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Sample records for targeting brugia pahangi

  1. Cytokine production in BALB/c mice immunized with radiation attenuated third stage larvae of the filarial nematode, Brugia pahangi

    International Nuclear Information System (INIS)

    Bancroft, A.J.; Devaney, E.; Grencis, R.K.; Else, K.J.

    1993-01-01

    BALB/c mice immunized with radiation-attenuated third stage larvae of the filarial nematode Brugia pahangi are strongly immune to challenge infection. Investigation of the profile of cytokines secreted by spleen cells from immune mice stimulated in vitro with either parasite Ag or with Con A revealed high levels of IL-5 and IL-9 and moderate levels of IL-4. In contrast, secretion of IFN-γ by spleen cells from immune animals was negligible. Spleen cells from control mice secreted low levels of all cytokines assayed. Levels of parasite-specific IgE were significantly elevated in immune animals and a peripheral blood eosinophilia was observed, which exhibited a biphasic distribution. Our results are consistent with the preferential expansion of Th2 cells in immune animals and provide the basis for dissecting the means by which radiation-attenuated larvae of filarial nematodes stimulate immunity. 5l refs., 3 figs., 3 tabs

  2. Macrofilaricidal and microfilaricidal effects of Neurolaena lobata, a Guatemalan medicinal plant, on Brugia pahangi.

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    Fujimaki, Y; Kamachi, T; Yanagi, T; Cáceres, A; Maki, J; Aoki, Y

    2005-03-01

    Twelve extracts of 11 Guatemalan medicinal plants were initially screened in vitro for potential macrofilaricidal activity against Brugia pahangi, a lymphatic dwelling filarial worm, using concentrations from 125 to 1000 microg ml(-1) of each extract that could be dissolved in the culture medium. Of 12 extracts used, the ethanol extract of leaves of Neurolaena lobata showed the strongest activity against the motility of adult worms. Subsequently, the extract of N. lobata was extensively examined in vitro for macro- and micro-filaricidal effects using a series of concentrations of 500, 250, 100, 50 and 10 microg ml(-1). The effects were assessed by worm motility, microfilarial release by female worms and a MTT assay. The effect on the motility of adult worms was observed in a concentration- and time-dependent manner. The time required to stop motility of both sexes of adult worms was 6 h at 500 microg ml(-1), 24 h at 250 microg ml(-1), and 3 days for females and 4 days for males at 100 microg ml(-1). The movement of females ceased at 4 days at a concentration of 50 microg ml(-1) whereas the motility of males was only reduced. The loss of worm's viability was confirmed by the MTT assay and was similar to the motility results. These concentrations, including 10 microg ml(-1), prevented microfilarial release by females in a concentration- and time-dependent manner. Concentrations higher than 100 microg ml(-1) even induced mortality of the microfilariae. The present study suggested that the ethanol extract of Neurolaena lobata has potential macro- and micro-filaricidal activities.

  3. Reactive oxygen species production and Brugia pahangi survivorship in Aedes polynesiensis with artificial Wolbachia infection types.

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    Elizabeth S Andrews

    Full Text Available Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated "MTB" experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive oxygen species (ROS in the MTB strain differ significantly relative to that of the wild-type, indicating an impaired ability to regulate oxidative stress. Following a challenge with Brugia pahangi, the number of filarial worms achieving the infective stage is significantly reduced in MTB as compared to the naturally infected and aposymbiotic strains. Survivorship of MTB differed significantly from that of the wild-type, with an interactive effect between survivorship and blood feeding. The results demonstrate a direct correlation between decreased ROS levels and decreased survival of adult female Aedes polynesiensis. The results are discussed in relation to the interaction of Wolbachia with ROS production and antioxidant expression, iron homeostasis and the insect immune system. We discuss the potential applied use of the MTB strain for impacting Ae. polynesiensis populations and strategies for reducing LF incidence in the South Pacific.

  4. Mining predicted essential genes of Brugia malayi for nematode drug targets.

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    Sanjay Kumar

    Full Text Available We report results from the first genome-wide application of a rational drug target selection methodology to a metazoan pathogen genome, the completed draft sequence of Brugia malayi, a parasitic nematode responsible for human lymphatic filariasis. More than 1.5 billion people worldwide are at risk of contracting lymphatic filariasis and onchocerciasis, a related filarial disease. Drug treatments for filariasis have not changed significantly in over 20 years, and with the risk of resistance rising, there is an urgent need for the development of new anti-filarial drug therapies. The recent publication of the draft genomic sequence for B. malayi enables a genome-wide search for new drug targets. However, there is no functional genomics data in B. malayi to guide the selection of potential drug targets. To circumvent this problem, we have utilized the free-living model nematode Caenorhabditis elegans as a surrogate for B. malayi. Sequence comparisons between the two genomes allow us to map C. elegans orthologs to B. malayi genes. Using these orthology mappings and by incorporating the extensive genomic and functional genomic data, including genome-wide RNAi screens, that already exist for C. elegans, we identify potentially essential genes in B. malayi. Further incorporation of human host genome sequence data and a custom algorithm for prioritization enables us to collect and rank nearly 600 drug target candidates. Previously identified potential drug targets cluster near the top of our prioritized list, lending credibility to our methodology. Over-represented Gene Ontology terms, predicted InterPro domains, and RNAi phenotypes of C. elegans orthologs associated with the potential target pool are identified. By virtue of the selection procedure, the potential B. malayi drug targets highlight components of key processes in nematode biology such as central metabolism, molting and regulation of gene expression.

  5. ASPEK ZOONOTIK PARASIT NEMATODA PADA KERA DAN BINATANG MENGERAT DI BENGKULU, SUMATERA. INDONESIA

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    Untung S.

    2012-09-01

    Full Text Available Twentyfive monkeys and 481 rats were examined for parasitic nematodes in Bengkulu, nine species of nematode were found infecting these animals. Five of filarían nematodes, i.e. Brugia malayi, Brugia pahangi, Dirofilaria magnilarvatum and Edesonfilaria malayensis were infecting monkeys and one speciesTBreinlia booliati, was found infecting rats. Three species of gastrointestinal helminths, i.e. Trichuris trichiura, Enterobius vermicularis and Oestophagomomum spp were found in monkeys; a lung worm, Angiostrongylus cantonensis, was found in rats. The most important nematode species is B. malayi, which was found in Presbytis cristatus (36.8 % and in Macaca fascicularis (20.0 %. T. trichiura was found in R. cristatus (47.9 % and A. cantonensis in Rattus argentiventer (4.0 % and Rattus tiomanicus (2.9%.

  6. Filarial worms reduce Plasmodium infectivity in mosquitoes.

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    Matthew T Aliota

    2011-02-01

    Full Text Available Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG. Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness.Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria parasite infections.These results could have an

  7. Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis.

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    Rajan, T V; Bailis, J M; Yates, J A; Shultz, L D; Greiner, D L; Nelson, F K

    1994-12-01

    We have used the severe combined immunodeficient C.B-17-scid/scid mouse to investigate the influences of maternal immune status and parasite burden on the susceptibility (or resistance) of offspring to infection with the human filarial parasite, Brugia malayi. C.B-17-scid/scid mice are permissive for infection while immunocompetent C.B-17(-)+/+ mice are uniformly resistant. Reciprocal matings of C.B-17-scid/scid and C.B-17(-)+/+ mice were performed. The C.B-17-scid/scid females were either naive or infected with Brugia malayi. The resulting immunocompetent C.B-17-scid/+ and C.B-17(-)+/scid progeny were challenged at weaning with an intraperitoneal injection of Brugia malayi third stage larvae known to produce patent infection in > 95% of C.B-17-scid/scid mice. We observed that 40.0%l (34/85) of the immunocompetent offspring of C.B-17-scid/scid females x C.B-17(-)+/+ males were permissive for the growth and development of Brugia malayi larvae to adults. No difference was observed in susceptibility to infection between the progeny of infected or uninfected C.B-17-scid/scid mothers mated with C.B-17(-)+/+ fathers, arguing against acquired immunological tolerance to the parasite in the former. In marked contrast, only 4.8% (2/42) of the heterozygous progeny of wild type C.B-17(-)+/+ females mated with C.B-17-scid/scid males were permissive. These observations document conversion of a 'resistant' phenotype to a 'susceptible' phenotype by manipulation of maternal immune status and provide clear evidence of maternal influence on offspring susceptibility to infection with Brugia malayi.

  8. Loiasis in a Japanese Traveler Returning from Central Africa

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    Kobayashi, Tetsuro; Hayakawa, Kayoko; Mawatari, Momoko; Itoh, Makoto; Akao, Nobuaki; Yotsu, Rie R.; Sugihara, Jun; Takeshita, Nozomi; Kutsuna, Satoshi; Fujiya, Yoshihiro; Kanagawa, Shuzo; Ohmagari, Norio; Kato, Yasuyuki

    2015-01-01

    We encountered a probable case of loiasis in a returned traveler from Central Africa. A 52-year-old Japanese woman presented to our hospital complaining of discomfort in her eyes and skin. She reported having frequently visited Central Africa over many years and having been extensively exposed to the rainforest climate and ecosystem. Although no microfilariae were found in her blood, there was an elevated level of IgG antibodies against the crude antigens of Brugia pahangi, which have cross-reactivity with Loa loa. She was treated with albendazole for 21 days, after which the antigen-specific IgG level decreased and no relapse occurred. PMID:26161033

  9. Identification of anti-filarial leads against aspartate semialdehyde dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular docking and molecular dynamics approaches.

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    Amala, Mathimaran; Rajamanikandan, Sundaraj; Prabhu, Dhamodharan; Surekha, Kanagarajan; Jeyakanthan, Jeyaraman

    2018-02-06

    Lymphatic filariasis is a debilitating vector borne parasitic disease that infects human lymphatic system by nematode Brugia malayi. Currently available anti-filarial drugs are effective only on the larval stages of parasite. So far, no effective drugs are available for humans to treat filarial infections. In this regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic pathway from Wolbachia endosymbiont Brugia malayi represents an attractive therapeutic target for the development of novel anti-filarial agents. In this present study, molecular modeling combined with molecular dynamics simulations and structure-based virtual screening were performed to identify potent lead molecules against ASDase. Based on Glide score, toxicity profile, binding affinity and mode of interactions with the ASDase, five potent lead molecules were selected. The molecular docking and dynamics results revealed that the amino acid residues Arg103, Asn133, Cys134, Gln161, Ser164, Lys218, Arg239, His246, and Asn321 plays a crucial role in effective binding of Top leads into the active site of ASDase. The stability of the ASDase-lead complexes was confirmed by running the 30 ns molecular dynamics simulations. The pharmacokinetic properties of the identified lead molecules are in the acceptable range. Furthermore, density functional theory and binding free energy calculations were performed to rank the lead molecules. Thus, the identified lead molecules can be used for the development of anti-filarial agents to combat the pathogenecity of Brugia malayi.

  10. The solution structure of the forkhead box-O DNA binding domain of Brugia malayi DAF-16a.

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    Casper, Sarah K; Schoeller, Scott J; Zgoba, Danielle M; Phillips, Andrew J; Morien, Thomas J; Chaffee, Gary R; Sackett, Peter C; Peterson, Francis C; Crossgrove, Kirsten; Veldkamp, Christopher T

    2014-12-01

    Brugia malayi is a parasitic nematode that causes lymphatic filariasis in humans. Here the solution structure of the forkhead DNA binding domain of Brugia malayi DAF-16a, a putative ortholog of Caenorhabditis elegans DAF-16, is reported. It is believed to be the first structure of a forkhead or winged helix domain from an invertebrate. C. elegans DAF-16 is involved in the insulin/IGF-I signaling pathway and helps control metabolism, longevity, and development. Conservation of sequence and structure with human FOXO proteins suggests that B. malayi DAF-16a is a member of the FOXO family of forkhead proteins. © 2014 Wiley Periodicals, Inc.

  11. Detection of a new focus of Brugia malayi infection in Orissa.

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    Rath, R N; Mohapatra, B N; Das, B

    1989-03-01

    526 people were surveyed in a village called Chudamani, in Balasore district of Orissa, for detection of asymptomatic microfilaria (mf) carriers. Of these 36 (6.8 per cent) were cases found to harbour mf; 19 cases had Brugia malayi, 4 Wuchereria bancrofti and 5 cases had mixed infection. In 8 cases, species could not be ascertained. For the first time after 1955, a focus of B. malayi has been detected in Orissa.

  12. The heme biosynthetic pathway of the obligate Wolbachia endosymbiont of Brugia malayi as a potential anti-filarial drug target.

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    Bo Wu

    2009-07-01

    Full Text Available Filarial parasites (e.g., Brugia malayi, Onchocerca volvulus, and Wuchereria bancrofti are causative agents of lymphatic filariasis and onchocerciasis, which are among the most disabling of neglected tropical diseases. There is an urgent need to develop macro-filaricidal drugs, as current anti-filarial chemotherapy (e.g., diethylcarbamazine [DEC], ivermectin and albendazole can interrupt transmission predominantly by killing microfilariae (mf larvae, but is less effective on adult worms, which can live for decades in the human host. All medically relevant human filarial parasites appear to contain an obligate endosymbiotic bacterium, Wolbachia. This alpha-proteobacterial mutualist has been recognized as a potential target for filarial nematode life cycle intervention, as antibiotic treatments of filarial worms harboring Wolbachia result in the loss of worm fertility and viability upon antibiotic treatments both in vitro and in vivo. Human trials have confirmed this approach, although the length of treatments, high doses required and medical counter-indications for young children and pregnant women warrant the identification of additional anti-Wolbachia drugs.Genome sequence analysis indicated that enzymes involved in heme biosynthesis might constitute a potential anti-Wolbachia target set. We tested different heme biosynthetic pathway inhibitors in ex vivo B. malayi viability assays and report a specific effect of N-methyl mesoporphyrin (NMMP, which targets ferrochelatase (FC, the last step. Our phylogenetic analysis indicates evolutionarily significant divergence between Wolbachia heme genes and their human homologues. We therefore undertook the cloning, overexpression and analysis of several enzymes of this pathway alongside their human homologues, and prepared proteins for drug targeting. In vitro enzyme assays revealed a approximately 600-fold difference in drug sensitivities to succinyl acetone (SA between Wolbachia and human 5

  13. Morphological and molecular characteristics of Malayfilaria sofiani Uni, Mat Udin & Takaoka n. g., n. sp. (Nematoda: Filarioidea) from the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia) in Peninsular Malaysia.

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    Uni, Shigehiko; Mat Udin, Ahmad Syihan; Agatsuma, Takeshi; Saijuntha, Weerachai; Junker, Kerstin; Ramli, Rosli; Omar, Hasmahzaiti; Lim, Yvonne Ai-Lian; Sivanandam, Sinnadurai; Lefoulon, Emilie; Martin, Coralie; Belabut, Daicus Martin; Kasim, Saharul; Abdullah Halim, Muhammad Rasul; Zainuri, Nur Afiqah; Bhassu, Subha; Fukuda, Masako; Matsubayashi, Makoto; Harada, Masashi; Low, Van Lun; Chen, Chee Dhang; Suganuma, Narifumi; Hashim, Rosli; Takaoka, Hiroyuki; Azirun, Mohd Sofian

    2017-04-20

    The filarial nematodes Wuchereria bancrofti (Cobbold, 1877), Brugia malayi (Brug, 1927) and B. timori Partono, Purnomo, Dennis, Atmosoedjono, Oemijati & Cross, 1977 cause lymphatic diseases in humans in the tropics, while B. pahangi (Buckley & Edeson, 1956) infects carnivores and causes zoonotic diseases in humans in Malaysia. Wuchereria bancrofti, W. kalimantani Palmieri, Pulnomo, Dennis & Marwoto, 1980 and six out of ten Brugia spp. have been described from Australia, Southeast Asia, Sri Lanka and India. However, the origin and evolution of the species in the Wuchereria-Brugia clade remain unclear. While investigating the diversity of filarial parasites in Malaysia, we discovered an undescribed species in the common treeshrew Tupaia glis Diard & Duvaucel (Mammalia: Scandentia). We examined 81 common treeshrews from 14 areas in nine states and the Federal Territory of Peninsular Malaysia for filarial parasites. Once any filariae that were found had been isolated, we examined their morphological characteristics and determined the partial sequences of their mitochondrial cytochrome c oxidase subunit 1 (cox1) and 12S rRNA genes. Polymerase chain reaction (PCR) products of the internal transcribed spacer 1 (ITS1) region were then cloned into the pGEM-T vector, and the recombinant plasmids were used as templates for sequencing. Malayfilaria sofiani Uni, Mat Udin & Takaoka, n. g., n. sp. is described based on the morphological characteristics of adults and microfilariae found in common treeshrews from Jeram Pasu, Kelantan, Malaysia. The Kimura 2-parameter distance between the cox1 gene sequences of the new species and W. bancrofti was 11.8%. Based on the three gene sequences, the new species forms a monophyletic clade with W. bancrofti and Brugia spp. The adult parasites were found in tissues surrounding the lymph nodes of the neck of common treeshrews. The newly described species appears most closely related to Wuchereria spp. and Brugia spp., but differs from these in

  14. Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin.

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    Hiruni Harischandra

    2018-04-01

    Full Text Available The filarial nematode Brugia malayi is an etiological agent of Lymphatic Filariasis. The capability of B. malayi and other parasitic nematodes to modulate host biology is recognized but the mechanisms by which such manipulation occurs are obscure. An emerging paradigm is the release of parasite-derived extracellular vesicles (EV containing bioactive proteins and small RNA species that allow secretion of parasite effector molecules and their potential trafficking to host tissues. We have previously described EV release from the infectious L3 stage B. malayi and here we profile vesicle release across all intra-mammalian life cycle stages (microfilariae, L3, L4, adult male and female worms. Nanoparticle Tracking Analysis was used to quantify and size EVs revealing discrete vesicle populations and indicating a secretory process that is conserved across the life cycle. Brugia EVs are internalized by murine macrophages with no preference for life stage suggesting a uniform mechanism for effector molecule trafficking. Further, the use of chemical uptake inhibitors suggests all life stage EVs are internalized by phagocytosis. Proteomic profiling of adult male and female EVs using nano-scale LC-MS/MS described quantitative and qualitative differences in the adult EV proteome, helping define the biogenesis of Brugia EVs and revealing sexual dimorphic characteristics in immunomodulatory cargo. Finally, ivermectin was found to rapidly inhibit EV release by all Brugia life stages. Further this drug effect was also observed in the related filarial nematode, the canine heartworm Dirofilaria immitis but not in an ivermectin-unresponsive field isolate of that parasite, highlighting a potential mechanism of action for this drug and suggesting new screening platforms for anti-filarial drug development.

  15. Brugia timori INFECTION IN LEKEBAI, FLORES: clinical aspects

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    Arbain Joesoef

    2012-09-01

    Full Text Available Pengamatan filariasis pada penduduk Nualolo-Lekebai, Pulau Flores telah dilakukan pada bulan Februari 1975. Kampung Nualolo-Lekebai berpenduduk 680 jiwa, pekerjaan bertani dan menganut agama Nasrani. Kebiasaan hidup di antara penduduk di daerah ini adalah menyerahkan pelaksanaan pekerjaan berat pada kaum wanita, baik di rumah ataupun di kebun. Dalam perjalanan jauh baik ke kebun atau ke pasar, kaum wanitanya selalu berjalan kaki sedangkan kaum prianya menunggang kuda. Sejumlah 80% dari penduduk kampung ini telah diperiksa terhadap infeksi parasit filaria dan terhadap gejala filariasis. Dari hasil yang ditemukan ternyata penduduk kampung ini menderita infeksi Brugia timori dengan angka derajat infeksi sebesar 7.0% dan angka derajat elephantiasis sebesar 10.3%. Hal yang menarik yang ditemukan dalam pengamatan ini adalah tingginya angka derajat elephantiasis pada kaum wanita dibandingkan dengan pada kaum pria. Fenomena ini mungkin disebabkan oleh kebiasaan hidup kaum wanita di daerah ini sehari-hari yang bekerja lebih berat dan berjalan kaki lebih sering dan lebih jauh dibandingkan kaum prianya.

  16. Effects of Doxycycline on gene expression in Wolbachia and Brugia malayi adult female worms in vivo

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    Rao Ramakrishna U

    2012-02-01

    Full Text Available Abstract Background Most filarial nematodes contain Wolbachia symbionts. The purpose of this study was to examine the effects of doxycycline on gene expression in Wolbachia and adult female Brugia malayi. Methods Brugia malayi infected gerbils were treated with doxycycline for 6-weeks. This treatment largely cleared Wolbachia and arrested worm reproduction. RNA recovered from treated and control female worms was labeled by random priming and hybridized to the Version 2- filarial microarray to obtain expression profiles. Results and discussion Results showed significant changes in expression for 200 Wolbachia (29% of Wolbachia genes with expression signals in untreated worms and 546 B. malayi array elements after treatment. These elements correspond to known genes and also to novel genes with unknown biological functions. Most differentially expressed Wolbachia genes were down-regulated after treatment (98.5%. In contrast, doxycycline had a mixed effect on B. malayi gene expression with many more genes being significantly up-regulated after treatment (85% of differentially expressed genes. Genes and processes involved in reproduction (gender-regulated genes, collagen, amino acid metabolism, ribosomal processes, and cytoskeleton were down-regulated after doxycycline while up-regulated genes and pathways suggest adaptations for survival in response to stress (energy metabolism, electron transport, anti-oxidants, nutrient transport, bacterial signaling pathways, and immune evasion. Conclusions Doxycycline reduced Wolbachia and significantly decreased bacterial gene expression. Wolbachia ribosomes are believed to be the primary biological target for doxycycline in filarial worms. B. malayi genes essential for reproduction, growth and development were also down-regulated; these changes are consistent with doxycycline effects on embryo development and reproduction. On the other hand, many B. malayi genes involved in energy production, electron

  17. Lymphatic filariasis-specific immune responses in relation to lymphoedema grade and infection status. II. Humoral responses

    DEFF Research Database (Denmark)

    Nielsen, N. O.; Bloch, P.; Simonsen, P. E.

    2002-01-01

    The filarial-specific humoral responses (IgG1, IgG2, IgG3, IgG4 and IgE) to a Brugia pahangi antigen was assessed in 9 groups of adult individuals from a Wuchereria bancrofti-endemic area in north-east Tanzania. In 5 of the groups, individuals were negative for microfilariae (mf) and circulating...... filarial antigen (CFA) and had leg lymphoedema of varying severity ranging from early to more advanced grades. A 6th group had mixed grades of lymphoedema and were actively infected with mf and/or CFA. Three groups of asymptomatic individuals with different infection status (mf+CFA+; mf-CFA+; mf-CFA-) were...... also included. No differences in the antibody levels were observed between the 5 uninfected pathology groups. However, groups with advanced lymphoedema had a significantly higher level of IgG3 as compared to groups with early lymphoedema. A decline in the IgG4/IgE ratios were observed when moving from...

  18. Comparison of an enzyme linked immunosorbent assay (ELISA) and a radioallergosorbent test (RAST) for detection of IgE antibodies to Brugia malayi

    NARCIS (Netherlands)

    Wahyuni, Sitti; van Ree, Ronald; Mangali, Andarias; Supali, Taniawati; Yazdanbakhsh, Maria; Sartono, Erliyani

    2003-01-01

    The enzyme linked immunosorbent assay (ELISA) for specific IgE antibodies to Brugia malayi was compared with the radioallergosorbent test (RAST) for use in immunoepidemiological studies of lymphatic filariasis. Sera used were from individuals (aged 5-82 years) living in an area endemic for lymphatic

  19. Expression of five acetylcholine receptor subunit genes in Brugia malayi adult worms

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    Ben-Wen Li

    2015-12-01

    Full Text Available Acetylcholine receptors (AChRs are required for body movement in parasitic nematodes and are targets of “classical” anthelmintic drugs such as levamisole and pyrantel and of newer drugs such as tribendimidine and derquantel. While neurotransmission explains the effects of these drugs on nematode movement, their effects on parasite reproduction are unexplained. The levamisole AChR type (L-AChRs in Caenorhabditis elegans is comprised of five subunits: Cel-UNC-29, Cel-UNC-38, Cel-UNC-63, Cel-LEV-1 and Cel-LEV-8. The genome of the filarial parasite Brugia malayi contains nine AChRs subunits including orthologues of Cel-unc-29, Cel-unc-38, and Cel-unc-63. We performed in situ hybridization with RNA probes to localize the expression of five AChR genes (Bm1_35890-Bma-unc-29, Bm1_20330-Bma-unc-38, Bm1_38195-Bma-unc-63, Bm1_48815-Bma-acr-26 and Bm1_40515-Bma-acr-12 in B. malayi adult worms. Four of these genes had similar expression patterns with signals in body muscle, developing embryos, spermatogonia, uterine wall adjacent to stretched microfilariae, wall of Vas deferens, and lateral cord. Three L-AChR subunit genes (Bma-unc-29, Bma-unc-38 and Bma-unc-63 were expressed in body muscle, which is a known target of levamisole. Bma-acr-12 was co-expressed with these levamisole subunit genes in muscle, and this suggests that its protein product may form receptors with other alpha subunits. Bma-acr-26 was expressed in male muscle but not in female muscle. Strong expression signals of these genes in early embryos and gametes in uterus and testis suggest that AChRs may have a role in nervous system development of embryogenesis and spermatogenesis. This would be consistent with embryotoxic effects of drugs that target these receptors in filarial worms. Our data show that the expression of these receptor genes is tightly regulated with regard to localization in adult worms and developmental stage in embryos and gametes. These results may help to explain the

  20. Deteksi Brugia malayi pada Armigeres subalbatus dan Culex quinquefasciatusyang diinfeksikan darah penderita filariasis dengan metode PCR

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    Yahya Yahya

    2015-01-01

    Full Text Available Abstract. Pemayungdistricts, Batanghari regency of Jambi province classified as filariasis endemic areas in Jambi province since the Mf rate reached 1.5% in 2011. A study was conducted to identify Brugia malayi on experimentally infected Ar. subalbatus and Cx. quinquefasciatus. An experimental study was performed with completely randomized design and six repetitions. Standard of treatment in this study was time (hours that selected for mosquitoes to bite the patients with filariasis (experimental infection. Selected time is at 9.00 a.m, 5.00 p.m, 9.00 p.m, and at 1.00 a.m. The results showed that filarial L3 larvae did not found on Ar. subalbatus and Cx. quinquefasciatus mosquitoes during surgery at day 11th to 13th after infection. Density of microfilariae in the blood of humans as a source of infection was 17 microfilariae per 20 micro liter blood. Otherwise, after detection by PCR, our study found positive B.malayi on Cx. quinquefasciatus thorax and proboscis. It indicates that Cx. quinquefasciatusas potential vector of B.malayi filariasis compared to Ar. subalbatus. Keywords: PCR, filariasis, Armigeres subalbatus, Culex quinquefasciatus, Brugia malayi   Abstrak. Kecamatan Pemayung Kabupaten Batanghari Provinsi Jambi merupakan wilayah endemis filariasis di Provinsi Jambi Karena angka Mf rate mencapai 1,5% pada tahun 2011. Penelitian ini untuk mengetahui tingkat kerentanan nyamuk Ar. subalbatus dan Cx. quinquefasciatus terhadap infeksi B. malayi subperiodik nokturna yang dilakukan pada tahun 2013, sehingga dapat dianalisis potensi nyamuk tersebut sebagai vektor filariasis di lokasi penelitian. Desain penelitian adalah eksperimental dengan rancangan acak lengkap dan enam kali pengulangan. Variabel perlakuan dalam penelitian ini adalah waktu (jam yang dipilih untuk menggigitkan nyamuk pada penderita filariasis (infeksi percobaan. Waktu yang dipilih adalah pukul 09.00 WIB, pukul 17.00 WIB, pukul 21.00 WIB dan pukul 01.00 WIB. Hasil penelitian

  1. Galactolipids from Bauhinia racemosa as a new class of antifilarial agents against human lymphatic filarial parasite, Brugia malayi.

    Science.gov (United States)

    Sashidhara, Koneni V; Singh, Suriya P; Misra, Sweta; Gupta, Jyoti; Misra-Bhattacharya, Shailja

    2012-04-01

    Bioassay guided fractionation of ethanolic extract of the leaves of Bauhinia racemosa led to the isolation of galactolipid and catechin class of the compounds (1-7) from the most active n-butanol fraction (F4). Among the active galactolipids, 1 emerged as the lead molecule which was active on both forms of lymphatic filarial parasite, Brugia malayi. It was found to be better than the standard drug ivermectin and diethylcarbamazine (DEC) in terms of dose and efficacy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  2. Functional analysis of the cathepsin-like cysteine protease genes in adult Brugia malayi using RNA interference.

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    Louise Ford

    Full Text Available Cathepsin-like enzymes have been identified as potential targets for drug or vaccine development in many parasites, as their functions appear to be essential in a variety of important biological processes within the host, such as molting, cuticle remodeling, embryogenesis, feeding and immune evasion. Functional analysis of Caenorhabditis elegans cathepsin L (Ce-cpl-1 and cathepsin Z (Ce-cpz-1 has established that both genes are required for early embryogenesis, with Ce-cpl-1 having a role in regulating in part the processing of yolk proteins. Ce-cpz-1 also has an important role during molting.RNA interference assays have allowed us to verify whether the functions of the orthologous filarial genes in Brugia malayi adult female worms are similar. Treatment of B. malayi adult female worms with Bm-cpl-1, Bm-cpl-5, which belong to group Ia of the filarial cpl gene family, or Bm-cpz-1 dsRNA resulted in decreased numbers of secreted microfilariae in vitro. In addition, analysis of the intrauterine progeny of the Bm-cpl-5 or Bm-cpl Pro dsRNA- and siRNA-treated worms revealed a clear disruption in the process of embryogenesis resulting in structural abnormalities in embryos and a varied differential development of embryonic stages.Our studies suggest that these filarial cathepsin-like cysteine proteases are likely to be functional orthologs of the C. elegans genes. This functional conservation may thus allow for a more thorough investigation of their distinct functions and their development as potential drug targets.

  3. Brugia malayi gene expression in response to the targeting of the Wolbachia endosymbiont by tetracycline treatment.

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    Elodie Ghedin

    2009-10-01

    Full Text Available Brugia malayi, like most human filarial parasite species, harbors an endosymbiotic bacterium of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female. Previous biochemical and genetic studies have established that communication with its endobacterium is essential for survival of the worm.We used electron microscopy to examine the effects of antibiotic treatment on Wolbachia cell structure. We have also used microarray and quantitative RT-PCR analyses to examine the regulation of the B. malayi transcripts altered in response to the anti-Wolbachia treatment. Microscopy of worms taken from animals treated with tetracycline for 14 and 21 days (14 d and 21 d demonstrated substantial morphologic effects on the Wolbachia endobacterium by 14 d and complete degeneration of the endobacterial structures by 21 d. We observed upregulation of transcripts primarily encoding proteins involved in amino acid synthesis and protein translation, and downregulation of transcripts involved in cuticle biosynthesis after both 7 d and 14 d of treatment. In worms exposed to tetracycline in culture, substantial effects on endobacteria morphology were evident by day 3, and extensive death of the endobacteria was observed by day 5. In a detailed examination of the expression kinetics of selected signaling genes carried out on such cultured worms, a bimodal pattern of regulation was observed. The selected genes were upregulated during the early phase of antibiotic treatment and quickly downregulated in the following days. These same genes were upregulated once more at 6 days post-treatment.Upregulation of protein translation and amino acid synthesis may indicate a generalized stress response induced in B. malayi due to a shortage of essential nutrients/factors that are otherwise supplied by Wolbachia. Downregulation of transcripts involved in cuticle biosynthesis perhaps reflects a disruption in the normal embryogenic program. This is

  4. Detection of circulating parasite-derived microRNAs in filarial infections.

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    Lucienne Tritten

    2014-07-01

    Full Text Available Filarial nematodes cause chronic and profoundly debilitating diseases in both humans and animals. Applications of novel technology are providing unprecedented opportunities to improve diagnosis and our understanding of the molecular basis for host-parasite interactions. As a first step, we investigated the presence of circulating miRNAs released by filarial nematodes into the host bloodstream. miRNA deep-sequencing combined with bioinformatics revealed over 200 mature miRNA sequences of potential nematode origin in Dirofilaria immitis-infected dog plasma in two independent analyses, and 21 in Onchocerca volvulus-infected human serum. Total RNA obtained from D. immitis-infected dog plasma was subjected to stem-loop RT-qPCR assays targeting two detected miRNA candidates, miR-71 and miR-34. Additionally, Brugia pahangi-infected dog samples were included in the analysis, as these miRNAs were previously detected in extracts prepared from this species. The presence of miR-71 and miR-34 discriminated infected samples (both species from uninfected samples, in which no specific miRNA amplification occurred. However, absolute miRNA copy numbers were not significantly correlated with microfilaraemia for either parasite. This may be due to the imprecision of mf counts to estimate infection intensity or to miRNA contributions from the unknown number of adult worms present. Nonetheless, parasite-derived circulating miRNAs are found in plasma or serum even for those species that do not live in the bloodstream.

  5. Wolbachia lipoproteins: abundance, localisation and serology of Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6 from Brugia malayi and Aedes albopictus.

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    Voronin, Denis; Guimarães, Ana F; Molyneux, Gemma R; Johnston, Kelly L; Ford, Louise; Taylor, Mark J

    2014-10-06

    Lipoproteins are the major agonists of Wolbachia-dependent inflammatory pathogenesis in filariasis and a validated target for drug discovery. Here we characterise the abundance, localisation and serology of the Wolbachia lipoproteins: Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6. We used proteomics to confirm lipoprotein presence and relative abundance; fractionation, immunoblotting and confocal and electron immuno-microscopy for localisation and ELISA for serological analysis. Proteomic analysis of Brugia malayi adult female protein extracts confirmed the presence of two lipoproteins, previously predicted through bioinformatics: Wolbachia peptidoglycan associated lipoprotein (wBmPAL) and the Type IV Secretion System component, VirB6 (wBmVirB6). wBmPAL was among the most abundant Wolbachia proteins present in an extract of adult female worms with wBmVirB6 only detected at a much lower abundance. This differential abundance was reflected in the immunogold-labelling, which showed wBmPAL localised at numerous sites within the bacterial membranes, whereas wBmVirB6 was present as a single cluster on each bacterial cell and also located within the bacterial membranes. Immunoblotting of fractionated extracts confirmed the localisation of wBmPAL to membranes and its absence from cytosolic fractions of C6/36 mosquito cells infected with wAlbB. In whole worm mounts, antibody labelling of both lipoproteins were associated with Wolbachia. Serological analysis showed that both proteins were immunogenic and raised antibody responses in the majority of individuals infected with Wuchereria bancrofti. Two Wolbachia lipoproteins, wBmPAL and wBmVirB6, are present in extracts of Brugia malayi with wBmPAL among the most abundant of Wolbachia proteins. Both lipoproteins localised to bacterial membranes with wBmVirB6 present as a single cluster suggesting a single Type IV Secretory System on each Wolbachia cell.

  6. Detection of human filarial parasite Brugia malayi in dogs by histochemical staining and molecular techniques.

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    Ambily, V R; Pillai, Usha Narayana; Arun, R; Pramod, S; Jayakumar, K M

    2011-09-27

    Human filariasis caused by Brugia malayi is still a public health problem in many countries of Asia including India, Indonesia, Malaysia and Thailand. The World Health Organization (WHO) has targeted to eliminate filariasis by the year 2020 by Mass annual single dose Diethylcarbamazine Administration (MDA). Results of the MDA programme after the first phase was less satisfactory than expected. Malayan filariasis caused by B. malayi is endemic in the south of Thailand where domestic cat serves as the major reservoir host. There is no report about the occurrence of B. malayi in dogs. The present work was carried out to find out the incidence of microfilariasis in dogs and also to detect the presence of human filarial infection in dogs, if any. One hundred dogs above 6 months of age presented to the veterinary college Hospital, Mannuthy, Kerala, with clinical signs suggestive of microfilariasis - fever, anorexia, conjunctivitis, limb and scrotal oedema - were screened for microfilariae by wet film examination. Positive cases were subjected to Giemsa staining, histochemical staining and molecular techniques. Results of the study showed that 80% of dogs had microfilariasis; out of which 20% had sheathed microfilaria. Giemsa and histochemical staining character, PCR and sequencing confirmed it as B. malayi. High prevalence of B. malayi in dogs in this study emphasized the possible role of dogs in transmission of human filariasis. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Physicochemical properties of the modeled structure of astacin metalloprotease moulting enzyme NAS-36 and mapping the druggable allosteric space of Heamonchus contortus, Brugia malayi and Ceanorhabditis elegans via molecular dynamics simulation.

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    Sharma, Om Prakash; Agrawal, Sonali; Kumar, M Suresh

    2013-12-01

    Nematodes represent the second largest phylum in the animal kingdom. It is the most abundant species (500,000) in the planet. It causes chronic, debilitating infections worldwide such as ascariasis, trichuriasis, hookworm, enterobiasis, strongyloidiasis, filariasis and trichinosis, among others. Molecular modeling tools can play an important role in the identification and structural investigation of molecular targets that can act as a vital candidate against filariasis. In this study, sequence analysis of NAS-36 from H. contortus (Heamonchus contortus), B. malayi (Brugia malayi) and C. elegans (Ceanorhabditis elegans) has been performed, in order to identify the conserved residues. Tertiary structure was developed for an insight into the molecular structure of the enzyme. Molecular Dynamics Simulation (MDS) studies have been carried out to analyze the stability and the physical properties of the proposed enzyme models in the H. contortus, B. malayi and C. elegans. Moreover, the drug binding sites have been mapped for inhibiting the function of NAS-36 enzyme. The molecular identity of this protease could eventually demonstrate how ex-sheathment is regulated, as well as provide a potential target of anthelmintics for the prevention of nematode infections.

  8. Inventory and analysis of ATP-binding cassette (ABC) systems in Brugia malayi.

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    Ardelli, B F; Stitt, L E; Tompkins, J B

    2010-07-01

    ABC systems are one of the largest described protein superfamilies. These systems have a domain organization that may contain 1 or more transmembrane domains (ABC_TM1F) and 1 or 2 ATP-binding domains (ABC_2). The functions (e.g., import, export and DNA repair) of these proteins distinguish the 3 classes of ABC systems. Mining and PCR-based cloning were used to identify 33 putative ABC systems from the Brugia malayi genome. There were 31 class 2 genes, commonly called ABC transporters, and 2 class 3 genes. The ABC transporters were divided into subfamilies. Three belonged to subfamily A, 16 to subfamily B, 5 to subfamily C, 1 to subfamily E and 3 to subfamilies F and G, respectively. None were placed in subfamilies D and H. Similar to other ABC systems, the ABC_2 domain of B. malayi genes was conserved and contained the Walker A and B motifs, the signature sequence/linker region and the switch region with the conserved histidine. The ABC_TM1F domain was less conserved. The relative abundance of ABC systems was quantified using real-time reverse transcription PCR and was significantly higher in female adults of B. malayi than in males and microfilaria, particularly those in subfamilies B and C, which are associated with drug resistance.

  9. Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6-phosphate phosphatase results in significant protection against homologous challenge infection.

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    Susheela Kushwaha

    Full Text Available Development of a vaccine to prevent or reduce parasite development in lymphatic filariasis would be a complementary approach to existing chemotherapeutic tools. Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP represents an attractive vaccine target due to its absence in mammals, prevalence in the major life stages of the parasite and immunoreactivity with human bancroftian antibodies, especially from endemic normal subjects. We have recently reported on the cloning, expression, purification and biochemical characterization of this vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of Bm-TPP was carried out against B. malayi larval challenge in a susceptible host Mastomys coucha and the protective ability of the recombinant protein was evaluated by observing the adverse effects on microfilarial density and adult worm establishment. Immunization caused 78.4% decrease in microfilaremia and 71.04% reduction in the adult worm establishment along with sterilization of 70.06% of the recovered live females. The recombinant protein elicited a mixed Th1/Th2 type of protective immune response as evidenced by the generation of both pro- and anti-inflammatory cytokines IL-2, IFN-γ, TNF-α, IL-4 and an increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus immunization with Bm-TPP conferred considerable protection against B. malayi establishment by engendering a long-lasting effective immune response and therefore emerges as a potential vaccine candidate against lymphatic filariasis (LF.

  10. Cofactor Independent Phosphoglycerate Mutase of Brugia malayi Induces a Mixed Th1/Th2 Type Immune Response and Inhibits Larval Development in the Host

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    Prashant K. Singh

    2014-01-01

    Full Text Available Lymphatic filariasis is a major debilitating disease, endemic in 72 countries putting more than 1.39 billion people at risk and 120 million are already infected. Despite the significant progress in chemotherapeutic advancements, there is still need for other measures like development of an effective vaccine or discovery of novel drug targets. In this study, structural and immunological characterization of independent phosphoglycerate mutase of filarial parasite Brugia malayi was carried out. Protein was found to be expressed in all major parasite life stages and as an excretory secretory product of adult parasites. Bm-iPGM also reacted to all the categories of human bancroftian patient’s sera including endemic normals. In vivo immunological behaviour of protein was determined in immunized BALB/c mice followed by prophylactic analysis in BALB/c mice and Mastomys coucha. Immunization with Bm-iPGM led to generation of a mixed Th1/Th2 type immune response offering 58.2% protection against larval challenge in BALB/c and 65–68% protection in M. coucha. In vitro studies confirmed participation of anti-Bm-iPGM antibodies in killing of B. malayi infective larvae and microfilariae through ADCC mechanism. The present findings reveal potential immunoprotective nature of Bm-iPGM advocating its worth as an antifilarial vaccine candidate.

  11. Production of Brugia malayi BmSXP Recombinant Protein Expressed in Escherichia coli

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    Khoo, T. K.

    2010-01-01

    Full Text Available A rapid antibody detection test is very useful for detection of lymphatic filariasis, especially for certification and surveillance of post-mass drug administration. One such kit, panLF RapidTM (commercialized by Malaysian BioDiagnostic Research Sdn. Bhd. had been developed in our laboratory for the detection of all species of filarial infections. It is based on the detection of anti-filarial IgG4 antibodies that react with recombinant Brugia malayi antigens, BmR1 and BmSXP. In this study, the growth of recombinant bacteria that produce BmSXP was optimized under shake flask fermentation for high yield of the recombinant antigen. The optimizations involved selection of suitable growth medium, IPTG concentration and induction time. The medium that yielded the highest biomass as well as total protein was Terrific Broth (TB medium, which is an undefined medium. Initiation of induction of protein expression was found to be best at mid-log phase (OD600 = 1.5, with IPTG concentration of 1.0 mM, and harvest time at 9 h post-induction. This study showed that under the optimized conditions, the shake flask culture produced 4 g/L biomass (dry cell weight of recombinant Escherichia coli BmSXP/pPROEXHTa/TOP10F’, which yielded 2.42 mg/L of purified BmSXP recombinant antigen. The purified antigen was analyzed by SDS-PAGE and the antigenicity of protein was confirmed by Western blot.

  12. Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model.

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    Elmarie Myburgh

    Full Text Available Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals.

  13. A Cell-Based Screen Reveals that the Albendazole Metabolite, Albendazole Sulfone, Targets Wolbachia

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    Bray, Walter M.; White, Pamela M.; Ruybal, Jordan; Lokey, R. Scott; Debec, Alain; Sullivan, William

    2012-01-01

    Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts. PMID:23028321

  14. Defining Brugia malayi and Wolbachia symbiosis by stage-specific dual RNA-seq.

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    Alexandra Grote

    2017-03-01

    Full Text Available Filarial nematodes currently infect up to 54 million people worldwide, with millions more at risk for infection, representing the leading cause of disability in the developing world. Brugia malayi is one of the causative agents of lymphatic filariasis and remains the only human filarial parasite that can be maintained in small laboratory animals. Many filarial nematode species, including B. malayi, carry an obligate endosymbiont, the alpha-proteobacteria Wolbachia, which can be eliminated through antibiotic treatment. Elimination of the endosymbiont interferes with development, reproduction, and survival of the worms within the mamalian host, a clear indicator that the Wolbachia are crucial for survival of the parasite. Little is understood about the mechanism underlying this symbiosis.To better understand the molecular interplay between these two organisms we profiled the transcriptomes of B. malayi and Wolbachia by dual RNA-seq across the life cycle of the parasite. This helped identify functional pathways involved in this essential symbiotic relationship provided by the co-expression of nematode and bacterial genes. We have identified significant stage-specific and gender-specific differential expression in Wolbachia during the nematode's development. For example, during female worm development we find that Wolbachia upregulate genes involved in ATP production and purine biosynthesis, as well as genes involved in the oxidative stress response.This global transcriptional analysis has highlighted specific pathways to which both Wolbachia and B. malayi contribute concurrently over the life cycle of the parasite, paving the way for the development of novel intervention strategies.

  15. Stage- and gender-specific proteomic analysis of Brugia malayi excretory-secretory products.

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    Yovany Moreno

    Full Text Available INTRODUCTION: While we lack a complete understanding of the molecular mechanisms by which parasites establish and achieve protection from host immune responses, it is accepted that many of these processes are mediated by products, primarily proteins, released from the parasite. Parasitic nematodes occur in different life stages and anatomical compartments within the host. Little is known about the composition and variability of products released at different developmental stages and their contribution to parasite survival and progression of the infection. METHODOLOGY/PRINCIPAL FINDINGS: To gain a deeper understanding on these aspects, we collected and analyzed through 1D-SDS PAGE and LC-MS/MS the Excretory-Secretory Products (ESP of adult female, adult male and microfilariae of the filarial nematode Brugia malayi, one of the etiological agents of human lymphatic filariasis. This proteomic analysis led to the identification of 228 proteins. The list includes 76 proteins with unknown function as well as also proteins with potential immunoregulatory properties, such as protease inhibitors, cytokine homologues and carbohydrate-binding proteins. Larval and adult ESP differed in composition. Only 32 proteins were shared between all three stages/genders. Consistent with this observation, different gene ontology profiles were associated with the different ESP. CONCLUSIONS/SIGNIFICANCE: A comparative analysis of the proteins released in vitro by different forms of a parasitic nematode dwelling in the same host is presented. The catalog of secreted proteins reflects different stage- and gender-specific related processes and different strategies of immune evasion, providing valuable insights on the contribution of each form of the parasite for establishing the host-parasite interaction.

  16. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

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    Juneja, Punita

    2015-03-27

    Many mosquito species are naturally polymorphic for their abilities to transmit parasites, a feature which is of great interest for controlling vector-borne disease. Aedes aegypti, the primary vector of dengue and yellow fever and a laboratory model for studying lymphatic filariasis, is genetically variable for its capacity to harbor the filarial nematode Brugia malayi. The genome of Ae. aegypti is large and repetitive, making genome resequencing difficult and expensive. We designed exome captures to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously mapped in a line established in 1936, suggesting that this polymorphism has been maintained in the wild for the at least 80 years. We then crossed resistant and susceptible mosquitoes to place both alleles of the gene into a common genetic background, and used RNA-seq to measure the effect of this locus on gene expression. We found evidence for Toll, IMD, and JAK-STAT pathway activity in response to early stages of B. malayi infection when the parasites are beginning to die in the resistant genotype. We also found that resistant mosquitoes express anti-microbial peptides at the time of parasite-killing, and that this expression is suppressed in susceptible mosquitoes. Together, we have found that a single resistance locus leads to a higher immune response in resistant mosquitoes, and we identify genes in this region that may be responsible for this trait.

  17. Identification and characterization of nematode specific protective epitopes of Brugia malayi TRX towards development of synthetic vaccine construct for lymphatic filariasis.

    Science.gov (United States)

    Madhumathi, Jayaprakasam; Prince, Prabhu Rajaiah; Anugraha, Gandhirajan; Kiran, Pote; Rao, Donthamsetty Nageswara; Reddy, Maryada Venkata Rami; Kaliraj, Perumal

    2010-07-12

    Although multi-epitope vaccines have been evaluated for various diseases, they have not yet been investigated for lymphatic filariasis. Here, we report for the first time identification of two immunodominant B epitopes (TRXP1 and TRXP2) from the antioxidant Brugia malayi thioredoxin by studying their immune responses in mice model and human subjects. TRXP1 was also found to harbor a T epitope recognized by human PBMCs and mice splenocytes. Further, the epitopic peptides were synthesized as a single peptide conjugate (PC1) and their prophylactic efficacy was tested in a murine model of filariasis with L3 larvae. PC1 conferred a significantly high protection (75.14%) (P TRX (63.03%) (P < 0.018) in experimental filariasis. Our results suggest that multi-epitope vaccines could be a promising strategy in the control of lymphatic filariasis.

  18. Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner.

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    Jan-Hendrik Schroeder

    2017-05-01

    Full Text Available Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators.

  19. Live Brugia malayi microfilariae inhibit transendothelial migration of neutrophils and monocytes.

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    Jan-Hendrik Schroeder

    Full Text Available Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi. Microfilariae (Mf circulate in the peripheral blood for 2-3 hours in synchronisation with maximal feeding of the mosquito vector. When absent from the peripheral blood, Mf sequester in the capillaries of the lungs. Mf are therefore in close contact with vascular endothelial cells (EC and may induce EC immune function and/or wound repair mechanisms such as angiogenesis. In this study, Mf were co-cultured with human umbilical vein EC (HUVEC or human lung microvascular EC (HLMVEC and the transendothelial migration of leukocyte subsets was analysed. In addition, the protein and/or mRNA expression of chemokine, cytokine and angiogenic mediators in endothelial cells in the presence of live microfilariae were measured by a combination of cDNA arrays, protein arrays, ELISA and fluorescence antibody tests.Surprisingly, our findings indicate that Mf presence partially blocked transendothelial migration of monocytes and neutrophils, but not lymphocytes. However, Mf exposure did not result in altered vascular EC expression of key mediators of the tethering stage of extravasation, such as ICAM-1, VCAM-1 and various chemokines. To further analyse the immunological function of vascular EC in the presence of Mf, we measured the mRNA and/or protein expression of a number of pro-inflammatory mediators. We found that expression levels of the mediators tested were predominantly unaltered upon B. malayi Mf exposure. In addition, a comparison of angiogenic mediators induced by intact Mf and Wolbachia-depleted Mf revealed that even intact Mf induce the expression of remarkably few angiogenic mediators in vascular EC. Our study suggests that live microfilariae are remarkably inert in their induction and/or activation of vascular cells in their immediate local environment. Overall, this work presents important insights into the immunological function of the vascular endothelium during

  20. Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3

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    Spiro David

    2009-06-01

    Full Text Available Abstract Background Filarial nematode parasites cause serious diseases such as elephantiasis and river blindness in humans, and heartworm infections in dogs. Third stage filarial larvae (L3 are a critical stage in the life cycle of filarial parasites, because this is the stage that is transmitted by arthropod vectors to initiate infections in mammals. Improved understanding of molecular mechanisms associated with this transition may provide important leads for development of new therapies and vaccines to prevent filarial infections. This study explores changes in gene expression associated with the transition of Brugia malayi third stage larvae (BmL3 from mosquitoes into mammalian hosts and how these changes are affected by radiation. Radiation effects are especially interesting because irradiated L3 induce partial immunity to filarial infections. The underlying molecular mechanisms responsible for the efficacy of such vaccines are unkown. Results Expression profiles were obtained using a new filarial microarray with 18, 104 64-mer elements. 771 genes were identified as differentially expressed in two-way comparative analyses of the three L3 types. 353 genes were up-regulated in mosquito L3 (L3i relative to cultured L3 (L3c. These genes are important for establishment of filarial infections in mammalian hosts. Other genes were up-regulated in L3c relative to L3i (234 or irradiated L3 (L3ir (22. These culture-induced transcripts include key molecules required for growth and development. 165 genes were up-regulated in L3ir relative to L3c; these genes encode highly immunogenic proteins and proteins involved in radiation repair. L3ir and L3i have similar transcription profiles for genes that encode highly immunogenic proteins, antioxidants and cuticle components. Conclusion Changes in gene expression that normally occur during culture under conditions that support L3 development and molting are prevented or delayed by radiation. This may explain

  1. Profiling the macrofilaricidal effects of flubendazole on adult female Brugia malayi using RNAseq

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    Maeghan O'Neill

    2016-12-01

    Full Text Available The use of microfilaricidal drugs for the control of onchocerciasis and lymphatic filariasis (LF necessitates prolonged yearly dosing. Prospects for elimination or eradication of these diseases would be enhanced by the availability of a macrofilaricidal drug. Flubendazole (FLBZ, a benzimidazole anthelmintic, is an appealing candidate. FLBZ has demonstrated potent macrofilaricidal effects in a number of experimental rodent models and in one human trial. Unfortunately, FLBZ was deemed unsatisfactory for use in mass drug administration campaigns due to its limited oral bioavailability. A new formulation that enables sufficient bioavailability following oral administration could render FLBZ an effective treatment for onchocerciasis and LF. Identification of drug-derived effects is important in ascertaining a dosage regimen which is predicted to be lethal to the parasite in situ. In previous histological studies, exposure to FLBZ induced damage to tissues required for reproduction and survival at pharmacologically relevant concentrations. However, more precise and quantitative indices of drug effects are needed. This study assessed drug effects using a transcriptomic approach to confirm effects observed histologically and to identify genes which were differentially expressed in treated adult female Brugia malayi. Comparative analysis across different concentrations (1 μM and 5 μM and durations (48 and 120 h provided an overview of the processes which are affected by FLBZ exposure. Genes with dysregulated expression were consistent with the reproductive effects observed via histology in our previous studies. This study revealed transcriptional changes in genes involved in embryo development. Additionally, significant downregulation was observed in genes encoding cuticle components, which may reflect changes in developing embryos, the adult worm cuticle or both. These data support the hypothesis that FLBZ acts predominantly on rapidly dividing

  2. Suppression of Brugia malayi (sub-periodic larval development in Aedes aegypti (Liverpool strain fed on blood of animals immunized with microfilariae

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    K Athisaya Mary

    2005-07-01

    Full Text Available Preliminary studies were carried out to investigate the role of filarial specific antibodies, raised in an animal model against the filarial parasite, Brugia malayi (sub-periodic, in blocking their early development in an experimental mosquito host, Aedes aegypti (Liverpool strain. In order to generate filarial specific antibodies, Mongolian gerbils, Meriones unguiculatus, were immunized either with live microfilariae (mf of B. malayi or their homogenate. Mf were harvested from the peritoneal cavity of Mongolian gerbils with patent infection of B. malayi and fed to A. aegypti along with the blood from immunized animals. Development of the parasite in infected mosquitoes was monitored until they reached infective stage larvae (L3. Fewer number of parasites developed to first stage (L1 and subsequently to L2 and L3 in mosquitoes fed with blood of immunized animals, when compared to those fed with blood of control animals. The results thus indicated that filarial parasite specific antibodies present in the blood of the immunized animals resulted in the reduction of number of larvae of B. malayi developing in the mosquito host.

  3. Repurposing auranofin as a lead candidate for treatment of lymphatic filariasis and onchocerciasis.

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    Christina A Bulman

    2015-02-01

    Full Text Available Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC, and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult Onchocerca volvulus and Brugia malayi worms (macrofilariae can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of Brugia spp. and Onchocerca ochengi, third-stage larvae (L3s of Onchocerca volvulus, and the microfilariae of both O. ochengi and Loa loa. We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective in vitro in killing both Brugia spp. and O. ochengi adult worms and in inhibiting the molting of L3s of O. volvulus with IC50 values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC50 against the microfilariae of L. loa compared with the IC50 for adult female O. ochengi, which may be beneficial if used in areas where Onchocerca and Brugia are co-endemic with L. loa, to prevent severe adverse reactions to the drug-induced death of L. loa microfilariae. Further testing indicated that auranofin is also effective in reducing Brugia adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

  4. The n-hexane and chloroform fractions of Piper betle L. trigger different arms of immune responses in BALB/c mice and exhibit antifilarial activity against human lymphatic filarid Brugia malayi.

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    Singh, Meghna; Shakya, Shilpy; Soni, Vishal Kumar; Dangi, Anil; Kumar, Nikhil; Bhattacharya, Shailja-Misra

    2009-06-01

    Modulation of immune functions by using herbal plants and their products has become fundamental regime of therapeutic approach. Piper betle Linn. (Piperaceae) is a widely distributed plant in the tropical and subtropical regions of the world and has been attributed as traditional herbal remedy for many diseases. We have recently reported the antifilarial and antileishmanial efficacy in the leaf extract of Bangla Mahoba landrace of P. betle which is a female plant. The present report describes the in vivo immunomodulatory efficacy of the crude methanolic extract and its n-hexane, chloroform, n-butanol fractions of the female plant at various dose levels ranging between 0.3 and 500 mg/kg in BALB/c. Attempts were also made to observe antifilarial activity of the active extracts and correlate it with the antigen specific immune responses in another rodent Mastomys coucha infected with human lymphatic filarial parasite Brugia malayi. The crude methanol extract and n-hexane fraction were found to potentiate significant (p<0.001) enhancement of both humoral (plaque forming cells, hemagglutination titre) as well as cell-mediated (lymphoproliferation, macrophage activation, delayed type hypersensitivity) immune responses in mice. The flow cytometric analysis of splenocytes of treated mice indicated enhanced population of T-cells (CD4(+), CD8(+)) and B-cells (CD19(+)). The n-hexane fraction (3 mg/kg) was found to induce biased type 2 cytokine response as revealed by increased IL-4(+) and decreased IFN-gamma(+) T-cell population while the chloroform fraction (10 mg/kg) produced a predominant type 1 cytokines. Crude methanolic extract (100 mg/kg) demonstrated a mixed type 1 and type 2 cytokine responses thus suggesting a remarkable immunomodulatory property in this plant. The induction of differential T-helper cell immune response appears ideal to overcome immunosuppression as observed in case of lymphatic, filarial Brugia malayi infection which may also be extended to other

  5. Infective Larvae of Brugia malayi Induce Polarization of Host Macrophages that Helps in Immune Evasion

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    Aditi Sharma

    2018-02-01

    Full Text Available Filarial parasites suppress, divert, or polarize the host immune response to aid their survival. However, mechanisms that govern the polarization of host MΦs during early filarial infection are not completely understood. In this study, we infected BALB/c mice with infective larvae stage-3 of Brugia malayi (Bm-L3 and studied their effect on the polarization of splenic MΦs. Results showed that MΦs displayed M2-phenotype by day 3 p.i. characterized by upregulated IL-4, but reduced IL-12 and Prostaglandin-D2 secretion. Increased arginase activity, higher arginase-1 but reduced NOS2 expression and poor phagocytic and antigen processing capacity was also observed. M2 MΦs supported T-cell proliferation and characteristically upregulated p-ERK but downregulated NF-κB-p65 and NF-κB-p50/105. Notably, Bm-L3 synergized with host regulatory T-cells (Tregs and polarized M2 MΦs to regulatory MΦs (Mregs by day 7 p.i., which secreted copious amounts of IL-10 and prostaglandin-E2. Mregs also showed upregulated expression levels of MHC-II, CD80, and CD86 and exhibited increased antigen-processing capacity but displayed impaired activation of NF-κB-p65 and NF-κB-p50/105. Neutralization of Tregs by anti-GITR + anti-CD25 antibodies checked the polarization of M2 MΦs to Mregs, decreased accumulation of regulatory B cells and inflammatory monocytes, and reduced secretion of IL-10, but enhanced IL-4 production and percentages of eosinophils, which led to Bm-L3 killing. In summary, we report hitherto undocumented effects of early Bm-L3 infection on the polarization of splenic MΦs and show how infective larvae deftly utilize the functional plasticity of host MΦs to establish themselves inside the host.

  6. Distribution of Brugia malayi larvae and DNA in vector and non-vector mosquitoes: implications for molecular diagnostics

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    Christensen Bruce M

    2009-11-01

    Full Text Available Abstract Background The purpose of this study was to extend prior studies of molecular detection of Brugia malayi DNA in vector (Aedes aegypti- Liverpool and non-vector (Culex pipiens mosquitoes at different times after ingestion of infected blood. Results Parasite DNA was detected over a two week time course in 96% of pooled thoraces of vector mosquitoes. In contrast, parasite DNA was detected in only 24% of thorax pools from non-vectors; parasite DNA was detected in 56% of midgut pools and 47% of abdomen pools from non-vectors. Parasite DNA was detected in vectors in the head immediately after the blood meal and after 14 days. Parasite DNA was also detected in feces and excreta of the vector and non-vector mosquitoes which could potentially confound results obtained with field samples. However, co-housing experiments failed to demonstrate transfer of parasite DNA from infected to non-infected mosquitoes. Parasites were also visualized in mosquito tissues by immunohistololgy using an antibody to the recombinant filarial antigen Bm14. Parasite larvae were detected consistently after mf ingestion in Ae. aegypti- Liverpool. Infectious L3s were seen in the head, thorax and abdomen of vector mosquitoes 14 days after Mf ingestion. In contrast, parasites were only detected by histology shortly after the blood meal in Cx. pipiens, and these were not labeled by the antibody. Conclusion This study provides new information on the distribution of filarial parasites and parasite DNA in vector and non-vector mosquitoes. This information should be useful for those involved in designing and interpreting molecular xenomonitoring studies.

  7. The role of polymorphisms in the spliced leader addition domain in determining promoter activity in Brugia malayi.

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    Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R

    2011-03-01

    Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Targeting the Wolbachia cell division protein FtsZ as a new approach for antifilarial therapy.

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    Zhiru Li

    2011-11-01

    Full Text Available The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans. Availability of genomic sequences for the Wolbachia (wBm present in the human filarial parasite Brugia malayi has enabled genome-wide searching for new potential drug targets. In the present study, we investigated the cell division machinery of wBm and determined that it possesses the essential cell division gene ftsZ which was expressed in all developmental stages of B. malayi examined. FtsZ is a GTPase thereby making the protein an attractive Wolbachia drug target. We described the molecular characterization and catalytic properties of Wolbachia FtsZ. We also demonstrated that the GTPase activity was inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. Furthermore, berberine was also effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel anti-symbiotic approach for controlling filarial infection. NOTE: The nucleotide sequences reported in this paper are available in GenBank™ Data Bank under the accession number wAlB-FtsZ (JN616286.

  9. Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling.

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    Sasisekhar Bennuru

    Full Text Available Relatively little is known about the filarial proteins that interact with the human host. Although the filarial genome has recently been completed, protein profiles have been limited to only a few recombinants or purified proteins of interest. Here, we describe a large-scale proteomic analysis using microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry to identify the excretory-secretory (ES products of the L3, L3 to L4 molting ES, adult male, adult female, and microfilarial stages of the filarial parasite Brugia malayi. The analysis of the ES products from adult male, adult female, microfilariae (Mf, L3, and molting L3 larvae identified 852 proteins. Annotation suggests that the functional and component distribution was very similar across each of the stages studied; however, the Mf contributed a higher proportion to the total number of identified proteins than the other stages. Of the 852 proteins identified in the ES, only 229 had previous confirmatory expressed sequence tags (ESTs in the available databases. Moreover, this analysis was able to confirm the presence of 274 "hypothetical" proteins inferred from gene prediction algorithms applied to the B. malayi (Bm genome. Not surprisingly, the majority (160/274 of these "hypothetical" proteins were predicted to be secreted by Signal IP and/or SecretomeP 2.0 analysis. Of major interest is the abundance of previously characterized immunomodulatory proteins such as ES-62 (leucyl aminopeptidase, MIF-1, SERPIN, glutathione peroxidase, and galectin in the ES of microfilariae (and Mf-containing adult females compared to the adult males. In addition, searching the ES protein spectra against the Wolbachia database resulted in the identification of 90 Wolbachia-specific proteins, most of which were metabolic enzymes that have not been shown to be immunogenic. This proteomic analysis extends our knowledge of the ES and provides insight into the host-parasite interaction.

  10. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach.

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    Gregory J Crowther

    Full Text Available BACKGROUND: The increased sequencing of pathogen genomes and the subsequent availability of genome-scale functional datasets are expected to guide the experimental work necessary for target-based drug discovery. However, a major bottleneck in this has been the difficulty of capturing and integrating relevant information in an easily accessible format for identifying and prioritizing potential targets. The open-access resource TDRtargets.org facilitates drug target prioritization for major tropical disease pathogens such as the mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni. METHODOLOGY/PRINCIPAL FINDINGS: Here we present strategies to prioritize pathogen proteins based on whether their properties meet criteria considered desirable in a drug target. These criteria are based upon both sequence-derived information (e.g., molecular mass and functional data on expression, essentiality, phenotypes, metabolic pathways, assayability, and druggability. This approach also highlights the fact that data for many relevant criteria are lacking in less-studied pathogens (e.g., helminths, and we demonstrate how this can be partially overcome by mapping data from homologous genes in well-studied organisms. We also show how individual users can easily upload external datasets and integrate them with existing data in TDRtargets.org to generate highly customized ranked lists of potential targets. CONCLUSIONS/SIGNIFICANCE: Using the datasets and the tools available in TDRtargets.org, we have generated illustrative lists of potential drug targets in seven tropical disease pathogens. While these lists are broadly consistent with the research community's current interest in certain specific proteins, and suggest

  11. Recombinant Brugia malayi pepsin inhibitor (rBm33) exploits host signaling events to regulate inflammatory responses associated with lymphatic filarial infections.

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    Sreenivas, Kirthika; Kalyanaraman, Haripriya; Babu, Subash; Narayanan, Rangarajan Badri

    2017-11-01

    Prolonged existence of filarial parasites and their molecules within the host modulate the host immune system to instigate their survival and induce inflammatory responses that contribute to disease progression. Recombinant Brugia malayi pepsin inhibitor (rBm33) modulates the host immune responses by skewing towards Th1 responses characterized by secretion of inflammatory molecules such as TNF-α, IL-6, nitric oxide (NO). Here we also specified the molecular signaling events triggered by rBm33 in peripheral blood mononuclear cells (PBMCs) of filarial endemic normals (EN). rBm33 predominantly enhanced the levels of nitric oxide in cultured PBMCs but did not result in oxidative stress to the host cells. Further, rBm33 treatment of human PBMCs resulted in higher GSH/GSSG levels. MYD88 dependent activation was found to be associated with rBm33 specific inflammatory cytokine production. rBm33 triggered intracellular signaling events also involved JNK activation in host PBMCs. In addition, c-Fos and not NF-κB was identified as the transcription factor regulating the expression of inflammatory cytokines in rBm33 stimulated PBMCs. rBm33 marked its role in filarial pathology by altered levels of growth factors but did not have a significant impact on matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) activity of host PBMCs. Thus, the study outlines the signaling network of rBm33 induced inflammatory responses within the host immune cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes

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    Slatko Barton E

    2010-10-01

    Full Text Available Abstract Background Lymphatic filariasis and onchocerciasis are debilitating diseases caused by filarial nematodes. Disease pathogenesis is induced by inflammatory responses following the death of the parasite. Wolbachia endosymbionts of filariae are potent inducers of innate and adaptive inflammation and bacterial lipoproteins have been identified as the ligands that bind toll-like receptors (TLR 2 and TLR6. Lipoproteins are important structural and functional components of bacteria and therefore enzymes involved in Wolbachia lipoprotein biosynthesis are potential chemotherapeutic targets. Results Globomycin, a signal peptidase II (LspA inhibitor, has activity against Gram-negative bacteria and a putative lspA gene has been identified from the Wolbachia genome of Brugia malayi (wBm. The amino acids required for function are strictly conserved and functionality was verified by complementation tests in a temperature-sensitive Escherichia coli lspA mutant. Also, transformation of wild type E. coli with Wolbachia lspA conferred significant globomycin resistance. A cell-based screen has been developed utilizing a Wolbachia-containing Aedes albopictus cell line to assay novel compounds active against Wolbachia. Globomycin was screened using this assay, which resulted in a dose-dependent reduction in Wolbachia load. Furthermore, globomycin was also effective in reducing the motility and viability of adult B. malayi in vitro. Conclusions These studies validate lipoprotein biosynthesis as a target in an organism for which no genetic tools are available. Further studies to evaluate drugs targeting this pathway are underway as part of the A-WOL drug discovery and development program.

  13. Poly(d,l)-lactide-co-glycolide (PLGA) microspheres as immunoadjuvant for Brugia malayi antigens.

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    Saini, Vinay; Verma, Shiv Kumar; Murthy, P Kalpana; Kohli, Dharmveer

    2013-08-28

    Recently we identified in Brugia malayi adult worm extract (BmA) a pro-inflammatory 54-68kDa SDS-PAGE resolved fraction F6 that protects the host from the parasite via Th1/Th2 type responses. We are currently investigating F6 as a potential source of vaccine candidate(s) and the present study is aimed at investigating the suitability of poly(d,l)-lactide-co-glycolide microspheres (PLGA-Ms) as immunoadjuvant for the antigen administration in a single dose. PLGA-Ms were prepared aseptically by a modified double emulsion (w/o/w) solvent evaporation technique and their size, shape, antigen adsorption efficiency, in-process stability, and antigen release were characterized. Swiss mice were immunized by a single subcutaneous administration of BmA and F6 adsorbed on PLGA-Ms (lactide:glycolide ratios 50:50 and 75:25) and the immune responses were compared with administration of 1 or 2 doses of plain BmA and F6. Specific IgG, IgG1, IgG2a, IgG2b, IgE levels in serum, cellular-proliferative response and release of IFN-γ, TNF-α and nitric oxide from the cells of immunized host in response to the antigens/LPS/Con A challenge and antibody-dependant cellular cytotoxicity (ADCC) to parasite life stages were determined. The average size of PLGA-Ms 50:50 was smaller than the size of PLGA-Ms 75:25 and the % antigen adsorption efficiency of PLGA-Ms 50:50 was greater than PLGA-Ms 75:25. Single shot injection of PLGA-Ms 50:50/75:25-BmA/F6 produced better and stronger IgG, IgG1/IgG2a and cell-mediated immune responses than even two injections of plain BmA or F6. Further, PLGA-Ms 50:50-F6 produced stronger responses than PLGA-Ms 50:50-BmA. Anti-PLGA-Ms 50:50-F6 antibodies elicited higher ADCC response to infective larval and microfilarial stages of the parasite than anti-PLGA-Ms 75:25-F6 antibodies. The findings demonstrate that PLGA-Ms 50:50 is an excellent adjuvant for use with F6 in a single administration. This is the first ever report on PLGA as immunoadjuvant for filarial antigens

  14. Diagnosis of brugian filariasis by loop-mediated isothermal amplification.

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    Catherine B Poole

    Full Text Available In this study we developed and evaluated a Brugia Hha I repeat loop-mediated isothermal amplification (LAMP assay for the rapid detection of Brugia genomic DNA. Amplification was detected using turbidity or fluorescence as readouts. Reactions generated a turbidity threshold value or a clear visual positive within 30 minutes using purified genomic DNA equivalent to one microfilaria. Similar results were obtained using DNA isolated from blood samples containing B. malayi microfilariae. Amplification was specific to B. malayi and B. timori, as no turbidity was observed using DNA from the related filarial parasites Wuchereria bancrofti, Onchocerca volvulus or Dirofilaria immitis, or from human or mosquito. Furthermore, the assay was most robust using a new strand-displacing DNA polymerase termed Bst 2.0 compared to wild-type Bst DNA polymerase, large fragment. The results indicate that the Brugia Hha I repeat LAMP assay is rapid, sensitive and Brugia-specific with the potential to be developed further as a field tool for diagnosis and mapping of brugian filariasis.

  15. Duration of detection of anti-BmR1 IgG4 antibodies after mass-drug administration (MDA) in Sarawak, Malaysia.

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    Noordin, R; Muhi, J; Md Idris, Z; Arifin, N; Kiyu, A

    2012-03-01

    The detection rates of brugian filariasis in three regions of Sarawak namely Central, North and South after three courses of mass drug administration (MDA) from year 2004 to 2006 was investigated. A recombinant BmR1 antigen-based IgG4 detection test, named Brugia Rapid and night blood smear for microfilaria (mf) detection were used. All three regions recorded a sharp fall in mf positive rates after a year post-MDA. Meanwhile Brugia Rapid positive rates declined more gradually to 3.8% and 5.6% of the pre-MDA levels in the Central and North regions, respectively. This study showed that in filariasis endemic areas in Sarawak, anti-filarial IgG4 antibodies to BmR1, as detected by the Brugia Rapid test, were positive for one to two years after mf disappearance.

  16. Tissue and stage-specific distribution of Wolbachia in Brugia malayi.

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    Kerstin Fischer

    2011-05-01

    Full Text Available BACKGROUND: Most filarial parasite species contain Wolbachia, obligatory bacterial endosymbionts that are crucial for filarial development and reproduction. They are targets for alternative chemotherapy, but their role in the biology of filarial nematodes is not well understood. Light microscopy provides important information on morphology, localization and potential function of these bacteria. Surprisingly, immunohistology and in situ hybridization techniques have not been widely used to monitor Wolbachia distribution during the filarial life cycle. METHODS/PRINCIPAL FINDINGS: A monoclonal antibody directed against Wolbachia surface protein and in situ hybridization targeting Wolbachia 16S rRNA were used to monitor Wolbachia during the life cycle of B. malayi. In microfilariae and vector stage larvae only a few cells contain Wolbachia. In contrast, large numbers of Wolbachia were detected in the lateral chords of L4 larvae, but no endobacteria were detected in the genital primordium. In young adult worms (5 weeks p.i., a massive expansion of Wolbachia was observed in the lateral chords adjacent to ovaries or testis, but no endobacteria were detected in the growth zone of the ovaries, uterus, the growth zone of the testis or the vas deferens. Confocal laser scanning and transmission electron microscopy showed that numerous Wolbachia are aligned towards the developing ovaries and single endobacteria were detected in the germline. In inseminated females (8 weeks p.i. Wolbachia were observed in the ovaries, embryos and in decreasing numbers in the lateral chords. In young males Wolbachia were found in distinct zones of the testis and in large numbers in the lateral chords in the vicinity of testicular tissue but never in mature spermatids or spermatozoa. CONCLUSIONS: Immunohistology and in situ hybridization show distinct tissue and stage specific distribution patterns for Wolbachia in B. malayi. Extensive multiplication of Wolbachia occurs in the

  17. ORF Alignment: NC_006833 [GENIUS II[Archive

    Lifescience Database Archive (English)

    Full Text Available TRS of Brugia malayi] ... Length = 188 ... Query: 439 HPLGFARCQVYNTYIIAEARGK...LIIVDQHAAHERLVYECLKQKSSIKRQKLLLSEVVEIK 498 ... HPLGFARCQVYNTYIIAEARGKLIIVDQHAAHERLVYECLKQKSSIKRQKLLLSEVVEIK Sbjct: 1 ... HPLGFAR

  18. Immunogenicity and Protective Efficacy of Brugia malayi Heavy Chain Myosin as Homologous DNA, Protein and Heterologous DNA/Protein Prime Boost Vaccine in Rodent Model.

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    Jyoti Gupta

    Full Text Available We earlier demonstrated the immunoprophylactic efficacy of recombinant heavy chain myosin (Bm-Myo of Brugia malayi (B. malayi in rodent models. In the current study, further attempts have been made to improve this efficacy by employing alternate approaches such as homologous DNA (pcD-Myo and heterologous DNA/protein prime boost (pcD-Myo+Bm-Myo in BALB/c mouse model. The gene bm-myo was cloned in a mammalian expression vector pcDNA 3.1(+ and protein expression was confirmed in mammalian Vero cell line. A significant degree of protection (79.2%±2.32 against L3 challenge in pcD-Myo+Bm-Myo immunized group was observed which was much higher than that exerted by Bm-Myo (66.6%±2.23 and pcD-Myo (41.6%±2.45. In the heterologous immunized group, the percentage of peritoneal leukocytes such as macrophages, neutrophils, B cells and T cells marginally increased and their population augmented further significantly following L3 challenge. pcD-Myo+Bm-Myo immunization elicited robust cellular and humoral immune responses as compared to pcD-Myo and Bm-Myo groups as evidenced by an increased accumulation of CD4+, CD8+ T cells and CD19+ B cells in the mouse spleen and activation of peritoneal macrophages. Though immunized animals produced antigen-specific IgG antibodies and isotypes, sera of mice receiving pcD-Myo+Bm-Myo or Bm-Myo developed much higher antibody levels than other groups and there was profound antibody-dependent cellular adhesion and cytotoxicity (ADCC to B. malayi infective larvae (L3. pcD-Myo+Bm-Myo as well as Bm-Myo mice generated a mixed T helper cell phenotype as evidenced by the production of both pro-inflammatory (IL-2, IFN-γ and anti-inflammatory (IL-4, IL-10 cytokines. Mice receiving pcD-Myo on contrary displayed a polarized pro-inflammatory immune response. The findings suggest that the priming of animals with DNA followed by protein booster generates heightened and mixed pro- and anti-inflammatory immune responses that are capable of

  19. Brugia malayi Antigen (BmA Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells.

    Directory of Open Access Journals (Sweden)

    Emily E I M Mouser

    Full Text Available One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA and excretory-secretory product 62 (ES-62 from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs.

  20. Attempts at immunization against Malayan filariasis using X-irradiated infective larvae

    International Nuclear Information System (INIS)

    Ramachandran, C.P.

    1975-01-01

    Recent studies on immunity to helminthic infections have shown that some degree of protective immunity may be stimulated by inoculations of attenuated living worms or their metabolites. Although much on these lines has been done with several helminths, little if any has been done with filarial infections in general. Experiments were designed to observe the effects of attempted immunization in the rhesus monkey as well as the domestic cat by the use of attenuated infective larvae of Brugia malayi. The sub-periodic strain of Brugia malayi, the major filarial parasite of man in Malaysia, maintained in the laboratory on experimentally infected cats and rhesus monkeys were used for the preparation of X-irradiated vaccines as well as for challenge inoculations. Third-stage infective larvae of Brugia malayi were obtained from experimentally fed Aedes togoi mosquitoes. Infective larvae were irradiated by X-rays, using a Dermopan X-ray unit at exposures between 10 - 40 kR. Rhesus monkeys and cats were inoculated twice with 100 - 400 attenuated larvae per inoculation at 2 week intervals and challenged about a month later by inoculation of 100 normal larvae. Control animals for each vaccination dose as well as for challenge doses were maintained. In rhesus monkeys persistent immunity to challenge infections (expressed as failure to cause microfilaraemia) were obtained in animals vaccinated with 200 infective larvae attenuated by X-irradiation at 20000 R. Encouraged with the results obtained on rhesus monkeys, similar experiments on an enlarged scale using varying strengths of the vaccines were carried out on the domestic cat, which is a more receptive animal host for Brugia malayi. However, all cats vaccinated when challenged came down with patent infection indicating lack of any definite immunity. In all these experiments, results of vaccine control animals showed that inoculation of irradiated larvae was not followed by the infection of microfilaria in the blood, indicating

  1. Transmission assessment surveys (TAS to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation.

    Directory of Open Access Journals (Sweden)

    Brian K Chu

    Full Text Available BACKGROUND: Lymphatic filariasis (LF is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA. Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS to determine if MDA can be stopped within an LF evaluation unit (EU after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. METHODOLOGY: The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community, eligible population (6-7 year olds or 1(st-2(nd graders, survey type (systematic or cluster-sampling, target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable. The primary diagnostic tools were the immunochromatographic (ICT test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF for Brugia spp. EUs. PRINCIPAL FINDINGS/CONCLUSIONS: In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post

  2. Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration: a multicenter evaluation.

    Science.gov (United States)

    Chu, Brian K; Deming, Michael; Biritwum, Nana-Kwadwo; Bougma, Windtaré R; Dorkenoo, Améyo M; El-Setouhy, Maged; Fischer, Peter U; Gass, Katherine; Gonzalez de Peña, Manuel; Mercado-Hernandez, Leda; Kyelem, Dominique; Lammie, Patrick J; Flueckiger, Rebecca M; Mwingira, Upendo J; Noordin, Rahmah; Offei Owusu, Irene; Ottesen, Eric A; Pavluck, Alexandre; Pilotte, Nils; Rao, Ramakrishna U; Samarasekera, Dilhani; Schmaedick, Mark A; Settinayake, Sunil; Simonsen, Paul E; Supali, Taniawati; Taleo, Fasihah; Torres, Melissa; Weil, Gary J; Won, Kimberly Y

    2013-01-01

    Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached a level low enough that it cannot be sustained even in the absence of drug intervention. Guidelines advanced by WHO call for a transmission assessment survey (TAS) to determine if MDA can be stopped within an LF evaluation unit (EU) after at least five effective rounds of annual treatment. To test the value and practicality of these guidelines, a multicenter operational research trial was undertaken in 11 countries covering various geographic and epidemiological settings. The TAS was conducted twice in each EU with TAS-1 and TAS-2 approximately 24 months apart. Lot quality assurance sampling (LQAS) formed the basis of the TAS survey design but specific EU characteristics defined the survey site (school or community), eligible population (6-7 year olds or 1(st)-2(nd) graders), survey type (systematic or cluster-sampling), target sample size, and critical cutoff (a statistically powered threshold below which transmission is expected to be no longer sustainable). The primary diagnostic tools were the immunochromatographic (ICT) test for W. bancrofti EUs and the BmR1 test (Brugia Rapid or PanLF) for Brugia spp. EUs. In 10 of 11 EUs, the number of TAS-1 positive cases was below the critical cutoff, indicating that MDA could be stopped. The same results were found in the follow-up TAS-2, therefore, confirming the previous decision outcome. Sample sizes were highly sex and age-representative and closely matched the target value after factoring in estimates of non-participation. The TAS was determined to be a practical and effective evaluation tool for stopping MDA although its validity for longer-term post-MDA surveillance requires further investigation.

  3. Dicty_cDB: Contig-U07003-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available aegypti infected with Brugia Mal... 50 0.090 1 ( DV278108 ) NAAF224TF Aedes aegypti - Fat Bodies Normalized ...(... 50 0.090 1 ( DV276715 ) NAAHF49TR Aedes aegypti - Fat Bodies Normalized (...

  4. SURVEI DARAH JARI FILARIASIS DI DESA BATUMARTA X KEC. MADANG SUKU III KABUPATEN OGAN KOMERING ULU (OKU TIMUR, SUMATERA SELATAN TAHUN 2012

    Directory of Open Access Journals (Sweden)

    R. Irpan Pahlepi

    2015-01-01

    Full Text Available AbstrakFilariasis atau penyakit kaki gajah adalah golongan penyakit menular yang disebabkan oleh cacing filaria  yang  ditularkan  melalui  berbagai  jenis  nyamuk.  Penyebaran  filariasis  hampir  meliputi  seluruh wilayah di Indonesia termasuk Kabupaten Ogan Komering Ulu (OKU Timur. Angka kesakitan filarisis di Kabupaten OKU Timur tahun 2007 sebesar 1,05%. Kegiatan pengobatan massal di Kabupaten OKU Timur belum pernah dilakukan sampai saat ini, sehingga perlu dilakukan penelitian yang bertujuan untuk mengetahui tingkat penyebaran penyakit filariasis. Penelitian ini merupakan penelitian survei dengan desain potong lintang. Pengambilan dan pemeriksaan sediaan darah jari dilakukan pada malam hari dimulai pukul 19.00 WIB. Jumlah penduduk yang diperiksa sebanyak 502. Hasil pemeriksaan diperoleh 4 orang positif mikrofilaria (Mf_ rate 0,8% dengan spesies Brugia  malayi  dan  kepadatan  rata-rata  200mf/ml.  Seluruh  kasus  yang  ditemukan  merupakan  kasus baru. Hasil penelitian ini menunjukkan bahwa penularan filariasis masih terjadi di Kabupaten OKU Timur sehingga perlu adanya pengobatan massal untuk mencegah penularan lebih lanjut.Kata kunci : Filariasis, Brugia malayi, Survei darah jari, OKU TimurAbstractFilariasis or elephantiasis is an infectious diseases caused by filarial worms that transmitted by various species of mosquitoes. Filariasis distributions almost covers all districts in Indonesia including East Ogan Komering Ulu (OKU. Filarisais morbidity in East OKU regency in 2007 was 1.05 %. Mass treatment in the district of East OKU have not been done yet, so it is necessary to do a research that aim to determine the prevalen of filariasis. This study is a cross-sectional survey design. Collection and examination of finger’s blood was done at night starting at 19:00. Number of people examined were 502. Examination results obtained 4 positive microfilariae (Mf_ rate 0.8 % of Brugia malayi and the average density of 200

  5. Dicty_cDB: Contig-U05658-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available ted with Brugia Mala... 44 2.4 1 ( DV286265 ) NAAI621TR Aedes aegypti - Fat Bodie...s Normalized (... 44 2.4 1 ( DV286264 ) NAAI621TF Aedes aegypti - Fat Bodies Normalized (... 44 2.4 1 ( CP00

  6. Primary structure of and immunoglobulin E response to the repeat subunit of gp15/400 from human lymphatic filarial parasites

    NARCIS (Netherlands)

    Paxton, W. A.; Yazdanbakhsh, M.; Kurniawan, A.; Partono, F.; Maizels, R. M.; Selkirk, M. E.

    1993-01-01

    We have isolated and sequenced clones encoding the repeated subunit of the surface-associated glycoprotein gp15/400 from the two nematode species predominantly responsible for lymphatic filariasis in humans: Brugia malayi and Wuchereria bancrofti. The amino acid sequence of the 15-kDa subunit,

  7. Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic human filariasis

    NARCIS (Netherlands)

    Kurniawan, A.; Yazdanbakhsh, M.; van Ree, R.; Aalberse, R.; Selkirk, M. E.; Partono, F.; Maizels, R. M.

    1993-01-01

    A population of 164 adult individuals resident in an area endemic for Brugia malayi lymphatic filariasis has been studied for humoral immune responses to filarial parasites. Antibody levels to Ag extracted from adult worms were determined for each of the IgG subclasses, for IgM and for IgE. The

  8. Cakupan Pemberian Obat Pencegahan Massal Filariasis di Kabupaten Sumba Barat Daya Tahun 2012-2013

    Directory of Open Access Journals (Sweden)

    Zahrotul Habibah

    2016-03-01

    Full Text Available Filariasis merupakan masalah kesehatan masyarakat terutama di Indonesia Timur antara lain di Kabupaten Sumba Barat Daya (SBD. Untuk mengeliminasi filariasis, WHO membuat program PemberianObat Pencegahan Masal (POPM dengan dietilkarbamazin sitrat dan albendazol setiap tahun selama 5tahun berturut-turut. Untuk mengetahui keberhasilan POPM, perlu dilakukan evaluasi cakupan POPM setiaptahun. Tujuan penelitian ini adalah mengetahui cakupan POPM di SBD pada tahun 2012-2013. Penelitanini menggunakan data POPM Dinas Kesehatan SBD pada tahun 2012 dan 2013. Cakupan POPM filariasisdihitung berdasarkan jumlah penduduk minum obat dibagi penduduk total dan jumlah penduduk sasaran.Target cakupan pengobatan penduduk sasaran adalah >85% dan dari penduduk total adalah  > 65%. Hasilpenelitian menunjukkan cakupan POPM filariasis berdasarkan penduduk total pada tahun 2012 adalah 1,96%dan tahun 2013 sebesar 1,13%. Cakupan POPM filariasis berdasarkan penduduk sasaran pada tahun 2012adalah 2,51% dan tahun 2013 adalah 1,35%. Disimpulkan bahwa cakupan POPM filariasis berdasarkanpenduduk sasaran dan penduduk total di SBD sangat rendah dan cakupan tahun 2013 lebih rendahdibandingkan tahun 2012. Kata kunci: W. bancrofti, B.malayi, B.timori, pemberian obat masal pencegahan, Sumba Barat Daya   Coverage of Mass Drugs Administration (MDA for Filariasis inSouth West Sumba on 2012-2013 AbstractFilariasis is a disease caused by Wuchereria bancrofti, Brugia malayi and Brugia timori. It is transmitted by mosquitos. It cause defect in patient’s physical condition, decrease social life, and increase health spending.WHO concepts a program to eliminate filariasis by Massal Drugs Administration (MDA of filariasis. It hasto be evaluated each year in five years by counting the coverage of MDA of filariasis in total population andtargeted population. This research used secondary data from Dinas Kesehatan in SBD to know the coverageof MDA of filariasis in SBD on 2012-2013. The coverage

  9. [Target volume margins for lung cancer: internal target volume/clinical target volume].

    Science.gov (United States)

    Jouin, A; Pourel, N

    2013-10-01

    The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

  10. Molecular Targets for Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Mather, S.J.

    2009-01-01

    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

  11. In vitro silencing of Brugia malayi trehalose-6-phosphate phosphatase impairs embryogenesis and in vivo development of infective larvae in jirds.

    Directory of Open Access Journals (Sweden)

    Susheela Kushwaha

    Full Text Available The trehalose metabolic enzymes have been considered as potential targets for drug or vaccine in several organisms such as Mycobacterium, plant nematodes, insects and fungi due to crucial role of sugar trehalose in embryogenesis, glucose uptake and protection from stress. Trehalose-6-phosphate phosphatase (TPP is one of the enzymes of trehalose biosynthesis that has not been reported in mammals. Silencing of tpp gene in Caenorhabditis elegans revealed an indispensable functional role of TPP in nematodes.In the present study, functional role of B. malayi tpp gene was investigated by siRNA mediated silencing which further validated this enzyme to be a putative antifilarial drug target. The silencing of tpp gene in adult female B. malayi brought about severe phenotypic deformities in the intrauterine stages such as distortion and embryonic development arrest. The motility of the parasites was significantly reduced and the microfilarial production as well as their in vitro release from the female worms was also drastically abridged. A majority of the microfilariae released in to the culture medium were found dead. B. malayi infective larvae which underwent tpp gene silencing showed 84.9% reduced adult worm establishment after inoculation into the peritoneal cavity of naïve jirds.The present findings suggest that B. malayi TPP plays an important role in the female worm embryogenesis, infectivity of the larvae and parasite viability. TPP enzyme of B. malayi therefore has the potential to be exploited as an antifilarial drug target.

  12. Exome and Transcriptome Sequencing of Aedes aegypti Identifies a Locus That Confers Resistance to Brugia malayi and Alters the Immune Response

    KAUST Repository

    Juneja, Punita; Ariani, Cristina V.; Ho, Yung Shwen; Akorli, Jewelna; Palmer, William J.; Pain, Arnab; Jiggins, Francis M.

    2015-01-01

    to target protein-coding regions of the genome, and used association mapping in a wild Kenyan population to identify a single, dominant, sex-linked locus underlying resistance. This falls in a region of the genome where a resistance locus was previously

  13. Organelle targeting: third level of drug targeting

    Directory of Open Access Journals (Sweden)

    Sakhrani NM

    2013-07-01

    Full Text Available Niraj M Sakhrani, Harish PadhDepartment of Cell and Molecular Biology, BV Patel Pharmaceutical Education and Research Development (PERD Centre, Gujarat, IndiaAbstract: Drug discovery and drug delivery are two main aspects for treatment of a variety of disorders. However, the real bottleneck associated with systemic drug administration is the lack of target-specific affinity toward a pathological site, resulting in systemic toxicity and innumerable other side effects as well as higher dosage requirement for efficacy. An attractive strategy to increase the therapeutic index of a drug is to specifically deliver the therapeutic molecule in its active form, not only into target tissue, nor even to target cells, but more importantly, into the targeted organelle, ie, to its intracellular therapeutic active site. This would ensure improved efficacy and minimize toxicity. Cancer chemotherapy today faces the major challenge of delivering chemotherapeutic drugs exclusively to tumor cells, while sparing normal proliferating cells. Nanoparticles play a crucial role by acting as a vehicle for delivery of drugs to target sites inside tumor cells. In this review, we spotlight active and passive targeting, followed by discussion of the importance of targeting to specific cell organelles and the potential role of cell-penetrating peptides. Finally, the discussion will address the strategies for drug/DNA targeting to lysosomes, mitochondria, nuclei and Golgi/endoplasmic reticulum.Keywords: intracellular drug delivery, cancer chemotherapy, therapeutic index, cell penetrating peptides

  14. Helminth Genomics: The Implications for Human Health

    Science.gov (United States)

    Brindley, Paul J.; Mitreva, Makedonka; Ghedin, Elodie; Lustigman, Sara

    2009-01-01

    More than two billion people (one-third of humanity) are infected with parasitic roundworms or flatworms, collectively known as helminth parasites. These infections cause diseases that are responsible for enormous levels of morbidity and mortality, delays in the physical development of children, loss of productivity among the workforce, and maintenance of poverty. Genomes of the major helminth species that affect humans, and many others of agricultural and veterinary significance, are now the subject of intensive genome sequencing and annotation. Draft genome sequences of the filarial worm Brugia malayi and two of the human schistosomes, Schistosoma japonicum and S. mansoni, are now available, among others. These genome data will provide the basis for a comprehensive understanding of the molecular mechanisms involved in helminth nutrition and metabolism, host-dependent development and maturation, immune evasion, and evolution. They are likely also to predict new potential vaccine candidates and drug targets. In this review, we present an overview of these efforts and emphasize the potential impact and importance of these new findings. PMID:19855829

  15. Heavy-ion targets

    International Nuclear Information System (INIS)

    Adair, H.L.; Kobisk, E.H.

    1985-01-01

    This chapter examines the characteristics of targets required in heavy-ion accelerator physics experiments. The effects of target parameters on heavy-ion experimental results are reviewed. The target fabrication and characterization techniques used to minimize experimental problems during heavy-ion bombardment are described. Topics considered include target thickness and uniformity, target lifetime, target purity, substrate materials, Doppler shift effects, metal preparations, and target preparation methods

  16. Lymphedema secondary to filariasis

    International Nuclear Information System (INIS)

    Leonard, J.C.; Humphrey, G.B.; Basmadjian, G.

    1985-01-01

    A 1-year-old immunodeficient boy developed brawny edema of the left foot. Lymphoscintigraphy revealed no evidence of left inguinal activity following pedal injection of Tc-99m-Sn phosphate. Over the next two months, the patient developed lymphedema on the right and repeat scintigraphy demonstrated no movement of isotope from the dorsum of either foot. Subsequent studies identified microfilaria in a nocturnal blood smear, which were thought to represent Brugia beaveri acquired by mosquito transmission in Oklahoma

  17. 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...

  18. Target laboratory

    International Nuclear Information System (INIS)

    Ephraim, D.C.; Pednekar, A.R.

    1993-01-01

    A target laboratory to make stripper foils for the accelerator and various targets for use in the experiments is set up in the pelletron accelerator facility. The facilities available in the laboratory are: (1) D.C. glow discharge setup, (2) carbon arc set up, and (3) vacuum evaporation set up (resistance heating), electron beam source, rolling mill - all for target preparation. They are described. Centrifugal deposition technique is used for target preparation. (author). 3 figs

  19. Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

    Science.gov (United States)

    Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

    2016-01-01

    The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

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

    Science.gov (United States)

    Thomas, Mark D; Williams, Carrick C

    2014-01-01

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

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

    Science.gov (United States)

    Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

    2017-06-06

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

  2. Study of target and non-target interplay in spatial attention task.

    Science.gov (United States)

    Sweeti; Joshi, Deepak; Panigrahi, B K; Anand, Sneh; Santhosh, Jayasree

    2018-02-01

    Selective visual attention is the ability to selectively pay attention to the targets while inhibiting the distractors. This paper aims to study the targets and non-targets interplay in spatial attention task while subject attends to the target object present in one visual hemifield and ignores the distractor present in another visual hemifield. This paper performs the averaged evoked response potential (ERP) analysis and time-frequency analysis. ERP analysis agrees to the left hemisphere superiority over late potentials for the targets present in right visual hemifield. Time-frequency analysis performed suggests two parameters i.e. event-related spectral perturbation (ERSP) and inter-trial coherence (ITC). These parameters show the same properties for the target present in either of the visual hemifields but show the difference while comparing the activity corresponding to the targets and non-targets. In this way, this study helps to visualise the difference between targets present in the left and right visual hemifields and, also the targets and non-targets present in the left and right visual hemifields. These results could be utilised to monitor subjects' performance in brain-computer interface (BCI) and neurorehabilitation.

  3. Using the Nova target chamber for high-yield targets

    International Nuclear Information System (INIS)

    Pitts, J.H.

    1987-01-01

    The existing 2.2-m-radius Nova aluminum target chamber, coated and lined with boron-seeded carbon shields, is proposed for use with 1000-MJ-yield targets in the next laser facility. The laser beam and diagnostic holes in the target chamber are left open and the desired 10 -2 Torr vacuum is maintained both inside and outside the target chamber; a larger target chamber room is the vacuum barrier to the atmosphere. The hole area available is three times that necessary to maintain a maximum fluence below 12 J/cm 2 on optics placed at a radius of 10 m. Maximum stress in the target chamber wall is 73 MPa, which complies with the intent of the ASME Pressure Vessel Code. However, shock waves passing through the inner carbon shield could cause it to comminute. We propose tests and analyses to ensure that the inner carbon shield survives the environment. 13 refs

  4. Ice targets

    International Nuclear Information System (INIS)

    Pacheco, C.; Stark, C.; Tanaka, N.; Hodgkins, D.; Barnhart, J.; Kosty, J.

    1979-12-01

    This report presents a description of ice targets that were constructed for research work at the High Resolution Spectrometer (HRS) and at the Energetic Pion Channel and Spectrometer (EPICS). Reasons for using these ice targets and the instructions for their construction are given. Results of research using ice targets will be published at a later date

  5. SeedVicious: Analysis of microRNA target and near-target sites.

    Science.gov (United States)

    Marco, Antonio

    2018-01-01

    Here I describe seedVicious, a versatile microRNA target site prediction software that can be easily fitted into annotation pipelines and run over custom datasets. SeedVicious finds microRNA canonical sites plus other, less efficient, target sites. Among other novel features, seedVicious can compute evolutionary gains/losses of target sites using maximum parsimony, and also detect near-target sites, which have one nucleotide different from a canonical site. Near-target sites are important to study population variation in microRNA regulation. Some analyses suggest that near-target sites may also be functional sites, although there is no conclusive evidence for that, and they may actually be target alleles segregating in a population. SeedVicious does not aim to outperform but to complement existing microRNA prediction tools. For instance, the precision of TargetScan is almost doubled (from 11% to ~20%) when we filter predictions by the distance between target sites using this program. Interestingly, two adjacent canonical target sites are more likely to be present in bona fide target transcripts than pairs of target sites at slightly longer distances. The software is written in Perl and runs on 64-bit Unix computers (Linux and MacOS X). Users with no computing experience can also run the program in a dedicated web-server by uploading custom data, or browse pre-computed predictions. SeedVicious and its associated web-server and database (SeedBank) are distributed under the GPL/GNU license.

  6. STUDI ENDEMISITAS FILARIASIS DI WILAYAH KECAMATAN PEMAYUNG, KABUPATEN BATANGHARI PASCA PENGOBATAN MASSAL TAHAP III

    Directory of Open Access Journals (Sweden)

    Yahya Yahya

    2013-05-01

    Full Text Available Abstract Filariasis endemicity research in District Pemayung, Batanghari Regency Post-Mass Drug Administration Phase III has been implemented. The study aims to determine the prevalence of filariasis, microfilaria worm species, the periodicity, reservoir determination and evaluate the results of mass treatment activities that have been 3 times. The number of people who checked their blood preparation for the examination as many as 538. Blood sampling for the periodicity of the parasite examinations performed on 4 persons, each carried out blood sampling every 2 hours for 24 hours. People microfilariae with microfilariae positive number as many as 8 people to rate microfilariae (Mf rate 1.5%.. The highest parasite density of 17.493 per 20 cu mm of blood occurred at 1:00 am and decresing to 0,415 per 20 cu mm of blood at 07.00 am. The parasite was found in sub periodic nokturna 3 subjects and 1 subject was found only be found in the morning and afternoon. The results of examination of 12 cats and two monkeys were found two positive cats with Brugia malayi microfilariae. Cats that were examined and the positive was one house cat and one stray cat. The conclusion from this study showed that filariasis was still endemic with periodicity of microfilariae was sub periodic nokturna and was zoonotic. Recommendations of this study was that mass treatment  was done by giving the drug directly and took medicine in front of the officers, examination and treatment of microfilariae positive cats. Key words: microfilariae rate, periodicity, Brugia malayi, reservoir. Abstrak  Submit : 28-03-2012  Review : 04-04-2012 Review : 11-06-2012 revisi : 29–08-2012Penelitian untuk menentukan tingkat endemisitas filariasis di wilayah Kecamatan Pemayung, Kabupaten Batanghari Pasca Pengobatan Massal Tahap III telah dilaksanakan. Penelitian bertujuan untuk mengetahui prevalensi filariasis, mengetahui spesies cacing mikrofilaria, periodisitas mikrofilaria dan pemeriksaan

  7. The drug target genes show higher evolutionary conservation than non-target genes.

    Science.gov (United States)

    Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

    2016-01-26

    Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

  8. Nova target experiments

    International Nuclear Information System (INIS)

    Drake, R.P.

    1985-11-01

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

  9. Memory for found targets interferes with subsequent performance in multiple-target visual search.

    Science.gov (United States)

    Cain, Matthew S; Mitroff, Stephen R

    2013-10-01

    Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  10. Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

    Science.gov (United States)

    Arrue, Lily; Ratjen, Lars

    2017-12-07

    The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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

  12. Molecular characterization and functional analysis of serine/threonine protein phosphatase of Toxocara canis.

    Science.gov (United States)

    Ma, Guang Xu; Zhou, Rong Qiong; Hu, Shi Jun; Huang, Han Cheng; Zhu, Tao; Xia, Qing You

    2014-06-01

    Toxocara canis (T. canis) is a widely prevalent zoonotic parasite that infects a wide range of mammalian hosts, including humans. We generated the full-length complementary DNA (cDNA) of the serine/threonine phosphatase gene of T. canis (Tc stp) using 5' rapid amplification of the cDNA ends. The 1192-bp sequence contained a continuous 942-nucleotide open reading frame, encoding a 313-amino-acid polypeptide. The Tc STP polypeptide shares a high level of amino-acid sequence identity with the predicted STPs of Loa loa (89%), Brugia malayi (86%), Oesophagostomum columbianum (76%), and Oesophagostomumdentatum (76%). The Tc STP contains GDXHG, GDXVDRG, GNHE motifs, which are characteristic of members of the phosphoprotein phosphatase family. Our quantitative real-time polymerase chain reaction analysis showed that the Tc STP was expressed in six different tissues in the adult male, with high-level expression in the spermary, vas deferens, and musculature, but was not expressed in the adult female, suggesting that Tc STP might be involved in spermatogenesis and mating behavior. Thus, STP might represent a potential molecular target for controlling T. canis reproduction. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. About miRNAs, miRNA seeds, target genes and target pathways.

    Science.gov (United States)

    Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas

    2017-12-05

    miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

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

    International Nuclear Information System (INIS)

    Rowland, J.R.; Shelton, K.W.; Stunkel, C.B.

    1983-02-01

    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

  15. Deuterium pass through target

    International Nuclear Information System (INIS)

    Alger, D.L.

    1975-01-01

    A neutron emitting target is described for use in neutron generating apparatus including a deuteron source and an accelerator vacuum chamber. The target consists of a tritium-containing target layer, a deuteron accumulation layer, and a target support containing passages providing communication between the accumulation layer and portions of the surface of the support exposed to the accelerator vacuum chamber. With this arrangement, deuterons passing through the target layer and implanting in and diffusing through the accumulation layer, diffuse into the communicating passages and are returned to the accelerator vacuum chamber. The invention allows the continuous removal of deuterons from the target in conventional water cooled neutron generating apparatus. Preferably, the target is provided with thin barrier layers to prevent undesirable tritium diffusion out of the target layer, as well as deuteron diffusion into the target layer

  16. Eye tracking a self-moved target with complex hand-target dynamics

    Science.gov (United States)

    Landelle, Caroline; Montagnini, Anna; Madelain, Laurent

    2016-01-01

    Previous work has shown that the ability to track with the eye a moving target is substantially improved when the target is self-moved by the subject's hand compared with when being externally moved. Here, we explored a situation in which the mapping between hand movement and target motion was perturbed by simulating an elastic relationship between the hand and target. Our objective was to determine whether the predictive mechanisms driving eye-hand coordination could be updated to accommodate this complex hand-target dynamics. To fully appreciate the behavioral effects of this perturbation, we compared eye tracking performance when self-moving a target with a rigid mapping (simple) and a spring mapping as well as when the subject tracked target trajectories that he/she had previously generated when using the rigid or spring mapping. Concerning the rigid mapping, our results confirmed that smooth pursuit was more accurate when the target was self-moved than externally moved. In contrast, with the spring mapping, eye tracking had initially similar low spatial accuracy (though shorter temporal lag) in the self versus externally moved conditions. However, within ∼5 min of practice, smooth pursuit improved in the self-moved spring condition, up to a level similar to the self-moved rigid condition. Subsequently, when the mapping unexpectedly switched from spring to rigid, the eye initially followed the expected target trajectory and not the real one, thereby suggesting that subjects used an internal representation of the new hand-target dynamics. Overall, these results emphasize the stunning adaptability of smooth pursuit when self-maneuvering objects with complex dynamics. PMID:27466129

  17. [Ultrastructural basis of interactions between prokaryotes and eukaryotes in different symbiotic models].

    Science.gov (United States)

    Sacchi, L

    2004-06-01

    symbiotic bacteria are transmitted transovarially and, during embryogenesis, they are integrated into the morphogenetic processes. In particular, we were able to demonstrate that the origin of the bacteriocyte should be looked for in the cells of the haemocyte line (embryonic plasmatocytes). The eggs are infected by the bacteria emerging from the bacteriocytes of the ovaric fat body and, at the end of the vitellogenesis, they are actively phagocytized by the egg membrane. In filarial nematodes, intracellular bacteria belonging to the genus Wolbachia have been described: they have evolved an obligatory mutualistic association with their host. In fact, antibiotic treatments lead to the clearance of bacteria and this loss produces a negative impact on reproduction and survival of the filarial host. We evidenced, by TEM, the degenerative events occurring during the embriogenesis of Brugia pahangi and Dirofilaria immitis after tetracycline treatment. The data suggest that the Wolbachia play a direct role in worm metabolism. Finally, a new additional model of the prokaryote-eukaryote interaction has been described: we have recently discovered a new intracellular alpha-proteobacterium, named Iric ES1, which resides in the ovarian tissues of the tick Ixodes ricinus. The intriguing characteristic of this bacterium is its ability to invade and consume the ovaric mitochondria. From an evolutionary perspective, it is interesting to note that Iric ES1 enters mitochondria in a similar way to that employed by the "predatory" bacterium Bdellovibrio bacteriovorus.

  18. Argus target chamber

    International Nuclear Information System (INIS)

    Rienecker, F. Jr.; Glaros, S.S.; Kobierecki, M.

    1975-01-01

    A target chamber for application in the laser fusion program must satisfy some very basic requirements. (1) Provide a vacuum on the order of 10 -6 torr. (2) Support a microscopically small target in a fixed point in space and verify its location within 5 micrometers. (3) Contain an adjustable beam focusing system capable of delivering a number of laser beams onto the target simultaneously, both in time and space. (4) Provide access for diagnostics to evaluate the results of target irradiation. (5) Have flexibility to allow changes in targets, focusing optics and number of beams. The ARGUS laser which is now under construction at LLL will have a target chamber which meets these requirements in a simple economic manner. The chamber and auxiliary equipment are described, with reference to two double beam focusing systems; namely, lenses and ellipsoidal mirrors. Provision is made for future operation with four beams, using ellipsoidal mirrors for two-sided illumination and lens systems for tetragonal and tetrahedral irradiation

  19. PRICE-LEVEL TARGETING – A VIABLE ALTERNATIVE TO INFLATION TARGETING?

    Directory of Open Access Journals (Sweden)

    Iulian Vasile Popescu

    2012-12-01

    Full Text Available The recent financial crisis that has led some central banks reaching the zero lower bound of their interest rate to use unconventional monetary policy instruments, has brought to the forefront theacademic discussions on the shift from inflation targeting (IT to price level targeting. This paper provides a comparative analysis on IT strategy and targeting the price level, assesses the implications and highlights the challenges of an eventual transition to a new monetary policy strategy. Balancing the advantages (mainly better anchored inflation expectations and disadvantages (communication difficulties generated by following a potential price-level targeting strategy and the necessary prerequisites for its functionality (predictive agents, fully familiar with the implications of such a strategy and with complete confidence in themonetary authority has led us to the conclusion that there is no common acceptance that price level targeting strategy might replace the present IT framework.

  20. Wake Shield Target Protection

    International Nuclear Information System (INIS)

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-01-01

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed

  1. Post-targeting strategy for ready-to-use targeted nanodelivery post cargo loading.

    Science.gov (United States)

    Zhu, J Y; Hu, J J; Zhang, M K; Yu, W Y; Zheng, D W; Wang, X Q; Feng, J; Zhang, X Z

    2017-12-14

    Based on boronate formation, this study reports a post-targeting methodology capable of readily installing versatile targeting modules onto a cargo-loaded nanoplatform in aqueous mediums. This permits the targeted nanodelivery of broad-spectrum therapeutics (drug/gene) in a ready-to-use manner while overcoming the PEGylation-dilemma that frequently occurs in conventional targeting approaches.

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

    Science.gov (United States)

    Sellers, Eric W.; Wang, Xingyu

    2013-01-01

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

  3. Monitoring production target thickness

    International Nuclear Information System (INIS)

    Oothoudt, M.A.

    1993-01-01

    Pion and muon production targets at the Clinton P. Anderson Meson Physics Facility consist of rotating graphite wheels. The previous target thickness monitoring Procedure scanned the target across a reduced intensity beam to determine beam center. The fractional loss in current across the centered target gave a measure of target thickness. This procedure, however, required interruption of beam delivery to experiments and frequently indicated a different fractional loss than at normal beam currents. The new monitoring Procedure compares integrated ups and downs toroid current monitor readings. The current monitors are read once per minute and the integral of readings are logged once per eight-hour shift. Changes in the upstream to downstream fractional difference provide a nonintrusive continuous measurement of target thickness under nominal operational conditions. Target scans are now done only when new targets are installed or when unexplained changes in the current monitor data are observed

  4. Liquid helium target

    International Nuclear Information System (INIS)

    Fujii, Y.; Kitami, T.; Torikoshi, M.

    1984-12-01

    A liquid helium target system has been built and used for the experiment on the reaction 4 He(γ, p). The target system has worked satisfactorily; the consumption rate of liquid helium is 360 ml/h and the cryogenic system retains liquid helium for about ten hours. The structure, operation and performance of the target system are reported. (author)

  5. The ISIS target

    International Nuclear Information System (INIS)

    Carne, A.; Broome, T.A.; Hogston, J.R.; Holding, M.

    1989-01-01

    This presentation discusses the two target failures that have occurred, gives the understanding of the causes and indicates the steps being taken to alleviate the problems. At the outset of the design it was understood that the target would have a finite lifetime, due to radiation damage effects, exacerbated by mechanical damage due to thermal cycling and fatigue. Estimates of target lifetime at full intensity are about 2 years for radiation damage swelling and about 10E4 gross thermal excursions. The latter number is the one which gives uncertainty in defining the life of the target, since it is dependent on the reliability of the accelerator and quality of the proton beam. The commissioning of an accelerator system and bringing it up to high beam intensities have their own special problems. There must be protection of components against uncontrolled beam loss, which produces thermal damage, prompt radiation and induced activity. Fast beam trips for beam loss protection, or equipment failures, result in quenches from high temperature in the target which get bigger with increasing beam intensity. But the target itself is a difficult device to make, taking about 12 months to manufacture. Further, changing one is a complex and time consuming task, not without its hazards. There is thus something of a balancing act to bring the accelerator towards specification before the target fails due to thermal cycling fatigue. In the early days of ISIS beam loss protection was the dominant consideration and the target was regarded somewhat as a sacrificial lamb to the goddess of machine reliability. 2 refs., 6 figs

  6. Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

    Science.gov (United States)

    Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

    2016-12-01

    Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med

  7. TargetSpy: a supervised machine learning approach for microRNA target prediction.

    Science.gov (United States)

    Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

    2010-05-28

    Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

  8. TargetSpy: a supervised machine learning approach for microRNA target prediction

    Directory of Open Access Journals (Sweden)

    Langenberger David

    2010-05-01

    Full Text Available Abstract Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I no seed match requirement, II seed match requirement, and III conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on

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

    Directory of Open Access Journals (Sweden)

    Shihua Zhang

    2018-02-01

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

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

    Science.gov (United States)

    Zhang, Shihua; Zhang, Liang; Wang, Yijun; Yang, Jian; Liao, Mingzhi; Bi, Shoudong; Xie, Zhongwen; Ho, Chi-Tang; Wan, Xiaochun

    2018-01-01

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

  11. PRICE-LEVEL TARGETING – A VIABLE ALTERNATIVE TO INFLATION TARGETING?

    OpenAIRE

    Iulian Vasile Popescu

    2012-01-01

    The recent financial crisis that has led some central banks reaching the zero lower bound of their interest rate to use unconventional monetary policy instruments, has brought to the forefront the academic discussions on the shift from inflation targeting (IT) to price level targeting. This paper provides a comparative analysis on IT strategy and targeting the price level, assesses the implications and highlights the challenges of an eventual transition to a new monetary policy strategy. Bala...

  12. Progress in ISOL target-ion source systems

    Energy Technology Data Exchange (ETDEWEB)

    Koester, U. [Institut Laue Langevin, 6 Rue Jules Horowitz, F-38042 Grenoble Cedex 9 (France); ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland)], E-mail: koester@ill.fr; Arndt, O. [HGF VISTARS and Institut fuer Kernchemie, Johannes-Gutenberg Universitaet Mainz, D-55128 Mainz (Germany); Bouquerel, E.; Fedoseyev, V.N. [ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland); Franberg, H. [ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland); Laboratory for Radio- and Environmental Chemistry, Paul Scherrer Institut, CH-5232 Villigen PSI (Switzerland); Joinet, A. [ISOLDE, CERN, CH-1211 Geneve 23 (Switzerland); Centre d' Etude Spatiale des Rayonnements, 9 Av. du Colonel Roche, F-31028 Toulouse Cedex 4 (France); Jost, C. [HGF VISTARS and Institut fuer Kernchemie, Johannes-Gutenberg Universitaet Mainz, D-55128 Mainz (Germany); Kerkines, I.S.K. [Laboratory of Physical Chemistry, National and Kapodistrian University of Athens, Department of Chemistry, Zografou 157 71, GR (Greece); Cherry L. Emerson Center for Scientific Computation and Department of Chemistry, Emory University, Atlanta, GA 30322 (United States); Kirchner, R. [Gesellschaft fuer Schwerionenforschung, Planckstr. 1, D-64291 Darmstadt (Germany)

    2008-10-15

    The heart of every ISOL (isotope separation on-line) facility is its target and ion source system. Its efficiency, selectivity and rapidity is decisive for the production of intense and pure ion beams of short-lived isotopes. Recent progress in ISOL target and ion source technology is discussed at the examples of radioactive ion beams of exotic zinc and tin isotopes that were purified by isothermal chromatography and molecular sideband separation respectively. An outlook is given to which other elements these purification methods are applicable.

  13. Progress in ISOL target-ion source systems

    International Nuclear Information System (INIS)

    Koester, U.; Arndt, O.; Bouquerel, E.; Fedoseyev, V.N.; Franberg, H.; Joinet, A.; Jost, C.; Kerkines, I.S.K.; Kirchner, R.

    2008-01-01

    The heart of every ISOL (isotope separation on-line) facility is its target and ion source system. Its efficiency, selectivity and rapidity is decisive for the production of intense and pure ion beams of short-lived isotopes. Recent progress in ISOL target and ion source technology is discussed at the examples of radioactive ion beams of exotic zinc and tin isotopes that were purified by isothermal chromatography and molecular sideband separation respectively. An outlook is given to which other elements these purification methods are applicable.

  14. Polarized targets and beams

    International Nuclear Information System (INIS)

    Meyer, W.

    1985-01-01

    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)

  15. Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    David Cheng

    2011-10-01

    Full Text Available Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  16. Targeted Radionuclide Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ersahin, Devrim, E-mail: devrimersahin@yahoo.com; Doddamane, Indukala; Cheng, David [Department of Diagnostic Radiology, School of Medicine, Yale University, 333 Cedar St., New Haven, CT 06520 (United States)

    2011-10-11

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

  17. Targeted Radionuclide Therapy

    International Nuclear Information System (INIS)

    Ersahin, Devrim; Doddamane, Indukala; Cheng, David

    2011-01-01

    Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose

  18. 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…

  19. Target size matters: target errors contribute to the generalization of implicit visuomotor learning.

    Science.gov (United States)

    Reichenthal, Maayan; Avraham, Guy; Karniel, Amir; Shmuelof, Lior

    2016-08-01

    The process of sensorimotor adaptation is considered to be driven by errors. While sensory prediction errors, defined as the difference between the planned and the actual movement of the cursor, drive implicit learning processes, target errors (e.g., the distance of the cursor from the target) are thought to drive explicit learning mechanisms. This distinction was mainly studied in the context of arm reaching tasks where the position and the size of the target were constant. We hypothesize that in a dynamic reaching environment, where subjects have to hit moving targets and the targets' dynamic characteristics affect task success, implicit processes will benefit from target errors as well. We examine the effect of target errors on learning of an unnoticed perturbation during unconstrained reaching movements. Subjects played a Pong game, in which they had to hit a moving ball by moving a paddle controlled by their hand. During the game, the movement of the paddle was gradually rotated with respect to the hand, reaching a final rotation of 25°. Subjects were assigned to one of two groups: The high-target error group played the Pong with a small ball, and the low-target error group played with a big ball. Before and after the Pong game, subjects performed open-loop reaching movements toward static targets with no visual feedback. While both groups adapted to the rotation, the postrotation reaching movements were directionally biased only in the small-ball group. This result provides evidence that implicit adaptation is sensitive to target errors. Copyright © 2016 the American Physiological Society.

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

    International Nuclear Information System (INIS)

    Alton, G.D.

    1993-01-01

    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

  1. TargetCompare: A web interface to compare simultaneous miRNAs targets.

    Science.gov (United States)

    Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-Dos-Santos, André M; Dos Santos, Andrea Ribeiro

    2014-01-01

    MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. http://lghm.ufpa.br/targetcompare.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  3. Structured cylindrical targets

    International Nuclear Information System (INIS)

    Arnold, R.

    1986-01-01

    A variety of experimental concepts using high-energy heavy-ion beams in cylindrical targets have been studied through numerical simulation. With an accelerator planned for GSl, plasma temperatures of 100 eV can be reached by cylindrical compression, using inhomogeneous hollow-shell targets. Magnetic insulation, using external fields, has been explored as an aid in reaching high core temperatures. Experiments on collision-pumped x-ray laser physics are also discussed. (ii) Two-dimensional PlC code simulations of homogeneous solid targets show hydrodynamic effects not found in previous 1-D calculations. (iii) Preliminary ideas for an experiment on non-equilibrium heavy-ion charge-states using an existing accelerator and a pre-formed plasma target are outlined. (author)

  4. Structured cylindrical targets

    International Nuclear Information System (INIS)

    Arnold, R.; Lackner-Russo, D.; Meyer-ter-Vehn, J.; Hoffmann, I.

    1986-01-01

    A variety of experimental concepts using high-energy heavy-ion beams in cylindrical targets have been studied through numerical simulation. With an accelerator planned for GSl, plasma temperatures of 100 eV can be reached by cylindrical compression, using inhomogenous hollow-shell targets. Magnetic insulation, using external fields, has been explored as an aid in reaching high core temperatures. Experiments on collision-pumped x-ray laser physics are also discussed. (ii) Two-dimensional PlC code simulations of homogeneous solid targets show hydrodynamic effects not found in previous l-D calculations. (iii) Preliminary ideas for an experiment on non-equilibrium heavy-ion charge-states using an existing accelerator and a pre-formed plasma target are outlined. (author)

  5. Target Price Accuracy

    Directory of Open Access Journals (Sweden)

    Alexander G. Kerl

    2011-04-01

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

  6. TargetRNA: a tool for predicting targets of small RNA action in bacteria

    OpenAIRE

    Tjaden, Brian

    2008-01-01

    Many small RNA (sRNA) genes in bacteria act as posttranscriptional regulators of target messenger RNAs. Here, we present TargetRNA, a web tool for predicting mRNA targets of sRNA action in bacteria. TargetRNA takes as input a genomic sequence that may correspond to an sRNA gene. TargetRNA then uses a dynamic programming algorithm to search each annotated message in a specified genome for mRNAs that evince basepair-binding potential to the input sRNA sequence. Based on the calculated basepair-...

  7. Development of distributed target

    CERN Document Server

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

    2002-01-01

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

  8. Internal targets for LEAR

    International Nuclear Information System (INIS)

    Kilian, K.; Gspann, J.; Mohl, D.; Poth, H.

    1984-01-01

    This chapter considers the use of thin internal targets in conjunction with phase-space cooling at the Low-Energy Antiproton Ring (LEAR). Topics considered include the merits of internal target operation; the most efficient use of antiprotons and of proton synchrotron (PS) protons, highest center-of-mass (c.m.) energy resolution; highest angular resolution and access to extreme angles; the transparent environment for all reaction products; a windowless source and pure targets; highest luminosity and count rates; access to lowest energies with increasing resolution; internal target thickness and vacuum requirements; required cooling performance; and modes of operation. It is demonstrated that an internal target in conjunction with phase-space cooling has the potential of better performance in terms of the economic use of antiprotons and consequently of PS protons; energy resolution; angular resolution; maximum reaction rate capability (statistical precision); efficient parasitic operation; transparency of the target for reaction products; access to low energies; and the ease of polarized target experiments. It is concluded that all p - experiments which need high statistics and high p - flux, such as studies of rare channels or broad, weak resonance structures, would profit from internal targets

  9. 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/.

  10. HIRFL–CSR internal cluster target

    International Nuclear Information System (INIS)

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

    2013-01-01

    Highlights: • An internal cluster target was built and installed at HIRFL–CSR. • The target thickness for H 2 amounts up to 6.6 × 10 12 atoms/cm 2 . • 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 10 12 atoms/cm 2 , and those of other targets are larger than 10 13 atoms/cm 2 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 Xe 54+ 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

  11. New type of metal targets

    International Nuclear Information System (INIS)

    Bukharov, A.V.; Ankudinov, V.B.; Ogorodnikov, V.P.; Marukhin, Y.A.

    2014-01-01

    Now the technologies based on interaction of high-intensity beams with substance of a target are being intensively developed. As a target it is possible to use the new type of monodisperse metal targets. The principal advantages of new targets type are: target cooling isn't required; there is no induced activity: the target can be used many times; small dispersion on the speed, the size and interaction points with a beam. The basis of a target is the jet of molten metal, following in the vacuum chamber .Under the influence of the special disturbance superimposed on the liquid jet, the jet disintegrated into identical drops. In the vacuum chamber the drops freeze and form into the solid granules. It is possible to receive monodisperse targets from different metals, alloys and salts (diameter of targets is from 30 .m to 1.5 mm). Dispersion by the sizes and speed is less than 1%. The technique allows to receive not only continuous targets, but also hollow targets with dispersion on thickness of wall within 1...2%.

  12. Heavy water jet target and a beryllium target for production of fast neutrons

    International Nuclear Information System (INIS)

    Logan, C.M.; Anderson, J.D.; Barschall, H.H.; Davis, J.C.

    1975-01-01

    A limitation on the neutron flux obtainable from proton or deuteron induced reactions is the heating of the target by the accelerated charged particles. The heat can be removed more easily if the target moves. The possibility of using a rotating Be target and a heavy water jet as a target for bombardment by 35-MeV deuterons was studied. In a thick Be metal target moving at 10 m/sec through such a beam of 1 cm diameter a temperature pulse of about 300 0 C will be produced by the 0.3 MW beam. The Be target should be able to withstand such a temperature pulse. A Be target suitable for 3 MW of power in a 1 cm diameter beam would require internal cooling and a higher velocity. A free jet of heavy water is also a possible target. Laser photographs of water jets in vacuum show small angles of divergence. The effect of heating by a 0.3 MW beam is probably not important because the temperature rise produced by the beam is small compared to the absolute temperature of the unheated jet. (auth)

  13. Laser targets: introduction

    International Nuclear Information System (INIS)

    Rosen, M.D.

    1985-01-01

    The laser target design group was engaged in three main tasks in 1984: (1) analyzing Novette implosion and hohlraum-scaling data, (2) planning for the first experiments on Nova, and (3) designing laboratory x-ray laser targets and experiments. The Novette implosion and hohlraum scaling data are mostly classified and are therefore not discussed in detail here. The authors achieved average final/initial pusher pr ratios of about 50, some 3 times higher than the value achieved in the best Shiva shots. These pr values imply a fuel compression to 100 times liquid density, although this figure and other aspects of the experiments are subject to further interpretation because of detailed questions of target symmetry and stability. Their main long-term goal for Nova is to produce a so-called hydrodynamically equivalent target (HET) - that is, a target whose hydrodynamic behavior (implosion velocity, convergence ratio, symmetry and stability requirements, etc.) is very much like that of a high-gain target, but one that is scaled down in size to match the energy available from Nova and is too small to achieve enough hot-spot pr to ignite the cold, near-Fermi-degenerate fuel around it. Their goal for Nova's first year is to do experiments that will teach them how to achieve the symmetry and stability conditions required by an HET

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

    International Nuclear Information System (INIS)

    Ammerman, D.J.

    1991-01-01

    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

  15. Immunotherapy Targets in Pediatric Cancer

    International Nuclear Information System (INIS)

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal

    2012-01-01

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

  16. Immunotherapy Targets in Pediatric Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal, E-mail: rimas.orentas@nih.gov, E-mail: mackallc@mail.nih.gov [Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States)

    2012-01-30

    Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

  17. Bradycardia During Targeted Temperature Management

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  18. 26 CFR 1.338-1 - General principles; status of old target and new target.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 4 2010-04-01 2010-04-01 false General principles; status of old target and new target. 1.338-1 Section 1.338-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... of old target and new target. (a) In general—(1) Deemed transaction. Elections are available under...

  19. 26 CFR 1.430(d)-1 - Determination of target normal cost and funding target.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Determination of target normal cost and funding target. 1.430(d)-1 Section 1.430(d)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... of target normal cost and funding target. (a) In general—(1) Overview. This section sets forth rules...

  20. Target support for inertial confinement fusion

    International Nuclear Information System (INIS)

    Schultz, K.R.

    1995-08-01

    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)

  1. Target-oriented chaos control

    International Nuclear Information System (INIS)

    Dattani, Justine; Blake, Jack C.H.; Hilker, Frank M.

    2011-01-01

    Designing intervention methods to control chaotic behavior in dynamical systems remains a challenging problem, in particular for systems that are difficult to access or to measure. We propose a simple, intuitive technique that modifies the values of the state variables directly toward a certain target. The intervention takes into account the difference to the target value, and is a combination of traditional proportional feedback and constant feedback methods. It proves particularly useful when the target corresponds to the equilibrium of the uncontrolled system, and is available or can be estimated from expert knowledge (e.g. in biology and economy). -- Highlights: → We propose a chaos control method that forces the system to a certain target. → The intervention takes into account the difference to the target value. → It can be seen as a combination of proportional and constant feedback methods. → The method is very robust and highly efficient in the long-term. → It is particularly applicable when suitable target values are known or available.

  2. 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...

  3. The effect of target and non-target similarity on neural classification performance: A boost from confidence

    Directory of Open Access Journals (Sweden)

    Amar R Marathe

    2015-08-01

    Full Text Available Brain computer interaction (BCI technologies have proven effective in utilizing single-trial classification algorithms to detect target images in rapid serial visualization presentation tasks. While many factors contribute to the accuracy of these algorithms, a critical aspect that is often overlooked concerns the feature similarity between target and non-target images. In most real-world environments there are likely to be many shared features between targets and non-targets resulting in similar neural activity between the two classes. It is unknown how current neural-based target classification algorithms perform when qualitatively similar target and non-target images are presented. This study address this question by comparing behavioral and neural classification performance across two conditions: first, when targets were the only infrequent stimulus presented amongst frequent background distracters; and second when targets were presented together with infrequent non-targets containing similar visual features to the targets. The resulting findings show that behavior is slower and less accurate when targets are presented together with similar non-targets; moreover, single-trial classification yielded high levels of misclassification when infrequent non-targets are included. Furthermore, we present an approach to mitigate the image misclassification. We use confidence measures to assess the quality of single-trial classification, and demonstrate that a system in which low confidence trials are reclassified through a secondary process can result in improved performance.

  4. Optimization of in-target yields for RIB production: Part 1: direct targets

    International Nuclear Information System (INIS)

    Chabod, S.; Thiolliere, N.; David, J.Ch.; Dore, D.; Ene, D.; Rapp, B.; Ridikas, D.; Chabod, S.; Blideanu, V.

    2008-03-01

    In the framework of the EURISOL-DS project and within Task-11, we have performed in-target yield calculations for different configurations of thick direct targets. The target materials tested are Al 2 O 3 , SiC, Pb(molten), Ta and UC 3 . The target was irradiated with protons of 0.5, 1.0, 1.5 and 2.0 GeV. The production rates have been computed using the MCNPX transport/generation code, coupled with the CINDER-90 evolution program. The yield distributions as a function of charge number Z and mass number A have been evaluated. Their production rates have been optimized for 11 selected elements (Li, Be, Ne, Mg, Ar, Ni, Ga, Kr, Hg, Sn and Fr) and 23 of their isotopes of interest. Finally, the isotopic distributions for each of these 11 elements have been optimized in terms of the target material, its geometry, and incident proton energy

  5. Targeted radionuclide therapy

    African Journals Online (AJOL)

    target for which a speci c treatment/drug is intended (Fig. 1). eranostics .... Using an anti-CD20 antibody as a delivery device to target the follicular ... systems combine diagnostic imaging (Ga-68-DOTATATE PET/CT) .... Intra-articular injected ...

  6. Identification of antigenic proteins of setaria cervi by immunoblotting technique

    International Nuclear Information System (INIS)

    Kaushal, N.A.; Kaushal, D.C.; Ghatak, S.

    1987-01-01

    Identification and characterization of antigenic proteins of Setaria cervi (bovine filarial parasite) adults and microfilariae was done by immunoblotting technique using hyperimmune rabbit sera against S. cervi and Brugia malayi. The antigens recognized by these sera were detected by using 125 I protein-A followed by autoradiography. Fifteen different antigens were observed to be common between adult and microfilarial stages of the parasite. Some stage specific antigens were also identified. Many antigens of S. cervi adults and microfilariae were also recognized by rabbit anti-B.malayi serum showing the existence of common antigenic determinants between the bovine and human filarial parasites

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

    Science.gov (United States)

    Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

    2018-03-15

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

  8. Energy deposition in a thin copper target downstream and off-axis of a proton-radiography target

    International Nuclear Information System (INIS)

    Greene, G.A.; Finfrock, C.C.; Snead, C.L.; Hanson, A.L.; Murray, M.M.

    2002-01-01

    A series of proton energy-deposition experiments was conducted to measure the energy deposited in a copper target located downstream and off-axis of a high-energy proton-radiography target. The proton/target interactions involved low-intensity bunches of protons at 24 GeV/c onto a spherical target consisting of concentric shells of tungsten and copper. The energy-deposition target was placed at five locations downstream of the proton-radiography target, off-axis of the primary beam transport, and was either unshielded or shielded by 5 or 10 cm of lead. Maximum temperature rises measured in the energy-deposition target due to single bunches of 5x10 10 protons on the proton-radiography target were approximately 20 mK per bunch. The data indicated that the scattered radiation was concentrated close to the primary transport axis of the beam line. The energy deposited in the energy-deposition target was reduced by moving the target radially away from the primary transport axis. Placing lead shielding in front of the target further reduced the energy deposition. The measured temperature rises of the energy-deposition target were empirically correlated with the distance from the source, the number of protons incident on the proton-radiography target, the thickness of the lead shielding, and the angle of the energy-deposition target off-axis of the beam line from the proton-radiography target. The correlation of the experimental data that was developed provides a starting point for the evaluation of the shielding requirements for devices downstream of proton-radiography targets such as superconducting magnets

  9. 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.

  10. 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 .

  11. 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

  12. Charged particle fusion targets

    International Nuclear Information System (INIS)

    Bangerter, R.O.; Meeker, D.J.

    1977-01-01

    The power, voltage, energy and other requirements of electron and ion beam fusion targets are reviewed. Single shell, multiple shell and magnetically insulated target designs are discussed. Questions of stability are also considered. In particular, it is shown that ion beam targets are stabilized by an energy spread in the ion beam

  13. Graphite targets at LAMPF

    International Nuclear Information System (INIS)

    Brown, R.D.; Grisham, D.L.

    1983-01-01

    Rotating polycrystalline and stationary pyrolytic graphite target designs for the LAMPF experimental area are described. Examples of finite element calculations of temperatures and stresses are presented. Some results of a metallographic investigation of irradiated pyrolytic graphite target plates are included, together with a brief description of high temperature bearings for the rotating targets

  14. A blow-in windowless gas target

    International Nuclear Information System (INIS)

    Sagara, K.; Motoshima, A.; Fujita, T.; Akiyoshi, H.; Nishimori, N.

    1996-01-01

    A new-type windowless gas target has been developed to realize a dense target with a low gas flow rate. The target is similar to the conventional differentially pumped windowless gas target except that the target gas is blown into the target region from both the side holes of the beam entrance and exit. Due to the gas-confining action caused by the blown-in gas, the target thickness is about twice increased and the target density sharply falls in the holes. Most of the target gas is at rest and the density is uniform. The gas flow rate is the same as that of the conventional target and is about an order of magnitude lower than that of the dense gas-jet target. (orig.)

  15. Simulations of effusion from ISOL target/ion source systems

    International Nuclear Information System (INIS)

    Mustapha, B.; Nolen, J.A.

    2004-01-01

    Monte Carlo simulations of the low- and high-conductivity Target/Ion Source systems used at Oak Ridge National Laboratory for effusion measurements are performed. Comparisons with the corresponding experimental data for the different geometries are presented and discussed. Independent checks of the simulation using data for simple geometries and using the conductance approach well known in vacuum technology are performed. A simulation-based comparison between the low- and high-conductivity systems is also presented

  16. 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...

  17. 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.

  18. STANFORD: Internal targets

    Energy Technology Data Exchange (ETDEWEB)

    Riordan, Michael

    1989-05-15

    Of burgeoning interest to many nuclear and particle physicists is a storage ring technique for fixed target experiments. It hinges on the use of gas-jet targets, shooting a narrow stream of atoms through a circulating beam of electrons or protons. Pioneered at CERN and the Soviet Novosibirsk Laboratory, more such 'internal targets' are being built or contemplated for storage rings in Europe, the Soviet Union, and the United States. From 9-12 January, physicists from around the world met at the Stanford Linear Accelerator Center (SLAC) to discuss prospects and problems in this expanding field.

  19. Burglar Target Selection

    Science.gov (United States)

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

    2015-01-01

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

  20. Targeted Nanotechnology for Cancer Imaging

    Science.gov (United States)

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

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  1. 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…

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

    International Nuclear Information System (INIS)

    Dukes, E.C.

    1993-01-01

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

  3. Target-Searching on Percolation

    International Nuclear Information System (INIS)

    Yang Shijie

    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.

  4. HomoTarget: a new algorithm for prediction of microRNA targets in Homo sapiens.

    Science.gov (United States)

    Ahmadi, Hamed; Ahmadi, Ali; Azimzadeh-Jamalkandi, Sadegh; Shoorehdeli, Mahdi Aliyari; Salehzadeh-Yazdi, Ali; Bidkhori, Gholamreza; Masoudi-Nejad, Ali

    2013-02-01

    MiRNAs play an essential role in the networks of gene regulation by inhibiting the translation of target mRNAs. Several computational approaches have been proposed for the prediction of miRNA target-genes. Reports reveal a large fraction of under-predicted or falsely predicted target genes. Thus, there is an imperative need to develop a computational method by which the target mRNAs of existing miRNAs can be correctly identified. In this study, combined pattern recognition neural network (PRNN) and principle component analysis (PCA) architecture has been proposed in order to model the complicated relationship between miRNAs and their target mRNAs in humans. The results of several types of intelligent classifiers and our proposed model were compared, showing that our algorithm outperformed them with higher sensitivity and specificity. Using the recent release of the mirBase database to find potential targets of miRNAs, this model incorporated twelve structural, thermodynamic and positional features of miRNA:mRNA binding sites to select target candidates. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. 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…

  6. Properties of Protein Drug Target Classes

    Science.gov (United States)

    Bull, Simon C.; Doig, Andrew J.

    2015-01-01

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

  7. Liquid hydrogen and deuterium targets

    International Nuclear Information System (INIS)

    Bougon, M.; Marquet, M.; Prugne, P.

    1961-01-01

    A description is given of 1) Atmospheric pressure target: liquid hydrogen, 400 mm thickness; thermal insulation: styrofoam; the hydrogen vapors are used to improve the target cooling; Mylar windows. 2) Vacuum target: 12 liter content: hydrogen or deuterium; liquid thickness 400 mm; thermal insulation is afforded by a vacuum vessel and a liquid nitrogen shield. Recovery and liquefaction of deuterium vapors are managed in the vacuum vessel which holds the target. The target emptying system is designed for operating in a few minutes. (author) [fr

  8. 76 FR 34953 - Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program...

    Science.gov (United States)

    2011-06-15

    ... Availability C. Location and Target Audience D. Maximum Award E. Project Period F. Description of Agreement..., 2011. C. Location and Target Audience The RMA Regional Offices that service the Targeted States are... marketing systems to pursue new markets. D. Purpose The purpose of the Targeted States Program is to provide...

  9. TARGET Research Goals

    Science.gov (United States)

    TARGET researchers use various sequencing and array-based methods to examine the genomes, transcriptomes, and for some diseases epigenomes of select childhood cancers. This “multi-omic” approach generates a comprehensive profile of molecular alterations for each cancer type. Alterations are changes in DNA or RNA, such as rearrangements in chromosome structure or variations in gene expression, respectively. Through computational analyses and assays to validate biological function, TARGET researchers predict which alterations disrupt the function of a gene or pathway and promote cancer growth, progression, and/or survival. Researchers identify candidate therapeutic targets and/or prognostic markers from the cancer-associated alterations.

  10. Modelling Recycling Targets

    DEFF Research Database (Denmark)

    hill, amanda; Leinikka Dall, Ole; Andersen, Frits Møller

    2014-01-01

    % 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...

  11. 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.

  12. Targeting and Persuasive Advertising

    OpenAIRE

    Egli, Alain (Autor/in)

    2015-01-01

    Firms face a prisoner's dilemma when advertising in a competitive environment. In a Hotelling framework with persuasive advertisingfirms counteract this prisoner's dilemma with targeting. The firms even solve the prisoner's problem if targeted advertising is effective enough. Advertising turns from wasteful competition into profits. This is in contrast to wasteful competition as argument for regulations. A further result is maximum advertising differentiation: thefirms target their advertisin...

  13. Target preparation

    International Nuclear Information System (INIS)

    Hinn, G.M.

    1984-01-01

    A few of the more interesting of the 210 targets prepared in the Laboratory last year are listed. In addition the author continues to use powdered silver mixed with /sup 9,10/BeO to produce sources for accelerator radio dating of Alaskan and South Polar snow. Currently, he is trying to increase production by multiple sample processing. Also the author routinely makes 3 μg/cm 2 cracked slacked carbon stripper foils and is continuing research with some degree of success in making enriched 28 Si targets starting with the oxide

  14. Preparation of thin nuclear targets

    International Nuclear Information System (INIS)

    Muggleton, A.H.F.

    1979-03-01

    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

  15. Electron beam fusion targets

    International Nuclear Information System (INIS)

    Clauser, M.J.; Sweeney, M.A.

    1975-01-01

    R The behavior of the DT filled gold shells when irradiated by a variety of pulse shapes was studied. In these pulses the power (and beam current) was varied, but the voltage was kept constant at 1 MeV. In general the performance of the target, for a given peak power, was not significantly affected by the pulse shape. Pulses with rise times of up to half the implosion time do not significantly degrade the target performance. The use of the ''optimal pulse'' of laser fusion with a fixed peak power does not appear to improve the performance of these targets. The main function of the ''optimal pulse'' is to produce a large rho r of the target during the thermonuclear burn. In e-beam targets a total rho r of 5--10 g/cm 2 can be obtained without pulse shaping; the problem here is one of achieving high enough temperatures to ignite the DT. (U.S.)

  16. Seedling root targets

    Science.gov (United States)

    Diane L. Haase

    2011-01-01

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

  17. Nuclear Security: Target Analysis-rev

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Surinder Paul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gibbs, Philip W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bultz, Garl A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-03-01

    The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

  18. Stanford polarized atomic beam target

    International Nuclear Information System (INIS)

    Mavis, D.G.; Dunham, J.S.; Hugg, J.W.; Glavish, H.F.

    1976-01-01

    A polarized atomic beam source was used to produce an atomic hydrogen beam which was in turn used as a polarized proton target. A target density of 2 x 10'' atoms/cm 3 and a target polarization of 0.37 without the use of rf transitions were measured. These measurements indicate that a number of experiments are currently feasible with a variety of polarized target beams

  19. Setting reference targets

    International Nuclear Information System (INIS)

    Ruland, R.E.

    1997-04-01

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

  20. Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.

    Science.gov (United States)

    Vlot, Anna H C; de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; van Westen, Gerard J P; de Lange, Elizabeth C M

    2017-12-04

    Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of the underlying (pharmacological) mechanisms and availability of directly applicable predictive methods complicates the prediction of selectivity. We explore the value of combining physiologically based pharmacokinetic (PBPK) modeling with quantitative structure-activity relationship (QSAR) modeling to predict the influence of the target dissociation constant (K D ) and the target dissociation rate constant on target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling demonstrated that the optimal values of the K D and k off for target and tissue selectivity were dependent on target concentration and tissue distribution kinetics. Interestingly, if the target concentration is high and the perfusion of the target site is low, the optimal K D value is often not the lowest K D value, suggesting that optimization towards high drug-target affinity can decrease the benefit-risk ratio. The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity.

  1. Impacts of transgenic poplar-cotton agro-ecosystems upon target pests and non-target insects under field conditions.

    Science.gov (United States)

    Zhang, D J; Liu, J X; Lu, Z Y; Li, C L; Comada, E; Yang, M S

    2015-07-27

    Poplar-cotton agro-ecosystems are the main agricultural planting modes of cotton fields in China. With increasing acres devoted to transgenic insect-resistant poplar and transgenic insect-resistant cotton, studies examining the effects of transgenic plants on target and non-target insects become increasingly important. We systematically surveyed populations of both target pests and non-target insects for 4 different combinations of poplar-cotton eco-systems over 3 years. Transgenic Bt cotton strongly resisted the target insects Fall webworm moth [Hyphantria cunea (Drury)], Sylepta derogata Fabrieius, and American bollworm (Heliothis armigera), but no clear impact on non-target insect cotton aphids (Aphis gossypii). Importantly, intercrops containing transgenic Pb29 poplar significantly increased the inhibitory effects of Bt cotton on Fall webworm moth in ecosystem IV. Highly resistant Pb29 poplar reduced populations of the target pests Grnsonoma minutara Hubner and non-target insect poplar leaf aphid (Chaitophorus po-pulialbae), while Fall webworm moth populations were unaffected. We determined the effects of Bt toxin from transgenic poplar and cotton on target and non-target pests in different ecosystems of cotton-poplar intercrops and identified the synergistic effects of such combinations toward both target and non-target insects.

  2. Online manual movement adjustments in response to target position changes and apparent target motion

    NARCIS (Netherlands)

    Oostwoud Wijdenes, L.; Brenner, E.; Smeets, J.B.J.

    2014-01-01

    This study set out to determine whether the fastest online hand movement corrections are only responses to changing judgments of the targets' position or whether they are also influenced by the apparent target motion. Introducing a gap between when a target disappears and when it reappears at a new

  3. 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.

  4. Deuterium high pressure target

    International Nuclear Information System (INIS)

    Perevozchikov, V.V.; Yukhimchuk, A.A.; Vinogradov, Yu.I.

    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

  5. Techniques for preparing isotopic targets

    International Nuclear Information System (INIS)

    Xu Guoji; Guan Shouren; Luo Xinghua; Sun Shuhua

    1987-12-01

    The techniques of making isotopic targets for nuclear physics experiments are introduced. Vacuum evaporation, electroplating, centrifugal precipitation, rolling and focused heavy-ion beam sputtering used to prepare various isotopic targets at IAE are described. Reduction-distillation with active metals and electrolytic reduction for converting isotope oxides to metals are mentioned. The stripping processes of producing self-supporting isotopic targets are summarized. The store methods of metallic targets are given

  6. Community composition of target vs. non-target fungi in fungicide treated wheat

    DEFF Research Database (Denmark)

    Knorr, Kamilla; Jørgensen, Lise Nistrup; Justesen, Annemarie Fejer

    2012-01-01

    disease in wheat and within the last decade, new aggressive strains of yellow rust has caused severe epidemics that lead to substantial yield losses. This study explored the community composition of target versus non-target fungi in yellow rust infected wheat as affected by treatment timing and dose......Fungicide treatments are common control strategies used to manage fungal pathogens in agricultural fields, however, effects of treatments on the composition of total fungal communities, including non-target fungi, in the phyllosphere is not well known. Yellow rust (Puccinia striiformis) is a common...

  7. Feature-based RNN target recognition

    Science.gov (United States)

    Bakircioglu, Hakan; Gelenbe, Erol

    1998-09-01

    Detection and recognition of target signatures in sensory data obtained by synthetic aperture radar (SAR), forward- looking infrared, or laser radar, have received considerable attention in the literature. In this paper, we propose a feature based target classification methodology to detect and classify targets in cluttered SAR images, that makes use of selective signature data from sensory data, together with a neural network technique which uses a set of trained networks based on the Random Neural Network (RNN) model (Gelenbe 89, 90, 91, 93) which is trained to act as a matched filter. We propose and investigate radial features of target shapes that are invariant to rotation, translation, and scale, to characterize target and clutter signatures. These features are then used to train a set of learning RNNs which can be used to detect targets within clutter with high accuracy, and to classify the targets or man-made objects from natural clutter. Experimental data from SAR imagery is used to illustrate and validate the proposed method, and to calculate Receiver Operating Characteristics which illustrate the performance of the proposed algorithm.

  8. Inertial-confinement-fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1982-01-01

    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

  9. Solid Polarized Targets and Applications

    International Nuclear Information System (INIS)

    Crabb, D. G.

    2008-01-01

    Examples are given of dynamically polarized targets in use today and how the subsystems have changed to meet the needs of todays experiments. Particular emphasis is placed on target materials such as ammonia and lithium deuteride. Recent polarization studies of irradiated materials such as butanol, deuterated butanol, polyethylene, and deuterated polyethylene are presented. The operation of two non-DNP target systems as well as applications of traditional DNP targets are briefly discussed

  10. Nova target diagnostics control system

    International Nuclear Information System (INIS)

    Severyn, J.R.

    1985-01-01

    During the past year the Nova target diagnostics control system was finished and put in service. The diagnostics loft constructed to the north of the target room provides the environmental conditions required to collect reliable target diagnostic data. These improvements include equipment cooling and isolation of the power source with strict control of instrumentation grounds to eliminate data corruption due to electromagnetic pulses from the laser power-conditioning system or from target implosion effects

  11. The effect of target and non-target similarity on neural classification performance: A boost from confidence

    OpenAIRE

    Amar R Marathe; Anthony J Ries; Vernon J Lawhern; Vernon J Lawhern; Brent J Lance; Jonathan eTouryan; Kaleb eMcDowell; Hubert eCecotti

    2015-01-01

    Brain computer interaction (BCI) technologies have proven effective in utilizing single-trial classification algorithms to detect target images in rapid serial visualization presentation tasks. While many factors contribute to the accuracy of these algorithms, a critical aspect that is often overlooked concerns the feature similarity between target and non-target images. In most real-world environments there are likely to be many shared features between targets and non-targets resulting in si...

  12. The effect of target and non-target similarity on neural classification performance: a boost from confidence

    OpenAIRE

    Marathe, Amar R.; Ries, Anthony J.; Lawhern, Vernon J.; Lance, Brent J.; Touryan, Jonathan; McDowell, Kaleb; Cecotti, Hubert

    2015-01-01

    Brain computer interaction (BCI) technologies have proven effective in utilizing single-trial classification algorithms to detect target images in rapid serial visualization presentation tasks. While many factors contribute to the accuracy of these algorithms, a critical aspect that is often overlooked concerns the feature similarity between target and non-target images. In most real-world environments there are likely to be many shared features between targets and non-targets resulting in si...

  13. 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

  14. 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.

  15. Fusion target design

    International Nuclear Information System (INIS)

    Bangerter, R.O.

    1978-01-01

    Most detailed fusion target design is done by numerical simulation using large computers. Although numerical simulation is briefly discussed, this lecture deals primarily with the way in which basic physical arguments, driver technology considerations and economical power production requirements are used to guide and augment the simulations. Physics topics discussed include target energetics, preheat, stability and symmetry. A specific design example is discussed

  16. Beam heating of target foils

    International Nuclear Information System (INIS)

    Corwin, W.C.

    1975-01-01

    A target rotator, built to reduce the effects of beam spot heating, is fully adjustable, holds three targets, is chamber independent, and takes up limited space. The expected temperature rise in the target is calculated from the Stefan--Boltzmann law

  17. Emotionally conditioning the target-speech voice enhances recognition of the target speech under "cocktail-party" listening conditions.

    Science.gov (United States)

    Lu, Lingxi; Bao, Xiaohan; Chen, Jing; Qu, Tianshu; Wu, Xihong; Li, Liang

    2018-05-01

    Under a noisy "cocktail-party" listening condition with multiple people talking, listeners can use various perceptual/cognitive unmasking cues to improve recognition of the target speech against informational speech-on-speech masking. One potential unmasking cue is the emotion expressed in a speech voice, by means of certain acoustical features. However, it was unclear whether emotionally conditioning a target-speech voice that has none of the typical acoustical features of emotions (i.e., an emotionally neutral voice) can be used by listeners for enhancing target-speech recognition under speech-on-speech masking conditions. In this study we examined the recognition of target speech against a two-talker speech masker both before and after the emotionally neutral target voice was paired with a loud female screaming sound that has a marked negative emotional valence. The results showed that recognition of the target speech (especially the first keyword in a target sentence) was significantly improved by emotionally conditioning the target speaker's voice. Moreover, the emotional unmasking effect was independent of the unmasking effect of the perceived spatial separation between the target speech and the masker. Also, (skin conductance) electrodermal responses became stronger after emotional learning when the target speech and masker were perceptually co-located, suggesting an increase of listening efforts when the target speech was informationally masked. These results indicate that emotionally conditioning the target speaker's voice does not change the acoustical parameters of the target-speech stimuli, but the emotionally conditioned vocal features can be used as cues for unmasking target speech.

  18. Influence of lateral target size on hot electron production and electromagnetic pulse emission from laser-irradiated metallic targets

    International Nuclear Information System (INIS)

    Chen Ziyu; Li Jianfeng; Yu Yong; Li Xiaoya; Peng Qixian; Zhu Wenjun; Wang Jiaxiang

    2012-01-01

    The influences of lateral target size on hot electron production and electromagnetic pulse emission from laser interaction with metallic targets have been investigated. Particle-in-cell simulations at high laser intensities show that the yield of hot electrons tends to increase with lateral target size, because the larger surface area reduces the electrostatic field on the target, owing to its expansion along the target surface. At lower laser intensities and longer time scales, experimental data characterizing electromagnetic pulse emission as a function of lateral target size also show target-size effects. Charge separation and a larger target tending to have a lower target potential have both been observed. The increase in radiation strength and downshift in radiation frequency with increasing lateral target size can be interpreted using a simple model of the electrical capacity of the target.

  19. Influence of lateral target size on hot electron production and electromagnetic pulse emission from laser-irradiated metallic targets

    Energy Technology Data Exchange (ETDEWEB)

    Chen Ziyu; Li Jianfeng; Yu Yong; Li Xiaoya; Peng Qixian; Zhu Wenjun [National Key Laboratory of Shock Wave and Detonation Physics, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang, Sichuan 621900 (China); Wang Jiaxiang [State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200062 (China)

    2012-11-15

    The influences of lateral target size on hot electron production and electromagnetic pulse emission from laser interaction with metallic targets have been investigated. Particle-in-cell simulations at high laser intensities show that the yield of hot electrons tends to increase with lateral target size, because the larger surface area reduces the electrostatic field on the target, owing to its expansion along the target surface. At lower laser intensities and longer time scales, experimental data characterizing electromagnetic pulse emission as a function of lateral target size also show target-size effects. Charge separation and a larger target tending to have a lower target potential have both been observed. The increase in radiation strength and downshift in radiation frequency with increasing lateral target size can be interpreted using a simple model of the electrical capacity of the target.

  20. Design of a covert RFID tag network for target discovery and target information routing.

    Science.gov (United States)

    Pan, Qihe; Narayanan, Ram M

    2011-01-01

    Radio frequency identification (RFID) tags are small electronic devices working in the radio frequency range. They use wireless radio communications to automatically identify objects or people without the need for line-of-sight or contact, and are widely used in inventory tracking, object location, environmental monitoring. This paper presents a design of a covert RFID tag network for target discovery and target information routing. In the design, a static or very slowly moving target in the field of RFID tags transmits a distinct pseudo-noise signal, and the RFID tags in the network collect the target information and route it to the command center. A map of each RFID tag's location is saved at command center, which can determine where a RFID tag is located based on each RFID tag's ID. We propose the target information collection method with target association and clustering, and we also propose the information routing algorithm within the RFID tag network. The design and operation of the proposed algorithms are illustrated through examples. Simulation results demonstrate the effectiveness of the design.

  1. Target-ion source unit ionization efficiency measurement by method of stable ion beam implantation

    CERN Document Server

    Panteleev, V.N; Fedorov, D.V; Moroz, F.V; Orlov, S.Yu; Volkov, Yu.M

    The ionization efficiency is one of the most important parameters of an on-line used target-ion source system exploited for production of exotic radioactive beams. The ionization efficiency value determination as a characteristic of a target-ion source unit in the stage of its normalizing before on-line use is a very important step in the course of the preparation for an on-line experiment. At the IRIS facility (Petersburg Nuclear Physics Institute, Gatchina) a reliable and rather precise method of the target-ion source unit ionization efficiency measurement by the method of stable beam implantation has been developed. The method worked out exploits an off-line mass-separator for the implantation of the ion beams of selected stable isotopes of different elements into a tantalum foil placed inside the Faraday cup in the focal plane of the mass-separator. The amount of implanted ions has been measured with a high accuracy by the current integrator connected to the Faraday cup. After the implantation of needed a...

  2. Target-present guessing as a function of target prevalence and accumulated information in visual search.

    Science.gov (United States)

    Peltier, Chad; Becker, Mark W

    2017-05-01

    Target prevalence influences visual search behavior. At low target prevalence, miss rates are high and false alarms are low, while the opposite is true at high prevalence. Several models of search aim to describe search behavior, one of which has been specifically intended to model search at varying prevalence levels. The multiple decision model (Wolfe & Van Wert, Current Biology, 20(2), 121--124, 2010) posits that all searches that end before the observer detects a target result in a target-absent response. However, researchers have found very high false alarms in high-prevalence searches, suggesting that prevalence rates may be used as a source of information to make "educated guesses" after search termination. Here, we further examine the ability for prevalence level and knowledge gained during visual search to influence guessing rates. We manipulate target prevalence and the amount of information that an observer accumulates about a search display prior to making a response to test if these sources of evidence are used to inform target present guess rates. We find that observers use both information about target prevalence rates and information about the proportion of the array inspected prior to making a response allowing them to make an informed and statistically driven guess about the target's presence.

  3. 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.

  4. Gas target neutron generator studies

    International Nuclear Information System (INIS)

    Chatoorgoon, V.

    1978-01-01

    The need for an intense neutron source for the study of radiation damage on materials has resulted in the proposal of various solid, liquid, and gas targets. Among the gas targets proposed have been the transonic gas target, two types of hypersonic gas target, and the subsonic gas target (SGT). It has been suggested that heat deposition in a subsonic channel might create a gas density step which would constitute an attractive gas target type. The first part of the present study examines this aspect of the SGT and shows that gas density gradients are indeed formed by heat deposition in subsonic flow. The variation of beam voltage, gas density, gas pressure, and gas temperature within the channel have been calculated as functions of the system parameters: beam voltage, beam current, channel diameter, stagnation tank temperature and pressure. The analysis is applicable to any beam particle and target gas. For the case of T + on D 2 , which is relevant to the fusion application, the 14 MeV neutron profiles are presented as a function of system parameters. It is found that the SGT is compatible with concentrated intense source operation. The possibility of instability was investigated in detail using a non-linear analysis which made it possible to follow the complete time development of the SGT. It was found that the SGT is stable against all small perturbations and certain types of large perturbations. It appears that the SGT is the most advantageous type of gas target, operating at a lower mass flow and less severe stagnation tank conditions than the other types. The second part of the thesis examines a problem associated with the straight hypersonic target, the deuterium spill into the tritium port. The regime of practical operation for this target is established. (auth)

  5. TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

    Science.gov (United States)

    Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

    2010-06-15

    We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

  6. Inertial-confinement-fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1981-01-01

    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

  7. Targets and teamwork

    DEFF Research Database (Denmark)

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

    2017-01-01

    differences in mean HbA1c between centers ranging from 7.3±0.8% (53mmol/mol±8.7) to 8.9±1.1% (74mmol/mol±12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams...

  8. Targets and processes for fabricating same

    Science.gov (United States)

    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.

  9. Targets and processes for fabricating same

    Science.gov (United States)

    Cowan, Thomas [Dresden, DE; Malekos, Steven [Reno, NV; Korgan, Grant [Reno, NV; Adams, Jesse [Reno, NV; Sentoku, Yasuhiko [Reno, NV; Le Galloudec, Nathalie [Reno, NV; Fuchs, Julien [Paris, FR

    2012-07-24

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

  10. Bispecific antibodies targeting human CD73

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to a bispecific antibody targeting CD73. In particular, the present invention relates to a bispecific antibody targeting different epitopes on CD73 or a bispecific antibody targeting an epitope on CD73 and an epitope on a different antigen.......The present invention relates to a bispecific antibody targeting CD73. In particular, the present invention relates to a bispecific antibody targeting different epitopes on CD73 or a bispecific antibody targeting an epitope on CD73 and an epitope on a different antigen....

  11. Targets for heavy ion fusion

    International Nuclear Information System (INIS)

    Clauser, M.J.

    1978-01-01

    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.) [de

  12. Experimental methods in radioactive ion-beam target/ion source development and characterization

    International Nuclear Information System (INIS)

    Welton, R.F.; Alton, G.D.; Cui, B.; Murray, S.N.

    1998-01-01

    We have developed off-line experimental techniques and apparatuses that permit direct measurement of effusive-flow delay times and ionization efficiencies for nearly any chemically reactive element in high-temperature target/ion sources (TIS) commonly used for on-line radioactive ion-beam (RIB) generation. The apparatuses include a hot Ta valve for effusive-flow delay-time measurements, a cooled molecular injection system for determination of ionization efficiencies, and a gas flow measurement/control system for introducing very low, well-defined molecular flows into the TIS. Measurements are performed on a test stand using molecular feed compounds containing stable complements of the radioactive nuclei of interest delivered to the TIS at flow rates commensurate with on-line RIB generation. In this article, the general techniques are described and effusive-flow delay times and ionization efficiency measurements are reported for fluorine in an electron-beam plasma target/ion source developed for RIB generation and operated in both positive- and negative-ion extraction modes. copyright 1998 American Institute of Physics

  13. Target Capture during Mos1 Transposition*

    Science.gov (United States)

    Pflieger, Aude; Jaillet, Jerôme; Petit, Agnès; Augé-Gouillou, Corinne; Renault, Sylvaine

    2014-01-01

    DNA transposition contributes to genomic plasticity. Target capture is a key step in the transposition process, because it contributes to the selection of new insertion sites. Nothing or little is known about how eukaryotic mariner DNA transposons trigger this step. In the case of Mos1, biochemistry and crystallography have deciphered several inverted terminal repeat-transposase complexes that are intermediates during transposition. However, the target capture complex is still unknown. Here, we show that the preintegration complex (i.e., the excised transposon) is the only complex able to capture a target DNA. Mos1 transposase does not support target commitment, which has been proposed to explain Mos1 random genomic integrations within host genomes. We demonstrate that the TA dinucleotide used as the target is crucial both to target recognition and in the chemistry of the strand transfer reaction. Bent DNA molecules are better targets for the capture when the target DNA is nicked two nucleotides apart from the TA. They improve strand transfer when the target DNA contains a mismatch near the TA dinucleotide. PMID:24269942

  14. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

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

    2017-06-01

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

  15. Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

    Science.gov (United States)

    Yoon, Hong Yeol; Shin, Min Lee; Shim, Man Kyu; Lee, Sangmin; Na, Jin Hee; Koo, Heebeom; Lee, Hyukjin; Kim, Jong-Ho; Lee, Kuen Yong; Kim, Kwangmeyung; Kwon, Ick Chan

    2017-05-01

    Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin α v β 3 with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.

  16. Strategic Targeted Advertising

    OpenAIRE

    Andrea Galeotti; Jose Luis Moraga

    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 random advertising --to induce an unequal distribution of information in the market-- and random pricing --to obtain profits from badly informed buyers--. We characterize a positive profits equilibrium...

  17. Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System.

    Science.gov (United States)

    Hinas, Ajmal; Roberts, Jonathan M; Gonzalez, Felipe

    2017-12-17

    In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV) for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act) loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

  18. Targeting radiation to tumours

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Greater Glasgow Health Board, Glasgow

    1994-01-01

    Biologically targeted radiotherapy entails the preferential delivery of radiation to solid tumours or individual tumour cells by means of tumour-seeking delivery vehicles to which radionuclides can be conjugated. Monoclonal antibodies have attracted attention for some years as potentially selective targeting agents, but advances in tumour and molecular biology are now providing a much wider choice of molecular species. General radiobiological principles may be derived which are applicable to most forms of targeted radiotherapy. These principles provide guidelines for the appropriate choice of radionuclide in specific treatment situations and its optimal combination with other treatment modalities. In future, the availability of gene targeting agents will focus attention on the use of Auger electron emitters whose high potency and short range selectivity makes them attractive choices for specific killing of cancer cells whose genetic peculiarities are known. (author)

  19. 75 FR 8902 - Funding Opportunity Title: Crop Insurance Education in Targeted States (Targeted States Program)

    Science.gov (United States)

    2010-02-26

    ... and Target Audience D. Maximum Award E. Project Period F. Description of Agreement Award--Awardee.... Location and Target Audience Targeted States serviced by RMA Regional Offices are listed below. Staff from... established farmers or ranchers who are converting production and marketing systems to pursue new markets. D...

  20. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

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

  1. Impact of Target Distance, Target Size, and Visual Acuity on the Video Head Impulse Test.

    Science.gov (United States)

    Judge, Paul D; Rodriguez, Amanda I; Barin, Kamran; Janky, Kristen L

    2018-05-01

    The video head impulse test (vHIT) assesses the vestibulo-ocular reflex. Few have evaluated whether environmental factors or visual acuity influence the vHIT. The purpose of this study was to evaluate the influence of target distance, target size, and visual acuity on vHIT outcomes. Thirty-eight normal controls and 8 subjects with vestibular loss (VL) participated. vHIT was completed at 3 distances and with 3 target sizes. Normal controls were subdivided on the basis of visual acuity. Corrective saccade frequency, corrective saccade amplitude, and gain were tabulated. In the normal control group, there were no significant effects of target size or visual acuity for any vHIT outcome parameters; however, gain increased as target distance decreased. The VL group demonstrated higher corrective saccade frequency and amplitude and lower gain as compared with controls. In conclusion, decreasing target distance increases gain for normal controls but not subjects with VL. Preliminarily, visual acuity does not affect vHIT outcomes.

  2. Target for production of X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Korenev, S.A. E-mail: sergey_korenev@steris.com

    2004-10-01

    The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented.

  3. Target for production of X-rays

    International Nuclear Information System (INIS)

    Korenev, S.A.

    2004-01-01

    The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented

  4. Target for production of X-rays

    Science.gov (United States)

    Korenev, S. A.

    2004-09-01

    The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented.

  5. Targets development at Sandia National Laboratories

    International Nuclear Information System (INIS)

    Smith, M.L.; Hebron, D.; Derzon, M.; Olson, R.; Alberts, T.

    1997-01-01

    For many years, Sandia National Laboratories under contract to the Department of Energy has produced targets designed to understand complex ion beam and z-pinch plasma physics. This poster focuses on the features of target designs that make them suitable for Z-pinch plasma physics applications. Precision diagnostic targets will prove critical in understanding the plasma physics model needed for future ion beam and z-pinch design. Targets are designed to meet specific physics needs; in this case the authors have fabricated targets to maximize information about the end-on versus side-on x-ray emission and z-pinch hohlraum development. In this poster, they describe the fabrication and characterization techniques. They include discussion of current targets under development as well as target fabrication capabilities. Advanced target designs are fabricated by Sandia National Laboratories in cooperation with General Atomics of San Diego, CA and W.J. Schafer Associates, Inc. of Livermore, CA

  6. Spallation source neutron target systems

    International Nuclear Information System (INIS)

    Russell, G.; Brown, R.; Collier, M.; Donahue, J.

    1996-01-01

    This is the final report for a two-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The project sought to design a next-generation spallation source neutron target system for the Manuel Lujan, Jr., Neutron Scattering Center (LANSCE) at Los Alamos. It has been recognized for some time that new advanced neutron sources are needed in the US if the country is to maintain a competitive position in several important scientific and technological areas. A recent DOE panel concluded that the proposed Advanced Neutron Source (a nuclear reactor at Oak Ridge National Laboratory) and a high-power pulsed spallation source are both needed in the near future. One of the most technically challenging designs for a spallation source is the target station itself and, more specifically, the target-moderator-reflector arrangement. Los Alamos has demonstrated capabilities in designing, building, and operating high-power spallation-neutron-source target stations. Most of the new design ideas proposed worldwide for target system design for the next generation pulsed spallation source have either been conceived and implemented at LANSCE or proposed by LANSCE target system designers. These concepts include split targets, flux-trap moderators, back scattering and composite moderators, and composite reflectors

  7. Modelling Recycling Targets

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  8. Utilizing random Forest QSAR models with optimized parameters for target identification and its application to target-fishing server.

    Science.gov (United States)

    Lee, Kyoungyeul; Lee, Minho; Kim, Dongsup

    2017-12-28

    The identification of target molecules is important for understanding the mechanism of "target deconvolution" in phenotypic screening and "polypharmacology" of drugs. Because conventional methods of identifying targets require time and cost, in-silico target identification has been considered an alternative solution. One of the well-known in-silico methods of identifying targets involves structure activity relationships (SARs). SARs have advantages such as low computational cost and high feasibility; however, the data dependency in the SAR approach causes imbalance of active data and ambiguity of inactive data throughout targets. We developed a ligand-based virtual screening model comprising 1121 target SAR models built using a random forest algorithm. The performance of each target model was tested by employing the ROC curve and the mean score using an internal five-fold cross validation. Moreover, recall rates for top-k targets were calculated to assess the performance of target ranking. A benchmark model using an optimized sampling method and parameters was examined via external validation set. The result shows recall rates of 67.6% and 73.9% for top-11 (1% of the total targets) and top-33, respectively. We provide a website for users to search the top-k targets for query ligands available publicly at http://rfqsar.kaist.ac.kr . The target models that we built can be used for both predicting the activity of ligands toward each target and ranking candidate targets for a query ligand using a unified scoring scheme. The scores are additionally fitted to the probability so that users can estimate how likely a ligand-target interaction is active. The user interface of our web site is user friendly and intuitive, offering useful information and cross references.

  9. A triple axes multiple target holder assembly

    International Nuclear Information System (INIS)

    Tribedi, L.C.; Narvekar, S.D.; Pillay, R.G.; Tandon, P.N.

    1993-01-01

    We have designed and fabricated a rotatable target holder assembly capable of accommodating 27 targets. The target foils are mounted along two concentric circles on a ss wheel. On the outer circle 18 targets can be mounted each 20deg apart, and on the inner circle the remaining targets are positioned each 40deg apart. The self supporting or carbon backed targets are mounted on thin frames and are placed concentrically at the targets are mounted on thin frames and are placed concentrically at the target position on the wheel. Three degrees of freedom are provided to the target holder assembly. (author). 1 fig

  10. Right on Target, or Is it? The Role of Distributional Shape in Variance Targeting

    Directory of Open Access Journals (Sweden)

    Stanislav Anatolyev

    2015-08-01

    Full Text Available Estimation of GARCH models can be simplified by augmenting quasi-maximum likelihood (QML estimation with variance targeting, which reduces the degree of parameterization and facilitates estimation. We compare the two approaches and investigate, via simulations, how non-normality features of the return distribution affect the quality of estimation of the volatility equation and corresponding value-at-risk predictions. We find that most GARCH coefficients and associated predictions are more precisely estimated when no variance targeting is employed. Bias properties are exacerbated for a heavier-tailed distribution of standardized returns, while the distributional asymmetry has little or moderate impact, these phenomena tending to be more pronounced under variance targeting. Some effects further intensify if one uses ML based on a leptokurtic distribution in place of normal QML. The sample size has also a more favorable effect on estimation precision when no variance targeting is used. Thus, if computational costs are not prohibitive, variance targeting should probably be avoided.

  11. Kettlebell swing targets semitendinosus and supine leg curl targets biceps femoris

    DEFF Research Database (Denmark)

    Zebis, Mette Kreutzfeldt; Skotte, Jørgen; Andersen, Christoffer H

    2013-01-01

    The medial hamstring muscle has the potential to prevent excessive dynamic valgus and external rotation of the knee joint during sports. Thus, specific training targeting the medial hamstring muscle seems important to avoid knee injuries.......The medial hamstring muscle has the potential to prevent excessive dynamic valgus and external rotation of the knee joint during sports. Thus, specific training targeting the medial hamstring muscle seems important to avoid knee injuries....

  12. Target cells in internal dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Goessner, W

    2003-07-01

    Data related to radium induced bone sarcomas in humans are used as a model for defining target cells on bone surfaces and in the bone marrow. The differential distribution of radiation induced bone sarcoma types with a high ratio of non-bone producing, mainly fibroblastic tumours, challenges the ICRP concept that the bone lining cells are target cells. Multipotential mesenchymal stem cells are located within the range of alpha particles, and are the most likely target cells for the fibroblastic type of bone sarcoma. The histogenesis of bone sarcomas after irradiation with alpha emitters shows that their final histopathology is not dependent on a single target cell. Each target cell has a microenvironment, which has to be regarded as a synergistic morpho-functional tissue unit. For this the concept of 'histion', a term used in general pathology, is proposed. Interactions between target cells that have been hit by alpha-particles, leading to lethal, mutational or transformation events with all components of a 'histion', will prove critical to understanding the pathogenesis of both deterministic and stochastic late effects. (author)

  13. Target cells in internal dosimetry

    International Nuclear Information System (INIS)

    Goessner, W.

    2003-01-01

    Data related to radium induced bone sarcomas in humans are used as a model for defining target cells on bone surfaces and in the bone marrow. The differential distribution of radiation induced bone sarcoma types with a high ratio of non-bone producing, mainly fibroblastic tumours, challenges the ICRP concept that the bone lining cells are target cells. Multipotential mesenchymal stem cells are located within the range of alpha particles, and are the most likely target cells for the fibroblastic type of bone sarcoma. The histogenesis of bone sarcomas after irradiation with alpha emitters shows that their final histopathology is not dependent on a single target cell. Each target cell has a microenvironment, which has to be regarded as a synergistic morpho-functional tissue unit. For this the concept of 'histion', a term used in general pathology, is proposed. Interactions between target cells that have been hit by alpha-particles, leading to lethal, mutational or transformation events with all components of a 'histion', will prove critical to understanding the pathogenesis of both deterministic and stochastic late effects. (author)

  14. Autonomous Target Ranging Techniques

    DEFF Research Database (Denmark)

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

    2003-01-01

    of this telescope, a fast determination of the range to and the motion of the detected targets are important. This is needed in order to prepare the future observation strategy for each target, i.e. when is the closest approach where imaging will be optimal. In order to quickly obtain such a 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...

  15. Drug-induced regulation of target expression

    DEFF Research Database (Denmark)

    Iskar, Murat; Campillos, Monica; Kuhn, Michael

    2010-01-01

    Drug perturbations of human cells lead to complex responses upon target binding. One of the known mechanisms is a (positive or negative) feedback loop that adjusts the expression level of the respective target protein. To quantify this mechanism systems-wide in an unbiased way, drug......-induced differential expression of drug target mRNA was examined in three cell lines using the Connectivity Map. To overcome various biases in this valuable resource, we have developed a computational normalization and scoring procedure that is applicable to gene expression recording upon heterogeneous drug treatments....... In 1290 drug-target relations, corresponding to 466 drugs acting on 167 drug targets studied, 8% of the targets are subject to regulation at the mRNA level. We confirmed systematically that in particular G-protein coupled receptors, when serving as known targets, are regulated upon drug treatment. We...

  16. 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)

  17. The influence of drug distribution and drug-target binding on target occupancy : The rate-limiting step approximation

    NARCIS (Netherlands)

    Witte, de W.E.A.; Vauquelin, G.; Graaf, van der P.H.; Lange, de E.C.M.

    2017-01-01

    The influence of drug-target binding kinetics on target occupancy can be influenced by drug distribution and diffusion around the target, often referred to as "rebinding" or "diffusion-limited binding". This gives rise to a decreased decline of the drug-target complex concentration as a result of a

  18. Target imaging and backlighting diagnosis

    International Nuclear Information System (INIS)

    Yaakobi, B.; Shvarts, D.; Marshall, F.J.; Epstein, R.; Su, Q.

    1995-01-01

    The expected backlighting and self-emission images of a particular CH target to be imploded on the Omega Upgrade are calculated for a variety of experimental parameters. It is shown that to overcome the problem of target self-emission, the image has to be monochromatized with a diffracting crystal. For the target studied, the two image components are then comparable in intensity and both provide useful information on target behavior. A particularly interesting feature is the appearance in the self-emission of a circular spike which closely delineates the fuel-shell interface, but requires high spatial resolution to be observed

  19. Target validation: linking target and chemical properties to desired product profile.

    Science.gov (United States)

    Wyatt, Paul G; Gilbert, Ian H; Read, Kevin D; Fairlamb, Alan H

    2011-01-01

    The discovery of drugs is a lengthy, high-risk and expensive business taking at least 12 years and is estimated to cost upwards of US$800 million for each drug to be successfully approved for clinical use. Much of this cost is driven by the late phase clinical trials and therefore the ability to terminate early those projects destined to fail is paramount to prevent unwanted costs and wasted effort. Although neglected diseases drug discovery is driven more by unmet medical need rather than financial considerations, the need to minimise wasted money and resources is even more vital in this under-funded area. To ensure any drug discovery project is addressing the requirements of the patients and health care providers and delivering a benefit over existing therapies, the ideal attributes of a novel drug needs to be pre-defined by a set of criteria called a target product profile. Using a target product profile the drug discovery process, clinical study design, and compound characteristics can be defined all the way back through to the suitability or druggability of the intended biochemical target. Assessment and prioritisation of the most promising targets for entry into screening programmes is crucial for maximising chances of success.

  20. Tritium target manufacturing for use in accelerators

    Science.gov (United States)

    Bach, P.; Monnin, C.; Van Rompay, M.; Ballanger, A.

    2001-07-01

    As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium target on copper substrate, and going to more sophisticated devices. A wide range of possible uses is covered, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets for higher lifetimes, or large size rotating targets for accelerators used in boron neutron therapy. Activity of targets lies in the 1 to 1000 Curie, diameter of targets being up to 30 cm. Special targets are also considered, including surface layer targets for lowering tritium desorption under irradiation, or those made from different kinds of occluders such as titanium, zirconium, erbium, scandium, with different substrates. It is then possible to optimize either neutron output, or lifetime and stability, or thermal behavior.

  1. ANITA (Advanced Network for Isotope and TArget laboratories) - The urgent need for a European target preparation network

    Science.gov (United States)

    Schumann, Dorothea; Sibbens, Goedele; Stolarz, Anna; Eberhardt, Klaus; Lommel, Bettina; Stodel, Christelle

    2018-05-01

    A wide number of research fields in the nuclear sector requires high-quality and well-characterized samples and targets. Currently, only a few laboratories own or have access to the equipment allowing fulfilling such demands. Coordination of activities and sharing resources is therefore mandatory to meet the increasing needs. This very urgent issue has now been addressed by six European target laboratories with an initiative called ANITA (Advanced Network for Isotope and TArget laboratories). The global aim of ANITA is to establish an overarching research infrastructure service for isotope and target production and develop a tight cooperation between the target laboratories in Europe in order to transfer the knowledge and improve the production techniques of well-characterized samples and targets. Moreover, the interaction of the target producers with the users shall be encouraged and intensified to deliver tailor-made targets best-suited to the envisaged experiments. For the realization of this ambitious goal, efforts within the European Commission and strong support by the target-using communities will be necessary. In particular, an appropriate funding instrument has to be found and applied, enabling ANITA to develop from an initiative employed by the interested parties to a real coordination platform.

  2. Ice targets for use at NTOF

    International Nuclear Information System (INIS)

    Mercer, D.J.

    1992-12-01

    This report describes ice targets which were used during an experiment at the Neutron Time of Flight facility (NTOF) at LAMPF. Reasons for using the ice targets are given, and the construction, refrigeration system, and target preparation are detailed. Results of the research using these ice targets will be published at a later date

  3. Shiva target irradiation facility

    International Nuclear Information System (INIS)

    Manes, K.R.; Ahlstrom, H.G.; Coleman, L.W.; Storm, E.K.; Glaze, J.A.; Hurley, C.A.; Rienecker, F.; O'Neal, W.C.

    1977-01-01

    The first laser/plasma studies performed with the Shiva laser system will be two sided irradiations extending the data obtained by other LLL lasers to higher powers. The twenty approximately 1 TW laser pulses will reach the target simultaneously from above and below in nested pentagonal clusters. The upper and lower clusters of ten beams each are radially polarized so that they strike the target in p-polarization and maximize absorption. This geometry introduces laser system isolation problems which will be briefly discussed. The layout and types of target diagnostics will be described and a brief status report on the facility given

  4. Legal Issues in Cyber Targeting

    DEFF Research Database (Denmark)

    Juhlin, Jonas Alastair

    Imagine this scenario: Two states are in armed conflict with each other. In order to gain an advantage, one side launches a cyber-attack against the opponent’s computer network. The malicious malware paralyze the military computer network, as intended, but the malware spreads into the civilian...... system with physical damage to follow. This can happen and the natural question arises: What must be considered lawful targeting according to the international humanitarian law in cyber warfare? What steps must an attacker take to minimize the damage done to unlawful targets when conducting an offensive...... operation? How can the attacker separate military targets from civilian targets in cyber space? This paper addresses these questions and argues that a network (civilian or military) consist of several software components and that it is the individual components that is the target. If the components are used...

  5. LANSCE target system performance

    International Nuclear Information System (INIS)

    Russell, G.J.; Gilmore, J.S.; Robinson, H.; Legate, G.L.; Bridge, A.; Sanchez, R.J.; Brewton, R.J.; Woods, R.; Hughes, H.G. III

    1989-01-01

    We measured neutron beam fluxes at LANSCE using gold foil activation techniques. We did an extensive computer simulation of the as-built LANSCE Target/Moderator/Reflector/Shield geometry. We used this mockup in a Monte Carlo calculation to predict LANSCE neutronic performance for comparison with measured results. For neutron beam fluxes at 1 eV, the ratio of measured data to calculated varies from ∼0.6-0.9. The computed 1 eV neutron leakage at the moderator surface is 3.9 x 10 10 n/eV-sr-s-μA for LANSCE high-intensity water moderators. The corresponding values for the LANSCE high-resolution water moderator and the liquid hydrogen moderator are 3.3 and 2.9 x 10 10 , respectively. LANSCE predicted moderator intensities (per proton) for a tungsten target are essentially the same as ISIS predicted moderator intensities for a depleted uranium target. The calculated LANSCE steady state unperturbed thermal (E 13 n/cm 2 -s. The unique LANSCE split-target/flux-trap-moderator system is performing exceedingly well. The system has operated without a target or moderator change for over three years at nominal proton currents of ∼25 μA of 800-MeV protons. (author)

  6. A comparison of prostate tumor targeting strategies using magnetic resonance imaging-targeted, transrectal ultrasound-guided fusion biopsy.

    Science.gov (United States)

    Martin, Peter R; Cool, Derek W; Fenster, Aaron; Ward, Aaron D

    2018-03-01

    Magnetic resonance imaging (MRI)-targeted, three-dimensional (3D) transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21-47% false-negative rate of clinical two-dimensional (2D) TRUS-guided systematic biopsy, but continues to yield false-negative results. This may be improved via needle target optimization, accounting for guidance system errors and image registration errors. As an initial step toward the goal of optimized prostate biopsy targeting, we investigated how needle delivery error impacts tumor sampling probability for two targeting strategies. We obtained MRI and 3D TRUS images from 49 patients. A radiologist and radiology resident assessed these MR images and contoured 81 suspicious regions, yielding tumor surfaces that were registered to 3D TRUS. The biopsy system's root-mean-squared needle delivery error (RMSE) and systematic error were modeled using an isotropic 3D Gaussian distribution. We investigated two different prostate tumor-targeting strategies using (a) the tumor's centroid and (b) a ring in the lateral-elevational plane. For each simulation, targets were spaced at equal arc lengths on a ring with radius equal to the systematic error magnitude. A total of 1000 biopsy simulations were conducted for each tumor, with RMSE and systematic error magnitudes ranging from 1 to 6 mm. The difference in median tumor sampling probability and probability of obtaining a 50% core involvement was determined for ring vs centroid targeting. Our simulation results indicate that ring targeting outperformed centroid targeting in situations where systematic error exceeds RMSE. In these instances, we observed statistically significant differences showing 1-32% improvement in sampling probability due to ring targeting. Likewise, we observed statistically significant differences showing 1-39% improvement in 50% core involvement probability due to ring targeting. Our results suggest that the optimal targeting scheme for prostate biopsy depends on

  7. Polarized targets in high energy physics

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-12-01

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

  8. Polarized targets in high energy physics

    International Nuclear Information System (INIS)

    Cates, G.D. Jr.

    1994-01-01

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

  9. Target-to-Target Repetition Cost and Location Negative Priming Are Dissociable: Evidence for Different Mechanisms

    Science.gov (United States)

    Chao, Hsuan-Fu

    2011-01-01

    In a location-selection task, the repetition of a prior distractor location as the target location would slow down the response. This effect is termed the location negative priming (NP) effect. Recently, it has been demonstrated that repetition of a prior target location as the current target location would also slow down response. Because such…

  10. 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.

  11. Targets of curcumin

    Science.gov (United States)

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

    2010-01-01

    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-κB), 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

  12. TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples.

    Science.gov (United States)

    Bandyopadhyay, Sanghamitra; Mitra, Ramkrishna

    2009-10-15

    Prediction of microRNA (miRNA) target mRNAs using machine learning approaches is an important area of research. However, most of the methods suffer from either high false positive or false negative rates. One reason for this is the marked deficiency of negative examples or miRNA non-target pairs. Systematic identification of non-target mRNAs is still not addressed properly, and therefore, current machine learning approaches are compelled to rely on artificially generated negative examples for training. In this article, we have identified approximately 300 tissue-specific negative examples using a novel approach that involves expression profiling of both miRNAs and mRNAs, miRNA-mRNA structural interactions and seed-site conservation. The newly generated negative examples are validated with pSILAC dataset, which elucidate the fact that the identified non-targets are indeed non-targets.These high-throughput tissue-specific negative examples and a set of experimentally verified positive examples are then used to build a system called TargetMiner, a support vector machine (SVM)-based classifier. In addition to assessing the prediction accuracy on cross-validation experiments, TargetMiner has been validated with a completely independent experimental test dataset. Our method outperforms 10 existing target prediction algorithms and provides a good balance between sensitivity and specificity that is not reflected in the existing methods. We achieve a significantly higher sensitivity and specificity of 69% and 67.8% based on a pool of 90 feature set and 76.5% and 66.1% using a set of 30 selected feature set on the completely independent test dataset. In order to establish the effectiveness of the systematically generated negative examples, the SVM is trained using a different set of negative data generated using the method in Yousef et al. A significantly higher false positive rate (70.6%) is observed when tested on the independent set, while all other factors are kept the

  13. Multisensory processing in the redundant-target effect

    DEFF Research Database (Denmark)

    Gondan, Matthias; Niederhaus, Birgit; Rösler, Frank

    2005-01-01

    Participants respond more quickly to two simultaneously presented target stimuli of two different modalities (redundant targets) than would be predicted from their reaction times to the unimodal targets. To examine the neural correlates of this redundant-target effect, event-related potentials...... (ERPs) were recorded to auditory, visual, and bimodal standard and target stimuli presented at two locations (left and right of central fixation). Bimodal stimuli were combinations of two standards, two targets, or a standard and a target, presented either from the same or from different locations...

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

    Science.gov (United States)

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

    2011-02-10

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

  15. Determination of spallation residues in thin target: toward an hybrid reactor lead target simulation

    International Nuclear Information System (INIS)

    Audouin, L.; Tassan-Got, L.; Bernas, M.; Rejmund, F.; Stephan, C.; Taieb, J.; Boudard, A.; Fernandez, B.; Legrain, R.; Leray, S.; Volant, C.; Wlazlo, W.; Benlliure, J.; Casajeros, E.; Pereira, J.; Czajkowski, S.

    2001-01-01

    The production of spallation primary residual nuclei in thin target has been studied by measurement of isotopic yields distributions for several systems. Issues relevant for the design of accelerator-driven systems are presented. Monte-Carlo code abilities to reproduce data are studied in details; it is shown that calculations do not reproduce data in a satisfactory way. Future work orientations leading to an improvement of thin targets calculations and ultimately to a thick target simulation are discussed. (author)

  16. Determination of spallation residues in thin target: toward an hybrid reactor lead target simulation

    Energy Technology Data Exchange (ETDEWEB)

    Audouin, L.; Tassan-Got, L.; Bernas, M.; Rejmund, F.; Stephan, C.; Taieb, J. [Paris-11 Univ., 91- Orsay (France). Inst. de Physique Nucleaire; Enqvist, T.; Armbruster, P.; Ricciardi, M.V.; Schmidt, K.H. [GSI, Planckstrasse 1, Darmstadt (Germany); Boudard, A.; Fernandez, B.; Legrain, R.; Leray, S.; Volant, C.; Wlazlo, W. [CEA Saclay, Dept. d' Astrophysique, de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, 91 - Gif sur Yvette (France); Benlliure, J.; Casajeros, E.; Pereira, J. [University of Santiago de Compostella (Spain); Czajkowski, S. [Centre d' Etudes Nucleaires de Bordeaux Gradignan, CENBG, CNRS-IN2P3, 33 - Gradignan (France)

    2001-07-01

    The production of spallation primary residual nuclei in thin target has been studied by measurement of isotopic yields distributions for several systems. Issues relevant for the design of accelerator-driven systems are presented. Monte-Carlo code abilities to reproduce data are studied in details; it is shown that calculations do not reproduce data in a satisfactory way. Future work orientations leading to an improvement of thin targets calculations and ultimately to a thick target simulation are discussed. (author)

  17. Internal magnetic target of proton synchrotron

    International Nuclear Information System (INIS)

    Gachurin, V.V.; Kats, M.M.; Kondrat'ev, L.N.; Rogal', A.D.; Rusinov, V.Yu.

    1988-01-01

    Proton extraction from a synchrotron by means of an internal target of magnetized iron is described. The particles that are aimed at the target pass directly through it and are deflected by the internal magnetic field of the target in the extraction direction. The general properties of magnetic targets are examined theoretically and a specific devices and results of its testing are described

  18. The Bering Target Tracking Instrumentation

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  19. Targeted marketing and public health.

    Science.gov (United States)

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

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

  20. Target reactor development problems

    International Nuclear Information System (INIS)

    Lathrop, K.D.; Vigil, J.C.

    1977-01-01

    Target-blanket design studies are discussed for an accelerator-breeder concept employing a linear accelerator in conjunction with a modified conventional power reactor to produce both fissile fuel and power. The following problems in target and blanket system design are discussed: radiation damage, heat removal, neutronic design, and economics

  1. Accelerator and neutron targets: a survey

    International Nuclear Information System (INIS)

    Kobisk, E.H.

    1974-01-01

    Although advances in electronics, ion source physics, detector technology, and other technical aspects of accelerator science have resulted in the capability of making highly sophisticated and accurate measurements of nuclear and atomic properties, the significance of such measurements is frequently dictated by the form, composition, and other characteristics of the target containing the nuclear species being studied. Consideration must be given to the impurity content, number of isotope nuclei per unit area, uniformity of nuclei distribution in the target, physical strength of the target, and myriad other factors. Most target characteristics are related to the mode(s) of preparation and to the quality of isotopic material used. A wide variety of target types and associated preparative methods are described and evaluated, together with methods of target characterization

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

    International Nuclear Information System (INIS)

    Ammerman, D.J.

    1993-01-01

    A mathematically rigorous method is developed for relating impacts with yielding targets to lower velocity impacts with unyielding targets. The method correctly models the mechanics of the impact and the conversion of kinetic energy to strain energy. An important result shown by the example problem is that apparent target hardness depends on the stiffness of the impacting package. For a cask with impact limiters a 26.8 m/s impact onto hard soil results in equivalent forces as a 13.9 m/s impact onto an unyielding target. For the same cask without impact limiters a 26.8 m/s impact onto hard soil is equivalent to a 1.74 m/s impact onto an unyielding target. This is one reason why non-technical members of the public often have difficulty realizing the severity of the regulatory impact. For most people, objects such as trucks and bridge columns appear to be very hard, but to many radioactive material shipping packages these objects are relatively soft. The method discussed in this paper for relating impacts with yielding targets to lower velocity impacts with unyielding targets helps to explain how the regulatory impact accident provides a high degree of safety to the public. This methodology is relatively simple to use, and can be applied to the 'What if' scenarios brought up by interveners. (J.P.N.)

  3. HPPD: ligand- and target-based virtual screening on a herbicide target.

    Science.gov (United States)

    López-Ramos, Miriam; Perruccio, Francesca

    2010-05-24

    Hydroxyphenylpyruvate dioxygenase (HPPD) has proven to be a very successful target for the development of herbicides with bleaching properties, and today HPPD inhibitors are well established in the agrochemical market. Syngenta has a long history of HPPD-inhibitor research, and HPPD was chosen as a case study for the validation of diverse ligand- and target-based virtual screening approaches to identify compounds with inhibitory properties. Two-dimensional extended connectivity fingerprints, three-dimensional shape-based tools (ROCS, EON, and Phase-shape) and a pharmacophore approach (Phase) were used as ligand-based methods; Glide and Gold were used as target-based. Both the virtual screening utility and the scaffold-hopping ability of the screening tools were assessed. Particular emphasis was put on the specific pitfalls to take into account for the design of a virtual screening campaign in an agrochemical context, as compared to a pharmaceutical environment.

  4. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  5. Design of the FMIT lithium target

    International Nuclear Information System (INIS)

    Hassberger, J.A.; Annese, C.E.; Greenwell, R.K.; Ingham, J.G.; Miles, R.R.; Miller, W.C.

    1981-01-01

    Development of the liquid lithium target for the Fusion Materials Irradiation Test (FMIT) Facility is described. The target concept, major design goals and design requirements are presented. Progress made in the research and development areas leading to detailed design of the target is discussed. This progress, including experimental and analytic results, demonstrates that the FMIT target design is capable of meeting its major design goals and requirements

  6. A two-cassette reporter system for assessing target gene translation and target gene product inclusion body formation

    DEFF Research Database (Denmark)

    2016-01-01

    The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....

  7. Tritium-target performance at RTNS-II

    International Nuclear Information System (INIS)

    Heikkinen, D.W.; Logan, C.M.

    1982-01-01

    The Rotating Target Neutron Source (RTNS-II) uses a 360-keV deuteron beam and the 3 He(d,n) 4 He reaction to generate 14-MeV neutrons. The neutrons are used for fusion materials damage studies. The tritium target consists of a band of titanium tritide on copper alloy substrates of 23- or 50-cm diameter. During operation, the substrates are internally cooled and rotated at approx. 4000 rpm to withstand beam intensities in excess of 100 mA. Neutron production data have been accumulated for fifty-eight 23-cm and five 50-cm targets. From these data, using a non-linear least-squares fitting procedure, target performance parameters have been obtained which permit a quantitative comparison of individual targets. Average parameters are obtained for the 23- and 50-cm targets

  8. New target solution for a muon collider or a muon-decay neutrino beam facility: The granular waterfall target

    Directory of Open Access Journals (Sweden)

    Han-Jie Cai

    2017-02-01

    Full Text Available A new target solution, the granular waterfall target, is proposed here for a muon collider or a muon-decay neutrino beam facility, especially for the moment which adopts a 15 MW continuous-wave (cw superconducting linac. Compared to the mercury jet target, the granular waterfall target works by a much simpler mechanism which can operate with a much more powerful beam, which are indicated by the detailed investigations into the heat depositions and the evaluations of the temperature increases for different target concepts. By varying proton beam kinetic energy and the geometrical parameters of the waterfall target, an overall understanding of the figure of merit concerning muon production for this target concept as the target solutions of the long-baseline neutrino factory and the medium-baseline moment is obtained. With 8 GeV beam energy and the optimal geometrical parameters, the influence on muon yield by adopting different beam-target interaction parameters is explored. Studies and discussions of the design details concerning beam dumping are also presented.

  9. Polymeric micelles for drug targeting.

    Science.gov (United States)

    Mahmud, Abdullah; Xiong, Xiao-Bing; Aliabadi, Hamidreza Montazeri; Lavasanifar, Afsaneh

    2007-11-01

    Polymeric micelles are nano-delivery systems formed through self-assembly of amphiphilic block copolymers in an aqueous environment. The nanoscopic dimension, stealth properties induced by the hydrophilic polymeric brush on the micellar surface, capacity for stabilized encapsulation of hydrophobic drugs offered by the hydrophobic and rigid micellar core, and finally a possibility for the chemical manipulation of the core/shell structure have made polymeric micelles one of the most promising carriers for drug targeting. To date, three generations of polymeric micellar delivery systems, i.e. polymeric micelles for passive, active and multifunctional drug targeting, have arisen from research efforts, with each subsequent generation displaying greater specificity for the diseased tissue and/or targeting efficiency. The present manuscript aims to review the research efforts made for the development of each generation and provide an assessment on the overall success of polymeric micellar delivery system in drug targeting. The emphasis is placed on the design and development of ligand modified, stimuli responsive and multifunctional polymeric micelles for drug targeting.

  10. Space based lidar shot pattern targeting strategies for small targets such as streams

    Science.gov (United States)

    Spiers, Gary D.

    2001-01-01

    An analysis of the effectiveness of four different types of lidar shot distribution is conducted to determine which is best for concentrating shots in a given location. A simple preemptive targeting strategy is found to work as adequately as a more involved dynamic strategy for most target sizes considered.

  11. A rotating target wheel system for gammasphere

    International Nuclear Information System (INIS)

    Greene, J. P.

    1999-01-01

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

  12. Fabrication of cryogenic inertial-confinement-fusion targets using target free-fall technique. Report No. 2-82

    International Nuclear Information System (INIS)

    Kim, K.; Murphy, M.J.

    1982-04-01

    Techniques for fabricating cryogenic inertial confinement fusion targets (i.e., spherical shells containing a uniform layer of DT ice) are investigated using target free-fall concept. Detection and characterization of the moving targets are effected by optoelectronic means, of which the principal is an RF ac-interferometer. This interferometer system demonstrates, for the first time, the speed capabilities of the phase-modulation ac-interferometry. New techiques developed for handling, holding, launching, and transporting targets are also described. Results obtained at both room and cryogenic temperatures are presented

  13. Retention of ferrofluid aggregates at the target site during magnetic drug targeting

    Energy Technology Data Exchange (ETDEWEB)

    Asfer, Mohammed, E-mail: asfer786@gmail.com [School of Engineering and Technology, BML Munjal University, Haryana (India); Saroj, Sunil Kumar [Department of Mechanical Engineering, IIT Kanpur, Kanpur (India); Panigrahi, Pradipta Kumar, E-mail: panig@iitk.ac.in [Department of Mechanical Engineering, IIT Kanpur, Kanpur (India)

    2017-08-15

    Highlights: • The present in vitro work reports the retention dynamics of ferrofluid aggregates at the target site against a bulk flow of DI water inside a micro capillary during magnetic drug targeting. • The recirculation zone at the downstream of the aggregate is found to be a function of aggregate height, Reynolds number and the degree of surface roughness of the outer boundary of the aggregate. • The reported results of the present work can be used as a guideline for the better design of MDT technique for in vivo applications. - Abstract: The present study reports the retention dynamics of a ferrofluid aggregate localized at the target site inside a glass capillary (500 × 500 µm{sup 2} square cross section) against a bulk flow of DI water (Re = 0.16 and 0.016) during the process of magnetic drug targeting (MDT). The dispersion dynamics of iron oxide nanoparticles (IONPs) into bulk flow for different initial size of aggregate at the target site is reported using the brightfield visualization technique. The flow field around the aggregate during the retention is evaluated using the µPIV technique. IONPs at the outer boundary experience a higher shear force as compared to the magnetic force, resulting in dispersion of IONPs into the bulk flow downstream to the aggregate. The blockage effect and the roughness of the outer boundary of the aggregate resulting from chain like clustering of IONPs contribute to the flow recirculation at the downstream region of the aggregate. The entrapment of seeding particles inside the chain like clusters of IONPs at the outer boundary of the aggregate reduces the degree of roughness resulting in a streamlined aggregate at the target site at later time. The effect of blockage, structure of the aggregate, and disturbed flow such as recirculation around the aggregate are the primary factors, which must be investigated for the effectiveness of the MDT process for in vivo applications.

  14. Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver

    International Nuclear Information System (INIS)

    Wulf, Joern; Haedinger, Ulrich; Oppitz, Ulrich; Thiele, Wibke; Flentje, Michael

    2003-01-01

    Background and purpose: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5 mm in axial and 5-10 mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). Materials and methods: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10 mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). Results: A decrease of TC to 3 . Conclusions: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV ≥95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm 3 are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins

  15. 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...

  16. Graphite target for the spiral project

    International Nuclear Information System (INIS)

    Putaux, J.C.; Ducourtieux, M.; Ferro, A.; Foury, P.; Kotfila, L.; Mueller, A.C.; Obert, J.; Pauwels, N.; Potier, J.C.; Proust, J.; Loiselet, M.

    1996-01-01

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

  17. Current progress in NIF target concepts

    International Nuclear Information System (INIS)

    Gobby, P.L.; Foreman, L.R.; Thoma, D.J.; Jacobson, L.A.; Hollis, R.V.; Barrera, J.; Mitchell, M.A.; Salazar, M.A.; Salzer, L.J.

    1996-01-01

    Target concepts for the National Ignition Facility (NIF) require progress in the art and science of target fabrication. Three distinct issues are addressed: beryllium fuel capsules, foam-buffered direct drive, and high-density gas-filled hohlraums. In all cases experiments on the existing Nova laser at LLNL are either in progress or planned for the near future to test the various concepts. Consequently, target fabrication must be able to deliver targets appropriate for each

  18. ISAC target operation with high proton currents

    CERN Document Server

    Dombsky, M; Schmor, P; Lane, M

    2003-01-01

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

  19. Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

    Science.gov (United States)

    Wulf, Jörn; Hädinger, Ulrich; Oppitz, Ulrich; Thiele, Wibke; Flentje, Michael

    2003-02-01

    Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). A decrease of TC to or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.

  20. Automated laser fusion target production concept

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1977-01-01

    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

  1. Climate targets for all countries: the options

    International Nuclear Information System (INIS)

    Philibert, C.; Pershing, J.

    2001-01-01

    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)

  2. Tumor-targeting peptides from combinatorial libraries*

    Science.gov (United States)

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

    2018-01-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

  3. Target production for inertial fusion energy

    International Nuclear Information System (INIS)

    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 ∼16 cents per target. At this level, target production represents about 6% of the estimated cost of electricity from a 1-GW 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

  4. Cooperative target convergence using multiple agents

    International Nuclear Information System (INIS)

    Kwok, K.S.; Driessen, B.J.

    1997-01-01

    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

  5. Cooperative target convergence using multiple agents

    Energy Technology Data Exchange (ETDEWEB)

    Kwok, K.S.; Driessen, B.J.

    1997-10-01

    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.

  6. Temperature simulations for the SPIRAL ISOL target

    International Nuclear Information System (INIS)

    Maunoury, L.; Bajeat, O.; Lichtenthaler, R.; Villari, A.C.C.

    2001-01-01

    Simulations of the power deposition and target temperature distributions in the SPIRAL ISOL target are presented. These simulations consider different heavy-ion beams with intensities corresponding to 2 and 6 kW on a carbon target. A new solutions, which corresponds to the splitting of the production target into two parts, where the first is cooled and the second is heated, allows keeping the overall size of the target ensemble relatively small. An extrapolation of the considered target geometry to primary beam intensities up to 1 MW is also presented. (authors)

  7. High heat flux cooling for accelerator targets

    International Nuclear Information System (INIS)

    Silverman, I.; Nagler, A.

    2002-01-01

    Accelerator targets, both for radioisotope production and for high neutron flux sources generate very high thermal power in the target material which absorbs the particles beam. Generally, the geometric size of the targets is very small and the power density is high. The design of these targets requires dealing with very high heat fluxes and very efficient heat removal techniques in order to preserve the integrity of the target. Normal heat fluxes from these targets are in the order of 1 kw/cm 2 and may reach levels of an order of magnitude higher

  8. National Ignition Facility Target Chamber

    International Nuclear Information System (INIS)

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

    2000-01-01

    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

  9. Multi-Agent Cooperative Target Search

    Directory of Open Access Journals (Sweden)

    Jinwen Hu

    2014-05-01

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

  10. Predicting drug-target interaction for new drugs using enhanced similarity measures and super-target clustering.

    Science.gov (United States)

    Shi, Jian-Yu; Yiu, Siu-Ming; Li, Yiming; Leung, Henry C M; Chin, Francis Y L

    2015-07-15

    Predicting drug-target interaction using computational approaches is an important step in drug discovery and repositioning. To predict whether there will be an interaction between a drug and a target, most existing methods identify similar drugs and targets in the database. The prediction is then made based on the known interactions of these drugs and targets. This idea is promising. However, there are two shortcomings that have not yet been addressed appropriately. Firstly, most of the methods only use 2D chemical structures and protein sequences to measure the similarity of drugs and targets respectively. However, this information may not fully capture the characteristics determining whether a drug will interact with a target. Secondly, there are very few known interactions, i.e. many interactions are "missing" in the database. Existing approaches are biased towards known interactions and have no good solutions to handle possibly missing interactions which affect the accuracy of the prediction. In this paper, we enhance the similarity measures to include non-structural (and non-sequence-based) information and introduce the concept of a "super-target" to handle the problem of possibly missing interactions. Based on evaluations on real data, we show that our similarity measure is better than the existing measures and our approach is able to achieve higher accuracy than the two best existing algorithms, WNN-GIP and KBMF2K. Our approach is available at http://web.hku.hk/∼liym1018/projects/drug/drug.html or http://www.bmlnwpu.org/us/tools/PredictingDTI_S2/METHODS.html. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Behavioral targeting: a European legal perspective

    NARCIS (Netherlands)

    Zuiderveen Borgesius, F.

    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

  12. Target system materials and engineering problems

    International Nuclear Information System (INIS)

    Fischer, W.E.

    1989-01-01

    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

  13. 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.

  14. FAKTOR-FAKTOR YANG MEMPENGARUHI KEJADIAN FILARIASIS DI INDONESIA (DATA RISKESDAS 2007

    Directory of Open Access Journals (Sweden)

    Mardiana Mardiana

    2012-11-01

    Full Text Available Filariasis or elephantiasis diseases which caused by filaria worm and contagious through mosquito bite, still the major community health problem in Indonesia. There are several type of filaria worm in Indonesia, i.e. Wuchereria bancrofti, Brugia malayi and Brugia timori. The vectors of filariasis are Culex quinquefasciatus in the urban area, Anopheles spp, Aedes spp and Mansonia spp in the rural area. The infection risk in some area of filariasis related to the situation of local area. Various factor of environmental area which area physical, biological and also cultural social to be influence to development of transmitted filariasis by mosquito. The analysis of data Riskesdas 2007 has been done to perform of factor influence filariasis case in Indonesia. Same parameters was analyzed to case of filariasis in last 12 months; gender, ages, educations, work, mosquito net usage, sources of water, effluent dismissal, residences, water dismissal channel, existence of livestock in house. From analysis inferential, show there is no relation between genders, age, education, work, and mosquito net usage, sources of water, water dismissal channel, and existence of livestock in house to case filariasis. Statistically indicates that there is significantly difference between residences in rural and in urban to case of filariasis in last 12 months. Responder who live in rural areas (0,05% have 2,4 times risk higher than responder who live in urban (0,03%. The same as condition of water dismissal channel shows to existence of significantly differences. Responder who have water dismissal channel without cover have high risk infections of filariasis in the last 12 months were 0,05%, while the responder have water dismissal channel with cover have high risk in last 12 months were 0,03%. Keywords: Filariasis, endemic area, factors

  15. 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...

  16. 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...

  17. Targets for the APEX experiment at ATLAS

    International Nuclear Information System (INIS)

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

    1994-01-01

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

  18. Fuzzy target selection using RFM variables

    NARCIS (Netherlands)

    Kaymak, U.

    2001-01-01

    An important data mining problem from the world of direct marketing is target selection. The main task in target selection is the determination of potential customers for a product from a client database. Target selection algorithms identify the profiles of customer groups for a particular product,

  19. A Cryogenic Infrared Calibration Target

    Science.gov (United States)

    Wollack, E. J.; Kinzer, R. E., Jr.; Rinehart, S. A.

    2014-01-01

    A compact cryogenic calibration target is presented that has a peak diffuse reflectance, R target. The resulting target assembly is lightweight, has a low-geometric profile, and has survived repeated thermal cycling from room temperature to approx.4 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 characterized and presented

  20. CACAO facility. Radioactive targets at Orsay

    International Nuclear Information System (INIS)

    Bacri, C.O.; Petitbon-Thevenet, V.; Mottier, J.; Lefort, H.; Durnez, A.; Fortuna, F.

    2014-01-01

    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 235,238 U and 232 Th 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)

  1. Ca-48 targets - Home and abroad!

    Science.gov (United States)

    Greene, John P.; Carpenter, Michael; Janssens, Robert V. F.

    2018-05-01

    Using the method of reduction/distillation, high-purity films of robust and ductile calcium metal were prepared for use as targets in nuclear physics experiments. These targets, however, are extremely air-sensitive and procedures must be developed for their handling and use without exposure to the air. In most instances, the thin 48Ca target is used on a carrier foil (backing) and a thin covering film of similar material is employed to further reduce re-oxidation. Un-backed metallic targets are rarely produced due to these concerns. In addition, the low natural abundance of the isotope 48Ca provided an increased incentive for the best efficiencies available in their preparation. Here, we describe the preparation of 48Ca targets employing a gold backing and thin gold cover for use at home, Argonne National Laboratory (ANL), as well as abroad, at Osaka University. For the overseas shipments, much care and preparation were necessary to ensure good targets and safe arrival to the experimental facilities.

  2. Polarized gas targets for storage rings

    International Nuclear Information System (INIS)

    Holt, R.J.

    1990-01-01

    It is widely recognized that polarized gas targets in electron storage rings represent a new opportunity for precision nuclear physics studies. New developments in polarized target technology specific to internal applications will be discussed. In particular, polarized gas targets have been used in the VEPP-3 electron ring in Novosibirsk. A simple storage cell was used to increase the total target thickness by a factor of 15 over the simple gas jet target from an atomic beam source. Results from the initial phase of this project will be reported. In addition, the plans for increasing the luminosity by an additional order or magnitude will be presented. The application of this work to polarized hydrogen and deuterium targets for the HERA ring will be noted. The influence of beam-induced depolarization, a phenomena encountered in short-pulse electron storage rings, will be discussed. Finally, the performance tests of laser-driven sources will be presented. 8 refs., 12 figs., 1 tab

  3. Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells.

    Science.gov (United States)

    Zhang, Jingzhu; Link, Daniel C

    2016-11-01

    The targeting specificity of tissue-specific Cre-recombinase transgenes is a key to interpreting phenotypes associated with their use. The Ocn-Cre and Dmp1-Cre transgenes are widely used to target osteoblasts and osteocytes, respectively. Here, we used high-resolution microscopy of bone sections and flow cytometry to carefully define the targeting specificity of these transgenes. These transgenes were crossed with Cxcl12 gfp mice to identify Cxcl12-abundant reticular (CAR) cells, which are a perivascular mesenchymal stromal population implicated in hematopoietic stem/progenitor cell maintenance. We show that in addition to osteoblasts, Ocn-Cre targets a majority of CAR cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset of CAR cells, in which expression of osteoblast-lineage genes is enriched. Finally, we introduce a new tissue-specific Cre-recombinase, Tagln-Cre, which efficiently targets osteoblasts, a majority of CAR cells, and both venous sinusoidal and arteriolar pericytes. These data show that Ocn-Cre and Dmp1-Cre target broader stromal cell populations than previously appreciated and may aid in the design of future studies. Moreover, these data highlight the heterogeneity of mesenchymal stromal cells in the bone marrow and provide tools to interrogate this heterogeneity. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  4. 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...

  5. Error Analysis of Fast Moving Target Geo-location in Wide Area Surveillance Ground Moving Target Indication Mode

    Directory of Open Access Journals (Sweden)

    Zheng Shi-chao

    2013-12-01

    Full Text Available As an important mode in airborne radar systems, Wide Area Surveillance Ground Moving Target Indication (WAS-GMTI mode has the ability of monitoring a large area in a short time, and then the detected moving targets can be located quickly. However, in real environment, many factors introduce considerable errors into the location of moving targets. In this paper, a fast location method based on the characteristics of the moving targets in WAS-GMTI mode is utilized. And in order to improve the location performance, those factors that introduce location errors are analyzed and moving targets are relocated. Finally, the analysis of those factors is proved to be reasonable by simulation and real data experiments.

  6. Strategic Targeted Advertising and Market Fragmentation

    OpenAIRE

    Lola Esteban; Jose M. Hernandez

    2007-01-01

    This paper proves that oligopolistic price competition with both targeted advertising and targeted prices can lead to a permanent fragmentation of the market into a local monopoly. However, compared to mass advertising, targeting increases social welfare and turns out to be more beneficial for consumers than for firms.

  7. 40 CFR 35.9020 - Planning targets.

    Science.gov (United States)

    2010-07-01

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

  8. Is it wise to protect false targets?

    International Nuclear Information System (INIS)

    Levitin, Gregory; Hausken, Kjell

    2011-01-01

    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.

  9. On the large COMPASS polarized deuteron target

    CERN Document Server

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

    2006-01-01

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

  10. Identifying Drug-Target Interactions with Decision Templates.

    Science.gov (United States)

    Yan, Xiao-Ying; Zhang, Shao-Wu

    2018-01-01

    During the development process of new drugs, identification of the drug-target interactions wins primary concerns. However, the chemical or biological experiments bear the limitation in coverage as well as the huge cost of both time and money. Based on drug similarity and target similarity, chemogenomic methods can be able to predict potential drug-target interactions (DTIs) on a large scale and have no luxurious need about target structures or ligand entries. In order to reflect the cases that the drugs having variant structures interact with common targets and the targets having dissimilar sequences interact with same drugs. In addition, though several other similarity metrics have been developed to predict DTIs, the combination of multiple similarity metrics (especially heterogeneous similarities) is too naïve to sufficiently explore the multiple similarities. In this paper, based on Gene Ontology and pathway annotation, we introduce two novel target similarity metrics to address above issues. More importantly, we propose a more effective strategy via decision template to integrate multiple classifiers designed with multiple similarity metrics. In the scenarios that predict existing targets for new drugs and predict approved drugs for new protein targets, the results on the DTI benchmark datasets show that our target similarity metrics are able to enhance the predictive accuracies in two scenarios. And the elaborate fusion strategy of multiple classifiers has better predictive power than the naïve combination of multiple similarity metrics. Compared with other two state-of-the-art approaches on the four popular benchmark datasets of binary drug-target interactions, our method achieves the best results in terms of AUC and AUPR for predicting available targets for new drugs (S2), and predicting approved drugs for new protein targets (S3).These results demonstrate that our method can effectively predict the drug-target interactions. The software package can

  11. X-ray tube target

    International Nuclear Information System (INIS)

    Weber, R.G.

    1980-01-01

    A target with an improved heat emissive surface for use in a rotating anode type x-ray tube is described. The target consists of a body having a first surface portion made of x-ray emissive material and a second surface portion made of a heat emissive material comprising at least one of hafnium boride, hafnium oxide, hafnium nitride, hafnium silicide, and hafnium aluminide. (U.K.)

  12. Drug-Target Interactions: Prediction Methods and Applications.

    Science.gov (United States)

    Anusuya, Shanmugam; Kesherwani, Manish; Priya, K Vishnu; Vimala, Antonydhason; Shanmugam, Gnanendra; Velmurugan, Devadasan; Gromiha, M Michael

    2018-01-01

    Identifying the interactions between drugs and target proteins is a key step in drug discovery. This not only aids to understand the disease mechanism, but also helps to identify unexpected therapeutic activity or adverse side effects of drugs. Hence, drug-target interaction prediction becomes an essential tool in the field of drug repurposing. The availability of heterogeneous biological data on known drug-target interactions enabled many researchers to develop various computational methods to decipher unknown drug-target interactions. This review provides an overview on these computational methods for predicting drug-target interactions along with available webservers and databases for drug-target interactions. Further, the applicability of drug-target interactions in various diseases for identifying lead compounds has been outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Effects of target bias voltage on indium tin oxide films deposited by high target utilisation sputtering

    International Nuclear Information System (INIS)

    Calnan, Sonya; Upadhyaya, Hari M.; Dann, Sandra E.; Thwaites, Mike J.; Tiwari, Ayodhya N.

    2007-01-01

    Indium tin oxide (ITO) films were deposited by reactive High Target Utilisation Sputtering (HiTUS) onto glass and polyimide substrates. The ion plasma was generated by an RF power source while the target bias voltage was varied from 300 V to 500 V using a separate DC power supply. The deposition rate, at constant target power, increased with DC target voltage due to increased ion energy reaching 34 nm/min at 500 V. All the films were polycrystalline and showed strong (400) and (222) reflections with the relative strength of latter increasing with target bias voltage. The resistivity was lowest at 500 V with values of 1.8 x 10 -4 Ω cm and 2.4 x 10 -4 Ω cm on glass and polyimide, respectively but was still less than 5 x 10 -4 Ω cm at 400 V. All films were highly transparent to visible light, (> 80%) but the NIR transmittance decreased with increasing target voltage due to higher free carrier absorption. Therefore, ITO films can be deposited onto semiconductor layers such as in solar cells, with minimal ion damage while maintaining low resistivity

  14. Laser ``M'egajoule'' cryogenic target program: from target fabrication to conformation of the deuterium-tritium ice layer

    Science.gov (United States)

    Collier, Rémy; Durut, Frédéric; Reneaume, Benoît; Chicane, Cédric; Théobald, Marc; Breton, Olivier; Martin, Michel; Fleury, Emmanuel; Vincent-Viry, Olivier; Bachelet, Franck; Jeannot, Laurent; Geoffray, Isabelle; Botrel, Ronan; Dauteuil, Christophe; Hermerel, Cyril; Choux, Alexandre; Bednarczyk, Sophie; Legaie, Olivier

    2008-11-01

    For the French inertial confinement fusion (ICF) experiments, cryogenic target assemblies (CTAs) for the LMJ program are manufactured and filled at CEA Valduc (Dijon) in the cryogenic targets filling station (IRCC). They will be moved at about 20 K into a transport cryostat for cryogenic targets and will be driven from CEA/Valduc to CEA/CESTA (Bordeaux). Cryogenic targets will then be transferred by several cryogenic grippers on the cryogenic target positioner before shots. The CTA has to meet severe specifications and involves a lot of challenging tasks for its manufacture. To fill CTAs by permeation with deuterium-tritium (DT), the IRCC need to meet strict thermal, mechanical and dimensional specifications. To obtain a good combustion yield, a very homogenous DT ice layer and very smooth roughness at 1.5 K below the DT triple point are also required. This paper deals with the up to date main issues in the different fields of the LMJ cryogenic target program.

  15. Serine protease inhibitors of parasitic helminths.

    Science.gov (United States)

    Molehin, Adebayo J; Gobert, Geoffrey N; McManus, Donald P

    2012-05-01

    Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.

  16. Dicty_cDB: Contig-U12802-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available cobacter cetorum strain MIT-0... 38 0.23 AF237484_1( AF237484 |pid:none) Dirofilaria immitis intermed...87 ( O97594 ) RecName: Full=Structural maintenance of chromosomes pro... 36 0.87 U00680_1( U00680 |pid:none) Brugia malayi intermed...1305( CP000879 |pid:none) Petrotoga mobilis SJ95, complet... 38 0.30 (Q9BZF9) RecName: Full=Uveal autoantigen with coiled...ns BAC clone RP11-764E7 from 2, complet... 34 0.79 6 ( FK620261 ) 454GmaGlobSeed354893 Soybean Seed...ditis elegans clone Y71H2X, *** SEQUENCI... 38 4.5 7 ( AC146972 ) Medicago truncatula clone mth2-128d9, compl

  17. Physical measurements of inertial-fusion targets

    International Nuclear Information System (INIS)

    Weinstein, B.W.

    1981-01-01

    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

  18. Uncertainties in thick-target PIXE analysis

    International Nuclear Information System (INIS)

    Campbell, J.L.; Cookson, J.A.; Paul, H.

    1983-01-01

    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.)

  19. Exploiting target amplitude information to improve multi-target tracking

    Science.gov (United States)

    Ehrman, Lisa M.; Blair, W. Dale

    2006-05-01

    Closely-spaced (but resolved) targets pose a challenge for measurement-to-track data association algorithms. Since the Mahalanobis distances between measurements collected on closely-spaced targets and tracks are similar, several elements of the corresponding kinematic measurement-to-track cost matrix are also similar. Lacking any other information on which to base assignments, it is not surprising that data association algorithms make mistakes. One ad hoc approach for mitigating this problem is to multiply the kinematic measurement-to-track likelihoods by amplitude likelihoods. However, this can actually be detrimental to the measurement-to-track association process. With that in mind, this paper pursues a rigorous treatment of the hypothesis probabilities for kinematic measurements and features. Three simple scenarios are used to demonstrate the impact of basing data association decisions on these hypothesis probabilities for Rayleigh, fixed-amplitude, and Rician targets. The first scenario assumes that the tracker carries two tracks but only one measurement is collected. This provides insight into more complex scenarios in which there are fewer measurements than tracks. The second scenario includes two measurements and one track. This extends naturally to the case with more measurements than tracks. Two measurements and two tracks are present in the third scenario, which provides insight into the performance of this method when the number of measurements equals the number of tracks. In all cases, basing data association decisions on the hypothesis probabilities leads to good results.

  20. 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)

  1. Laval nozzles for cluster-jet targets

    Energy Technology Data Exchange (ETDEWEB)

    Grieser, Silke; Bonaventura, Daniel; Hergemoeller, Ann-Katrin; Hetz, Benjamin; Koehler, Esperanza; Lessmann, Lukas; Khoukaz, Alfons [Institut fuer Kernphysik, Westfaelische Wilhelms-Universitaet Muenster, 48149 Muenster (Germany)

    2016-07-01

    Cluster-jet targets are highly suited for storage ring experiments due to the fact that they provide high and constant beam densities. Therefore, a cluster-jet target is planned to be the first internal target for the PANDA experiment at FAIR. A cluster source generates a continuous flow of cryogenic solid clusters by the expansion of pre-cooled gases within fine Laval nozzles. For the production of clusters the geometry of the nozzle is crucial. The production of such nozzles with their complex inner geometry represents a major technical challenge. The possibility to produce new fine Laval nozzles ensures the operation of cluster-jet targets, e.g. for the PANDA experiment, and opens the way for future investigations on the cluster production process to match the required targets performance. Optimizations on the recently developed production process and the fabrication of new glass nozzles were done. Initial measurements of these nozzles at the PANDA cluster-jet target prototype and the investigation of the cluster beam origin within the nozzle will be presented and discussed. For the future more Laval nozzles with different geometries will be produced and additional measurements with these new nozzles at the PANDA cluster-jet target prototype towards higher performance will be realized.

  2. Non-targeted effects of ionising radiation

    International Nuclear Information System (INIS)

    Belyakov, O.V.

    2008-01-01

    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.)

  3. Vascular targeting with peptide libraries

    Energy Technology Data Exchange (ETDEWEB)

    Pasqualini, R. [La Jolla Cancer Research Center The Burnham Inst., La Jolla CA (United States)

    1999-06-01

    The authors have developed an 'in vivo' selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, they have isolate several organ and tumor-homing peptides. They have shown that each of those peptides binds of different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are up regulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animals models decrease toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angio genesis and lead to advances to extend the potential for targeting of drugs, genes and radionuclides in the context of many diseases.

  4. Performance Targets and External Market Prices

    DEFF Research Database (Denmark)

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

    2012-01-01

    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.......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...

  5. 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....... Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow...

  6. Development of targeted radiotherapy systems

    International Nuclear Information System (INIS)

    Ferro, Guillermina; Villarreal, Jose E.; Garcia, Laura; Tendilla, Jose I.; Paredes, Lydia; Murphy, Consuelo A.; Pedraza, Martha

    2001-01-01

    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. Multiple Target Laser Designator (MTLD)

    Science.gov (United States)

    2007-03-01

    Optimized Liquid Crystal Scanning Element Optimize the Nonimaging Predictive Algorithm for Target Ranging, Tracking, and Position Estimation...commercial potential. 3.0 PROGRESS THIS QUARTER 3.1 Optimization of Nonimaging Holographic Antenna for Target Tracking and Position Estimation (Task 6) In

  8. Targets and special materials

    International Nuclear Information System (INIS)

    Blanc, R.; Bouriant, M.; Richaud, J.P.

    1997-01-01

    The target preparation group supplied a large number of samples to nuclear physicists for experiments using SARA and also other accelerators throughout the world. Particular preparation and projects include: 208 Pb, 116 Cd, 6 LiF, 123 Sb, In and Ta targets, strippers for SARA and GANIL, optical silicone disks for POLDER and GRAAL experiments, active participations for the AMS project and finally filament preparation for the GENEPI project. (authors)

  9. Development of annular targets for 99Mo production

    International Nuclear Information System (INIS)

    Conner, C.; Lewandowski, E.F.; Snelgrove, J.L.; Liberatore, M.W.; Walker, D.E.; Wiencek, T.C.; McGann, D.J.; Hofman, G.L.; Vandegrift, G.F.

    1999-01-01

    During 1999, significant progress was made in the development of a low-enriched uranium (LEU) target for production of 99 Mo. Successful conversion requires an inexpensive, reliable target. To keep the target geometry the same when changing from high-enriched uranium (HEU) to LEU targets, a denser form of uranium is required in order to increase the amount of uranium per target by a factor of approximately five. Targets containing LEU in the form of a metal foil are being developed for producing 99 Mo from the fissioning of 235 U. A new annular target was developed this year, and seven targets were irradiated in the Indonesian RSG-GAS reactor. Results of development of this annular target and its performance during irradiation are described. (author)

  10. Deep-Learning-Based Drug-Target Interaction Prediction.

    Science.gov (United States)

    Wen, Ming; Zhang, Zhimin; Niu, Shaoyu; Sha, Haozhi; Yang, Ruihan; Yun, Yonghuan; Lu, Hongmei

    2017-04-07

    Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

  11. Dynamic nuclear polarization of irradiated target materials

    International Nuclear Information System (INIS)

    Seely, M.L.

    1982-01-01

    Polarized nucleon targets used in high energy physics experiments usually employ the method of dynamic nuclear polarization (DNP) to polarize the protons or deuterons in an alcohol. DNP requires the presence of paramagnetic centers, which are customarily provided by a chemical dopant. These chemically doped targets have a relatively low polarizable nucleon content and suffer from loss of polarization when subjected to high doses of ionizing radiation. If the paramagnetic centers formed when the target is irradiated can be used in the DNP process, it becomes possible to produce targets using materials which have a relatively high polarizable nucleon content, but which are not easily doped by chemical means. Furthermore, the polarization of such targets may be much more radiation resistant. Dynamic nuclear polarization in ammonia, deuterated ammonia, ammonium hydroxide, methylamine, borane ammonia, butonal, ethane and lithium borohydride has been studied. These studies were conducted at the Stanford Linear Accelerator Center using the Yale-SLAC polarized target system. Results indicate that the use of ammonia and deuterated ammonia as polarized target materials would make significant increases in polarized target performance possible

  12. Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality.

    Science.gov (United States)

    Hussain, Netha; Alt Murphy, Margit; Sunnerhagen, Katharina S

    2018-01-01

    Kinematic analysis using virtual reality (VR) environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation. To determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls. Sixty-seven participants with moderate (32-57 points) or mild (58-65 points) stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg-SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement. The movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate) compared to controls. Movement trajectories in stroke more frequently showed clustering (spider's web) close to the target indicating deficits in movement precision. The target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale. The trial was registered with register number NCT01115348 at clinicaltrials.gov, on May 4, 2010. URL: https://clinicaltrials.gov/ct2

  13. Upper Limb Kinematics in Stroke and Healthy Controls Using Target-to-Target Task in Virtual Reality

    Directory of Open Access Journals (Sweden)

    Netha Hussain

    2018-05-01

    Full Text Available BackgroundKinematic analysis using virtual reality (VR environment provides quantitative assessment of upper limb movements. This technique has rarely been used in evaluating motor function in stroke despite its availability in stroke rehabilitation.ObjectiveTo determine the discriminative validity of VR-based kinematics during target-to-target pointing task in individuals with mild or moderate arm impairment following stroke and in healthy controls.MethodsSixty-seven participants with moderate (32–57 points or mild (58–65 points stroke impairment as assessed with Fugl-Meyer Assessment for Upper Extremity were included from the Stroke Arm Longitudinal study at the University of Gothenburg—SALGOT cohort of non-selected individuals within the first year of stroke. The stroke groups and 43 healthy controls performed the target-to-target pointing task, where 32 circular targets appear one after the other and disappear when pointed at by the haptic handheld stylus in a three-dimensional VR environment. The kinematic parameters captured by the stylus included movement time, velocities, and smoothness of movement.ResultsThe movement time, mean velocity, and peak velocity were discriminative between groups with moderate and mild stroke impairment and healthy controls. The movement time was longer and mean and peak velocity were lower for individuals with stroke. The number of velocity peaks, representing smoothness, was also discriminative and significantly higher in both stroke groups (mild, moderate compared to controls. Movement trajectories in stroke more frequently showed clustering (spider’s web close to the target indicating deficits in movement precision.ConclusionThe target-to-target pointing task can provide valuable and specific information about sensorimotor impairment of the upper limb following stroke that might not be captured using traditional clinical scale.Trial registration detailsThe trial was registered with register number

  14. Targets and tactics

    DEFF Research Database (Denmark)

    Woo, V; Shestakova, M V; Ørskov, C

    2008-01-01

    BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro-vascular ......BACKGROUND: The incidence of type 2 diabetes is reaching pandemic proportions, impacting patients and healthcare systems across the globe. Evidence suggests that a majority of patients are not achieving recommended blood glucose targets resulting in an increased risk of micro- and macro...... diabetes has never been more compelling; with a clear focus on strategies for glycaemic control, the impact of the diabetes pandemic can be limited....

  15. Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

    Science.gov (United States)

    Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

    2012-01-01

    Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

  16. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  17. Spinning targets for laser fusion

    International Nuclear Information System (INIS)

    Baldwin, D.E.; Ryutov, D.D.

    1995-09-01

    Several techniques for spinning the ICF targets up prior to or in the course of their compression are suggested. Interference of the rotational shear flow with Rayleigh-Taylor instability is briefly discussed and possible consequences for the target performance are pointed out

  18. TARGET EXCITATION IN BARE ION XE/AR COLLISIONS STUDIED BY ELECTRON TARGET ION COINCIDENCES

    NARCIS (Netherlands)

    DENIJS, G; HOEKSTRA, R; MORGENSTERN, R

    We present electron spectra resulting from collisions of bare ions N-15(7+) and C-13(6+) on Ar and the charge state distribution of target ions resulting from C-13(6+)-Xe collisions. From both type of experiments we find evidence that electron capture accompanied by target excitation is an important

  19. Brain tumor-targeted drug delivery strategies

    Directory of Open Access Journals (Sweden)

    Xiaoli Wei

    2014-06-01

    Full Text Available Despite the application of aggressive surgery, radiotherapy and chemotherapy in clinics, brain tumors are still a difficult health challenge due to their fast development and poor prognosis. Brain tumor-targeted drug delivery systems, which increase drug accumulation in the tumor region and reduce toxicity in normal brain and peripheral tissue, are a promising new approach to brain tumor treatments. Since brain tumors exhibit many distinctive characteristics relative to tumors growing in peripheral tissues, potential targets based on continuously changing vascular characteristics and the microenvironment can be utilized to facilitate effective brain tumor-targeted drug delivery. In this review, we briefly describe the physiological characteristics of brain tumors, including blood–brain/brain tumor barriers, the tumor microenvironment, and tumor stem cells. We also review targeted delivery strategies and introduce a systematic targeted drug delivery strategy to overcome the challenges.

  20. JAERI/KEK target material program overview

    International Nuclear Information System (INIS)

    Kikuchi, Kenji; Kogawa, Hiroyuki; Sasa, Toshinobu

    2001-01-01

    Mercury target was designed for megawatt neutron scattering facility in JAERI/KEK spallation neutron source. The incident proton energy and current are 3 GeV and 333 μA, respectively: the total proton energy is 1 MW in short pulses at a frequency of 25 Hz. Under the guide rule the mercury target was designed: the maximum temperature of target window is 170degC and induced stresses for the type 316 stainless steel are within limits of design guide. In order to demonstrate ADS (Accelerator Driven Systems) transmutation critical and engineering facilities have been designed conceptually. In engineering facility lead-bismuth spallation target station is to be planned. Objective to build the facility is to demonstrate material irradiation. According to neutronics calculation irradiation damage of the target vessel window will be 5 dpa per year. (author)

  1. 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.

  2. Target injection methods for inertial fusion energy

    International Nuclear Information System (INIS)

    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 2 . The total required accuracy of target injection, tracking and beam pointing of ±0.4 mm appears achievable but will require development and experimental verification

  3. 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......–Zhabotinsky reaction catalyzed by ruthenium-tris-bipyridyl are presented. Moving target and spiral foci are found, and the speed and direction of movement of single as well as double spiral foci are investigated. For the experiments analyzed in this paper it is found that the movement of a focus correlates with foci...

  4. Project Plan Remote Target Fabrication Refurbishment Project

    International Nuclear Information System (INIS)

    Bell, Gary L.; Taylor, Robin D.

    2009-01-01

    In early FY2009, the DOE Office of Science - Nuclear Physics Program reinstated a program for continued production of 252 Cf and other transcurium isotopes at the Radiochemical Engineering Development Center (REDC) at Oak Ridge National Laboratory (ORNL). The FY2009 major elements of the workscope are as follows: (1) Recovery and processing of seven transuranium element targets undergoing irradiation at the High Flux Isotope Reactor (HFIR) at ORNL; (2) Development of a plan to manufacture new targets for irradiation beginning in early- to mid-FY10 to supply irradiated targets for processing Campaign 75 (TRU75); and (3) Refurbishment of the target manufacturing equipment to allow new target manufacture in early FY10 The 252 Cf product from processing Campaign 74 (recently processed and currently shipping to customers) is expected to supply the domestic demands for a period of approximately two years. Therefore it is essential that new targets be introduced for irradiation by the second quarter of FY10 (HFIR cycle 427) to maintain supply of 252 Cf; the average irradiation period is ∼10 HFIR cycles, requiring about 1.5 calendar years. The strategy for continued production of 252 Cf depends upon repairing and refurbishing the existing pellet and target fabrication equipment for one additional target production campaign. This equipment dates from the mid-1960s to the late 1980s, and during the last target fabrication campaign in 2005- 2006, a number of component failures and operations difficulties were encountered. It is expected that following the target fabrication and acceptance testing of the targets that will supply material for processing Campaign 75 a comprehensive upgrade and replacement of the remote hot-cell equipment will be required prior to subsequent campaigns. Such a major refit could start in early FY 2011 and would take about 2 years to complete. Scope and cost estimates for the repairs described herein were developed, and authorization for the work

  5. Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos

    Directory of Open Access Journals (Sweden)

    E.Y. Kong

    2016-08-01

    Full Text Available The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio, as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP. The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf revealed through acridine orange (AO staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies.

  6. Optimum target thickness for polarimeters

    International Nuclear Information System (INIS)

    Sitnik, I.M.

    2003-01-01

    Polarimeters with thick targets are a tool to measure the proton polarization. But the question about the optimum target thickness is still the subject of discussion. An attempt to calculate the most common parameters concerning this problem, in a few GeV region, is made

  7. Review of polarized ammonium target

    International Nuclear Information System (INIS)

    Matsuda, Tatsuo

    1987-01-01

    Recently, ammonia (NH 3 ) and deutron ammonia (ND 3 ), instead of conventional alcohol substances, have been used more frequently as a polarized target substance for experiments of polarization at high energy regions. This article reviews major features of the polarized (deutron) ammonia targets. The dynamic nuclear polarization (DNT) method is widely used in high energy polarization experiments. While only a low polarization degree of hydrogen nucleus of 1.7 percent can be obtained by the Brute force method, DNP can produce polarization as high as ∼ 90 percent (2.5 T, ∼ 200 mK). In 1979, ammonia was irradiated with radiations to form NH 2 free radicals, resulting in the achievement of a high polarization degree of greater than 90 percent (hydrogen). Since then, ammonia and deutron ammonia have increasingly been replacing alcohols including butanol. Irradiation of a target substance with radiations destroys the structure of the substance, leading to a decrease in polarization degree. However, ammonia produces unpaired electrons as a result of irradiation, allowing it to be highly resistant to radiation. This report also present some study results, including observations on effects of radiation on the polarization degree of a target, effects of annealing, and polarization of 14 N. A process for producing an ammonia target is also described. (Nogami, K.)

  8. Developing conservation targets in social-ecological systems

    Directory of Open Access Journals (Sweden)

    Phillip S. Levin

    2015-12-01

    Full Text Available The development of targets is foundational in conservation. Although progress has been made in setting targets, the diverse linkages among ecological and social components make target setting for coupled social-ecological systems extremely challenging. Developing integrated social-ecological targets is difficult because it forces policy makers to consider how management actions propagate throughout social-ecological systems, and because ultimately it is society, not scientists, that defines targets. We developed an interdisciplinary approach for identifying management targets and illustrate this approach using an example motivated by Puget Sound, USA. Our approach blends ecological modeling with empirical social science to articulate trade-offs and reveal societal preferences for different social-ecological states. The framework aims to place information in the hands of decision makers and promote discussion in the appropriate forums. Our ultimate objective is to encourage the informed participation of citizens in the development of social-ecological targets that reflect their values while also protecting key ecosystem attributes.

  9. Evaluation of a dietary targets monitor.

    Science.gov (United States)

    Lean, M E J; Anderson, A S; Morrison, C; Currall, J

    2003-05-01

    To evaluate a two-page food frequency list for use as a Dietary Targets Monitor in large scale surveys to quantify consumptions of the key foods groups targeted in health promotion. Intakes of fruit and vegetables, starchy foods and fish estimated from a validated food frequency questionnaire (FFQ) were compared with a short food frequency list (the Dietary Targets Monitor) specifically designed to assess habitual frequency of consumption of foods in relation to dietary targets which form the basis of a National (Scottish) Food and Health Policy. A total of 1085 adults aged 25-64 y from the Glasgow MONICA Study. : The two questionnaires both collected data on frequencies of food consumption for fruit and vegetables, starchy foods and fish. Comparing the two questionnaires, there were consistent biases, best expressed as ratios (FFQ:Dietary Targets Monitor) between the methods for fruit and vegetables (1.33, 95% CI 1.29, 1.38) and 'starchy foods' (1.08, 95% CI 1.05, 1.12), the DTM showing systematic under-reporting by men. For fish consumption, there was essentially no bias between the methods (0.99, 95% CI 0.94, 1.03). Using calibration factors to adjust for biases, the Dietary Targets Monitor indicated that 16% of the subjects were achieving the Scottish Diet food target (400 g/day) for fruit and vegetable consumption. Nearly one-third (32%) of the subjects were eating the recommended intakes of fish (three portions per week). The Dietary Targets Monitor measure of starchy foods consumption was calibrated using FFQ data to be able to make quantitative estimates: 20% of subjects were eating six or more portions of starchy food daily. A similar estimation of total fat intake and saturated fat intake (g/day) allowed the categorization of subjects as low, moderate or high fat consumers, with broad agreement between the methods. The levels of agreement demonstrated by Bland-Altman analysis, were insufficient to permit use of the adjusted DTM to estimate quantitative

  10. Development of the HERA-Β-target-control system and study of target operation at the HERA storage ring

    International Nuclear Information System (INIS)

    Issever, S.

    2001-03-01

    The HERA-B experiment investigates the physics of heavy quarks, which are produced in pN reactions of the 920 GeV protons of HERA with the HERA-B internal fixed target. It consists out of eight wires, which surround the proton beam from four sides and is a high luminosity particle source. As being the closest mechanical device to the proton beam, it has to be operated very carefully and thus needs a secure and automatic control system, which additionally must be efficient and reliable to guarantee an efficient HERA-B data taking. The implementation of the target control system and its performance as well as dedicated studies of target-beam physics are presented. These include the measurement of the aperture limitation, usual target operational position, target efficiency, target independent proton loss in HERA and the scrape velocity of the target. The source of rate fluctuations is investigated in detail; among many dependencies environmental noise has a major impact on the rate fluctuations. Further studies include the analysis of beam position fluctuations and its correlation to the rate fluctuations; the rate changes about a factor of 2, if the beam is changing its position by 10 μm. This rate sensitivity is also verified directly by means of step function measurements. Furthermore the step function measurements can be used to study target-beam dynamics on time scales as short as a second. Experiments to reduce the rate sensitivity - the so called beam tail shaping measurements - are presented as well. During target operation a current, which is proportional to the interaction rate, is measured and used to determine the rate of each single wire. It is shown, that the source of this current is delta electron production. Finally the multiwire performance of the target control system is presented. (orig.)

  11. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Science.gov (United States)

    Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

    2017-01-01

    Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

  12. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Directory of Open Access Journals (Sweden)

    Leslie Regad

    Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

  13. NIF Target Assembly Metrology Methodology and Results

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-01-01

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

  14. 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...

  15. Novel targets for ATM-deficient malignancies

    Science.gov (United States)

    Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

    2014-01-01

    Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

  16. Drug-targeting methodologies with applications: A review

    Science.gov (United States)

    Kleinstreuer, Clement; Feng, Yu; Childress, Emily

    2014-01-01

    Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

  17. A Plutonium Ceramic Target for MASHA

    International Nuclear Information System (INIS)

    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, Y T; Yeremin, A V; Dmitriev, S N

    2004-01-01

    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. Performance of the cluster-jet target for PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Hergemoeller, Ann-Katrin; Bonaventura, Daniel; Grieser, Silke; Hetz, Benjamin; Koehler, Esperanza; Khoukaz, Alfons [Institut fuer Kernphysik, Westfaelische Wilhelms-Universitaet Muenster, 48149 Muenster (Germany)

    2016-07-01

    The success of storage ring experiments strongly depends on the choice of the target. For this purpose, a very appropriate internal target for such an experiment is a cluster-jet target, which will be the first operated target at the PANDA experiment at FAIR. In this kind of target the cluster beam itself is formed due to the expansion of pre-cooled gases within a Laval nozzle and is prepared afterwards via two orifices, the skimmer and the collimator. The target prototype, operating successfully for years at the University of Muenster, provides routinely target thicknesses of more than 2 x 10{sup 15} (atoms)/(cm{sup 2}) in a distance of 2.1 m behind the nozzle. Based on the results of the performance of the cluster target prototype the final cluster-jet target source was designed and set into operation in Muenster as well. Besides the monitoring of the cluster beam itself and the thickness with two different monitoring systems at this target, investigations on the cluster mass via Mie scattering will be performed. In this presentation an overview of the cluster target design, its performance and the Mie scattering method are presented and discussed.

  19. The Antibiotic Resistant Target Seeker (ARTS), an exploration engine for antibiotic cluster prioritization and novel drug target discovery

    DEFF Research Database (Denmark)

    Alanjary, Mohammad; Kronmiller, Brent; Adamek, Martina

    2017-01-01

    and identifying gene clusters for compounds active against specific and novel targets. Here we introduce the 'Antibiotic Resistant Target Seeker' (ARTS) available at https://arts.ziemertlab.com. ARTS allows for specific and efficient genome mining for antibiotics with interesting and novel targets. The aim...

  20. Polarized targets at triangle universities nuclear laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Seely, M.L. [North Carolina State Univ., Raleigh, NC (United States); Gould, C.R. [North Carolina State Univ., Raleigh, NC (United States); Haase, D.G. [North Carolina State Univ., Raleigh, NC (United States); Huffman, P.R. [Triangle Universities Nuclear Laboratory, Durham, NC 27708 (United States); Keith, C.D. [North Carolina State Univ., Raleigh, NC (United States); Roberson, N.R. [Triangle Universities Nuclear Laboratory, Durham, NC 27708 (United States); Tornow, W. [Triangle Universities Nuclear Laboratory, Durham, NC 27708 (United States); Wilburn, W.S. [Triangle Universities Nuclear Laboratory, Durham, NC 27708 (United States)

    1995-03-01

    A summary of the polarized and aligned nuclear targets which have been constructed and used at the Triangle Universities Nuclear Laboratory is given. Statically polarized targets, typically operating at a temperature of 12 mK and a magnetic field of 7 T, have provided significant nuclear polarization in {sup 1}H, {sup 3}He, {sup 27}Al, {sup 93}Nb and {sup 165}Ho. A rotating, aligned {sup 165}Ho target is also in use. A {sup 3}He melting curve thermometer has been developed for use in statically polarized targets. A dynamically polarized proton target is under construction. ((orig.))

  1. Thermal features of spallation window targets

    International Nuclear Information System (INIS)

    Martinez-Val, J. M.; Sordo, F.; Leon, P. T.

    2007-01-01

    Subcritical nuclear reactors have been proposed for a number of applications, from energy production to fertile-to-fissile conversion, and to transmutation of long-lived radio nuclei into stable or much shorter-lived nuclei. The main advantage of subcritical reactors is their large reactivity margin for not to attain prompt-supercritical power surges. On the contrary, subcritical reactors present some economic drawbacks and technical complexities that deserve suitable attention in the Research and Development phase. Namely, they need a very intense neutron source in order to keep the neutron flux and the reactor power at the required level. The most intense neutron source seems to be based on the proton-induced (or deuteron-induced) spallation reaction in heavy nuclei targets, which present very demanding thermal features that must be properly limited. Those limits pose upper bounds to the neutron yield of the target. In turn, the limits depend on the features of the impinging particle beam and the material composition and geometry of the target. Although the potential design window for spallation targets is rather wide, the analysis presented in this paper identifies specific topics that must properly be covered in the detailed project of a spallation source, in order to avoid unacceptable temperatures and mechanical stresses in the most critical parts of the source. In this paper, some calculations are reported on solid targets (water cooled or helium cooled) and molten metals targets. It is seen that thermal-hydraulic and mechanical calculations of spallation targets are fundamental elements in the coherent design of this type of very intense neutron sources. This coherence implies the need of a suitable trade-off among the relevant beam parameters (proton energy, total intensity and cross-section shape) and the features of the target (structural materials, coolant characteristics and target geometry). The goal of maximizing the neutron yield has to be checked

  2. Criteria for selection of target materials and design of high-efficiency-release targets for radioactive ion beam generation

    CERN Document Server

    Alton, G D; Liu, Y

    1999-01-01

    In this report, we define criteria for choosing target materials and for designing, mechanically stable, short-diffusion-length, highly permeable targets for generation of high-intensity radioactive ion beams (RIBs) for use at nuclear physics and astrophysics research facilities based on the ISOL principle. In addition, lists of refractory target materials are provided and examples are given of a number of successful targets, based on these criteria, that have been fabricated and tested for use at the Holifield Radioactive Ion Beam Facility (HRIBF).

  3. A mathematical analysis of multiple-target SELEX.

    Science.gov (United States)

    Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

    2010-10-01

    SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following

  4. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2014-05-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  5. Virtual target screening to rapidly identify potential protein targets of natural products in drug discovery

    Directory of Open Access Journals (Sweden)

    Yuri Pevzner

    2015-08-01

    Full Text Available Inherent biological viability and diversity of natural products make them a potentially rich source for new therapeutics. However, identification of bioactive compounds with desired therapeutic effects and identification of their protein targets is a laborious, expensive process. Extracts from organism samples may show desired activity in phenotypic assays but specific bioactive compounds must be isolated through further separation methods and protein targets must be identified by more specific phenotypic and in vitro experimental assays. Still, questions remain as to whether all relevant protein targets for a compound have been identified. The desire is to understand breadth of purposing for the compound to maximize its use and intellectual property, and to avoid further development of compounds with insurmountable adverse effects. Previously we developed a Virtual Target Screening system that computationally screens one or more compounds against a collection of virtual protein structures. By scoring each compound-protein interaction, we can compare against averaged scores of synthetic drug-like compounds to determine if a particular protein would be a potential target of a compound of interest. Here we provide examples of natural products screened through our system as we assess advantages and shortcomings of our current system in regards to natural product drug discovery.

  6. Targeted assembly of short sequence reads.

    Directory of Open Access Journals (Sweden)

    René L Warren

    Full Text Available As next-generation sequence (NGS production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled stringently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming genomic mutations, polymorphisms, fusions and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly.

  7. Scheduling with target start times

    NARCIS (Netherlands)

    Hoogeveen, J.A.; Velde, van de S.L.; Klein Haneveld, W.K.; Vrieze, O.J.; Kallenberg, L.C.M.

    1997-01-01

    We address the single-machine problem of scheduling n independent jobs subject to target start times. Target start times are essentially release times that may be violated at a certain cost. The goal is to minimize an objective function that is composed of total completion time and maximum

  8. High performance inertial fusion targets

    International Nuclear Information System (INIS)

    Nuckolls, J.H.; Bangerter, R.O.; Lindl, J.D.; Mead, W.C.; Pan, Y.L.

    1978-01-01

    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

  9. Materials considerations in accelerator targets

    International Nuclear Information System (INIS)

    Peacock, H.B. Jr.; Iyer, N.C.; Louthan, M.R. Jr.

    1994-01-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from the coextruded product was modeled from experimental and operational data. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes the manufacturing technologies evaluated and presents the model for tritium retention in aluminum clad, aluminum-lithium alloy tritium production targets

  10. Similar clinical benefits from below-target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial.

    Science.gov (United States)

    Lam, Phillip H; Dooley, Daniel J; Fonarow, Gregg C; Butler, Javed; Bhatt, Deepak L; Filippatos, Gerasimos S; Deedwania, Prakash; Forman, Daniel E; White, Michel; Fletcher, Ross D; Arundel, Cherinne; Blackman, Marc R; Adamopoulos, Chris; Kanonidis, Ioannis E; Aban, Inmaculada B; Patel, Kanan; Aronow, Wilbert S; Allman, Richard M; Anker, Stefan D; Pitt, Bertram; Ahmed, Ali

    2018-02-01

    To examine associations of below-target and target dose of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial. Two thousand five hundred and sixty-nine patients with HFrEF (ejection fraction ≤35%) were randomized to below-target (5-10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post-randomization, blind up-titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up-titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60-0.81; P target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below-target dose enalapril (vs. below-target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 0.68; 95% CI 0.57-0.81; P target (vs. below-target) dose had no association with the combined endpoint of heart failure hospitalization or all-cause mortality (adjusted HR 1.04; 95% CI 0.87-1.23; P = 0.695). In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below-target and target doses. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  11. Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

    Directory of Open Access Journals (Sweden)

    Reini F Luco

    2008-05-01

    Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

  12. Purity of targets prepared on Cu substrates

    Science.gov (United States)

    Méens, A.; Rossini, I.; Sens, J. C.

    1993-09-01

    The purity of several elemental self-supporting targets usually prepared by evaporation onto soluble Cu substrates has been studied. The targets were analysed by Rutherford backscattering and instrumental neutron activation analysis. Because of the high percentage of Cu observed in some Si targets, further measurements, including transmission electron microscopy, have been performed on Si targets deposited by e-gun bombardment onto Cu and ion-beam sputtering onto betaine.

  13. CFD aspects of ADSS target design

    International Nuclear Information System (INIS)

    Shashi Kumar, G.N.; Mahendra, A.K.; Sanyal, A.; Gouthaman, G.

    2004-03-01

    The preliminary studies on CFD aspects of Accelerator Driven Sub-critical System (ADSS) target design has been presented in this report. The studies involve the thermal hydraulic analysis of the Liquid Metal Spallation Target (LMST) using Lead Bismuth Eutectic (LBE) as the target material. Apart from acting as Spallation medium LBE is used to remove the heat deposited by High Energy Proton Beam. Window of the target ( one side vacuum and other side LBE) has been reported in literature to be the most critical zone where high temperatures are reached. Numerical Simulations are carried out with Artificial Neural Network coupled Computational Fluid Dynamics (CFD) code, Various studies were carried out after the verification and validation of the initial results. Window being, the main parameter to be optimised, various designs of window were tried, along with change in the window material. The best possible combination has been proposed. The thermal hydraulic studies were carried out to arrive at the acceptable operating conditions for the target. (author)

  14. 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.

  15. Progress on LMJ targets for ignition

    International Nuclear Information System (INIS)

    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

    2009-01-01

    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.

  16. Novel targeted agents for gastric cancer

    Directory of Open Access Journals (Sweden)

    Liu Lian

    2012-06-01

    Full Text Available Abstract Contemporary advancements have had little impact on the treatment of gastric cancer (GC, the world’s second highest cause of cancer death. Agents targeting human epidermal growth factor receptor mediated pathways have been a common topic of contemporary cancer research, including monoclonal antibodies (mAbs and receptor tyrosine kinase inhibitors (TKIs. Trastuzumab is the first target agent evidencing improvements in overall survival in HER2-positive (human epidermal growth factor receptor 2 gastric cancer patients. Agents targeting vascular epithelial growth factor (VEGF, mammalian target of rapamycin (mTOR, and other biological pathways are also undergoing clinical trials, with some marginally positive results. Effective targeted therapy requires patient selection based on predictive molecular biomarkers. Most phase III clinical trials are carried out without patient selection; therefore, it is hard to achieve personalized treatment and to monitor patient outcome individually. The trend for future clinical trials requires patient selection methods based on current understanding of GC biology with the application of biomarkers.

  17. Targeted Therapy for Melanoma

    International Nuclear Information System (INIS)

    Quinn, Thomas; Moore, Herbert

    2016-01-01

    The research project, entitled ''Targeted Therapy for Melanoma,'' was focused on investigating the use of kidney protection measures to lower the non-specific kidney uptake of the radiolabeled Pb-DOTA-ReCCMSH peptide. Previous published work demonstrated that the kidney exhibited the highest non-target tissue uptake of the "2"1"2"P"b"/"2"0"3Pb radiolabeled melanoma targeting peptide DOTA-ReCCMSH. The radiolabeled alpha-melanocyte stimulating hormone (α-MSH) peptide analog DOTA-Re(Arg"1"1)CCMSH, which binds the melanocortin-1 receptor over-expressed on melanoma tumor cells, has shown promise as a PRRT agent in pre-clinical studies. High tumor uptake of "2"1"2Pb labeled DOTA-Re(Arg"1"1)CCMSH resulted in tumor reduction or eradication in melanoma therapy studies. Of particular note was the 20-50% cure rate observed when melanoma mice were treated with alpha particle emitter "2"1"2Pb. However, as with most PRRT agents, high radiation doses to the kidneys where observed. To optimize tumor treatment efficacy and reduce nephrotoxicity, the tumor to kidney uptake ratio must be improved. Strategies to reduce kidney retention of the radiolabeled peptide, while not effecting tumor uptake and retention, can be broken into several categories including modification of the targeting peptide sequence and reducing proximal tubule reabsorption.

  18. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  19. 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.

  20. Targeted Therapy for Melanoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-12-05

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

  1. Maximizing in vivo target clearance by design of pH-dependent target binding antibodies with altered affinity to FcRn.

    Science.gov (United States)

    Yang, Danlin; Giragossian, Craig; Castellano, Steven; Lasaro, Marcio; Xiao, Haiguang; Saraf, Himanshu; Hess Kenny, Cynthia; Rybina, Irina; Huang, Zhong-Fu; Ahlberg, Jennifer; Bigwarfe, Tammy; Myzithras, Maria; Waltz, Erica; Roberts, Simon; Kroe-Barrett, Rachel; Singh, Sanjaya

    2017-10-01

    Antibodies with pH-dependent binding to both target antigens and neonatal Fc receptor (FcRn) provide an alternative tool to conventional neutralizing antibodies, particularly for therapies where reduction in antigen level is challenging due to high target burden. However, the requirements for optimal binding kinetic framework and extent of pH dependence for these antibodies to maximize target clearance from circulation are not well understood. We have identified a series of naturally-occurring high affinity antibodies with pH-dependent target binding properties. By in vivo studies in cynomolgus monkeys, we show that pH-dependent binding to the target alone is not sufficient for effective target removal from circulation, but requires Fc mutations that increase antibody binding to FcRn. Affinity-enhanced pH-dependent FcRn binding that is double-digit nM at pH 7.4 and single-digit nM at pH 6 achieved maximal target reduction when combined with similar target binding affinities in reverse pH directions. Sustained target clearance below the baseline level was achieved 3 weeks after single-dose administration at 1.5 mg/kg. Using the experimentally derived mechanistic model, we demonstrate the essential kinetic interplay between target turnover and antibody pH-dependent binding during the FcRn recycling, and identify the key components for achieving maximal target clearance. These results bridge the demand for improved patient dosing convenience with the "know-how" of therapeutic modality by design.

  2. PENETAPAN TARGET TERHADAP STICKINESS COST

    Directory of Open Access Journals (Sweden)

    Windyastuti Windyastuti

    2017-03-01

    Full Text Available This study aimed to analyze the influence of manager targeting to the stickiness cost. The research data was amanufacturing company’s financial statements during 1999-2011 published at BEI. The research data includedcost of sales, administration and general, net sales and Price Earnings Ratio (PER. This study used adynamic panel data regression analysis. The results showed that cost of sales, administration and general weresticky. Furthermore, manager targeting caused the stickiness degree of sales, administration and general costlower. Manager targeting changed the manager’s behavior. When the net sales declined, manager reduced theresource use drastically so the cost of sales, administration and general also decreased drastically.

  3. Moller Polarimetry with Atomic Hydrogen Targets

    International Nuclear Information System (INIS)

    Chudakov, Eugene; Luppov, V.

    2012-01-01

    A proposal to use polarized atomic hydrogen gas as the target for electron beam polarimetry based on the Moller scattering is described. Such a gas, stored in an ultra-cold magnetic trap, would provide a target of practically 100% polarized electrons. It is conceivable to reach a ∼0.3% systematic accuracy of the beam polarimetry with such a target. Feasibility studies for the CEBAF electron beam have been performed

  4. Static nuclear polarisation and polarised targets

    International Nuclear Information System (INIS)

    Heeringa, W.

    1984-12-01

    Recent progress and status of statically polarised nuclear targets are reviewed. Special attention is given to polarised 1 H and 3 He. An important quantity in the determination of the target polarisation is the thermal gradient over the target sample. The dependence of this gradient on heat input, sample geometry, and thermal conductivity of the sample is discussed. Possibilities of performing experiments with proton beams are indicated. (orig.) [de

  5. Shock waves in P-bar target

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Zhijing; Anderson, K.

    1991-11-01

    The deposition of large amount of beam energy in short time will cause high temperature and pressure in the center of P-bar Target, and this disturbance will propagate outwards as a shock wave. Shock wave induced material changes which are of our concern include void growth and accompanying density decrease which will decrease antiproton yield, and crack formation and fracture as was observed in tungsten target which will destroy the integrity of the target. Our objective is to analyze the shock wave behavior in the target, optimize its design so that the destructive effects of shock wave can be minimized, the integrity of the target can be maintained, and a reasonably high yield of antiproton production can be achieved. In this report we put together some results of our analysis of a cylindrical copper target. We hope that it will provide a general overview of the shock wave phenomena in the target, establish a basis for further research, and facilitate the target design. First, energy deposition data are analyzed, and it is justified that as an approximation, the problem can be treated as axi-symmetric. The average data therefore are used as energy profile, however, the maximum energy deposition are still used as the peak value. Next some basic estimations are made as to what temperature and pressure can reach at present level of energy deposition. Then some characteristics of wave propagation in a thermal shock loaded solid are illustrated with a one-dimensional model. Since there is no analytical solution available for cylindrical geometry, our understanding of the problem relies on numerical model, which are performed via finite element package ANSYS. results of numerical analysis are summarized, sources of potential danger are identified, and design ideas to minimize the damage are proposed.

  6. Shock waves in P-bar target

    International Nuclear Information System (INIS)

    Tang, Zhijing; Anderson, K.

    1991-11-01

    The deposition of large amount of beam energy in short time will cause high temperature and pressure in the center of P-bar Target, and this disturbance will propagate outwards as a shock wave. Shock wave induced material changes which are of our concern include void growth and accompanying density decrease which will decrease antiproton yield, and crack formation and fracture as was observed in tungsten target which will destroy the integrity of the target. Our objective is to analyze the shock wave behavior in the target, optimize its design so that the destructive effects of shock wave can be minimized, the integrity of the target can be maintained, and a reasonably high yield of antiproton production can be achieved. In this report we put together some results of our analysis of a cylindrical copper target. We hope that it will provide a general overview of the shock wave phenomena in the target, establish a basis for further research, and facilitate the target design. First, energy deposition data are analyzed, and it is justified that as an approximation, the problem can be treated as axi-symmetric. The average data therefore are used as energy profile, however, the maximum energy deposition are still used as the peak value. Next some basic estimations are made as to what temperature and pressure can reach at present level of energy deposition. Then some characteristics of wave propagation in a thermal shock loaded solid are illustrated with a one-dimensional model. Since there is no analytical solution available for cylindrical geometry, our understanding of the problem relies on numerical model, which are performed via finite element package ANSYS. results of numerical analysis are summarized, sources of potential danger are identified, and design ideas to minimize the damage are proposed

  7. Collaborative filtering on a family of biological targets.

    Science.gov (United States)

    Erhan, Dumitru; L'heureux, Pierre-Jean; Yue, Shi Yi; Bengio, Yoshua

    2006-01-01

    Building a QSAR model of a new biological target for which few screening data are available is a statistical challenge. However, the new target may be part of a bigger family, for which we have more screening data. Collaborative filtering or, more generally, multi-task learning, is a machine learning approach that improves the generalization performance of an algorithm by using information from related tasks as an inductive bias. We use collaborative filtering techniques for building predictive models that link multiple targets to multiple examples. The more commonalities between the targets, the better the multi-target model that can be built. We show an example of a multi-target neural network that can use family information to produce a predictive model of an undersampled target. We evaluate JRank, a kernel-based method designed for collaborative filtering. We show their performance on compound prioritization for an HTS campaign and the underlying shared representation between targets. JRank outperformed the neural network both in the single- and multi-target models.

  8. Development of IFE target systems on the NIF

    International Nuclear Information System (INIS)

    Schultz, K.R.; Fagaly, R.L.; Bernat, T.; Meier, W.; Petzoldt, R.; Foreman, L.

    1995-01-01

    The Target Systems session of the Workshop on NIF Experiments for IFE developed a list of critical issues for inertial fusion energy (IFE) target systems, and considered the potential of the National Ignition Facility (NIF) to help in the resolution of these issues and in the development of IFE target systems. This paper describes the IFE Target System issues, categorized into target fabrication issues and target transport issues, describes potential NIF IFE target systems experiments, considers the impact of these experiments on the NIF and discusses the development required before these experiments could be done. Most target systems issues must be resolved by development in the laboratory, not in the NIF, and some must be resolved before the NIF can be successful. However, experiments done in the NIF could play a valuable role in developing target systems for IFE. These experiments should have modest impact on the basic design of the NIF, but could require several hundred dedicated, high yield shots

  9. Fibers as solid, internal targets for storage rings

    International Nuclear Information System (INIS)

    Przewoski, B.v.

    1994-01-01

    It has been demonstrated that fibers or micro ribbons provide the possibility to expose solid targets to a stored ion beam. Compared to gas targets or micro particle targets fiber targets require a relatively small technical effort, since differential pumping systems are not necessary to maintain the ring vacuum. Since stationary fibers are often too thick to allow for long enough lifetimes of the stored beam to be useful for experiments, a methods has been developed to move the fiber periodically through the beam. That way, the time averaged target thickness is small compared to the thickness the same fiber would have, if it were stationary in the path of the beam. In addition, the time averaged thickness can be adjusted if the amplitude of the fiber motion is increased or decreased to obtain a thinner or thicker target respectively. Measurements that compare the lifetime of the stored beam in the presence of a fiber target with the lifetime of a stored beam in the presence of a gas target show that a fiber target of a certain time averaged target thickness is equivalent to a homogeneous target of the same thickness. The data are in good agreement with Monte Carlo calculations

  10. Detection of Moving Targets Using Soliton Resonance Effect

    Science.gov (United States)

    Kulikov, Igor K.; Zak, Michail

    2013-01-01

    The objective of this research was to develop a fundamentally new method for detecting hidden moving targets within noisy and cluttered data-streams using a novel "soliton resonance" effect in nonlinear dynamical systems. The technique uses an inhomogeneous Korteweg de Vries (KdV) equation containing moving-target information. Solution of the KdV equation will describe a soliton propagating with the same kinematic characteristics as the target. The approach uses the time-dependent data stream obtained with a sensor in form of the "forcing function," which is incorporated in an inhomogeneous KdV equation. When a hidden moving target (which in many ways resembles a soliton) encounters the natural "probe" soliton solution of the KdV equation, a strong resonance phenomenon results that makes the location and motion of the target apparent. Soliton resonance method will amplify the moving target signal, suppressing the noise. The method will be a very effective tool for locating and identifying diverse, highly dynamic targets with ill-defined characteristics in a noisy environment. The soliton resonance method for the detection of moving targets was developed in one and two dimensions. Computer simulations proved that the method could be used for detection of singe point-like targets moving with constant velocities and accelerations in 1D and along straight lines or curved trajectories in 2D. The method also allows estimation of the kinematic characteristics of moving targets, and reconstruction of target trajectories in 2D. The method could be very effective for target detection in the presence of clutter and for the case of target obscurations.

  11. Technological aspects of cryogenic laser-fusion targets

    International Nuclear Information System (INIS)

    Musinski, D.L.; Henderson, T.M.; Simms, R.J.; Pattinson, T.R.; Jacobs, R.B.

    1980-01-01

    Most current laser-fusion targets consist of hollow spherical glass shells which have been filled with a mixture of gaseous deuterium-tritium fuel. Theoretical considerations suggest that optimum yields can be obtained from these targets if the fuel is condensed as a uniform liquid or solid layer on the inner surface of the glass shell at the time it is irradiated. In principle, this can be accomplished in a straightforward way by cooling the target below the condensation or freezing point of the fuel. In practice, cryogenic targets can appear in routine laser experiments only when the necessary cryogenic technology is reliably integrated into experimental target chambers. Significant progress has been made recently in this field. The authors will discuss the scientific basis and the various technological features of a system which has allowed the successful irradiation of uniform solid-fuel-layer targets

  12. 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.

  13. Optimal exploration target zones

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2008-09-01

    Full Text Available -of-evidence (WofE) method logistic regression canonical favorability analysis neural networks evidential belief functions Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study... for the following equation: n∑ i=r ( n i ) pi(1− p)n−i = 0.95 . (1) Optimal Exploration Target Zones Debba, Carranza, Stein, van der Meer Introduction to Remote Sensing Background and Objective of the study Methodology Results METHODS (cont. . . ): FITNESS FUNCTION...

  14. China's energy efficiency target 2010

    International Nuclear Information System (INIS)

    Yang Ming

    2008-01-01

    The Chinese government has set an ambitious target: reducing China's energy intensity by 20%, or 4.36% each year between 2006 and 2010 on the 2005 level. Real data showed that China missed its target in 2006, having reduced its energy intensity only by 1.3%. The objective of this study is to evaluate the feasibility and potential of the Chinese to achieve the target. This paper presents issues of macro-economy, population migration, energy savings, and energy efficiency policy measures to achieve the target. A top-down approach was used to analyse the relationship between the Chinese economic development and energy demand cycles and to identify the potentials of energy savings in sub-sectors of the Chinese economy. A number of factors that contribute to China's energy intensity are identified in a number of energy-intensive sectors. This paper concludes that China needs to develop its economy at its potential GDP growth rate; strengthen energy efficiency auditing, monitoring and verification; change its national economy from a heavy-industry-dominated mode to a light industry or a commerce-dominated mode; phase out inefficient equipment in industrial sectors; develop mass and fast railway transportation; and promote energy-efficient technologies at the end use. This paper transfers key messages to policy makers for designing their policy to achieve China's energy efficiency target

  15. Targeted integration of genes in Xenopus tropicalis

    DEFF Research Database (Denmark)

    Shi, Zhaoying; Tian, Dandan; Xin, Huhu

    2017-01-01

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

  16. Drug target identification in protozoan parasites.

    Science.gov (United States)

    Müller, Joachim; Hemphill, Andrew

    2016-08-01

    Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

  17. Plasma flow interaction with a solid target

    International Nuclear Information System (INIS)

    Karlykuanov, N.G.; Martynenko, Yu.V.; Matveenko, Yu.I.

    1996-01-01

    The physical-mathematical model of plasma interactions with a solid target wherein equations with a solid target of ion levels population and radiation transport in lines and continuum as well as kinetics of the target destruction and evaporation is presented

  18. One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

    Science.gov (United States)

    Shim, Hyunbo

    2011-10-31

    To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

  19. 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.

  20. Cellular Targets of Dietary Polyphenol Resveratrol

    National Research Council Canada - National Science Library

    Wu, Joseph M

    2006-01-01

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

  1. Safety targets for nuclear power plants

    International Nuclear Information System (INIS)

    Herttrich, P.M.

    1985-01-01

    By taking as an example the safety targets of the American nuclear energy authority US-NRC, this paper explains what is meant by global, quantitative safety targets for nuclear power plants and what expectations are associated with the selecton of such safety targets. It is shown how probabilistic methods can be an appropriate completion of proven deterministic methods and what are the sectors where their application may become important in future. (orig./HP) [de

  2. Power plant production of inertial confinement fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.; Johnson, W.L.

    1979-01-01

    Many of the current techniques for fabricating experimental targets appear to be directly extendable to the high-rate, low-cost production of reactor targets. This report describes several new techniques that, in conjunction with the expansion of existing techniques, can constitute a target factory. We have evaluated this concept on the basis of a generalized reactor target design and the projected specifications of reactor-grade targets

  3. Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages.

    Science.gov (United States)

    Qian, Yuan; Qiao, Sha; Dai, Yanfeng; Xu, Guoqiang; Dai, Bolei; Lu, Lisen; Yu, Xiang; Luo, Qingming; Zhang, Zhihong

    2017-09-26

    Tumor-associated macrophages (TAMs) are a promising therapeutic target for cancer immunotherapy. Targeted delivery of therapeutic drugs to the tumor-promoting M2-like TAMs is challenging. Here, we developed M2-like TAM dual-targeting nanoparticles (M2NPs), whose structure and function were controlled by α-peptide (a scavenger receptor B type 1 (SR-B1) targeting peptide) linked with M2pep (an M2 macrophage binding peptide). By loading anti-colony stimulating factor-1 receptor (anti-CSF-1R) small interfering RNA (siRNA) on the M2NPs, we developed a molecular-targeted immunotherapeutic approach to specifically block the survival signal of M2-like TAMs and deplete them from melanoma tumors. We confirmed the validity of SR-B1 for M2-like TAM targeting and demonstrated the synergistic effect of the two targeting units (α-peptide and M2pep) in the fusion peptide (α-M2pep). After being administered to tumor-bearing mice, M2NPs had higher affinity to M2-like TAMs than to tissue-resident macrophages in liver, spleen, and lung. Compared with control treatment groups, M2NP-based siRNA delivery resulted in a dramatic elimination of M2-like TAMs (52%), decreased tumor size (87%), and prolonged survival. Additionally, this molecular-targeted strategy inhibited immunosuppressive IL-10 and TGF-β production and increased immunostimulatory cytokines (IL-12 and IFN-γ) expression and CD8 + T cell infiltration (2.9-fold) in the tumor microenvironment. Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8 + T cells and stimulated their IFN-γ secretion (6.2-fold), indicating the restoration of T cell immune function. Thus, the dual-targeting property of M2NPs combined with RNA interference provides a potential strategy of molecular-targeted cancer immunotherapy for clinical application.

  4. MicroRNA target finding by comparative genomics.

    Science.gov (United States)

    Friedman, Robin C; Burge, Christopher B

    2014-01-01

    MicroRNAs (miRNAs) have been implicated in virtually every metazoan biological process, exerting a widespread impact on gene expression. MicroRNA repression is conferred by relatively short "seed match" sequences, although the degree of repression varies widely for individual target sites. The factors controlling whether, and to what extent, a target site is repressed are not fully understood. As an alternative to target prediction based on sequence alone, comparative genomics has emerged as an invaluable tool for identifying miRNA targets that are conserved by natural selection, and hence likely effective and important. Here we present a general method for quantifying conservation of miRNA seed match sites, separating it from background conservation, controlling for various biases, and predicting miRNA targets. This method is useful not only for generating predictions but also as a tool for empirically evaluating the importance of various target prediction criteria.

  5. A He-gas Cooled, Stationary Granular Target

    CERN Document Server

    Pugnat, P

    2003-01-01

    In the CERN approach to the design of a neutrino factory, the repetition frequency of the proton beam is high enough to consider stationary solid targets as a viable solution for multi-MW beams. The target consists of high density tantalum spheres of 2 mm diameter which can efficiently be cooled by passing a high mass flow He-gas stream through the voids between the Ta-granules. Very small thermal shocks and stresses will arise in this fine grained structure due to the relatively long burst of 3.3 ms from the SPL-proton linac. In a quadruple target system where each target receives only one quarter of the total beam power of 4 MW, conservative temperature levels and adequate lifetimes of the target are estimated in its very high radiation environment. A conceptual design of the integration of the target into the magnetic horn-pion-collector is presented.

  6. Enhanced target normal sheath acceleration of protons from intense laser interaction with a cone-tube target

    Directory of Open Access Journals (Sweden)

    K. D. Xiao

    2016-01-01

    Full Text Available Laser driven proton acceleration is proposed to be greatly enhanced by using a cone-tube target, which can be easily manufactured by current 3D-print technology. It is observed that energetic electron bunches are generated along the tube and accelerated to a much higher temperature by the combination of ponderomotive force and longitudinal electric field which is induced by the optical confinement of the laser field. As a result, a localized and enhanced sheath field is produced at the rear of the target and the maximum proton energy is about three-fold increased based on the two-dimentional particle-in-cell simulation results. It is demonstrated that by employing this advanced target scheme, the scaling of the proton energy versus the laser intensity is much beyond the normal target normal sheath acceleration (TNSA case.

  7. Ion backscattering from layered targets

    International Nuclear Information System (INIS)

    Oen, O.S.; Robinson, M.T.

    1985-01-01

    The present work investigated the reflection of hydrogen atoms, whose incident energy ranged from 0.01 to 1 keV, from layered targets. The calculations used the binary collisions computer program MARLOWE modified to treat layered target structures. Briefly, the projectile ion strikes the surface normally and is followed collision-by-collision until it leaves the surface again or until its energy falls below a present value (1 eV). Each collision consists of an elastic and an inelastic part. The elastic part is treated by classical scattering mechanics using the Moliere approximation to the Thomas-Fermi interatomic potential with the screening lengths proposed by Firsov. The inelastic part is described by the (nonlocal) electronic stopping theory of Lindhard et al. The calculations were made using MARLOWE to simulate amorphous solids, and a typical run consisted of following the motions of 1000-2000 incident particles. The targets studied were chosen to have large differences between the atomic numbers of the overlayer and the substrate in order to emphasize possible reflection differences from that of monoatomic targets

  8. Evolutionary Transitions of MicroRNA-Target Pairs

    KAUST Repository

    Nozawa, Masafumi; Fujimi, Mai; Iwamoto, Chie; Onizuka, Kanako; Fukuda, Nana; Ikeo, Kazuho; Gojobori, Takashi

    2016-01-01

    How newly generated microRNA (miRNA) genes are integrated into gene regulatory networks during evolution is fundamental in understanding the molecular and evolutionary bases of robustness and plasticity in gene regulation. A recent model proposed that after the birth of a miRNA, the miRNA is generally integrated into the network by decreasing the number of target genes during evolution. However, this decreasing model remains to be carefully examined by considering in vivo conditions. In this study, we therefore compared the number of target genes among miRNAs with different ages, combining experiments with bioinformatics predictions. First, we focused on three Drosophila miRNAs with different ages. As a result, we found that an older miRNA has a greater number of target genes than a younger miRNA, suggesting the increasing number of targets for each miRNA during evolution (increasing model). To further confirm our results, we also predicted all target genes for all miRNAs in D. melanogaster, considering co-expression of miRNAs and mRNAs in vivo. The results obtained also do not support the decreasing model but are reasonably consistent with the increasing model of miRNA-target pairs. Furthermore, our large-scale analyses of currently available experimental data of miRNA-target pairs also showed a weak but the same trend in humans. These results indicate that the current decreasing model of miRNA-target pairs should be reconsidered and the increasing model may be more appropriate to explain the evolutionary transitions of miRNA-target pairs in many organisms.

  9. 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.

  10. Evolutionary Transitions of MicroRNA-Target Pairs

    KAUST Repository

    Nozawa, Masafumi

    2016-04-27

    How newly generated microRNA (miRNA) genes are integrated into gene regulatory networks during evolution is fundamental in understanding the molecular and evolutionary bases of robustness and plasticity in gene regulation. A recent model proposed that after the birth of a miRNA, the miRNA is generally integrated into the network by decreasing the number of target genes during evolution. However, this decreasing model remains to be carefully examined by considering in vivo conditions. In this study, we therefore compared the number of target genes among miRNAs with different ages, combining experiments with bioinformatics predictions. First, we focused on three Drosophila miRNAs with different ages. As a result, we found that an older miRNA has a greater number of target genes than a younger miRNA, suggesting the increasing number of targets for each miRNA during evolution (increasing model). To further confirm our results, we also predicted all target genes for all miRNAs in D. melanogaster, considering co-expression of miRNAs and mRNAs in vivo. The results obtained also do not support the decreasing model but are reasonably consistent with the increasing model of miRNA-target pairs. Furthermore, our large-scale analyses of currently available experimental data of miRNA-target pairs also showed a weak but the same trend in humans. These results indicate that the current decreasing model of miRNA-target pairs should be reconsidered and the increasing model may be more appropriate to explain the evolutionary transitions of miRNA-target pairs in many organisms.

  11. Striatal activity is modulated by target probability.

    Science.gov (United States)

    Hon, Nicholas

    2017-06-14

    Target probability has well-known neural effects. In the brain, target probability is known to affect frontal activity, with lower probability targets producing more prefrontal activation than those that occur with higher probability. Although the effect of target probability on cortical activity is well specified, its effect on subcortical structures such as the striatum is less well understood. Here, I examined this issue and found that the striatum was highly responsive to target probability. This is consistent with its hypothesized role in the gating of salient information into higher-order task representations. The current data are interpreted in light of that fact that different components of the striatum are sensitive to different types of task-relevant information.

  12. Conductive cooling of high-power RIB targets

    International Nuclear Information System (INIS)

    Talbert, W.L.; Drake, D.M.; Wilson, M.T.; Lenz, J.W.; Hsu, H.-H.

    2002-01-01

    A short review is presented of target cooling approaches suggested for targets irradiated by intense high-energy proton beams to produce radioactive species for use in a broad range of physics studies. This work reports on conductive cooling approaches for operation at temperatures lower than effective for radiative cooling. The possibilities for conductive cooling are discussed, and a prototype test target is described. This target was constructed for an experiment, designed to validate the numerical analysis approaches, at the TRIUMF/ISAC facility. Fabrication issues and the results of the experiment are presented, followed by a discussion of the implications of the experiment outcome for future development of targets to produce intense beams of radioactive ions

  13. Manifold structure preservative for hyperspectral target detection

    Science.gov (United States)

    Imani, Maryam

    2018-05-01

    A nonparametric method termed as manifold structure preservative (MSP) is proposed in this paper for hyperspectral target detection. MSP transforms the feature space of data to maximize the separation between target and background signals. Moreover, it minimizes the reconstruction error of targets and preserves the topological structure of data in the projected feature space. MSP does not need to consider any distribution for target and background data. So, it can achieve accurate results in real scenarios due to avoiding unreliable assumptions. The proposed MSP detector is compared to several popular detectors and the experiments on a synthetic data and two real hyperspectral images indicate the superior ability of it in target detection.

  14. Automatic measurement of target crossing speed

    Science.gov (United States)

    Wardell, Mark; Lougheed, James H.

    1992-11-01

    The motion of ground vehicle targets after a ballistic round is launched can be a major source of inaccuracy for small (handheld) anti-armour weapon systems. A method of automatically measuring the crossing component to compensate the fire control solution has been devised and tested against various targets in a range of environments. A photodetector array aligned with the sight's horizontal reticle obtains scene features, which are digitized and processed to separate target from sight motion. Relative motion of the target against the background is briefly monitored to deduce angular crossing rate and a compensating lead angle is introduced into the aim point. Research to gather quantitative data and optimize algorithm performance is described, and some results from field testing are presented.

  15. FABRICATION AND CHARACTERIZATION OF FAST IGNITION TARGETS

    International Nuclear Information System (INIS)

    HILL, D.W; CASTILLO, E; CHEN, K.C; GRANT, S.E; GREENWOOD, A.L; KAAE, J.L; NIKROO, A; PAGUIO, S.P; SHEARER, C; SMITH, J.N Jr.; STEPHENS, R.B; STEINMAN, D.A; WALL, J.

    2003-09-01

    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

  16. Performance of a frozen spin polarised proton target

    International Nuclear Information System (INIS)

    Russell, F.M.

    1977-12-01

    The operational performance of a frozen spin polarised proton target specifically designed to give an unusually large angular access to the target has been examined. It is concluded that the mean absolute proton polarisation was held at about 64 +- 2% throughout the majority of HEP data recording. An excessive heat input to the target caused by inadequate cooling of the coaxial cable coupling to the nmr coil in the cavity seriously reduced the dwell-time of the target for HEP data collection. However, the short cooldown time of the target and minimal depolarisation associated with recycling of the target between polarising and HEP data collection positions resulted in only a small overall reduction in mean target polarisation and operational efficiency. (author)

  17. Hypersonic sliding target tracking in near space

    Directory of Open Access Journals (Sweden)

    Xiang-yu Zhang

    2015-12-01

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

  18. Design of the LBNF Beamline Target Station

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-10-01

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

  19. The Holistic Targeting (HOT) methodology as the means to improve Information Operations (IO) target development and prioritization

    OpenAIRE

    Ieva, Christopher S.

    2008-01-01

    Prioritization. In response to this challenge, this study proposes five recommendations to enhance IO integration into the Joint Targeting Cycle: the use of interim IO Joint Munitions Effectiveness Manual (JMEM) techniques to better forecast cognitive effects, the adoption of the Measure of Worth (MOW) model to assess IO effects, the HOT methodology to develop and prioritize IO targets, the use of compendium software facilitate targeting problem understanding and the network analysis to...

  20. Ne beam-Kr target interaction

    Energy Technology Data Exchange (ETDEWEB)

    Fortov, V E; Kostin, V V; Vorob` ev, V S [Russian Academy of Sciences, Moscow (Russian Federation). High Energy Density Research Center; Kulish, M I; Mintsev, V B [Russian Academy of Sciences, Chernogolovka (Russian Federation). Inst. of Chemical Physics; Hoffman, [Gesellschaft fuer Schwerionenforschung, Darmstadt (Germany)

    1997-12-31

    Energetic heavy ions of Ne - crystal Kr target interaction is investigated both experimentally and with the help of a 2-D computer code. The dynamics of the target matter heating, expansion, and destruction are described. A new equation of state for Kr was obtained and tested within a wide range of parameters. (author). 2 figs., 10 refs.

  1. Novel GABA receptor pesticide targets.

    Science.gov (United States)

    Casida, John E; Durkin, Kathleen A

    2015-06-01

    The γ-aminobutyric acid (GABA) receptor has four distinct but overlapping and coupled targets of pesticide action importantly associated with little or no cross-resistance. The target sites are differentiated by binding assays with specific radioligands, resistant strains, site-directed mutagenesis and molecular modeling. Three of the targets are for non-competitive antagonists (NCAs) or channel blockers of widely varied chemotypes. The target of the first generation (20th century) NCAs differs between the larger or elongated compounds (NCA-IA) including many important insecticides of the past (cyclodienes and polychlorocycloalkanes) or present (fiproles) and the smaller or compact compounds (NCA-IB) highly toxic to mammals and known as cage convulsants, rodenticides or chemical threat agents. The target of greatest current interest is designated NCA-II for the second generation (21st century) of NCAs consisting for now of isoxazolines and meta-diamides. This new and uniquely different NCA-II site apparently differs enough between insects and mammals to confer selective toxicity. The fourth target is the avermectin site (AVE) for allosteric modulators of the chloride channel. NCA pesticides vary in molecular surface area and solvent accessible volume relative to avermectin with NCA-IBs at 20-22%, NCA-IAs at 40-45% and NCA-IIs at 57-60%. The same type of relationship relative to ligand-docked length is 27-43% for NCA-IBs, 63-71% for NCA-IAs and 85-105% for NCA-IIs. The four targets are compared by molecular modeling for the Drosophila melanogaster GABA-R. The principal sites of interaction are proposed to be: pore V1' and A2' for NCA-IB compounds; pore A2', L6' and T9' for NCA-IA compounds; pore T9' to S15' in proximity to M1/M3 subunit interface (or alternatively an interstitial site) for NCA-II compounds; and M1/M3, M2 interfaces for AVE. Understanding the relationships of these four binding sites is important in resistance management and in the discovery and use

  2. Molecular Therapeutic Targets for Glioma Angiogenesis

    Directory of Open Access Journals (Sweden)

    Shingo Takano

    2010-01-01

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

  3. Neutronic performances of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, S.; Bringer, O.; Chabod, S.; Dupont, E.; Letourneau, A. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee (DSM/DAPNIA/SPhN), 91- Gif sur Yvette (France); Beauvais, P.; Lotrus, P.; Molinie, F.; Toussaint, J.Ch. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee (DSM/DAPNIA), 91- Gif sur Yvette (France); Chartier, F. [CEA Saclay, Dept. de Physico-Chimie (DEN/DPC/SECR), 91 - Gif sur Yvette (France); Oriol, L. [CEA Cadarache, Dept. d' Etudes des Reacteurs (DEN/DER/SPEX), 13 - Saint Paul lez Durance (France)

    2008-07-01

    The MEGAPIE project is a key experiment on the road to Accelerator Driven Systems and it provides the scientific community with unique data on the behavior of a liquid lead-bismuth spallation target under realistic and long term irradiation conditions. The neutronic of such target is of course of prime importance when considering its final destination as an intense neutron source. This is the motivation to characterize the inside neutron flux of the target in operation. A complex detector, made of 8 'micro' fission-chambers, has been built and installed in the core of the target, few tens of centimeters from the proton/Pb-Bi interaction zone. This detector is designed to measure the absolute neutron flux inside the target, to give its spatial distribution and to correlate its temporal variations with the beam intensity. Moreover, integral information on the neutron energy distribution as a function of the position along the beam axis could be extracted, giving integral constraints on the neutron production models implemented in transport codes such as MCNPX. (authors)

  4. Radiochemical separations of target-like reaction products from Au-, Pt-, and Th-targets after irradiation with GeV protons

    International Nuclear Information System (INIS)

    Szweryn, B.; Bruechle, W.; Schausten, B.; Schaedel, M.

    1988-08-01

    Chemical separation procedures for separations of reaction products after spallation reactions with 2.6 GeV protons and heavy element targets are presented. To determine independent cross sections of individual isotopes the elements Au, Pt, Ir, Os, Re, W, Ta, Hf, (Lu, Yb, Tm, Er), (Gd, Eu, Sm), were separated from gold targets, Pt, Ir, Os, W, Ta, Hf, (Lu, Yb, Tm, Er), (Gd, Eu, Sm) from a platinum target and Au, Tl from a thorium target. (orig.)

  5. MEGAPIE spallation target: Design, manufacturing and preliminary tests of the first pro-typical spallation target for future ADS

    International Nuclear Information System (INIS)

    Latge, Ch.; Laffont, G.; Groeschel, F.; Thomsen, K.; Wagner, W.; Agostini, P.; Dierckx, M.; Fazio, C.; Kirchner, T.; Kurata, Y.; Song, T.; Woloshun, K.

    2006-01-01

    Partitioning and Transmutation (P and T) techniques could contribute to reduce the radioactive inventory and its associated radiotoxicity. Sub-critical Accelerator Driven Systems (ADS) are potential candidates as dedicated transmutation systems, and thus their development is a relevant R and D topic in Europe. Following a first phase focused on the understanding of the basic principles of ADS (e.g. the programme MUSE), the R and D has been streamlined and focused on practical demonstration key issues. These demonstrations cover high intensity proton accelerators (beam current in the range 1 to 20 mA), spallation targets of high power and their effective coupling with a subcritical core. Presently there is general consensus that up to 1 MW of beam power solid targets are feasible from a heat removal point of view. For higher power levels liquid metal targets are the option of choice because of their higher heat removal capability, higher spallation material density in the volume and lower specific radioactivity, Therefore, a key experiment in the ADS road map, the Megawatt Pilot Experiment (MEGAPIE) (1 MW) was initiated in 1999 in order to design and build a liquid lead-bismuth spallation target, then to operate it into the Swiss spallation neutron facility SINQ at Paul Scherrer Institute (PSI). It has to be equipped to provide the largest possible amount of scientific and technical information without jeopardizing its safe operation. The minimum design service life has been fixed at 1 year (6000 mAh). Whereas the interest of the partner institutes is driven by the development needs of ADS, PSI interest lies also in the potential use of a LM target as a SINQ standard target providing a higher neutron flux than the current solid targets. Calculations of the radial distribution of the undisturbed thermal neutron flux for the LBE target in comparison to the former Zircaloy and current steel-clad solid lead target were done with different nuclear codes; nevertheless

  6. Uranium targets sandwiched between carbon layers for use on target wheels and on a Wobbler in heavy-ion bombardments

    International Nuclear Information System (INIS)

    Folger, H.; Hartmann, W.; Klemm, J.; Thalheimer, W.

    1989-01-01

    Uranium layers of ≅ 0.4 mg/cm 2 are evaporated by means of a 6 kW electron-beam gun onto 0.04 mg/cm 2 thick carbon films in a high-vacuum process; a protecting layer of ≅ 0.01 mg/cm 2 of carbon is added in the same vacuum cycle. The evaporation- and deposition yields are discussed and measurements of target characteristics are described. C/U/C sandwich targets in the shape of a sector of an annulus are prepared for use on rotating target wheels of 155 mm radius to be bombarded with a pulsed beam of heavy ions. One type of circular targets of 20 mm in diameter is mounted to a target wobbler. Both, wheel and wobbler, distribute the intensity of the heavy-ion beam to a larger area to reduce radiation damages. Examples of target applications will be mentioned. (orig.)

  7. 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 ...

  8. The SPES High Power ISOL production target

    Science.gov (United States)

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

    2016-11-01

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

  9. Polarized target physics at the Bonn electron accelerators

    International Nuclear Information System (INIS)

    Meyer, W.

    1988-12-01

    At the BONN 2.5 GeV electron synchrotron experiments with polarized nucleon targets have a long tradition. Starting with measurements of the target asymmetry in single pion photoproduction off polarized protons, resp. neutrons, the experiments have been concentrated on photodisintegration measurements of polarized deuterons. Parallel to these activities a considerable progress in the field of the target technology, e.g. cryogenics and target materials, has been made, by which all the measurements have profitted enormously. Especially the development of the new target material ammonia has allowed the first use of a polarized deuteron (ND 3 ) target in an intense electron beam. The construction of a frozen spin target, which will be used in combination with a tagged polarized photon beam, makes a new generation of polarized target experiments in photon induced reactions possible. Together with electron scattering off polarized deuterons and neutrons they will be a main activity in the physics program at the new stretcher accelerator ELSA in BONN. (orig.)

  10. Addressing key science and technology issues for IFE chambers, target fabrication and target injection

    International Nuclear Information System (INIS)

    Meier, W.R.; Goodin, D.T.; Nobile, A.

    2003-01-01

    Significant progress has been made in the development of high repetition rate chambers, target fabrication and injection for inertial fusion energy (IFE) for both heavy ion and laser drivers. Research is being conducted in a coordinated manner by national laboratories, universities and industry. This paper provides an overview of U.S. research activities and discusses how interface considerations (such as beam propagation and target survival during injection) impact design choices. (author)

  11. Counter-Leadership Targeting and Conflict Termination

    National Research Council Canada - National Science Library

    Taylor, Bradly

    1999-01-01

    .... Can the leader be found? And, is it legal and ethical to attack the leader? Analysis rarely has been conducted to determine whether the targeted organization is vulnerable to Counter Leadership Targeting (CLT...

  12. AA antiproton production target

    CERN Multimedia

    CERN PhotoLab

    1979-01-01

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

  13. Targeting the right journal.

    Science.gov (United States)

    Piterman, L; McCall, L

    1999-07-01

    While research is scientific, publication is a mixture of science and political pragmatism. Targeting the right journal is influenced by the following factors: the discipline that best represents the subject; the purpose of the message; the audience who are to be recipients of the message; the realities of geographic parochialism; the desire of authors to maximise personal and professional opportunities. If the originally targeted journal rejects the article, authors should have alternative publication strategies that give them professional recognition without requiring them to compromise the message or their ethics.

  14. Possible approaches to fast quality control of IFE targets

    International Nuclear Information System (INIS)

    Koresheva, E.R.; Nikitenko, A.I.; Aleksandrova, I.V.; Bazdenkov, S.V.; Belolipetskiy, A.A.; Chtcherbakov, V.I.; Osipov, I.E.

    2006-01-01

    In recent years, research into the development of reliable methods and techniques for characterization and quality control of ICF/IFE targets has been carried out very actively. This is motivated by the need to provide the means for precise and accurate knowledge of cryogenic target parameters. On the other hand, particular emphasis should be paid to the fact that fuelling of a commercial power plant requires ∼6 targets each second. This indicates that the development of fast quality control techniques is of critical importance as well. Therefore, in this report we discuss the issues underlying the construction of different algorithms for characterization and quality control of ICF/IFE targets. Among them are: (a) algorithm banks and their structure, (b) algorithm testing, (c) target reconstruction experiments. The algorithm bank incorporates the algorithms for two stages of target production: the stage of fuel layering technique development (motionless target) and the stage of cryogenic target delivery (injected target). In the first case an inverse algorithm for individual target characterization (3D target reconstruction) and two threshold algorithms for fast control of target quality are presented. They are based on tomographic information processing methods. Experimentally, tomographic data acquisition is carried out by a hundred projections microtomograph. The spatial resolution of the optical system of the microtomograph is 1 μm for 490 nm wavelength, the accuracy of target angular positioning is ±1.5-2.5 min. In the second case we describe the algorithm based on Fourier transform holography for ultra fast target characterization during its injection. The performed computer experiments have demonstrated much promise of this approach in the following directions: recognition of the target imperfections in both low- and high- harmonics; quality control of both a single target and a target batch; simultaneous control of both an injected target quality and

  15. Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

    Science.gov (United States)

    Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

    2018-02-01

    RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

  16. Remote handling for an ISIS target change

    International Nuclear Information System (INIS)

    Broome, T.A.; Holding, M.

    1989-01-01

    During 1987 two ISIS targets were changed. This document describes the main features of the remote handling aspects of the work. All the work has to be carried out using remote handling techniques. The radiation level measured on the surface of the reflector when the second target had been removed was about 800 mGy/h demonstrating that hands on operations on any part of the target reflector moderator assembly is not practical. The target changes were the first large scale operations in the Target Station Remote Handling Cell and a great deal was learned about both equipment and working practices. Some general principles emerged which are applicable to other active handling tasks on facilities like ISIS and these are discussed below. 8 figs

  17. Concepts for fabrication of inertial fusion energy targets

    Energy Technology Data Exchange (ETDEWEB)

    Nobile, A. (Arthur), Jr.; Hoffer, J. K. (James K.); Gobby, P. L. (Peter L.); Steckle, W. P. (Warren P.), Jr.; Goodin, D. T. (Daniel T.); Besenbruch, G. E. (Gottfried E.); Schultz, K. R. (Kenneth R.)

    2001-01-01

    Future inertial fusion energy (IFE) power plants will have a Target Fabrication Facility (TFF) that must produce approximately 500,000 targets per day. To achieve a relatively low cost of electricity, the cost to produce these targets will need to be less than approximately $0.25 per target. In this paper the status on the development of concepts for a TFF to produce targets for a heavy ion fusion (HIF) reactor, such as HYLIFE II, and a laser direct drive fusion reactor such as Sombrero, is discussed. The baseline target that is produced in the HIF TFF is similar to the close-coupled indirect drive target designed by Callahan-Miller and Tabak at Lawrence Livermore Laboratory. This target consists of a cryogenic hohlraum that is made of a metal case and a variety of metal foams and metal-doped organic foams. The target contains a DT-filled CH capsule. The baseline direct drive target is the design developed by Bodner and coworkers at Naval Research Laboratory. HIF targets can be filled with DT before or after assembly of the capsule into the hohlraum. Assembly of targets before filling allows assembly operations to be done at room temperature, but tritium inventories are much larger due to the large volume that the hohlraum occupies in the fill system. Assembly of targets cold after filling allows substantial reduction in tritium inventory, but this requires assembly of targets at cryogenic temperature. A model being developed to evaluate the tritium inventories associated with each of the assembly and fill options indicates that filling targets before assembling the capsule into the hohlraum, filling at temperatures as high as possible, and reducing dead-volumes in the fill system as much as possible offers the potential to reduce tritium inventories to acceptable levels. Use of enhanced DT ice layering techniques, such as infrared layering can reduce tritium inventories significantly by reducing the layering time and therefore the number of capsules being layered

  18. [Resistance to target-based therapy and its circumvention].

    Science.gov (United States)

    Nishio, Kazuto

    2004-07-01

    Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

  19. Tumor-targeted nanomedicines for cancer theranostics

    Science.gov (United States)

    Lammers, Twan; Shi, Yang

    2017-01-01

    Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and the target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple different types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments. PMID:27865762

  20. Targeted Cancer Therapies

    Science.gov (United States)

    ... are sometimes referred to as the product of "rational" drug design.) One approach to identify potential targets ... molecules that stimulate new blood vessel growth. Immunotherapies trigger the immune system to destroy cancer cells. Some ...

  1. Target recognition by wavelet transform

    International Nuclear Information System (INIS)

    Li Zhengdong; He Wuliang; Zheng Xiaodong; Cheng Jiayuan; Peng Wen; Pei Chunlan; Song Chen

    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

  2. Fluctuations in Echo Level Associated with Changes in Target Aspect and Target Frequency Response (abstract only)

    NARCIS (Netherlands)

    Zampolli, M.; Ainslie, M.A.; Zon, T. van

    2011-01-01

    Ping-to-ping variations in echo level can be caused by time variations in sonar parameters (source level, orientation), target aspect, relative and absolute motion of sonar and target, and time varying environment (e.g. surface waves). Quantifying and understanding such fluctuations are important,

  3. Radiation responses of stem cells: targeted and non-targeted effects

    International Nuclear Information System (INIS)

    Kavanagh, J.N.; Waring, E.J.; Prise, K.M.

    2015-01-01

    Stem cells are fundamental to the development of any tissue or organism via their ability to self-renew, which is aided by their unlimited proliferative capacity and their ability to produce fully differentiated offspring, often from multiple lineages. Stems cells are long lived and have the potential to accumulate mutations, including in response to radiation exposure. It is thought that stem cells have the potential to be induced into a cancer stem cell phenotype and that these may play an important role in resistance to radiotherapy. For radiation-induced carcinogenesis, the role of targeted and non-targeted effects is unclear with tissue or origin being important. Studies of genomic instability and bystander responses have shown consistent effects in haematopoietic models. Several models of radiation have predicted that stem cells play an important role in tumour initiation and that bystander responses could play a role in proliferation and self-renewal. (authors)

  4. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    Science.gov (United States)

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  5. Diffuse scattering from laser-irradiated plane targets

    International Nuclear Information System (INIS)

    Kessel, C.G.M. van; Olsen, J.N.; Sachsenmaier, P.; Sigel, R.; Eidmann, K.; Godwin, R.P.

    1976-11-01

    Optical calorimetry of the laser radiation scattered from plane targets irradiated by 0.3 Joule/30 ps Nd-laser pulses with intensities up to 10 16 W cm -2 has been performed with an emphasis on diffuse scattering. Diffuse scattering outside the solid angle of the focusing lens is found to be a major reflection loss from the target. A fraction of 0.3 to 0.5 of the incident pulse energy was absorbed in the target with only a very weak dependence on pulse energy and target material. (orig.) [de

  6. Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.

    Science.gov (United States)

    Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Zhong, Lu; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; He, Zhonggui

    2017-04-01

    Designing active targeting nanocarriers with increased cellular accumulation of chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we report a novel active targeting strategy based on the large amino acid transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1-targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and cytotoxicity was observed in LAT1-targeting nanoparticles compared to the unmodified ones. More interestingly, the internalized LAT1 together with targeting nanoparticles could recycle back to the cell membrane within 3 h, guaranteeing sufficient transporters on cell membrane for continuous cellular uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and antitumor effects. These results suggested that the overexpressed LAT1 on cancer cells holds a great potential to be a high-efficiency target for the rational design of active-targeting nanosystems. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Tumor target amplification: Implications for nano drug delivery systems.

    Science.gov (United States)

    Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

    2018-04-10

    Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)

    DEFF Research Database (Denmark)

    Peyrin-Biroulet, L; Sandborn, W; Sands, B E

    2015-01-01

    OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-t...... target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life....

  9. Space moving target detection using time domain feature

    Science.gov (United States)

    Wang, Min; Chen, Jin-yong; Gao, Feng; Zhao, Jin-yu

    2018-01-01

    The traditional space target detection methods mainly use the spatial characteristics of the star map to detect the targets, which can not make full use of the time domain information. This paper presents a new space moving target detection method based on time domain features. We firstly construct the time spectral data of star map, then analyze the time domain features of the main objects (target, stars and the background) in star maps, finally detect the moving targets using single pulse feature of the time domain signal. The real star map target detection experimental results show that the proposed method can effectively detect the trajectory of moving targets in the star map sequence, and the detection probability achieves 99% when the false alarm rate is about 8×10-5, which outperforms those of compared algorithms.

  10. Preparation of isotopically enriched mercury sulphide targets

    Energy Technology Data Exchange (ETDEWEB)

    Szerypo, J.; Friebel, H.U.; Frischke, D.; Grossman, R.; Maier, H.J. [Dept. fuer Physik, Univ. Muenchen (LMU) (Germany); Maier-Leibnitz-Lab. (MLL), Garching (Germany)

    2007-07-01

    The primary difficulty in performing nuclear reactions on mercury is to obtain a suitable target. The primary difficulty in performing nuclear reactions on mercury is to obtain a suitable target. The utilization of amalgam targets has been reported in early publications. These targets, however, were lacking homogeneity and in-beam stability. A thorough investigation of literature shows, that HgS, because of its comparatively high chemical and mechanical stability, is one of the more adequate Hg compounds for accelerator target applications. In this presentation we describe the production of HgS targets consisting of an enriched Hg isotope and S of natural isotopic abundance, starting up from HgO. Following the outline given in [3], in this special case HgS can be prepared by dissolving HgO in diluted HNO{sub 3} and subsequent precipitation of the black HgS modification with gaseous H{sub 2}S. Last step of the target production procedure is evaporation-condensation of HgS in vacuum. In the present case, HgS layers of 500 {mu}g/cm{sup 2} on a backing carbon foil of 26 {mu}g/cm{sup 2} with a protective carbon layer of about 20 {mu}g/cm{sup 2} thickness on top of the HgS layer were produced. (orig.)

  11. The Bochum Polarized Target

    International Nuclear Information System (INIS)

    Reicherz, G.; Goertz, S.; Harmsen, J.; Heckmann, J.; Meier, A.; Meyer, W.; Radtke, E.

    2001-01-01

    The Bochum 'Polarized Target' group develops the target material 6 LiD for the COMPASS experiment at CERN. Several different materials like alcohols, alcanes and ammonia are under investigation. Solid State Targets are polarized in magnetic fields higher than B=2.5T and at temperatures below T=1K. For the Dynamic Nuclear Polarization process, paramagnetic centers are induced chemically or by irradiation with ionizing beams. The radical density is a critical factor for optimization of polarization and relaxation times at adequate magnetic fields and temperatures. In a high sensitive EPR--apparatus, an evaporator and a dilution cryostat with a continuous wave NMR--system, the materials are investigated and optimized. To improve the polarization measurement, the Liverpool NMR-box is modified by exchanging the fixed capacitor for a varicap diode which not only makes the tuning very easy but also provides a continuously tuned circuit. The dependence of the signal area upon the circuit current is measured and it is shown that it follows a linear function

  12. Study Identifies New Lymphoma Treatment Target

    Science.gov (United States)

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

  13. Targeted drugs in radiation therapy

    International Nuclear Information System (INIS)

    Favaudon, V.; Hennequin, C.; Hennequin, C.

    2004-01-01

    New drugs aiming at the development of targeted therapies have been assayed in combination with ionizing radiation over the past few years. The rationale of this concept comes from the fact that the cytotoxic potential of targeted drugs is limited, thus requiring concomitant association with a cytotoxic agent for the eradication of tumor cells. Conversely a low level of cumulative toxicity is expected from targeted drugs. Most targeted drugs act through inhibition of post-translational modifications of proteins, such as dimerization of growth factor receptors, prenylation reactions, or phosphorylation of tyrosine or serine-threonine residues. Many systems involving the proteasome, neo-angiogenesis promoters, TGF-β, cyclooxygenase or the transcription factor NF-κB, are currently under investigation in hopes they will allow a control of cell proliferation, apoptosis, cell cycle progression, tumor angiogenesis and inflammation. A few drugs have demonstrated an antitumor potential in particular phenotypes. In most instances, however, radiation-drug interactions proved to be strictly additive in terms of cell growth inhibition or induced cell death. Strong potentiation of the response to radiotherapy is expected to require interaction with DNA repair mechanisms. (authors)

  14. Radioligand Recognition of Insecticide Targets.

    Science.gov (United States)

    Casida, John E

    2018-04-04

    Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH + ubiquinone oxidoreductase. Pyrethroids and other Na + channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.

  15. Improving scanner wafer alignment performance by target optimization

    Science.gov (United States)

    Leray, Philippe; Jehoul, Christiane; Socha, Robert; Menchtchikov, Boris; Raghunathan, Sudhar; Kent, Eric; Schoonewelle, Hielke; Tinnemans, Patrick; Tuffy, Paul; Belen, Jun; Wise, Rich

    2016-03-01

    In the process nodes of 10nm and below, the patterning complexity along with the processing and materials required has resulted in a need to optimize alignment targets in order to achieve the required precision, accuracy and throughput performance. Recent industry publications on the metrology target optimization process have shown a move from the expensive and time consuming empirical methodologies, towards a faster computational approach. ASML's Design for Control (D4C) application, which is currently used to optimize YieldStar diffraction based overlay (DBO) metrology targets, has been extended to support the optimization of scanner wafer alignment targets. This allows the necessary process information and design methodology, used for DBO target designs, to be leveraged for the optimization of alignment targets. In this paper, we show how we applied this computational approach to wafer alignment target design. We verify the correlation between predictions and measurements for the key alignment performance metrics and finally show the potential alignment and overlay performance improvements that an optimized alignment target could achieve.

  16. A 20 kw beam-on-target test of a high-power liquid lithium target for RIA

    International Nuclear Information System (INIS)

    Reed, Claude B.; Nolen, Jerry A.; Specht, James R.; Novick, Vincent J.; Plotkin, Perry

    2004-01-01

    The high-power heavy-ion beams produced by the Rare Isotope Accelerator (RIA) driver linac have large energy deposition density in solids and in many cases no solid materials would survive the full beam power. Liquid lithium technology has been proposed to solve this problem in RIA. Specifically, a windowless target for the production of radioactive ions via fragmentation, consisting of a jet of about 3 cm thickness of flowing liquid lithium, exposed to the beamline vacuum [1,2] is being developed. To demonstrate that power densities equivalent to a 200-kW RIA uranium beam, deposited in the first 4 mm of a flowing lithium jet, can be handled by the windowless target design, a high power 1 MeV Dynamitron was leased and a test stand prepared to demonstrate the target's capability of absorbing and carrying away a 20kW heat load without disrupting either the 5 mm x 10 mm flowing lithium jet target or the beam line vacuum

  17. Application of target costing in machining

    Science.gov (United States)

    Gopalakrishnan, Bhaskaran; Kokatnur, Ameet; Gupta, Deepak P.

    2004-11-01

    In today's intensely competitive and highly volatile business environment, consistent development of low cost and high quality products meeting the functionality requirements is a key to a company's survival. Companies continuously strive to reduce the costs while still producing quality products to stay ahead in the competition. Many companies have turned to target costing to achieve this objective. Target costing is a structured approach to determine the cost at which a proposed product, meeting the quality and functionality requirements, must be produced in order to generate the desired profits. It subtracts the desired profit margin from the company's selling price to establish the manufacturing cost of the product. Extensive literature review revealed that companies in automotive, electronic and process industries have reaped the benefits of target costing. However target costing approach has not been applied in the machining industry, but other techniques based on Geometric Programming, Goal Programming, and Lagrange Multiplier have been proposed for application in this industry. These models follow a forward approach, by first selecting a set of machining parameters, and then determining the machining cost. Hence in this study we have developed an algorithm to apply the concepts of target costing, which is a backward approach that selects the machining parameters based on the required machining costs, and is therefore more suitable for practical applications in process improvement and cost reduction. A target costing model was developed for turning operation and was successfully validated using practical data.

  18. Targeting therapeutics to the glomerulus with nanoparticles.

    Science.gov (United States)

    Zuckerman, Jonathan E; Davis, Mark E

    2013-11-01

    Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  19. Targeting Virus-host Interactions of HIV Replication.

    Science.gov (United States)

    Weydert, Caroline; De Rijck, Jan; Christ, Frauke; Debyser, Zeger

    2016-01-01

    Cellular proteins that are hijacked by HIV in order to complete its replication cycle, form attractive new targets for antiretroviral therapy. In particular, the protein-protein interactions between these cellular proteins (cofactors) and viral proteins are of great interest to develop new therapies. Research efforts have led to the validation of different cofactors and some successes in therapeutic applications. Maraviroc, the first cofactor inhibitor approved for human medicinal use, provided a proof of concept. Furthermore, compounds developed as Integrase-LEDGF/p75 interaction inhibitors (LEDGINs) have advanced to early clinical trials. Other compounds targeting cofactors and cofactor-viral protein interactions are currently under development. Likewise, interactions between cellular restriction factors and their counteracting HIV protein might serve as interesting targets in order to impair HIV replication. In this respect, compounds targeting the Vif-APOBEC3G interaction have been described. In this review, we focus on compounds targeting the Integrase- LEDGF/p75 interaction, the Tat-P-TEFb interaction and the Vif-APOBEC3G interaction. Additionally we give an overview of currently discovered compounds presumably targeting cellular cofactor-HIV protein interactions.

  20. Progress on the SNS target station

    International Nuclear Information System (INIS)

    Carne, A.

    1983-01-01

    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

  1. Preparation of targets by ion implantation

    International Nuclear Information System (INIS)

    Santry, D.C.

    1976-01-01

    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)

  2. Development of RI Target Production Technology

    International Nuclear Information System (INIS)

    Jeong, Do Young; Ko, Kwang Hoon; Kim, Cheol Jung; Kim, Taek Soo; Rho, Si Pyo; Park, Hyun Min; Lim, Gwon; Cha, Yong Ho; Han, Jae Min

    2010-04-01

    This project was accomplished with an aim of productive technical development on the 'enriched target' which is used essentially in radioisotope production. The research was advanced systematically with target production pilot system configuration and core technical development. We composed Yb-176 productive pilot system which equip the chemical purification technique of medical treatment level and proved its capability. Possibilities to separate Zn-67 by the method of using the polarizing light in principle and to separate Zn-70 by the method of using the double optical pumping in theory were also proved. RI target production technologies are recognized excessively with monopolistic techniques of part atomic energy advanced nations such as Russia and US and they are come, but we prepared the opportunity will be able to complete a full cycle of like (RI material production -> RI target production -> RI application) with this project accomplishment. When considering only the direct demand of stable isotope which is used in various industrial, we forecast with the fact that RI target markets will become larger with the approximately 5 billion dollars in 2020 and this technology will contribute in the domestic rising industry creation with high value added

  3. Ignition target and laser-plasma instabilities

    International Nuclear Information System (INIS)

    Laffite, S.; Loiseau, P.

    2010-01-01

    For the first time indirect drive ignition targets have been designed with the constraint of limiting laser-plasma instabilities. The amplification of these instabilities is directly proportional to the luminous flux density, it means to the sizes of the focal spots too. This study shows that increasing the sizes of the focal spots does not reduce linear amplification gains in a proportional way because the global optimization of the target implies changes in hydrodynamical conditions that in turn have an impact on the value of the amplification gain. The design of the target is a 2-step approach: the first step aims at assuring a uniform irradiation and compression of the target. The first step requires information concerning the laser focusing spots, the dimensions of the hohlraum, the inert gas contained in it, the materials of the wall. The second step is an optimization approach whose aim is to reduce the risk of laser-plasmas instabilities. This optimization is made through simulations of the amplification gains of stimulated Raman and Brillouin backscattering. This method has allowed us to design an optimized target for a rugby-shaped hohlraum. (A.C.)

  4. Physics with polarized electrons and targets

    International Nuclear Information System (INIS)

    Donnelly, T.W.

    1984-01-01

    With the advent of electron stretcher or storage rings electron scattering from polarized targets becomes a general new tool for nuclear structure studies. Without such facilities it is necessary to have very dense polarized targets for use with the typical (less or approximately equal 50 μA) electron beams available and very few measurements of this type have been attempted. On the other hand, with electron rings the effective circulating current can be greatly increased. In this case much thinner internal targets may be used while still maintaining the same luminosity as in external beam experiments. In ancticipation of such new experimental capabilities we have re-developed the theoretical basis for discussions of electron scattering from polarized targets using either unpolarized or polarized electron beams. This work takes the formalism of unpolarized (e,e') and extends it in a straightforward way to include general polarizations of electrons, target nuclei, recoil nuclei or any combinations of these polarizations. In the present context it is only possible to provide a brief summary of the general form of the cross section and to present a few illustrative examples of the nuclear structure information that may be extracted from such polarization measurements

  5. COST OF ADDRESSING TARGETS OF UNEQUAL VALUE; FINAL

    International Nuclear Information System (INIS)

    G.H. CANAVAN

    2001-01-01

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

  6. Gas target with thin wall

    International Nuclear Information System (INIS)

    Korenchenko, A.S.; Korenchenko, S.M.; Kravchuk, N.P.; Filippov, A.I.; Fursov, A.P.

    1992-01-01

    The technology of targets manufacture with thin wall diameter 100 mm and lengthwise 700 mm from composition kevlar + epoxy resin is described. The test's results on pressure and vacuum are reported. The created targets are supposed to be used on the installation ARES for an investigation of muons and pions interactions with light nuclei and rare pions decay 'on flying'. 5 refs.; 2 figs.; 2 tabs

  7. A high-power target experiment

    CERN Document Server

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

    2005-01-01

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

  8. uPAR as anti-cancer target

    DEFF Research Database (Denmark)

    Lund, Ida K; Illemann, Martin; Thurison, Tine

    2011-01-01

    , and a potential diagnostic and predictive impact of the different uPAR forms has been reported. Hence, pericellular proteolysis seems to be a suitable target for anti-cancer therapy and numerous approaches have been pursued. Targeting of this process may be achieved by preventing the binding of uPA to u...... using mouse monoclonal antibodies (mAbs) against mouse uPA or uPAR. These reagents will target uPA and uPAR in both stromal cells and cancer cells, and their therapeutic potential can now be assessed in syngenic mouse cancer models....

  9. 29 mm Diameter Target Test Report

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-10-23

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

  10. Materials considerations in accelerator targets

    International Nuclear Information System (INIS)

    Peacock, H. B. Jr.; Iyer, N. C.; Louthan, M. R. Jr.

    1995-01-01

    Future nuclear materials production and/or the burn-up of long lived radioisotopes may be accomplished through the capture of spallation produced neutrons in accelerators. Aluminum clad-lead and/or lead alloys has been proposed as a spallation target. Aluminum was the cladding choice because of the low neutron absorption cross section, fast radioactivity decay, high thermal conductivity, and excellent fabricability. Metallic lead and lead oxide powders were considered for the target core with the fabrication options being casting or powder metallurgy (PM). Scoping tests to evaluate gravity casting, squeeze casting, and casting and swaging processes showed that, based on fabricability and heat transfer considerations, squeeze casting was the preferred option for manufacture of targets with initial core cladding contact. Thousands of aluminum clad aluminum-lithium alloy core targets and control rods for tritium production have been fabricated by coextrusion processes and successfully irradiated in the SRS reactors. Tritium retention in, and release from, the coextruded product was modeled from experimental and operational data. The model assumed that tritium atoms, formed by the 6Li(n,a)3He reaction, were produced in solid solution in the Al-Li alloy. Because of the low solubility of hydrogen isotopes in aluminum alloys, the irradiated Al-Li rapidly became supersaturated in tritium. Newly produced tritium atoms were trapped by lithium atoms to form a lithium tritide. The effective tritium pressure required for trap or tritide stability was the equilibrium decomposition pressure of tritium over a lithium tritide-aluminum mixture. The temperature dependence of tritium release was determined by the permeability of the cladding to tritium and the local equilibrium at the trap sites. The model can be used to calculate tritium release from aluminum clad, aluminum-lithium alloy targets during postulated accelerator operational and accident conditions. This paper describes

  11. Bioinformatics for cancer immunotherapy target discovery

    DEFF Research Database (Denmark)

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

    2014-01-01

    therapy target discovery in a bioinformatics analysis pipeline. We describe specialized bioinformatics tools and databases for three main bottlenecks in immunotherapy target discovery: the cataloging of potentially antigenic proteins, the identification of potential HLA binders, and the selection epitopes...

  12. Polarized few-nucleon targets: new developments

    International Nuclear Information System (INIS)

    Haeusser, O.

    1992-09-01

    We discuss recent improvements in producing polarized few-nucleon targets for nuclear and particle physics experiments. The emphasis is on progress with polarized gas targets intended for experiments at electron and proton storage rings. (author) 54 refs., 1 tab

  13. Polarized few-nucleon targets: new developments

    Energy Technology Data Exchange (ETDEWEB)

    Haeusser, O

    1992-09-01

    We discuss recent improvements in producing polarized few-nucleon targets for nuclear and particle physics experiments. The emphasis is on progress with polarized gas targets intended for experiments at electron and proton storage rings. (author) 54 refs., 1 tab.

  14. X-ray tube targets

    International Nuclear Information System (INIS)

    Hirsch, H.H.

    1980-01-01

    In rotary targets for X-ray tubes warping is a problem which causes X-ray deficiency. A rotary target is described in which warping is reduced by using alloys of molybdenum with 0.05 to 10% iron, silicon, cobalt, tantalum, niobium, hafnium, stable metal oxide or mixture thereof. Suitable mixtures are 0.5 to 10% of tantalum, niobium or hafnium with from 0.5 to 5% yttrium oxide, or 0.05 to 0.3% of cobalt or silicon. Optionally 0.1 to 5% by weight of additional material may be alloyed with the molybdenum, such as tantalum or hafnium carbides. (author)

  15. Common features of microRNA target prediction tools

    Directory of Open Access Journals (Sweden)

    Sarah M. Peterson

    2014-02-01

    Full Text Available The human genome encodes for over 1800 microRNAs, which are short noncoding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one microRNA to target multiple gene transcripts, microRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of microRNA targets is a critical initial step in identifying microRNA:mRNA target interactions for experimental validation. The available tools for microRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to microRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all microRNA target prediction tools, four main aspects of the microRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MicroRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output.

  16. Target injection and tracking for inertial fusion energy

    Energy Technology Data Exchange (ETDEWEB)

    Petzoldt, R.W. [Lawrence Livermore National Lab., CA (United States); Moir, R.W. [Lawrence Livermore National Lab., CA (United States)

    1996-11-01

    In an inertial fusion power plant, several cryogenic targets must be injected each second into a reaction chamber with speeds of about 100 m s{sup -1}. This speed can be achieved with an acceleration in the range from 1000 to 10 000 m s{sup -2}. The total accuracy of driver beam pointing and target position prediction must be less than {+-}0.6 mm for a 3 mm beam spot radius. A 0.1 {mu}m thick dual membrane supporting the capsule in the hohlraum will allow nearly 2000 m s{sup -2} acceleration. The strength of frozen DT in the capsule is calculated to allow acceleration in excess of 10 000 m s{sup -2} if the DT temperature is less than 17 K. A gas gun is the preferred device for injecting indirect drive targets owing to its simplicity and proven reliability. The amount of gas required for each target (about 10-100 mg) is acceptable. A revolver loading mechanism is recommendced with a cam-operated poppet valve to control the gas flow. Slots near the muzzle of the gun barrel are recommended to vent gas and thereby to improve accuracy and to aid gas pumping. Optical target tracking and electronic timing devices can predict target arrival time with sufficient accuracy. Target steering by electrostatic deflection of the in-flight target is shown to be feasible and would avoid the need to point the beams actively. Calculations show that induced tumble from electrostatically steering the target is not excessive. An experiment has been designed to develop target injection and to verify the predicted accuracy of sequential injection and tracking of multiple targets. (orig.)

  17. The Bering Autonomous Target Detection

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  18. Resource implications of a national health target

    DEFF Research Database (Denmark)

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

    2014-01-01

    Background The Shorter Stays in Emergency Departments health target was introduced in New Zealand in 2009. District Health Boards (DHBs) are expected to meet the target with no additional funding or incentives. The costs of implementing such targets have not previously been studied. Method A survey.......03), whereas expenditure in the hospital was not (r = 0.08, P = 0.75). Conclusion The fact that estimated expenditure on the target was over $50 million without additional funding suggests that DHBs were able to make savings through improved efficiencies and/or that funds were reallocated from other services...

  19. A new transfer system for solid targets

    Science.gov (United States)

    Klug, J.; Buckley, K. R.; Zeisler, S. K.; Dodd, M.; Tsao, P.; Hoehr, C.; Economou, C.; Corsaut, J.; Appiah, J. P.; Kovacs, M. S.; Valliant, J. F.; Benard, F.; Ruth, T. J.; Schaffer, P.

    2012-12-01

    As part of a collaborative research project funded by Natural Resources Canada, TRIUMF has designed and manufactured solid target and solid target processing systems for the production of technetium-99m using small medical cyclotrons. The system described herein is capable of transporting the target from a hotcell, where the target is loaded and processed, to the cyclotron and back again. The versatility of the transfer system was demonstrated through the successful installation and operation on the ACSI TR 19 at the BC Cancer Agency, the GE PETtrace cyclotrons at Lawson Health Research (LHRI) and the Centre for Probe Development and Commercialization (CDPC).

  20. Targeting human breast cancer cells by an oncolytic adenovirus using microRNA-targeting strategy.

    Science.gov (United States)

    Shayestehpour, Mohammad; Moghim, Sharareh; Salimi, Vahid; Jalilvand, Somayeh; Yavarian, Jila; Romani, Bizhan; Mokhtari-Azad, Talat

    2017-08-15

    MicroRNA-targeting strategy is a promising approach that enables oncolytic viruses to replicate in tumor cells but not in normal cells. In this study, we targeted adenoviral replication toward breast cancer cells by inserting ten complementary binding sites for miR-145-5p downstream of E1A gene. In addition, we evaluated the effect of increasing miR-145 binding sites on inhibition of virus replication. Ad5-control and adenoviruses carrying five or ten copies of miR145-5p target sites (Ad5-5miR145T, Ad5-10miR145T) were generated and inoculated into MDA-MB-453, BT-20, MCF-7 breast cancer cell lines and human mammary epithelial cells (HMEpC). Titer of Ad5-10miR145T in HMEpC was significantly lower than Ad5-control titer. Difference between the titer of these two viruses at 12, 24, 36, and 48h after infection was 1.25, 2.96, 3.06, and 3.77 log TCID 50 . No significant difference was observed between the titer of both adenoviruses in MDA-MB-453, BT-20 and MCF-7 cells. The infectious titer of adenovirus containing 10 miR-145 binding sites in HMEpC cells at 24, 36, and 48h post-infection was 1.7, 2.08, and 4-fold, respectively, lower than the titer of adenovirus carrying 5 miR-145 targets. Our results suggest that miR-145-targeting strategy provides selectivity for adenovirus replication in breast cancer cells. Increasing the number of miRNA binding sites within the adenoviral genome confers more selectivity for viral replication in cancer cells. Copyright © 2017. Published by Elsevier B.V.

  1. Low-enriched uranium high-density target project. Compendium report

    Energy Technology Data Exchange (ETDEWEB)

    Vandegrift, George; Brown, M. Alex; Jerden, James L.; Gelis, Artem V.; Stepinski, Dominique C.; Wiedmeyer, Stanley; Youker, Amanda; Hebden, Andrew; Solbrekken, G; Allen, C; Robertson., D; El-Gizawy, Sherif; Govindarajan, Srisharan; Hoyer, Annemarie; Makarewicz, Philip; Harris, Jacob; Graybill, Brian; Gunn, Andy; Berlin, James; Bryan, Chris; Sherman, Steven; Hobbs, Randy; Griffin, F. P.; Chandler, David; Hurt, C. J.; Williams, Paul; Creasy, John; Tjader, Barak; McFall, Danielle; Longmire, Hollie

    2016-09-01

    At present, most 99Mo is produced in research, test, or isotope production reactors by irradiation of highly enriched uranium targets. To achieve the denser form of uranium needed for switching from high to low enriched uranium (LEU), targets in the form of a metal foil (~125-150 µm thick) are being developed. The LEU High Density Target Project successfully demonstrated several iterations of an LEU-fission-based Mo-99 technology that has the potential to provide the world’s supply of Mo-99, should major producers choose to utilize the technology. Over 50 annular high density targets have been successfully tested, and the assembly and disassembly of targets have been improved and optimized. Two target front-end processes (acidic and electrochemical) have been scaled up and demonstrated to allow for the high-density target technology to mate up to the existing producer technology for target processing. In the event that a new target processing line is started, the chemical processing of the targets is greatly simplified. Extensive modeling and safety analysis has been conducted, and the target has been qualified to be inserted into the High Flux Isotope Reactor, which is considered above and beyond the requirements for the typical use of this target due to high fluence and irradiation duration.

  2. Electrostatics, small particles, and laser fusion targets

    International Nuclear Information System (INIS)

    Hendricks, C.D.

    1978-01-01

    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

  3. Diversity, expression and mRNA targeting abilities of Argonaute-targeting miRNAs among selected vascular plants.

    Science.gov (United States)

    Jagtap, Soham; Shivaprasad, Padubidri V

    2014-12-02

    Micro (mi)RNAs are important regulators of plant development. Across plant lineages, Dicer-like 1 (DCL1) proteins process long ds-like structures to produce micro (mi) RNA duplexes in a stepwise manner. These miRNAs are incorporated into Argonaute (AGO) proteins and influence expression of RNAs that have sequence complementarity with miRNAs. Expression levels of AGOs are greatly regulated by plants in order to minimize unwarranted perturbations using miRNAs to target mRNAs coding for AGOs. AGOs may also have high promoter specificity-sometimes expression of AGO can be limited to just a few cells in a plant. Viral pathogens utilize various means to counter antiviral roles of AGOs including hijacking the host encoded miRNAs to target AGOs. Two host encoded miRNAs namely miR168 and miR403 that target AGOs have been described in the model plant Arabidopsis and such a mechanism is thought to be well conserved across plants because AGO sequences are well conserved. We show that the interaction between AGO mRNAs and miRNAs is species-specific due to the diversity in sequences of two miRNAs that target AGOs, sequence diversity among corresponding target regions in AGO mRNAs and variable expression levels of these miRNAs among vascular plants. We used miRNA sequences from 68 plant species representing 31 plant families for this analysis. Sequences of miR168 and miR403 are not conserved among plant lineages, but surprisingly they differ drastically in their sequence diversity and expression levels even among closely related plants. Variation in miR168 expression among plants correlates well with secondary structures/length of loop sequences of their precursors. Our data indicates a complex AGO targeting interaction among plant lineages due to miRNA sequence diversity and sequences of miRNA targeting regions among AGO mRNAs, thus leading to the assumption that the perturbations by viruses that use host miRNAs to target antiviral AGOs can only be species-specific. We also show

  4. Climate and energy targets of the European Union

    International Nuclear Information System (INIS)

    Stolwijk, H.; Veenendaal, P.

    2007-01-01

    Attention is paid to two important parts of the targets for climate and energy which were determined by the European Council in March 2007 for the year 2020: (1) the impact of the emission reduction target and the correlations with the sustainable development targets; and (2) the obstacles for the European Union on the way to thar 20% renewable energy target [nl

  5. Flash trajectory imaging of target 3D motion

    Science.gov (United States)

    Wang, Xinwei; Zhou, Yan; Fan, Songtao; He, Jun; Liu, Yuliang

    2011-03-01

    We present a flash trajectory imaging technique which can directly obtain target trajectory and realize non-contact measurement of motion parameters by range-gated imaging and time delay integration. Range-gated imaging gives the range of targets and realizes silhouette detection which can directly extract targets from complex background and decrease the complexity of moving target image processing. Time delay integration increases information of one single frame of image so that one can directly gain the moving trajectory. In this paper, we have studied the algorithm about flash trajectory imaging and performed initial experiments which successfully obtained the trajectory of a falling badminton. Our research demonstrates that flash trajectory imaging is an effective approach to imaging target trajectory and can give motion parameters of moving targets.

  6. Design and features of the target tracker of the Opera's target: study of the electron channel events

    International Nuclear Information System (INIS)

    Chon-Sen, N.

    2009-01-01

    Neutrino oscillations are now well acknowledged, the purpose of the Opera experiment is to show how ν τ appear in a ν μ beam. The ν μ beam is produced at CERN and crosses the earth crust on a distance of 732 km before being detected in the Gran-Sasso underground laboratory. The Opera experiment uses the technique of the photographic emulsion. The detector target is a series of walls of lead bricks, each brick being made of photographic emulsions intercalated with lead sheets. A target tracker enables the localization of the brick in which the neutrino interaction has happened. As soon as the brick is found, the brick is removed from the detector and the emulsion is developed and analysed. the target tracker is made up of plastic scintillator bars on which optic fibers are stuck to collect photons and send them to photomultipliers. The main purpose of this work is the calibration of the target tracker. The first chapter introduces the standard model, the neutrino and the neutrino oscillation phenomenon. The second chapter reviews the neutrino experiments worldwide. The third chapter describes the Opera experiment while chapter 4 and 5 are dedicated to the design and operation of the target tracker. The last chapter studies through simulation the behaviour of the target tracker when submitted to an electron beam in order to use it as a complementary tool for the identification of the τ → e channel. (A.C.)

  7. Folate targeted polymeric 'green' nanotherapy for cancer

    International Nuclear Information System (INIS)

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

    2010-01-01

    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 IC 50 values were lowered by a factor of ∼ 3 for FA-NanoGSE compared to the free drug, indicating substantially enhanced bioavailability to the tumor cells, sparing the normal ones. Receptor targeting of FA-NanoGSE resulted in a significant increase in apoptotic index, which was also quantified by flow cytometry and fluorescence microscopy. This in vitro study provides a basis for the use of nanoparticle mediated delivery of anticancer nutraceuticals to enhance bioavailability and effectively target cancer by a 'green' approach.

  8. The evaluation study of high performance gas target system

    International Nuclear Information System (INIS)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2008-06-01

    The object of this study is a improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, deep hole grid was designed for improvement of beam entrance. Using FEM(Finite Elements Method) analysis, it was verified that this design is more effective than the old one. 2. Improvement of target gas loading and withdrawing system : For the targetry, Helium gas and vacuum lines was installed for evaluating the production yields. Using these lines, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Improvement of target cooling efficiency : In case of the cylindrical target, it is more effective to use short length of target cavity for the high production yields. For improving the cooling efficiency, cooling fin was suggested to the target design. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production

  9. The evaluation study of high performance gas target system

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Min Goo; Yang, Seung Dae; Kim, Sang Wook

    2008-06-15

    The object of this study is a improvement of a gas target and targetry for increasing the radioisotope production yields. The main results are as follows 1. Improvement of beam entrance of the gas target : In this work, deep hole grid was designed for improvement of beam entrance. Using FEM(Finite Elements Method) analysis, it was verified that this design is more effective than the old one. 2. Improvement of target gas loading and withdrawing system : For the targetry, Helium gas and vacuum lines was installed for evaluating the production yields. Using these lines, it was proved that the recovery yields was improved and the residual impurity was reduced. 3. Improvement of target cooling efficiency : In case of the cylindrical target, it is more effective to use short length of target cavity for the high production yields. For improving the cooling efficiency, cooling fin was suggested to the target design. It is more effective to put the cooling fins inside the target cavity for the suppressed target pressure and density reduction effect during the proton beam irradiation. In conclusion, the target with fins inside the target cavity was better for high current irradiation and mass RI production.

  10. Human immune cell targeting of protein nanoparticles - caveospheres

    Science.gov (United States)

    Glass, Joshua J.; Yuen, Daniel; Rae, James; Johnston, Angus P. R.; Parton, Robert G.; Kent, Stephen J.; de Rose, Robert

    2016-04-01

    Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.

  11. Heavy ion fusion targets; issues for fast ignition

    International Nuclear Information System (INIS)

    Bangerter, Roger O.

    2014-01-01

    During the last 36 years researchers have suggested and evaluated a large number of target designs for heavy ion inertial fusion. The different target designs can be classified according to their mode of ignition, their method of implosion, and their size. Ignition modes include hot-spot ignition and fast ignition. Methods of implosion include direct drive and indirect drive. Historically there has been significant work on indirectly driven targets with hot-spot ignition. Recently there has been increasing interest in directly driven targets with ion driven fast ignition. In principle, fast ignition might lead to improved target performance. On the other hand, fast ignition imposes stringent requirements on accelerators and beam physics. Furthermore, fast ignition magnifies the importance of a number of traditional target physics issues associated with ion beam energy deposition and fuel preheat. This paper will discuss the advantages and disadvantages of the various classes of targets. It will also discuss some issues that must be resolved to assess the feasibility of ion fast ignition

  12. IFE Target Injection Tracking and Position Prediction Update

    International Nuclear Information System (INIS)

    Petzoldt, Ronald W.; Jonestrask, Kevin

    2005-01-01

    To achieve high gain in an inertial fusion energy power plant, driver beams must hit direct drive targets with ±20 μm accuracy (±100 μm for indirect drive). Targets will have to be tracked with even greater accuracy. The conceptual design for our tracking system, which predicts target arrival position and timing based on position measurements outside of the reaction chamber was previously described. The system has been built and has begun tracking targets at the first detector station. Additional detector stations are being modified for increased field of view. After three tracking stations are operational, position predictions at the final station will be compared to position measurements at that station as a measure of target position prediction accuracy.The as-installed design will be described together with initial target tracking and position prediction accuracy results. Design modifications that allow for improved accuracy and/or in-chamber target tracking will also be presented

  13. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2017-04-07

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around the monopulse antenna boresight. In this study, a new approach is proposed, which uses the outputs of four antennas to rapidly localise two point targets present in the hemisphere. If both targets have the same elevation angle, the proposed scheme cannot detect them. To detect such targets, a second set of antennas is required. In this study, to detect two targets at generalised locations, the antenna array is divided into multiple overlapping sets each of four antennas. Two algorithms are proposed to combine the outputs from multiple sets and improve the detection performance. Simulation results show that the algorithm is able to localise both targets with <;2° mean square error in azimuth and elevation.

  14. Optimal random search for a single hidden target.

    Science.gov (United States)

    Snider, Joseph

    2011-01-01

    A single target is hidden at a location chosen from a predetermined probability distribution. Then, a searcher must find a second probability distribution from which random search points are sampled such that the target is found in the minimum number of trials. Here it will be shown that if the searcher must get very close to the target to find it, then the best search distribution is proportional to the square root of the target distribution regardless of dimension. For a Gaussian target distribution, the optimum search distribution is approximately a Gaussian with a standard deviation that varies inversely with how close the searcher must be to the target to find it. For a network where the searcher randomly samples nodes and looks for the fixed target along edges, the optimum is either to sample a node with probability proportional to the square root of the out-degree plus 1 or not to do so at all.

  15. Design of the MYRRHA Spallation Target Assembly

    International Nuclear Information System (INIS)

    Keijers, S.; Fernandez, R.; Stankovskiy, A.; Kennedy, G.; Van Tichelen, K.

    2015-01-01

    MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) is a multi-purpose research facility currently being developed at SCK.CEN. MYRRHA is based on the ADS (Accelerator Driven System) concept where a proton accelerator, a spallation target and a subcritical reactor are coupled. MYRRHA will demonstrate the ADS full concept by coupling these three components at a reasonable power level. As a flexible irradiation facility, the MYRRHA research reactor will be able to work in both critical and subcritical modes. In this way, MYRRHA will allow fuel developments for innovative reactor systems, material research for GEN IV and fusion reactors, and radioisotope production for medical and industrial applications. MYRRHA will be cooled by Lead Bismuth Eutectic (LBE) and will play an important role in the development of the Pb-alloys technology needed for the LFR (Lead Fast Reactor) GEN IV concept. This paper describes the evolution of the MYRRHA spallation target design. In the early phase of the MYRRHA project (XT-ADS), the target design was based on a dedicated spallation loop inside the primary reactor vessel. Within the core, the 3 central fuel assembly positions were occupied by the spallation target, which enabled a windowless design created by a free surface of LBE facing the proton beam. The windowless option was preferred because of high heat loads in combination with severe irradiation damage in the target region would result in unacceptably short lifetimes of a target window. The LBE in the loop served as spallation target and as target coolant, but was separated from the LBE cooling the reactor core. The loop was equipped with its own pump, heat exchanger and conditioning system. The change from cyclotron to linear accelerator allowed the increase in proton energy from 350 MeV to 600 MeV. This modification led to an important reduction of the specific heat load at the target level and an improvement of the neutronic performance. In addition to

  16. A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

    Science.gov (United States)

    Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

    2018-01-19

    The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the

  17. Dual-target cost in visual search for multiple unfamiliar faces.

    Science.gov (United States)

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

    2017-08-01

    The efficiency of visual search for one (single-target) and either of two (dual-target) unfamiliar faces was explored to understand the manifestations of capacity and guidance limitations in face search. The visual similarity of distractor faces to target faces was manipulated using morphing (Experiments 1 and 2) and multidimensional scaling (Experiment 3). A dual-target cost was found in all experiments, evidenced by slower and less accurate search in dual- than single-target conditions. The dual-target cost was unequal across the targets, with performance being maintained on one target and reduced on the other, which we label "preferred" and "non-preferred" respectively. We calculated the capacity for each target face and show reduced capacity for representing the non-preferred target face. However, results show that the capacity for the non-preferred target can be increased when the dual-target condition is conducted after participants complete the single-target conditions. Analyses of eye movements revealed evidence for weak guidance of fixations in single-target search, and when searching for the preferred target in dual-target search. Overall, the experiments show dual-target search for faces is capacity- and guidance-limited, leading to superior search for 1 face over the other in dual-target search. However, learning faces individually may improve capacity with the second face. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. 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...

  19. Targets for high power neutral beams

    International Nuclear Information System (INIS)

    Kim, J.

    1980-01-01

    Stopping high-power, long-pulse beams is fast becoming an engineering challenge, particularly in neutral beam injectors for heating magnetically confined plasmas. A brief review of neutral beam target technology is presented along with heat transfer calculations for some selected target designs

  20. Targeting BRCAness in Gastric Cancer

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-16-1-0470 TITLE: Targeting BRCAness in Gastric Cancer PRINCIPAL INVESTIGATOR: Yelena Janjigian CONTRACTING ORGANIZATION...Sloan-Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: October 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical...Targeting BRCAness in Gastric Cancer 5b. GRANT NUMBER W81XWH-16-1-0473 (Ashworth) 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Eric Collisson, David