polarized targets as well as conventionally-produced polarized atomic beams is included

  4. Oxygen Saturation Targeting and Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Darlow, Brian A; Morley, Colin J

    2015-12-01

    Oxygen saturation targeting is widely used in neonatal intensive care, but the optimal target range in very preterm infants has been uncertain and is the subject of recent debate and research. This review briefly discusses the technology of oxygen monitoring and the role of oxygen toxicity in preterm infants. The background to the recent trials of oxygen saturation targeting in acute and continuing care of very preterm infants is reviewed, and the findings and implications of the recent trials, particularly with respect to bronchopulmonary dysplasia, are discussed. PMID:26593080

  5. Stereotactic radiosurgery: a "targeted" therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Liang-Fu Han

    2012-01-01

    The developments of medicine always follow innovations in science and technology.In the past decade,such innovations have made cancer-related targeted therapies possible.In general,the term "targeted therapy" has been used in reference to cellular and molecular level oriented therapies.However,improvements in the delivery and planning of traditional radiation therapy have also provided cancer patients more options for "targeted" treatment,notably stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT).In this review,the progress and controversies of SRS and SBRT are discussed to show the role of stereotactic radiation therapy in the ever evolving multidisciplinary care of cancer patients.

  6. A laser strain gauge for accelerator targets

    International Nuclear Information System (INIS)

    Multi megawatt accelerators can deliver sufficient power to a target to destroy it in a few pulses. In order to look at the response of solid and liquid targets under these high power pulses, we are developing optical methods of measuring surface deformations with time resolutions limited by laser pulse lengths. These methods can be used to examine the surfaces of solids and liquids during elastic deformation and unstable hydrodynamic flows. We present preliminary results of a system designed for target tests using the Brookhaven AGS and the Argonne CHM linac

  7. A windowless frozen hydrogen target system

    International Nuclear Information System (INIS)

    A cryogenic target system has been constructed in which gaseous mixtures of all three hydrogen isotopes have been frozen onto a thin, 65 mm diameter gold foil. The foil is cooled to 3 K while inside a 70 K radiation shield, all of which is mounted in a vacuum system maintained at 10-9 torr. Stable multi-layer hydrogen targets of known uniformity and thickness have been maintained for required measurement times of up to several days. To date, hundreds of targets have been successfully used in muon-catalyzed fusion experiments at TRIUMF. (author). 12 refs., 6 figs

  8. On the Chinese Carbon Reduction Target

    Directory of Open Access Journals (Sweden)

    Michinori Uwasu

    2010-06-01

    Full Text Available In November 2009, China pledged a 40–45% decrease in CO2 emissions per GDP by 2020, as compared with the 2005 level. Although carbon intensity (emission targets by nature are ambiguous, this study demonstrates that China’s pledge is consistent with the current Chinese domestic agenda that simultaneously pursues economic growth and energy security. The target numbers in the pledge seem reasonable, given the technological feasibility and measures, considered along with the assumption that moderate economic growth will occur. However, the study also argues that financial and institutional constraints exist as potential obstacles to achieving the target if the trend of the current economic tendencies continues.

  9. Targeting engineering synchronization in chaotic systems

    Science.gov (United States)

    Bhowmick, Sourav K.; Ghosh, Dibakar

    2016-07-01

    A method of targeting engineering synchronization states in two identical and mismatch chaotic systems is explained in detail. The method is proposed using linear feedback controller coupling for engineering synchronization such as mixed synchronization, linear and nonlinear generalized synchronization and targeting fixed point. The general form of coupling design to target any desire synchronization state under unidirectional coupling with the help of Lyapunov function stability theory is derived analytically. A scaling factor is introduced in the coupling definition to smooth control without any loss of synchrony. Numerical results are done on two mismatch Lorenz systems and two identical Sprott oscillators.

  10. Direct-illumination spherical-target experiments

    International Nuclear Information System (INIS)

    A set of spherical target experiments was designed to evaluate the effectiveness of three techniques for achieving higher convergence implosions. They are (1) cryogenically frozen fuel layers, (2) submicron wavelength laser light, and (3) temporally tailored pulse shapes. A second set of experiments provides information about energy transport by thermal and suprathermal electrons and uses multilayered targets as an integral component of the diagnostics. These results, in conjunction with existing laser-target coupling data, provide a more comprehensive test of our understanding of laser plasma interaction, energy transport, and hydrodynamic response of small scale spherical laser fusion experiments

  11. TARGET Publication Guidelines | Office of Cancer Genomics

    Science.gov (United States)

    Like other NCI large-scale genomics initiatives, TARGET is a community resource project and data are made available rapidly after validation for use by other researchers. To act in accord with the Fort Lauderdale principles and support the continued prompt public release of large-scale genomic data prior to publication, researchers who plan to prepare manuscripts containing descriptions of TARGET pediatric cancer data that would be of comparable scope to an initial TARGET disease-specific comprehensive, global analysis publication, and journal editors who receive such manuscripts, are stron

  12. Thickness and uniformity measurements of nuclear targets

    International Nuclear Information System (INIS)

    This paper introduces the methods of target thickness and uniformity measurements including weighing, α-particle thickness gauge, quartz thickness gauge, optical transmittance and Rutherford backscattering. An α-particle gauging which measures target thicknesses up to several μm is metioned. A fast thickness measurements for C, Au and Cu targets by spectrophotometer is given. A high sensitive quartz gauge which can measure minimum deposit of 0.04 μg/cm2 is described. Thickness and impurity determinations by RBS with accuracy better than 5% are summarized

  13. Equitable setting target by using DEA

    Directory of Open Access Journals (Sweden)

    Kavous Soleimani Damane

    2015-01-01

    Full Text Available One application of DEA to apply fixed costs to input sourcear or setting target in out put that is done by decision maker for units. At first, Mr Cook and Kress in troduced DEA as an approach for allocating fixed costs, many people introduced such models [3]. For completing this issue, one model for equitable allocation of costs or sorce was introduced by Wade D. Cook and Joe Zhu [6]. In this proposal obtaining a model for fixed equtable setting target in units was proposed in order to efficiency before and after the setting target nevar changed.

  14. 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

  15. Optoelectronic System Measures Distances to Multiple Targets

    Science.gov (United States)

    Liebe, Carl Christian; Abramovici, Alexander; Bartman, Randall; Chapsky, Jacob; Schmalz, John; Coste, Keith; Litty, Edward; Lam, Raymond; Jerebets, Sergei

    2007-01-01

    An optoelectronic metrology apparatus now at the laboratory-prototype stage of development is intended to repeatedly determine distances of as much as several hundred meters, at submillimeter accuracy, to multiple targets in rapid succession. The underlying concept of optoelectronic apparatuses that can measure distances to targets is not new; such apparatuses are commonly used in general surveying and machining. However, until now such apparatuses have been, variously, constrained to (1) a single target or (2) multiple targets with a low update rate and a requirement for some a priori knowledge of target geometry. When fully developed, the present apparatus would enable measurement of distances to more than 50 targets at an update rate greater than 10 Hz, without a requirement for a priori knowledge of target geometry. The apparatus (see figure) includes a laser ranging unit (LRU) that includes an electronic camera (photo receiver), the field of view of which contains all relevant targets. Each target, mounted at a fiducial position on an object of interest, consists of a small lens at the output end of an optical fiber that extends from the object of interest back to the LRU. For each target and its optical fiber, there is a dedicated laser that is used to illuminate the target via the optical fiber. The targets are illuminated, one at a time, with laser light that is modulated at a frequency of 10.01 MHz. The modulated laser light is emitted by the target, from where it returns to the camera (photodetector), where it is detected. Both the outgoing and incoming 10.01-MHz laser signals are mixed with a 10-MHz local-oscillator to obtain beat notes at 10 kHz, and the difference between the phases of the beat notes is measured by a phase meter. This phase difference serves as a measure of the total length of the path traveled by light going out through the optical fiber and returning to the camera (photodetector) through free space. Because the portion of the path

  16. 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/.

  17. Logarithm Laws and Shrinking Target Properties

    Indian Academy of Sciences (India)

    J S Athreya

    2009-09-01

    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.

  18. Logarithm laws and shrinking target properties

    OpenAIRE

    Athreya, Jayadev S.

    2008-01-01

    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.

  19. Consumer responses to ethnic targeted marketing

    NARCIS (Netherlands)

    A.-S.I.A. Lenoir (Anne-Sophie); S. Puntoni (Stefano)

    2014-01-01

    markdownabstract__Abstract__ Marketing is impacted more than ever by demographic change, to the extent that practitioners targeting ethnic groups should re-think their approach depending upon the strength with which different generations identify with their cultural heritage.

  20. Discovering the 'Magic' of Target Marketing.

    Science.gov (United States)

    Grier, Linda J.; Ackenbom, Charles R.

    1988-01-01

    Describes target marketing of children's summer camps, emphasizing the benefits of collaborative advertising campaigns. Discusses the scope and economics of four model campaigns. Outlines the design, implementation, and evaluation of collaborative marketing projects. (SV)

  1. Parametric estimation of ultra wideband radar targets

    Institute of Scientific and Technical Information of China (English)

    Fan Ping; Jing Zhanrong

    2009-01-01

    Based on the analysis of impulse response properties, a scattering model of ultra wideband (UWB) radar targets is developed to estimate the target parameters exactly. With this model, two algorithms of multiple signal classification (MUSIC), and matrix pencil (MP), are introduced to calculate the scattering center parame-ters of targets and their performances are compared. The simulation experiments show that there are no differ-ences in the estimation precision of MUSIC and MP methods when the signal-to-noise ratio (SNR) is larger than 13 dB. However, the MP method has a better performance than that of MUSIC method when the SNR is smaller than 13 dB. Besides, the time consuming of MP method is leas than that of MUSIC method. Therefore, the MP algorithm is preferred for the parametric estimation of UWB radar targets.

  2. Fabrication of Simple Step-Target

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>Step-target was used to measure the shock velocity. If we can measure the shock velocity and particle velocity together, we get one point in the shock compress line. If we measure a series of shock velocity

  3. "UCx fission targets oxidation test stand"

    CERN Document Server

    Lacroix, Rachel

    2014-01-01

    "Set up a rig dedicated to the oxidation of UCx and define a procedure for repeatable, reliable and safe method for converting UC2 fission targets into an acceptable uranium carbide oxide waste for subsequent disposal by the Swiss Authorities."

  4. 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...

  5. 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...

  6. Scaling law in target-hunting processes

    Science.gov (United States)

    Yang, Shi-Jie

    2004-05-01

    We study a hunting process for a target, in which the hunter tracks the goal by smelling odors it emits. The odor intensity is supposed to decrease with the diffusion distance. The Monte Carlo experiment is carried out on a two-dimensional square lattice. Having no idea of the location of the target, the hunter determines its moves only by random attempts in each direction. By sorting the searching time in each simulation and introducing a variable x to reflect the sequence of searching times, we obtain a curve with a wide plateau, indicating the most probable time of successfully finding the target. The simulations reveal a scaling law for the searching time versus the distance to the position of the target. The scaling exponent depends on the sensitivity of the hunter. Our model may be a prototype in studying such searching processes as various food-foraging behaviors of wild animals.

  7. Target-driven merging of Taxonomies

    CERN Document Server

    Raunich, Salvatore

    2010-01-01

    The proliferation of ontologies and taxonomies in many domains increasingly demands the integration of multiple such ontologies. The goal of ontology integration is to merge two or more given ontologies in order to provide a unified view on the input ontologies while maintaining all information coming from them. We propose a new taxonomy merging algorithm that, given as input two taxonomies and an equivalence matching between them, can generate an integrated taxonomy in a fully automatic manner. The approach is target-driven, i.e. we merge a source taxonomy into the target taxonomy and preserve the structure of the target ontology as much as possible. We also discuss how to extend the merge algorithm providing auxiliary information, like additional relationships between source and target concepts, in order to semantically improve the final result. The algorithm was implemented in a working prototype and evaluated using synthetic and real-world scenarios.

  8. Brain-targeted nasal clonazepam microspheres

    Directory of Open Access Journals (Sweden)

    Shaji J

    2009-01-01

    Full Text Available Gelatin-chitosan mucoadhesive microspheres of clonazepam were prepared using the emulsion cross linking method. Mirospheres were evaluated using the in vitro and ex vivo drug release patterns. In vivo CNS drug distribution studies were carried out in rats by administering the clonazepam microspheres intra-nasally and clonazepam solution intravenously. From the drug levels in plasma and CSF, drug targeting index and drug targeting efficiency were calculated. Results obtained indicated that intranasally administered clonazepam microspheres resulted in higher brain levels with a drug targeting index of 2.12. Gelatin-chitosan cross linked mucoadhesive microspheres have the potential to be developed as a brain-targeted drug delivery system for clonazepam.

  9. Cell survival studies for moving targets

    International Nuclear Information System (INIS)

    More than 330 patients with static tumors have been treated at GSI with a scanned C-12 beam. For targets that are subject to respiratory motion, treatment is not yet possible because target motion and scanning motion interfere. GSI is developing a motion compensation system to compensate target motion by adaptation of each individual Bragg peak position. Within this project, the GSI treatment planning software TRiP was extended to calculate physical dose distributions in the presence of motion. These motion extensions were experimentally validated. Recently we included the calculation of cell survival for moving targets. To validate the software, a program of experimental studies with biological samples has been started. In a first set of experiments, living cell cultures were placed on a periodically moving table and irradiated with and without motion compensation. Results are compared to reference cell cultures that were static during standard irradiations. Furthermore, measured cell survival distributions are compared to calculated distributions for all irradiation schemes

  10. 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.

  11. 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.

  12. Covalent targeting of acquired cysteines in cancer.

    Science.gov (United States)

    Visscher, Marieke; Arkin, Michelle R; Dansen, Tobias B

    2016-02-01

    The thiolate side chain of cysteine has a unique functionality that drug hunters and chemical biologists have begun to exploit. For example, targeting cysteine residues in the ATP-binding pockets of kinases with thiol-reactive molecules has afforded increased selectivity and potency to drugs like imbrutinib, which inhibits the oncogene BTK, and CO-1686 and AZD9291 that target oncogenic mutant EGFR. Recently, disulfide libraries and targeted GDP-mimetics have been used to selectively label the G12C oncogenic mutation in KRAS. We reasoned that other oncogenes contain mutations to cysteine, and thus screened the Catalog of Somatic Mutations in Cancer for frequently acquired cysteines. Here, we describe the most common mutations and discuss how these mutations could be potential targets for cysteine-directed personalized therapeutics. PMID:26629855

  13. [Individual pressure tolerance--a "target" pressure?].

    Science.gov (United States)

    Bogdănici, C; Vancea, P P

    1999-01-01

    In literature there are many meanings for the limit between normal and pathological intraocular pressure: "normative pressure", "critic pressure", "individual tolerance pressure" and "target pressure". The aim of this paper is to demonstrate that these terms are synonymous. PMID:10756882

  14. The expected radiation damage of CSNS target

    Science.gov (United States)

    Yin, W.; Yu, Q. Z.; Lu, Y. L.; Wang, S. L.; Tong, J. F.; Liang, T. J.

    2012-12-01

    The radiation damage to the tungsten target and its SS316 vessel for Chinese Spallation Neutron Source (CSNS) has been estimated with a Monte-Carlo simulation code MCNPX2.5.0. We compare the effects on the radiation damage due to two different proton beam profiles: a uniform distribution and a Gaussian distribution. We also discuss the dependence of the radiation damage estimation on different physics models. The results show the peak displacement productions in vessel and the fourth target plate are 2.5 and 5.5 dpa/y, respectively, under a Gaussian proton beam. The peak helium productions in the vessel and the fourth target are 305 and 353 appm/y, respectively, under the same proton beam. Based on these results and the allowable dpa values we have estimated the lifetime of the tungsten target and its vessel.

  15. The expected radiation damage of CSNS target

    Energy Technology Data Exchange (ETDEWEB)

    Yin, W., E-mail: wenyin@aphy.iphy.ac.cn [Engineering Center of CSNS Target Station and Instruments, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Yu, Q.Z. [Engineering Center of CSNS Target Station and Instruments, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China); Lu, Y.L.; Wang, S.L.; Tong, J.F. [Experimental System of CSNS, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Liang, T.J. [Engineering Center of CSNS Target Station and Instruments, Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China)

    2012-12-15

    The radiation damage to the tungsten target and its SS316 vessel for Chinese Spallation Neutron Source (CSNS) has been estimated with a Monte-Carlo simulation code MCNPX2.5.0. We compare the effects on the radiation damage due to two different proton beam profiles: a uniform distribution and a Gaussian distribution. We also discuss the dependence of the radiation damage estimation on different physics models. The results show the peak displacement productions in vessel and the fourth target plate are 2.5 and 5.5 dpa/y, respectively, under a Gaussian proton beam. The peak helium productions in the vessel and the fourth target are 305 and 353 appm/y, respectively, under the same proton beam. Based on these results and the allowable dpa values we have estimated the lifetime of the tungsten target and its vessel.

  16. EMC effect: asymptotic freedom with nuclear targets

    International Nuclear Information System (INIS)

    General features of the EMC effect are discussed within the framework of quantum chromodynamics as expressed via the operator product expansion and asymptotic freedom. These techniques are reviewed with emphasis on the target dependence. 22 references

  17. a Plutonium Ceramic Target for Masha

    Science.gov (United States)

    Wilk, P. A.; Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Patin, J. B.; Lougheed, R. W.; Ebbinghaus, B. B.; Landingham, R. L.; Oganessian, Yu. Ts.; Yeremin, A. V.; Dmitriev, S. N.

    2005-09-01

    We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 °C. Promising candidates for the target include oxides and carbides, although more research into their thermodynamic properties will be required. Reaction products will diffuse out of the target into an ion source, where they will then be transported through the separator to a position-sensitive focal-plane detector array. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments where the chemical properties of the heaviest elements are studied.

  18. A Thick Target for Synchrotrons and Betatrons

    Science.gov (United States)

    McMillan, E. M.

    1950-09-19

    If a wide x-ray beam from an electron synchrotron or betatron is desired, in radiographic work with large objects for example, the usually very thin target may be replaced by a thick one, provided the resulting distortion of the x-ray spectrum due to multiple radiative processes is permissible. It is difficult to make the circulating electron beam traverse a thick target directly because of the small spacing between successive turns. Mounting a very thin beryllium, or other low-z material, fin on the edge of the thick target so that the fin projects into the beam will cause the beam to lose sufficient energy, and therefore radium, to strike the thick target the next time around. Sample design calculations are given.

  19. Polarized proton and deuteron solid HD targets

    International Nuclear Information System (INIS)

    A decade has now elapsed since HD was proposed as a polarized proton and deuteron target with exceptionally desirable properties. These include a very high free proton proportion, independently polarizable proton and deuteron systems, and a ''frozen-spin'' mode of operation which allows separation of the functions of production and utilization of the highly polarized target. A discussion is given of what can be expected of the polarized HD system right now, without further research. The basic features of solid HD pertinent to its use as a ''frozen-spin'' target are outlined, then a summary is given of the particular experimental results which support the contention that the target will perform successfully, and finally, some feasible operating modes and the expected performances from them are presented

  20. Heavy ions, targets, and research at HHIRF

    International Nuclear Information System (INIS)

    The Holifield Heavy Ion Research Facility (HHIRF) typifies a new generation of heavy ion accelerators capable of producing high resolution beams with sufficient energy to study nuclear reactions across the periodic table. Exploiting the capabilities of the machine depends on the availability of thin foils at each stage of the experimental process. Rugged carbon foils are needed in the tandem and cyclotron to strip injected ions up to high charge states. Experimental success largely depends on the availability of a suitable target for bombardment which imposes new demands on the target maker. Many experiments use large solid angle gaseous counters with very thin foils as windows. The accelerators, experimental apparatus, and beam characteristics will be described. Target requirements demanded by different types of experiments will be discussed. These requirements have lead to the construction of specialized apparatus such as the supersonic gas jet target and the single crystal goniometer for blocking measurements

  1. Scaling laws for simple heavy ion targets

    International Nuclear Information System (INIS)

    We have examined the behavior of single shell DT gas filled spherical targets irradiated by a constant power heavy ion beam pulse. For targets in which the ion range is less than the shell thickness, our computational results suggest that the target can be divided into three regions: (1) the absorber (100 to 400 eV for the energies we have considered), (2) the cold pusher (a few eV), and (3) the DT gas fuel. We have examined the pusher collapse time, velocity, and maximum kinetic energy variations as functions of the various target parameters and ion beam energy. The results are expressed in analytic terms and verified by computer simulation

  2. Extended Target Recognition in Cognitive Radar Networks

    Directory of Open Access Journals (Sweden)

    Xiqin Wang

    2010-11-01

    Full Text Available We address the problem of adaptive waveform design for extended target recognition in cognitive radar networks. A closed-loop active target recognition radar system is extended to the case of a centralized cognitive radar network, in which a generalized likelihood ratio (GLR based sequential hypothesis testing (SHT framework is employed. Using Doppler velocities measured by multiple radars, the target aspect angle for each radar is calculated. The joint probability of each target hypothesis is then updated using observations from different radar line of sights (LOS. Based on these probabilities, a minimum correlation algorithm is proposed to adaptively design the transmit waveform for each radar in an amplitude fluctuation situation. Simulation results demonstrate performance improvements due to the cognitive radar network and adaptive waveform design. Our minimum correlation algorithm outperforms the eigen-waveform solution and other non-cognitive waveform design approaches.

  3. Manufacture for prototype Mo-99 irradiation target

    International Nuclear Information System (INIS)

    The prototype of target to produce Mo-99 by fission has been manufactured. Extension equipment using oil pressure is specially designed and fabricated in order to prepare the Mo-99 target of high quality to be irradiated in a research reactor. The target of an annular type of inner and outer Al tubes and uranium foil in between is extended using a dedicated tool with a draw plug. The inner tube is plastically deformed while the outer tube is elastically deformed. This makes the Al tubes and foil contacted closely. Top and bottom ends of the target are welded by TIG in order to provide a hermetic sealing which will prevent the release of fission gases during the irradiation

  4. 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.

  5. Proteomic screening of molecular targets of crocin

    OpenAIRE

    Hosseinzadeh, Hossein; Mehri, Soghra; Heshmati, Ali; Ramezani, Mohammad; Sahebkar, Amirhossein; Abnous, Khalil

    2014-01-01

    Background Traditional drug discovery approaches are mainly relied on the observed phenotypic changes following administration of a plant extract, drug candidate or natural product. Recently, target-based approaches are becoming more popular. The present study aimed to identify the cellular targets of crocin, the bioactive dietary carotenoid present in saffron, using an affinity-based method. Methods Heart, kidney and brain tissues of BALB/c mice were homogenized and extracted for the experim...

  6. Using target cost in determining price

    OpenAIRE

    Aurelian Ionut CEAUSESCU; Cecilia VADUVA

    2010-01-01

    The target cost method was designed as a comprehensive set of tools for cost planning, cost management and cost control. This method is based on the idea that the selling price of a product is fixed at the market. Price does not therefore depend on cost. Target costing method is not only a method for calculating the costs, but also a method which uses modern management techniques on the study assessed the market value analysis, reducing the diversity of technolog...

  7. Google attention and target price run ups

    OpenAIRE

    Siganos, A.

    2013-01-01

    We explore the increase in the share prices of target firms before their merger announcements. We use a novelty Google search volume to proxy the market expectation hypothesis according to which firms with an abnormal upward change in Google searches are identified as firms with potential merger activity. We find that Google indicators can explain a larger percentage of the price increase in target firms before their mergers than the Financial Times. However even the Google proxy of the marke...

  8. Macrophages as novel targets for erythropoietin

    OpenAIRE

    Lifshitz, L; Tabak, G; Mittelman, M.; Gassmann, M.; Neumann, D.

    2010-01-01

    BackgroundOur original demonstration of immunomodulatory effects of erythropoietin in multiple myeloma, led us to the search of the cells in the immune system that are direct targets to erythropoietin. The finding that lymphocytes do not express erythropoietin receptors, has led to the hypothesis that other cells act as direct targets and thus mediate the erythropoietin effects. Having found erythropoietin effects on dendritic cells thus led to the question of whether macrophages act as targe...

  9. Fighting power, targeting and cyber operations

    OpenAIRE

    Ducheine, P.A.L.; Haaster, van, A.J.M.

    2014-01-01

    This article aims to contribute to the operationalisation of military cyber operations in general, and for targeting purposes (either in defence or offence) in particular. The position of cyber operations in military doctrine will be clarified, their contribution to fighting power conceptualised and the ramifications on targeting processes discussed. Cyberspace poses unique challenges and opportunities; we distinguish new elements that may be utilized for ‘targeting’, namely: cyber objects an...

  10. Single-domain antibodies for brain targeting

    OpenAIRE

    Lalatsa, Katerina; Moreira Leite, Diana

    2014-01-01

    Smaller recombinant antibody fragments as single-domain antibodies (sdAbs) are emerging as credible alternatives because of their target specificity, high affinity, and cost-effective recombinant production. sdAbs have been forged into multivalent and multispecif ic therapeutics, or targeting moieties, that are able to shuttle their linked therapeutic cargo (i.e., drugs, nanoparticles, toxins, enzymes, and radionuclides) to the receptor of interest. Their ability to permeate across the blood ...

  11. Ghana : Improving the Targeting of Social Programs

    OpenAIRE

    World Bank

    2011-01-01

    This study, a draft of which was shared with the Government of Ghana in November 2009, provides a basic diagnostic of the benefit incidence and targeting performance of a large number of social programs in Ghana. Both broad-based programs (such as spending for education and health, and subsidies for food, oil-related products, and electricity) as well as targeted programs (such as Liveliho...

  12. Nanogel Carrier Design for Targeted Drug Delivery

    OpenAIRE

    Eckmann, D.M.; Composto, R. J.; Tsourkas, A; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanoge...

  13. Shielding calculations for the antiproton target area

    International Nuclear Information System (INIS)

    Shielding calculations performed in conjunction with the design of the Fermilab antiproton target hall are summarized. The following radiological considerations were examined: soil activation, residual activity of components, and beam-on radiation. In addition, at the request of the designers, the energy deposition in the proposed graphite beam dump was examined for several targeting conditions in order to qualitatively determine its ability to survive

  14. Targeted Therapies in Epithelial Ovarian Cancer

    OpenAIRE

    Jurjees Hasan; Loaie El-Helw; Emma Dean

    2010-01-01

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the a...

  15. Fabrication of /sup 26/Al targets

    Energy Technology Data Exchange (ETDEWEB)

    Buchmann, L.; Baumeister, H.; Rolfs, C.

    1984-06-01

    Targets with up to 1.4x10/sup 16/ /sup 26/Al atoms have been fabricated. The artificial production of the /sup 26/Al nuclei via the reaction /sup 26/Mg(p, n)/sup 26/Al was carried out at the cyclotrons in Juelich and Muenchen. The experimental procedures in the fabrication of these targets as well as some test measurements are described.

  16. Antibacterial Targets in Fatty Acid Biosynthesis

    OpenAIRE

    Wright, H. Tonie; Reynolds, Kevin A.

    2007-01-01

    The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for development of new anti-bacterial agents. The extended use of the anti-tuberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for anti-bacterial development. Differences in subcellular organization of the bacterial and eukaryotic multi-enzyme fatty acid synthase systems offer the prospect of inhibitors with host vs...

  17. Nominal Income Targeting; A Critical Evaluation

    OpenAIRE

    Victor E. Argy

    1991-01-01

    This paper evaluates the proposal that government authorities ought to target nominal income. It begins by viewing the literature in some detail. It then undertakes a theoretical analysis of the proposal first for the small country and next for the large country. There is then a general discussion of various issues posed by nominal income targeting. Finally, the paper summarizes the empirical work to date. We show that traditional theoretical analysis tends to be too simple and overly biased ...

  18. Brain-Targeted Nasal Clonazepam Microspheres

    OpenAIRE

    Shaji J; Poddar A; Iyer S

    2009-01-01

    Gelatin-chitosan mucoadhesive microspheres of clonazepam were prepared using the emulsion cross linking method. Mirospheres were evaluated using the in vitro and ex vivo drug release patterns. In vivo CNS drug distribution studies were carried out in rats by administering the clonazepam microspheres intra-nasally and clonazepam solution intravenously. From the drug levels in plasma and CSF, drug targeting index and drug targeting efficiency were calculated. Results obtained indicated that int...

  19. Target costing in construction: a comparative study

    OpenAIRE

    Melo, Reymard Savio Sampaio De; Kaushik, Amit; Koskela, Lauri; Granja, Ariovaldo Denis; Keraminiyage, Kaushal; Tzortzopoulos, Patricia

    2014-01-01

    Target costing is an approach for the development of new products in the automobile industry, aimed at reducing their life-cycle costs while ensuring quality, reliability and other client requirements, by examining all possible ideas for cost reduction at the product planning, research and development and prototyping phases. Prior studies have attempted to adapt the manufacturing target costing process to the project-based nature of the construction industry. This paper aims to provide insigh...

  20. The potential therapeutic targets for cervical cancer

    OpenAIRE

    L Priyanka Dwarampudi; Gowthamarajan, K.; Shanmugam, R; Madhuri, K.; Nilani, P.; M N Satish Kumar

    2013-01-01

    In case of invasive cervical carcinoma several molecular events were reported and these molecular events resulting in multiple genetic abnormalities. In order to control these tumors multiple molecular therapeutic targets are needed with different molecular mechanisms. Unfortunately, these molecular targets were in early stages of development. Because of less degree of success of conventional therapeutics for late stages of cervical cancer and lowering of prognosis of patients there is an inc...

  1. BISTATIC SONOBUOY DEPLOYMENT CONFIGURATION FOR STATIONARY TARGETS

    OpenAIRE

    KARATAŞ, Mümtaz; Gülşen AKMAN

    2015-01-01

    Countering submerged targets using bistatic and multistatic sonobuoy systems is a fundamental problem in Anti-Submarine Warfare. A key question is: what is the best deployment geometry of sensors to successfully detect a submarine threat in a field of interest? The unique properties of these systems distinguish this problem from the conventional ones. This paper examines the optimum deployment strategies of bistatic sonobuoys against stationary or low speed targets

  2. Targeted genome modification via triple helix formation.

    Science.gov (United States)

    Ricciardi, Adele S; McNeer, Nicole A; Anandalingam, Kavitha K; Saltzman, W Mark; Glazer, Peter M

    2014-01-01

    Triplex-forming oligonucleotides (TFOs) are capable of coordinating genome modification in a targeted, site-specific manner, causing mutagenesis or even coordinating homologous recombination events. Here, we describe the use of TFOs such as peptide nucleic acids for targeted genome modification. We discuss this method and its applications and describe protocols for TFO design, delivery, and evaluation of activity in vitro and in vivo. PMID:25030921

  3. Targeted Social Distancing Designs for Pandemic Influenza

    OpenAIRE

    Glass, Robert J.; Glass, Laura M; Walter E. Beyeler; Min, H. Jason

    2006-01-01

    Targeted social distancing to mitigate pandemic influenza can be designed through simulation of influenza's spread within local community social contact networks. We demonstrate this design for a stylized community representative of a small town in the United States. The critical importance of children and teenagers in transmission of influenza is first identified and targeted. For influenza as infectious as 1957–58 Asian flu (≈50% infected), closing schools and keeping children and teenagers...

  4. Panorama: A Targeted Proteomics Knowledge Base

    OpenAIRE

    Sharma, Vagisha; Eckels, Josh; Taylor, Greg K.; Shulman, Nicholas J.; Stergachis, Andrew B.; Joyner, Shannon A.; Yan, Ping; Whiteaker, Jeffrey R.; Halusa, Goran N; Schilling, Birgit; Gibson, Bradford W.; Colangelo, Christopher M.; Paulovich, Amanda G.; Carr, Steven A.; Jaffe, Jacob D

    2014-01-01

    Panorama is a web application for storing, sharing, analyzing, and reusing targeted assays created and refined with Skyline,1 an increasingly popular Windows client software tool for targeted proteomics experiments. Panorama allows laboratories to store and organize curated results contained in Skyline documents with fine-grained permissions, which facilitates distributed collaboration and secure sharing of published and unpublished data via a web-browser interface. It is fully integrated wit...

  5. Bayesian target tracking based on particle filter

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    For being able to deal with the nonlinear or non-Gaussian problems, particle filters have been studied by many researchers. Based on particle filter, the extended Kalman filter (EKF) proposal function is applied to Bayesian target tracking. Markov chain Monte Carlo (MCMC) method, the resampling step, etc novel techniques are also introduced into Bayesian target tracking. And the simulation results confirm the improved particle filter with these techniques outperforms the basic one.

  6. Protein targeting to ATP-dependent proteases

    OpenAIRE

    Inobe, Tomonao; Matouschek, Andreas

    2008-01-01

    ATP-dependent proteases control diverse cellular processes by degrading specific regulatory proteins. Understanding how these regulatory proteins are targeted to ATP-dependent proteases is of central importance to understanding their biological role as regulators. Recent work has shown that protein substrates are specifically transferred to ATP-dependent proteases through different routes. These routes can function in parallel or independently. In all of these targeting mechanisms it can be u...

  7. Fabrication of glass sphere laser fusion targets

    International Nuclear Information System (INIS)

    We have developed processes at LLL for mass producing the high quality glass microspheres required for current laser fusion targets. Here we describe the methods and the materials used in our liquid-droplet and dried-gel systems. Glass microspheres ranging from 70 to 600 microns O.D., with walls from 0.5 to 18 microns thick and which satisfy the exacting surface and symmetry specifications of targets for high density experiments are now produced routinely

  8. Towards Inflation Targeting in Sri Lanka

    OpenAIRE

    Ding Ding; Rahul Anand; Shanaka J. Peiris

    2011-01-01

    This paper develops a practical model-based forecasting and policy analysis system (FPAS) to support a transition to an inflation forecast targeting regime in Sri Lanka. The FPAS model provides a relatively good forecast for inflation and a framework to evaluate policy trade-offs. The model simulations suggest that an open-economy inflation targeting rule can reduce macroeconomic volatility and anchor inflationary expectations given the size and type of shocks faced by the economy. Sri Lanka ...

  9. Functionalized Nanosystems for Targeted Mitochondrial Delivery

    OpenAIRE

    Durazo, Shelley A.; Kompella, Uday B.

    2011-01-01

    Mitochondrial dysfunction including oxidative stress and DNA mutations underlies the pathology of various diseases including Alzheimer’s disease and diabetes, necessitating the development of mitochondria targeted therapeutic agents. Nanotechnology offers unique tools and materials to target therapeutic agents to mitochondria. As discussed in this paper, a variety of functionalized nanosystems including polymeric and metallic nanoparticles as well as liposomes are more effective than plain dr...

  10. Complementarity of Dark Matter Direct Detection Targets

    OpenAIRE

    Pato, M.; Baudis, L.; Bertone, G.; Ruiz de Austri, R.; Strigari, L.; Trotta, R.

    2010-01-01

    We investigate the reconstruction capabilities of the dark matter mass and spin-independent cross section from future ton-scale direct detection experiments using germanium, xenon, or argon as targets. Adopting realistic values for the exposure, energy threshold, and resolution of dark matter experiments which will come online within 5 to 10 years, the degree of complementarity between different targets is quantified. We investigate how the uncertainty in the astrophysical parameters controll...

  11. Fire in targeting urban/industrial areas

    International Nuclear Information System (INIS)

    A preliminary study of the parameters pertinent to considerations of fire in urban targeting illustrated the dominance of some factors and the insensitivity to damage assessments of others. The factors considered, together with the simple assumptions and approximations used in this scoping study supported the assumption that fire may add significantly to the damage to urban/industrial targets. The influence of uncertainties and unknowns were evaluated, and the consequent implications for research were assessed

  12. Cross-field diode sputtering target assembly

    International Nuclear Information System (INIS)

    An improved cross-field diode sputtering target assembly adapted for sputtering a selected material having an ion target wherein a selected surface is formed of a selected material in a predetermined closed loop pattern having a central opening therein, and wherein the selected surface has spaced edges and is formed of a material adapted to be controllably eroded in a diode sputtering process, walls positioned contiguous or adjacent to each of the spaced edges of the selected surface wherein each of the walls extend substantially normal from and beyond each spaced edge of the selected surface of the ion target and a magnetic member having poles positioned in an opposed spaced relationship to each other and enclosing the walls and the ion target for providing a linear magnetic field through the walls, over the selected surface and through the ion target and wherein the magnetic member has a linear magnetic field of sufficient strength for plasma entrapment between the walls and over the selected surface wherein the selected surface is adapted to have an electric field applied thereacross at a direction substantially normal to the magnetic field to develop a BXE field and to entrap secondary electrons at the selected surface to control the erosion pattern thereof is shown. A method for utilizing the improved cross-field diode sputtering target assembly is also shown

  13. 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.

  14. Rotating target wheel for the FMA

    Energy Technology Data Exchange (ETDEWEB)

    Back, B.B.; Davids, C.N.; Falout, J. [and others

    1995-08-01

    In anticipation of high intensity beams that will be available from the PII-ECR source injector to ATLAS, a new rotating target wheel was developed for the sliding seal chamber at the FMA. The wheel is 9 inch in diameter and contains up to ten targets. The rotation of the wheel is achieved by a DC motor, a ferrofluidic feedthrough, and a gear mechanism that allows both target rotation and changing the target angle relative to the beam. The nominal rotation speed is 1000 RPM, although higher speeds can be achieved if necessary. The assembly is equipped with an absolute encoder which is read out via a newly developed CAMAC module. This module provides the following main functions: (1) a TTL signal to be used for sweeping the beam when a target frame is about to pass through the beam, (2) a read-out of the target position that can be included in the data event structure, (3) programmable set points for the beam-off signal. The system is presently being tested and will be used in experiments scheduled for March 1995.

  15. 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 ...

  16. 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.

  17. Screening closing scenarios for tactical targets

    Science.gov (United States)

    Sefcik, Jason A.; Lee, Harry C.; Olson, Teresa L. P.

    2002-07-01

    The first step in an automatic image target acquisition system is determining the location of candidate objects. Screening for targets must also be done within a tactical scenario timeframe. The screening process must only require a portion of the processing workload since other algorithms must execute in the same time frame. The detection of these candidate objects is allocated to two functions within the same algorithm. The first is a pre-screener and other is a clutter rejection component that will categorize the object nomination into target or non-target classes. This paper describes a screener that meets the necessary requirements for tactical operations. It uses the magnitude and direction of the image gradient. Locations are nominated by looking at local neighborhoods in this gradient space. Regions of interest are then selected and various features are extracted. These features are selected both for their information content and their ease of calculation. Using a Bayes approach, target candidates are selected as plausible targets of interest.

  18. PROS AND CONS OF INFLATION TARGETING STRATEGY

    Directory of Open Access Journals (Sweden)

    Mihaela SUDACEVSCHI

    2011-12-01

    Full Text Available The purpose of this paper is to define the inflation targeting strategy and its characteristics. Inflation targeting is a monetary policy strategy in which the central bank projected estimates and makes public, or “target” inflation rate and then, attempts to steer actual inflation towards the target through the use of interest rate changes and other monetary tools. Early proposals of monetary systems targeting the price level or the inflation rate, rather then exchange rate, followed the general crisis of the gold standard after the World War I. Inflation is usually measured as the change of prices for consumer goods, called Consumer Price Index (CPI. Inflation targeting assumes that this figure accurately represents growth or money supply, but is not always the case. The most serious exception occurs when factors external to the national economy are the cause of the price increase. A more essential objection to the strategy of inflation targeting is that it does not really comprise a specific set of monetary policy recommendation would traditional monetarism did, but just constitutes an explicit statement of the aims of the monetary authority.

  19. 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 . PMID:27167132

  20. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99mTc as a radionuclide. We developed 99mTc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99mTc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99mTc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99mTc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques