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Sample records for 25k fp gene

  1. Mutations within the Autographa californica nucleopolyhedrovirus FP25K gene decrease the accumulation of ODV-E66 and alter its intranuclear transport.

    PubMed

    Braunagel, S C; Burks, J K; Rosas-Acosta, G; Harrison, R L; Ma, H; Summers, M D

    1999-10-01

    Previous reports indicate that mutations within the Autographa californica nucleopolyhedrosis virus FP25K gene (open reading frame 61) significantly reduce incorporation of enveloped nucleocapsids into viral occlusions. We report that FP25K is a nucleocapsid protein of both the budded virus (BV) and occluded virus (ODV), and we describe the effects of two FP25K mutations (480-1 [N-terminal truncation] and FP-betagal [C-terminal fusion]) on the expression and cellular localization of ODV-E66 and ODV-E25. Significantly decreased amounts of ODV-E66 are detected in cells infected with 480-1 or FP-betagal viral mutants, even though during FP-betagal infection, steady-state levels of ODV-E66 transcripts remain unchanged. While ODV-E66 is normally detected in intranuclear microvesicles and ODV envelopes by 24 h postinfection (p.i.), ODV-E66 remains cytosolic throughout infection in cells infected with 480-1 virus (up to 96 h p.i.), and its intranuclear localization is not detected until 96 h p.i. in cells infected with the FP-betagal mutant virus. The nuclear localization of ODV-E25 is not affected during infection by the FP-betagal mutant; however, its trafficking is significantly delayed during infection by the 480-1 mutant. Temporal Western blot analyses of cell lysates show that both 480-1 and FP-betagal mutant virus infections result in altered accumulation patterns of several structural proteins, including gp67, BV/ODV-E26, and the major capsid protein p39. In addition to BV/ODV-E26, ODV-E66 and gp67 may interact with FP25K, and ODV-E25 and p39 may also be components of a protein complex containing ODV-E66 and FP25K. Together, these data suggest that FP25K and its associated protein complex(es) may play an important role in the targeting and intracellular transport of viral proteins during infection.

  2. Baculovirus FP25K Localization: Role of the Coiled-Coil Domain.

    PubMed

    Garretson, Tyler A; McCoy, Jason C; Cheng, Xiao-Wen

    2016-11-01

    Two types of viruses are produced during the baculovirus life cycle: budded virus (BV) and occlusion-derived virus (ODV). A particular baculovirus protein, FP25K, is involved in the switch from BV to ODV production. Previously, FP25K from the model alphabaculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) was shown to traffic ODV envelope proteins. However, FP25K localization and the domains involved are inconclusive. Here we used a quantitative approach to study FP25K subcellular localization during infection using an AcMNPV bacmid virus that produces a functional AcMNPV FP25K-green fluorescent protein (GFP) fusion protein. During cell infection, FP25K-GFP localized primarily to the cytoplasm, particularly amorphous structures, with a small fraction being localized in the nucleus. To investigate the sequences involved in FP25K localization, an alignment of baculovirus FP25K sequences revealed that the N-terminal putative coiled-coil domain is present in all alphabaculoviruses but absent in betabaculoviruses. Structural prediction indicated a strong relatedness of AcMNPV FP25K to long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p), which contains an N-terminal coiled-coil domain responsible for cytoplasmic retention. Point mutations and deletions of this domain lead to a change in AcMNPV FP25K localization from cytoplasmic to nuclear. The coiled-coil and C-terminal deletion viruses increased BV production. Furthermore, a betabaculovirus FP25K protein lacking this N-terminal coiled-coil domain localized predominantly to the nucleus and exhibited increased BV production. These data suggest that the acquisition of this N-terminal coiled-coil domain in FP25K is important for the evolution of alphabaculoviruses. Moreover, with the divergence of preocclusion nuclear membrane breakdown in betabaculoviruses and membrane integrity in alphabaculoviruses, this domain represents an alphabaculovirus adaptation for nuclear trafficking

  3. Reduction of polyhedrin mRNA and protein expression levels in Sf9 and Hi5 cell lines, but not in Sf21 cells, infected with Autographa californica multiple nucleopolyhedrovirus fp25k mutants.

    PubMed

    Cheng, Xin-Hua; Hillman, Christopher C; Zhang, Chuan-Xi; Cheng, Xiao-Wen

    2013-01-01

    During cell infection, the fp25k gene of baculoviruses frequently mutates, producing the few polyhedra (FP) per cell phenotype with reduced polyhedrin (polh) expression levels compared with wild-type baculoviruses. Here we report that the fp25k gene of the model baculovirus, Autographa californica multiple nucleopolyhedrovirus (AcMNPV), contains two hypermutable seven-adenine (A7) mononucleotide repeats (MNRs) that were mutated to A8 MNRs and a TTAA site that had host DNA insertions, producing fp25k mutants during Sf21 cell infection. The FP phenotype in Sf9 and Hi5 cells was more pronounced than in Sf21 cells. AcMNPV fp25k mutants produced similar levels of polyhedra or enhanced GFP, which were both under the control of the AcMNPV polh promoter for expression, in Sf21 cells but lower levels in Sf9 and Hi5 cells compared with AcMNPV with an intact fp25k gene. This correlated with the polh mRNA levels detected in each cell line. The majority of Sf21 cells infected with fp25 mutants showed high polh promoter-mediated GFP expression levels. Two cell lines subcloned from Sf21 cells that were infected with fp25k mutants showed different GFP expression levels. Furthermore, a small proportion of Hi5 cells infected with fp25k mutants showed higher production of polyhedra and GFP expression than the rest, and the latter was not correlated with increased m.o.i. Therefore, these data suggest that AcMNPV polh promoter-mediated gene expression activities differ in the three cell lines and are influenced by different cells within the cell line.

  4. Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42.

    PubMed Central

    Shinjo, K; Koland, J G; Hart, M J; Narasimhan, V; Johnson, D I; Evans, T; Cerione, R A

    1990-01-01

    We have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated Gp (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human Gp protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins (approximately 50% identical), and the rac proteins (approximately 70% identical). The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell-division-cycle protein CDC42. The human placental gene, which we designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein. Images PMID:2124704

  5. Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42.

    PubMed

    Shinjo, K; Koland, J G; Hart, M J; Narasimhan, V; Johnson, D I; Evans, T; Cerione, R A

    1990-12-01

    We have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated Gp (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human Gp protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins (approximately 50% identical), and the rac proteins (approximately 70% identical). The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell-division-cycle protein CDC42. The human placental gene, which we designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein.

  6. Molecular cloning of the gene for the human placental GTP-binding protein G sub p (G25K): Identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42

    SciTech Connect

    Shinjo, K.; Koland, J.G.; Hart, M.J.; Narasimhan, V.; Cerione, R.A. ); Johnson, D.I. ); Evans, T. )

    1990-12-01

    The authors have isolated cDNA clones from a human placental library that code for a low molecular weight GTP-binding protein originally designated G{sub p} (also called G25K). This identification is based on comparisons with the available peptide sequences for the purified human G{sub p} protein and the use of two highly specific anti-peptide antibodies. The predicted amino acid sequence of the protein is very similar to those of various members of the ras superfamily of low molecular weight GTP-binding proteins, including the N-, Ki-, and Ha-ras proteins (30-35% identical), the rho proteins and the rac proteins. The highest degree of sequence identity (80%) is found with the Saccharomyces cerevisiae cell division-cycle protein CDC42. The human placental gene, which they designate CDC42Hs, complements the cdc42-1 mutation in S. cerevisiae, which suggests that this GTP-binding protein is the human homolog of the yeast protein.

  7. 25 kW power module evolution study

    NASA Technical Reports Server (NTRS)

    Overall, J. W., Jr.

    1979-01-01

    This paper presents a study of evolutionary growth concepts for the 25 kW power module to augment STS mission support future capabilities. The study aimed to establish user payload requirements, define evolution methods for system initial operational capability, and formulate a development program and conceptual designs. The payload requirements analysis focused on material processing in space, public services, and solar terrestrial observations; evolutionary system concepts were evaluated to derive the power module and system support requirements, and four reference orbits were used to construct the nominal program scenario. The mission accomodations analysis evaluated the capability of the nominal program scenario and associated power module concepts to meet user needs. Finally, the recommended modular design consisting of electric power, attitude control, thermal control, and command and data handling is described, and it is concluded that the 25 kW power module is a logical first step to support the near term NASA sortie and free-flyer mission requirements.

  8. K25/K27 Characterization for Demonstrating Criticality Incredibility K-25 / K-27 D and D Project

    SciTech Connect

    Haghighi, Mahmoud H.; Howe, Kathleen E.; Chandler, John R.

    2008-01-15

    The K-25 and K-27 Buildings are currently undergoing decontamination and decommissioning (D and D) as part of a non-time critical removal action. When the enrichment process was shut-down, the process gas equipment and piping was purged to remove UF{sub 6}, but the process gas system was not generally chemically treated to remove solid holdup. Generally, chemical treatment was completed it was not very effective in removing the larger deposits. Because of this, uranium deposits continue to reside throughout the process gas system. There is the potential for unreacted UF{sub 6} to be present, as well. A key part of this project is to locate the remaining significant uranium deposits and manage them appropriately. Since some process gas components in the K-25 and K-27 Buildings contain enriched uranium holdup, it is important to ensure nuclear criticality safety during demolition or subsequent loading and transport of waste. Therefore, a major task in preparation for demolition is to demonstrate that 'criticality is incredible (CI)' in each building area. The U.S. Department of Energy (DOE) and Bechtel Jacobs Company LLC (BJC) are in agreement that proper and thorough characterization of fissile holdup material in the K-25 and K-27 process gas components is a key element in achieving and demonstrating that criticality is incredible, as well as in management of demolition wastes and collection of holdup material. While the classic project scheduling wisdom may indicate that performing all of the data quality objectives (DQO) and planning before the field work starts, the size of the K-25 / K-27 D and D Project combined with the evolving decommissioning plans and re-plans have indicated that a fresh look at what further characterization data are needed to meet the current project requirements. Performing a DQO in the middle of the project allowed a much greater degree of accuracy of the real project data needs than was possible even 22 months ago. The outcome of the

  9. E2-25K SUMOylation inhibits proteasome for cell death during cerebral ischemia/reperfusion

    PubMed Central

    Jeong, Eun Il; Chung, Hae Won; Lee, Won Jea; Kim, Seo-Hyun; Kim, Hyunjoo; Choi, Seon-Guk; Jung, Yong-Keun

    2016-01-01

    Cerebral ischemia/reperfusion (I/R) causes brain damage accompanied by ubiquitin accumulation and impairment of proteasome activity. In this study, we report that E2-25K, an E2-conjugating enzyme, is SUMOylated during oxidative stress and regulates cerebral I/R-induced damage. Knockdown of E2-25K expression protects against oxygen/glucose deprivation and reoxygenation (OGD/R)-induced neuronal cell death, whereas ectopic expression of E2-25K stimulates it. Compared with the control mice, cerebral infarction lesions and behavioral/neurological disorders are ameliorated in E2-25K knockout mice during middle cerebral artery occlusion and reperfusion. In particular, E2-25K is SUMOylated at Lys14 under oxidative stress, OGD/R and I/R to prompt cell death. Further, E2-25K downregulates the proteasome subunit S5a to impair proteasome complex and thus restrain proteasome activity under oxidative stress. This proteasome inhibitory activity of E2-25K is dependent on its SUMOylation. These results suggest that E2-25K has a crucial role in oxidative stress and cerebral I/R-induced damage through inhibiting proteasome via its SUMOylation. PMID:28032866

  10. The 25 kW power module evolution study. Part 2: Payload supports system evolution

    NASA Technical Reports Server (NTRS)

    1978-01-01

    The addition of system elements for the 25 kW power module and logical evolutionary paths, by discrete growth stages, to provide capability for accommodating the increasing mission requirements through the early 1990's within reasonable resources are conceptualized.

  11. Draft Genome Sequence of Enterotoxigenic Escherichia coli Strain W25K.

    PubMed

    Ren, Wenkai; Liu, Gang; Yin, Jie; Chen, Shuai; Li, Tiejun; Kong, Xiangfeng; Peng, Yuanyi; Yin, Yulong; Hardwidge, Philip R

    2014-06-26

    Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease in humans and newly weaned pigs. Here, we report the draft genome sequence of ETEC strain W25K, which causes diarrhea in piglets.

  12. Draft Genome Sequence of Enterotoxigenic Escherichia coli Strain W25K

    PubMed Central

    Ren, Wenkai; Liu, Gang; Yin, Jie; Chen, Shuai; Li, Tiejun; Kong, Xiangfeng; Peng, Yuanyi; Hardwidge, Philip R.

    2014-01-01

    Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease in humans and newly weaned pigs. Here, we report the draft genome sequence of ETEC strain W25K, which causes diarrhea in piglets. PMID:24970825

  13. Knockdown of pre-mRNA cleavage factor Im 25 kDa promotes neurite outgrowth

    SciTech Connect

    Fukumitsu, Hidefumi; Soumiya, Hitomi; Furukawa, Shoei

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer CFIm25 knockdown promoted NGF-induced neurite out growth from PC12 cells. Black-Right-Pointing-Pointer Depletion of CFIm25 did not influence the morphology of proliferating PC12 cells. Black-Right-Pointing-Pointer CFIm regulated NGF-induced neurite outgrowth via coordinating RhoA activity. Black-Right-Pointing-Pointer CFIm25 knockdown increase the number of primary dendrites of hippocampal neurons. -- Abstract: Mammalian precursor mRNA (pre-mRNA) cleavage factor I (CFIm) plays important roles in the selection of poly(A) sites in a 3 Prime -untranslated region (3 Prime -UTR), producing mRNAs with variable 3 Prime ends. Because 3 Prime -UTRs often contain cis elements that impact stability or localization of mRNA or translation, alternative polyadenylation diversifies utilization of primary transcripts in mammalian cells. However, the physiological role of CFIm remains unclear. CFIm acts as a heterodimer comprising a 25 kDa subunit (CFIm25) and one of the three large subunits-CFIm59, CFIm68, or CFIm72. CFIm25 binds directly to RNA and introduces and anchors the larger subunit. To examine the physiological roles of CFIm, we knocked down the CFIm25 gene in neuronal cells using RNA interference. Knockdown of CFIm25 increased the number of primary dendrites of developing hippocampal neurons and promoted nerve growth factor (NGF)-induced neurite extension from rat pheochromocytoma PC12 cells without affecting the morphology of proliferating PC12 cells. On the other hand, CFIm25 knockdown did not influence constitutively active or dominantly negative RhoA suppression or promotion of NGF-induced neurite extension from PC12 cells, respectively. Taken together, our results indicate that endogenous CFIm may promote neuritogenesis in developing neurons by coordinating events upstream of NGF-induced RhoA inactivation.

  14. Dielectric relaxation near 25 K in multiferroic BiFeO3 ceramics

    NASA Astrophysics Data System (ADS)

    Ramachandran, B.; Dixit, A.; Naik, R.; Lawes, G.; Ramachandra Rao, M. S.

    2011-11-01

    Our investigations using low-temperature Raman spectroscopy, dielectric, and magnetodielectric studies of as-prepared and vacuum-annealed BiFeO3 ceramics revealed two dielectric anomalies near 25 and 281 K. Systematic studies were carried out to probe the anomaly near 25 K which exhibits clear frequency dependence and falls close to a previously observed magnetic transition. The low-temperature dielectric relaxation behavior yielded characteristic energy scales of ˜30 and ˜34 meV for the as-prepared and vacuum-annealed BiFeO3 samples, respectively. Raman spectra showed hardening of the E(TO6) and E(TO9) modes near 25 K, and the Raman shift in phonon frequencies is found to be broader in the vacuum-annealed BiFeO3 than in the as-prepared BiFeO3. We observed a linear magnetodielectric coupling in both samples at 25 K. These experimental results suggest that coupling among spin, lattice, and dielectric properties persist to low temperatures in BiFeO3.

  15. A hybrid Michelson-FP interference fiber sensor

    NASA Astrophysics Data System (ADS)

    Liu, Zhihai; Zhang, Yaxun; Wang, Zhenzhen; Zhang, Yu; Zhao, Enming; Zhou, Ai; Yuan, Libo

    2015-09-01

    A novel hybrid Michelson-FP (M-FP) interference fiber sensor based on a twin-core fiber has been proposed. It consists of an in-fiber integrated Michelson interferometer and an air FP cavities. The radial strain and axial strain sensing properties are explored and analyzed. By using this novel structure, we can measure radial strain and axial strain simultaneously.

  16. The 25 kW power module evolution study. Part 1: Payload requirements and growth scenarios

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Payload power level requirements and their general impact on the baseline and growth versions of the 25 kW power module during the 1983 to 1990 period are discussed. Extended duration Orbiter sortie flight, supported by a power module, with increased payload power requirements per flight, and free-flyer payload missions are included. Other payload disciplines considered, but not emphasized for the 1983 to 1986 period include astrophysics/astronomy, earth observations, solar power satellite, and life sciences. Of these, only the solar power satellite is a prime driver for the power module.

  17. Assessment of 25 kW free-piston Stirling technology alternatives for solar applications

    NASA Technical Reports Server (NTRS)

    Erbeznik, Raymond M.; White, Maurice A.; Penswick, L. B.; Neely, Ronald E.; Ritter, Darren C.; Wallace, David A.

    1992-01-01

    The final design, construction, and testing of a 25-kW free-piston advanced Stirling conversion system (ASCS) are examined. The final design of the free-piston hydraulic ASCS consists of five subsystems: heat transport subsystem (solar receiver and pool boiler), free-piston hydraulic Stirling engine, hydraulic subsystem, cooling subsystem, and electrical and control subsystem. Advantages and disadvantages are identified for each technology alternative. Technology alternatives considered are gas bearings vs flexure bearings, stationary magnet linear alternator vs moving magnetic linear alternator, and seven different control options. Component designs are generated using available in-house procedures to meet the requirements of the free-piston Stirling convertor configurations.

  18. A Langmuir Blodgett film presenting a ferromagnetic state below 25 K

    NASA Astrophysics Data System (ADS)

    Lafuente, C.; Mingotaud, C.; Delhaes, P.

    1999-03-01

    A positively charged monolayer spread on a sub-phase containing copper hexacyanoferrate leads to hybrid inorganic-organic LB films. Those multilayers present a spin ordering below 25 K. The Curie temperature of the LB films is found to be independent of the multilayer thickness. Their magnetization is clearly proportional to the number of transferred layers, demonstrating that the deposition process is perfectly regular. These results show that a bulk ferromagnetic behavior can be observed in this hybrid material, even if the distance between magnetic layers is considered as large.

  19. Three-year performance study of the Mead, Nebraska, 25-kWp photovoltaic power system

    NASA Astrophysics Data System (ADS)

    Bullwinkel, H. J.; Hopkinson, R. F.

    1981-03-01

    The performance of a 25 kWp photovoltaic (PV) solar energy system was studied. Electrical energy produced by the PV system provided 100% of the power needed throughout the growing season to meet the irrigation requirements for an 80 acre cornfield, as well as significant portions of power required for PV related crop drying and fertilizer manufacturing experiments. Field data indicate that the PV system performs up to expectations, if allowance is made for component degradation and seasonal soil/snow accumulation on the array.

  20. A programmable power processor for a 25 kW power module. [on Shuttle Orbiter

    NASA Technical Reports Server (NTRS)

    Kapustka, R. E.; Lanier, J. R., Jr.

    1978-01-01

    The paper presents the concept and major design problems of a programmable power processor for the 25 kW electrical power system for the Shuttle Orbiter. The load will be handled by three parallel power stages operated in phase sequence with each power transistor having its own commutating diode and filter inductor. The power stages will be run at a fixed frequency of 10 kHz with the 'on'-time variable up to 100%. The input filter bank in the breadboard programmable power processor is planned to be a series-parallel combination of tantalum cased tantalum wet-slug capacitors.

  1. Assessment of 25 kW free-piston Stirling technology alternatives for solar applications

    NASA Astrophysics Data System (ADS)

    Erbeznik, Raymond M.; White, Maurice A.; Penswick, L. B.; Neely, Ronald E.; Ritter, Darren C.; Wallace, David A.

    The final design, construction, and testing of a 25-kW free-piston advanced Stirling conversion system (ASCS) are examined. The final design of the free-piston hydraulic ASCS consists of five subsystems: heat transport subsystem (solar receiver and pool boiler), free-piston hydraulic Stirling engine, hydraulic subsystem, cooling subsystem, and electrical and control subsystem. Advantages and disadvantages are identified for each technology alternative. Technology alternatives considered are gas bearings vs flexure bearings, stationary magnet linear alternator vs moving magnetic linear alternator, and seven different control options. Component designs are generated using available in-house procedures to meet the requirements of the free-piston Stirling convertor configurations.

  2. Theoretical spectroscopy and the fp shell

    NASA Astrophysics Data System (ADS)

    Poves, A.; Zuker, A.

    1981-04-01

    The recently developed quasiconfiguration method is applied to fp shell nuclei. Second order degenerate perturbation theory is shown to be sufficient to produce, for low lying states, the same results as large diagonalizations in the full ( f{7}/{2}p{3}/{2}p{1}/{2}f{5}/{2}) n space, due to the operation of linked cluster mechanisms. Realistic interactions with minimal monopole changes are shown to be successful in reproducing spectra, binding energies, quadrupole moments and transition rates. Large shell model spaces are seen to exhibit typical many body behaviour. Quasiconfigurations allow insight into the underlying coupling schemes.

  3. 20 kHz, 25 kVA node power transformer

    NASA Technical Reports Server (NTRS)

    Hussey, S.

    1989-01-01

    The electrical and mechanical design information and the electrical and thermal testing performed on the 440-208-V rms, 20-kHz, 25-kVa prototype node transformer are summarized. The calculated efficiency of the node transformer is 99.3 percent based on core loss and copper loss test data, and its maximum calculated load regulation is 0.7 percent. The node transformer has a weight of 19.7 lb and has a power density of 0.8 lb/kW. The hot-spot temperature rise is estimated to be 33 C above the cold plate mounting base. This proof-of-concept transformer design is a viable candidate for the space station Freedom application.

  4. Engineering aspects of a thermal control subsystem for the 25 kW power module

    NASA Technical Reports Server (NTRS)

    Schroeder, P. E.

    1979-01-01

    The paper presents the key trade study results, analysis results, and the recommended thermal control approach for the 25 kW power module defined by NASA. Power conversion inefficiencies and component heat dissipation results in a minimum heat rejection requirement of 9 kW to maintain the power module equipment at desired temperature levels. Additionally, some cooling capacity should be provided for user payloads in the sortie and free-flying modes. The baseline thermal control subsystem includes a dual-loop-pumped Freon-21 coolant with the heat rejected from deployable existing orbiter radiators. Thermal analysis included an assessment of spacecraft orientations, radiator shapes and locations, and comparison of hybrid heat pipe and all liquid panels.

  5. Design of a 25-kWe Surface Reactor System Based on SNAP Reactor Technologies

    NASA Astrophysics Data System (ADS)

    Dixon, David D.; Hiatt, Matthew T.; Poston, David I.; Kapernick, Richard J.

    2006-01-01

    A Hastelloy-X clad, sodium-potassium (NaK-78) cooled, moderated spectrum reactor using uranium zirconium hydride (UZrH) fuel based on the SNAP program reactors is a promising design for use in surface power systems. This paper presents a 98 kWth reactor for a power system the uses multiple Stirling engines to produce 25 kWe-net for 5 years. The design utilizes a pin type geometry containing UZrHx fuel clad with Hastelloy-X and NaK-78 flowing around the pins as coolant. A compelling feature of this design is its use of 49.9% enriched U, allowing it to be classified as a category III-D attractiveness and reducing facility costs relative to highly-enriched space reactor concepts. Presented below are both the design and an analysis of this reactor's criticality under various safety and operations scenarios.

  6. The 25 kW resonant dc/dc power converter

    NASA Technical Reports Server (NTRS)

    Robson, R. R.

    1983-01-01

    The feasibility of processing 25-kW of power with a single, transistorized, series resonant converter stage was demonstrated by the successful design, development, fabrication, and testing of such a device which employs four Westinghouse D7ST transistors in a full-bridge configuration and operates from a 250-to-350 Vdc input bus. The unit has an overall worst-case efficiency of 93.5% at its full rated output of 1000 V and 25 A dc. A solid-state dc input circuit breaker and output-transient-current limiters are included in and integrated into the design. Full circuit details of the converter are presented along with the test data.

  7. Validation and substantiation of 25 kGy as sterilization dose for lyophilized human amnion membrane.

    PubMed

    Djefal, A; Tahtat, D; Khodja, A Nacer; Bouzid, S Saad; Remane, N

    2007-01-01

    The validation and substantiation of sterilization dose for lyophilized human amnion membrane by gamma irradiation delivered by Co60 source were investigated. The validation experiments were conducted according to ISO 13409 method B. A total of 120 human amnion membranes were collected. Of these, 10 membranes were used for estimation of bioburden and 20 membranes were used for the individual sterility test at verification dose. The average bioburden per product unit with sample item portion (SIP = 1) for lyophilized human amnion membrane was 572 cfu. The verification dose experiments were done at dose of 8.1 kGy and the results of sterility tests showed that human amnion membrane got one positive. Consequently, the sterilization dose of 25 kGy was confirmed and substantiated.

  8. Design of a 25-kWe Surface Reactor System Based on SNAP Reactor Technologies

    SciTech Connect

    Dixon, David D.; Hiatt, Matthew T.; Poston, David I.; Kapernick, Richard J.

    2006-01-20

    A Hastelloy-X clad, sodium-potassium (NaK-78) cooled, moderated spectrum reactor using uranium zirconium hydride (UZrH) fuel based on the SNAP program reactors is a promising design for use in surface power systems. This paper presents a 98 kWth reactor for a power system the uses multiple Stirling engines to produce 25 kWe-net for 5 years. The design utilizes a pin type geometry containing UZrHx fuel clad with Hastelloy-X and NaK-78 flowing around the pins as coolant. A compelling feature of this design is its use of 49.9% enriched U, allowing it to be classified as a category III-D attractiveness and reducing facility costs relative to highly-enriched space reactor concepts. Presented below are both the design and an analysis of this reactor's criticality under various safety and operations scenarios.

  9. Gifford-McMahon/Joule-Thomson Refrigerator Cools to 2.5 K

    NASA Technical Reports Server (NTRS)

    Britcliffe, Michael; Fernandez, Jose; Hanson, Theodore

    2005-01-01

    A compact refrigerator designed specifically for cooling a microwave maser low-noise amplifier is capable of removing heat at a continuous rate of 180 mW at a temperature of 2.5 K. This refrigerator is a combination of (1) a commercial Gifford-McMahon (GM) refrigerator nominally rated for cooling to 4 K and (2) a Joule-Thomson (J-T) circuit. The GM refrigerator pre-cools the J-T circuit, which provides the final stage of cooling. The refrigerator is compact and capable of operating in any orientation. Moreover, in comparison with a typical refrigerator heretofore used to cool a maser to 4.5 K, this refrigerator is simpler and can be built at less than half the cost.

  10. Status of the advanced Stirling conversion system project for 25 kW dish Stirling applications

    NASA Astrophysics Data System (ADS)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    Technology development for Stirling convertors directed toward a dynamic power source for space applications is discussed. Space power requirements include high reliability with very long life, low vibration, and high system efficiency. The free-piston Stirling engine has the potential for future high power space conversion systems, either nuclear or solar powered. Although these applications appear to be quite different, their requirements complement each other. The advanced Stirling conversion system (ASCS) project at NASA Lewis Research Center is described. Each system design features a solar receiver/liquid metal heat transport system and a free-piston Stirling convertor with a means to provide nominally 25 kW of electric power to utility grid while meeting the US Department of Energy (DOE) performance and long term cost goals. The design is compared with other ASCS designs.

  11. The 25 kW resonant dc/dc power converter

    NASA Astrophysics Data System (ADS)

    Robson, R. R.

    1983-09-01

    The feasibility of processing 25-kW of power with a single, transistorized, series resonant converter stage was demonstrated by the successful design, development, fabrication, and testing of such a device which employs four Westinghouse D7ST transistors in a full-bridge configuration and operates from a 250-to-350 Vdc input bus. The unit has an overall worst-case efficiency of 93.5% at its full rated output of 1000 V and 25 A dc. A solid-state dc input circuit breaker and output-transient-current limiters are included in and integrated into the design. Full circuit details of the converter are presented along with the test data.

  12. A 25kW fiber-coupled diode laser for pumping applications

    NASA Astrophysics Data System (ADS)

    Malchus, Joerg; Krause, Volker; Koesters, Arnd; Matthews, David G.

    2014-03-01

    In this paper we report the development of a new fiber-coupled diode laser for pumping applications capable of generating 25 kW with four wavelengths. The delivery fiber has 2.0 mm core diameter and 0.22 NA resulting in a Beam Parameter Product (BPP) of 220 mm mrad. To achieve the specifications mentioned above a novel beam transformation technique has been developed combining two high power laser stacks in one common module. After fast axis collimation and beam reformatting a beam with a BPP of 200 mm mrad x 40 mm mrad in the slow and fast-axis is generated. Based on this architecture a customer-specific pump laser with 25 kW optical output power has been developed, in which two modules are polarization multiplexed for each wavelength (980nm, 1020nm, 1040m and 1060nm). After slow-axis collimation these wavelengths are combined using dense wavelength coupling before focusing onto the fiber endface. This new laser is based on a turn-key platform, allowing straight-forward integration into any pump application. The complete system has a footprint of less than 1.4m² and a height of less than 1.8m. The laser diodes are water cooled, achieve a wall-plug efficiency of up to 60%, and have a proven lifetime of <30,000 hours. The new beam transformation techniques open up prospects for the development of pump sources with more than 100kW of optical output power.

  13. Operation of the 25kW NASA Lewis Research Center Solar Regenerative Fuel Cell Tested Facility

    NASA Technical Reports Server (NTRS)

    Moore, S. H.; Voecks, G. E.

    1997-01-01

    Assembly of the NASA Lewis Research Center(LeRC)Solar Regenerative Fuel Cell (RFC) Testbed Facility has been completed and system testing has proceeded. This facility includes the integration of two 25kW photovoltaic solar cell arrays, a 25kW proton exchange membrane (PEM) electrolysis unit, four 5kW PEM fuel cells, high pressure hydrogen and oxygen storage vessels, high purity water storage containers, and computer monitoring, control and data acquisition.

  14. Lazy evaluation of FP programs: A data-flow approach

    SciTech Connect

    Wei, Y.H.; Gaudiot, J.L.

    1988-12-31

    This paper presents a lazy evaluation system for the list-based functional language, Backus` FP in data-driven environment. A superset language of FP, called DFP (Demand-driven FP), is introduced. FP eager programs are transformed into DFP lazy programs which contain the notions of demands. The data-driven execution of DFP programs has the same effects of lazy evaluation. DFP lazy programs have the property of always evaluating a sufficient and necessary result. The infinite sequence generator is used to demonstrate the eager-lazy program transformation and the execution of the lazy programs.

  15. Biomolecular solid state NMR with magic-angle spinning at 25 K

    PubMed Central

    Thurber, Kent R.; Tycko, Robert

    2009-01-01

    A magic-angle spinning (MAS) probe has been constructed which allows the sample to be cooled with helium, while the MAS bearing and drive gases are nitrogen. The sample can be cooled to 25 K using roughly 3 liters/hour of liquid helium, while the 4 mm diameter rotor spins at 6.7 kHz with good stability (±5 Hz) for many hours. Proton decoupling fields up to at least 130 kHz can be applied. This helium-cooled MAS probe enables a variety of one-dimensional and two-dimensional NMR experiments on biomolecular solids and other materials at low temperatures, with signal-to-noise proportional to 1/T. We show examples of low-temperature 13C NMR data for two biomolecular samples, namely the peptide Aβ14–23 in the form of amyloid fibrils and the protein HP35 in frozen glycerol/water solution. Issues related to temperature calibration, spin-lattice relaxation at low temperatures, paramagnetic doping of frozen solutions, and 13C MAS NMR linewidths are discussed. PMID:18922715

  16. Preliminary designs for 25 kWe advanced Stirling conversion systems for dish electric applications

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    1990-01-01

    Under the Department of Energy's (DOE) Solar Thermal Technology Program, Sandia National Laboratories is evaluating heat engines for terrestrial Solar Distributed Heat Receivers. The Stirling engine has been identified by Sandia as one of the most promising engines for terrestrial applications. The Stirling engine also has the potential to meet DOE's performance and cost goals. The NASA Lewis Research Center is conducting Stirling engine technology development activities directed toward a dynamic power source for space applications. Space power systems requirements include high reliability, very long life, low vibration and high efficiency. The free-piston Stirling engine has the potential for future high power space conversion systems, either nuclear or solar powered. Although both applications appear to be quite different, their requirements complement each other. Preliminary designs feature a free-piston Stirling engine, a liquid metal heat transport system, and a means to provide nominally 25 kW electric power to a utility grid while meeting DOE's performance and long term cost goals. The Cummins design incorporates a linear alternator to provide the electrical output, while the STC design generates electrical power indirectly through a hydraulic pump/motor coupled to an induction generator. Both designs for the ASCS's will use technology which can reasonably be expected to be available in the early 1990's.

  17. Pool boiler heat transport system for a 25 kWe advanced Stirling conversion system

    NASA Technical Reports Server (NTRS)

    Anderson, W. G.; Rosenfeld, J. H.; Saaski, E. L.; Noble, J.; Tower, L.

    1990-01-01

    Experiments to determine alkali metal/enhanced surface combinations that have stable boiling at the temperatures and heat fluxes that occur in the Stirling engine are reported. Two enhanced surfaces and two alkali metal working fluids were evaluated. The enhanced surfaces were an EDM hole covered surface and a sintered-powder-metal porous layer surface. The working fluids tested were potassium and eutectic sodium-potasium alloy (NaK), both with and without undissolved noncondensible gas. Noncondensible gas (He and Xe) was added to the system to provide gas in the nucleation sites, preventing quenching of the sites. The experiments demonstrated the potential of an alkali metal pool boiler heat transport system for use in a solar-powered Stirling engine. The most favorable fluid/surface combination tested was NaK boiling on a -100 +140 mesh 304L stainless steel sintered porous layer with no undissolved noncondensible gas. This combination provided stable, high-performance boiling at the operating temperature of 700 C. Heat fluxes into the system ranged from 10 to 50 W/sq cm. The transition from free convection to nucleate boiling occurred at temperatures near 540 C. Based on these experiments, a pool boiler was designed for a full-scale 25-kWe Stirling system.

  18. Alkali metal pool boiler life tests for a 25 kWe advanced Stirling conversion system

    NASA Technical Reports Server (NTRS)

    Anderson, W. G.; Rosenfeld, J. H.; Noble, J.

    1991-01-01

    The overall operating temperature and efficiency of solar-powered Stirling engines can be improved by adding an alkali metal pool boiler heat transport system to supply heat more uniformly to the heater head tubes. One issue with liquid metal pool boilers is unstable boiling. Stable boiling is obtained with an enhanced boiling surface containing nucleation sites that promote continuous boiling. Over longer time periods, it is possible that the boiling behavior of the system will change. An 800-h life test was conducted to verify that pool boiling with the chosen fluid/surface combination remains stable as the system ages. The apparatus uses NaK boiling on a - 100 + 140 stainless steel sintered porous layer, with the addition of a small amount of xenon. Pool boiling remained stable to the end of life test. The pool boiler life test included a total of 82 cold starts, to simulate startup each morning, and 60 warm restarts, to simulate cloud cover transients. The behavior of the cold and warm starts showed no significant changes during the life test. In the experiments, the fluid/surface combination provided stable, high-performance boiling at the operating temperature of 700 C. Based on these experiments, a pool boiler was designed for a full-scale 25-kWe Stirling system.

  19. The 25 kWe solar thermal Stirling hydraulic engine system: Conceptual design

    NASA Technical Reports Server (NTRS)

    White, Maurice; Emigh, Grant; Noble, Jack; Riggle, Peter; Sorenson, Torvald

    1988-01-01

    The conceptual design and analysis of a solar thermal free-piston Stirling hydraulic engine system designed to deliver 25 kWe when coupled to a 11 meter test bed concentrator is documented. A manufacturing cost assessment for 10,000 units per year was made. The design meets all program objectives including a 60,000 hr design life, dynamic balancing, fully automated control, more than 33.3 percent overall system efficiency, properly conditioned power, maximum utilization of annualized insolation, and projected production costs. The system incorporates a simple, rugged, reliable pool boiler reflux heat pipe to transfer heat from the solar receiver to the Stirling engine. The free-piston engine produces high pressure hydraulic flow which powers a commercial hydraulic motor that, in turn, drives a commercial rotary induction generator. The Stirling hydraulic engine uses hermetic bellows seals to separate helium working gas from hydraulic fluid which provides hydrodynamic lubrication to all moving parts. Maximum utilization of highly refined, field proven commercial components for electric power generation minimizes development cost and risk.

  20. Crystal Structure of the 25 kDa Subunit of Human Cleavage Factor I{m}

    SciTech Connect

    Coseno,M.; Martin, G.; Berger, C.; Gilmartin, G.; Keller, W.; Doublie, S.

    2008-01-01

    Cleavage factor Im is an essential component of the pre-messenger RNA 3'-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor Im is an oligomer composed of a small 25 kDa subunit (CF Im25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein-protein interactions are thought to be facilitated by the Nudix domain of CF Im25, a hydrolase motif with a characteristic {alpha}/{beta}/{alpha} fold and a conserved catalytic sequence or Nudix box. We present here the crystal structures of human CF Im25 in its free and diadenosine tetraphosphate (Ap4A) bound forms at 1.85 and 1.80 Angstroms, respectively. CF Im25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF Im25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap4A. The complex and apo protein structures provide insight into the active oligomeric state of CF Im and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3'-end processing.

  1. Operation of the 25 kW NASA Lewis Solar Regenerative Fuel Cell Testbed Facility

    SciTech Connect

    Voecks, G.E.; Rohatgi, N.K.; Moore, S.H.

    1996-12-31

    Assembly of the NASA Lewis Research Center Solar Regenerative Fuel Cell Testbed Facility has recently been completed and system testing is in progress. This facility includes the integration of 50 kW photovoltaic solar cell arrays, a 25 kW proton exchange membrane (PEM) electrolysis unit, four 5 kW PEM fuel cells, high pressure hydrogen and oxygen storage vessels, high purity water storage containers, and computer monitoring, control and data acquisition. The purpose of this facility is multi-faceted, but was originally intended to serve as a testbed for evaluating a closed-loop powerplant for future NASA extended life support operations, such as a Lunar outpost, and also as a terrestrial powerplant example for remote or continuous back-up support operations. The fuel cell and electrolyzer subsystems design and assembly were conducted by the Jet Propulsion Laboratory (JPL), the photovoltaic arrays and electrical interconnect to the electrolyzer were provided by the US Navy/China Lake Naval Weapons Center, and testing and operations are being carried out by JPL.

  2. Concentrated solar power on demand demonstration: Construction and operation of a 25 kW prototype

    NASA Astrophysics Data System (ADS)

    Gil, Antoni; Codd, Daniel S.; Zhou, Lei; Trumper, David; Calvet, Nicolas; Slocum, Alexander H.

    2016-05-01

    Currently, the majority of concentrated solar power (CSP) plants built worldwide integrate thermal energy storage (TES) systems which enable dispatchable output and higher global plant efficiencies. TES systems are typically based on two tank molten salt technology which involves inherent drawbacks such as parasitic pumping losses and electric tracing of pipes, risk of solidification and high capital costs. The concept presented in this paper is based on a single tank where the concentrated sunlight is directly focused on the molten salt. Hot and cold volumes of salt (at 565 °C and 280 °C, respectively) are axially separated by an insulated divider plate which helps maintain the thermal gradient. The concept, based on existing technologies, seeks to avoid the listed drawbacks as well as reducing the final cost of the TES system. In order to demonstrate its feasibility, Masdar Institute (MI) and Massachusetts Institute of Technology are developing a 25 kW prototype to be tested in the Masdar Solar Platform beam down facility.

  3. Preliminary designs for 25 kWe advanced Stirling conversion systems for dish electric applications

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    1990-01-01

    Under the Department of Energy's (DOE) Solar Thermal Technology Program, Sandia National Laboratories is evaluating heat engines for terrestrial Solar Distributed Heat Receivers. The Stirling engine has been identified by Sandia as one of the most promising engines for terrestrial applications. The Stirling engine also has the potential to meet DOE's performance and cost goals. The NASA Lewis Research Center is conducting Stirling engine technology development activities directed toward a dynamic power source for space applications. Space power systems requirements include high reliability, very long life, low vibration and high efficiency. The free-piston Stirling engine has the potential for future high power space conversion systems, either nuclear or solar powered. Although both applications appear to be quite different, their requirements complement each other. Preliminary designs feature a free-piston Stirling engine, a liquid metal heat transport system, and a means to provide nominally 25 kW electric power to a utility grid while meeting DOE's performance and long term cost goals. The Cummins design incorporates a linear alternator to provide the electrical output, while the STC design generates electrical power indirectly through a hydraulic pump/motor coupled to an induction generator. Both designs for the ASCS's will use technology which can reasonably be expected to be available in the early 1990's

  4. Preliminary designs for 25 kWe advanced Stirling conversion systems for dish electric applications

    NASA Astrophysics Data System (ADS)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    Under the Department of Energy's (DOE) Solar Thermal Technology Program, Sandia National Laboratories is evaluating heat engines for terrestrial Solar Distributed Heat Receivers. The Stirling engine has been identified by Sandia as one of the most promising engines for terrestrial applications. The Stirling engine also has the potential to meet DOE's performance and cost goals. The NASA Lewis Research Center is conducting Stirling engine technology development activities directed toward a dynamic power source for space applications. Space power systems requirements include high reliability, very long life, low vibration and high efficiency. The free-piston Stirling engine has the potential for future high power space conversion systems, either nuclear or solar powered. Although both applications appear to be quite different, their requirements complement each other. Preliminary designs feature a free-piston Stirling engine, a liquid metal heat transport system, and a means to provide nominally 25 kW electric power to a utility grid while meeting DOE's performance and long term cost goals. The Cummins design incorporates a linear alternator to provide the electrical output, while the STC design generates electrical power indirectly through a hydraulic pump/motor coupled to an induction generator. Both designs for the ASCS's will use technology which can reasonably be expected to be available in the early 1990's.

  5. 2.5-kHz magnetostrictive Tonpilz sonar transducer design

    NASA Astrophysics Data System (ADS)

    Butler, Stephen C.

    2002-07-01

    Naval Undersea Warfare Center has fabricated and tested a 2.5 kHz magnetostrictive sonar transducer to validate various modeling techniques. The transducer selected is a longitudinal vibrator Tonpilz type consisting of Terfenol-D driver, tail mass, radiating head mass, and stress rod bolt with 21 MPa (3000 psi) prestress. The Terfenol-D drive rod is interlaced with three samarium cobalt magnets, one in the center and one on either end magnetically biasing the Terfenol to 60 kA/m (750 Oe). Both the Terfenol-D rods and magnets were laminated to reduce eddy currents. The magnetic circuit is comprised of pole piece discs on each end of the Terfenol-D magnet assembly and an external magnetic cylinder (return path) made of a high-permeability, high-resistivity, high-saturation powdered metal 'T2'. The transducer has a 25 cm (9.8in) diameter radiating face (piston), is 28 cm (11 in.) long, and weighs 15 kg (32 lb.) without the housing. It is 41 cm (16 in.) long and 25 kg (56 lb.) with the underwater housing. The measured results are compared to a finite element model using 'ATILA' and distributed plane wave element equivalent circuit model. The coupling coefficient, permeability and mechanical loss effects for different prestress loads were measured on a resonant Terfenol 'dumbbell' device. The in-water measured results indicate a mechanical Q of 2.5, an effective coupling coefficient of 0.36, an electro-acoustic efficiency of 60 percent, beam pattern directivity index of 6 dB, a maximum Source Level of 214.6 dB re 1uPa/m at 15 Amps AC drive and bandwidth of 2 kHz to 5.4 kHz +/- 1.5 dB.

  6. Status of the Advanced Stirling Conversion System Project for 25 kW dish Stirling applications

    SciTech Connect

    Shaltens, R.K.; Schreiber, J.G.

    1991-01-01

    Under the Department of Energy's (DOE) Solar Thermal Technology Program, Sandia National Laboratories is evaluating heat engines for terrestrial Solar Heat Receivers. The Stirling engine has been identified by Sandia as one of the most promising heat engines for terrestrial applications. The Stirling engine also has the potential to meet DOE's performance and cost goals. The NASA Lewis Research Center is conducting technology development for Stirling convertors directed toward a dynamic power source for space applications. Space power requirements include high reliability with very long life, low vibration and high system efficiency. The free-piston Stirling engine has the potential for future high power space conversion systems, either nuclear or solar powered. Although both applications appear to be quite different, their requirements complement each other. NASA Lewis is providing management of the Advanced Stirling Conversion System (ASCS) Project through an Interagency Agreement (IAA) with the DOE. Parallel contracts continue with both Cummins Engine Company (CEC), Columbus, Indiana, and Stirling Technology Company (STC), Richland, Washington for the designs of an ASCS. Each system'' design features a solar receiver/liquid metal heat transport system, and a free-piston Stirling convertor with a means to provide nominally 25 kW of electric power to a utility grid while meeting DOE's performance and long-term'' cost goals. The Cummins free- piston Stirling convertor incorporates a linear alternator to directly provide the electrical output, while the STC design generates electrical power indirectly through a hydraulic pump/motor coupled to an induction generator. Both the Cummins and STC ASCS designs will use technology which can reasonably be expected to be available in the early 1990's. 17 refs., 7 figs., 3 tabs.

  7. PanFP: Pangenome-based functional profiles for microbial communities

    SciTech Connect

    Jun, Se -Ran; Hauser, Loren John; Schadt, Christopher Warren; Gorin, Andrey A.; Robeson, Michael S.

    2015-09-26

    For decades there has been increasing interest in understanding the relationships between microbial communities and ecosystem functions. Current DNA sequencing technologies allows for the exploration of microbial communities in two principle ways: targeted rRNA gene surveys and shotgun metagenomics. For large study designs, it is often still prohibitively expensive to sequence metagenomes at both the breadth and depth necessary to statistically capture the true functional diversity of a community. Although rRNA gene surveys provide no direct evidence of function, they do provide a reasonable estimation of microbial diversity, while being a very cost effective way to screen samples of interest for later shotgun metagenomic analyses. However, there is a great deal of 16S rRNA gene survey data currently available from diverse environments, and thus a need for tools to infer functional composition of environmental samples based on 16S rRNA gene survey data. As a result, we present a computational method called pangenome based functional profiles (PanFP), which infers functional profiles of microbial communities from 16S rRNA gene survey data for Bacteria and Archaea. PanFP is based on pangenome reconstruction of a 16S rRNA gene operational taxonomic unit (OTU) from known genes and genomes pooled from the OTU s taxonomic lineage. From this lineage, we derive an OTU functional profile by weighting a pangenome s functional profile with the OTUs abundance observed in a given sample. We validated our method by comparing PanFP to the functional profiles obtained from the direct shotgun metagenomic measurement of 65 diverse communities via Spearman correlation coefficients. These correlations improved with increasing sequencing depth, within the range of 0.8 0.9 for the most deeply sequenced Human Microbiome Project mock community samples. PanFP is very similar in performance to another recently released tool, PICRUSt, for almost all of survey data analysed here. But, our

  8. PanFP: Pangenome-based functional profiles for microbial communities

    DOE PAGES

    Jun, Se -Ran; Hauser, Loren John; Schadt, Christopher Warren; ...

    2015-09-26

    For decades there has been increasing interest in understanding the relationships between microbial communities and ecosystem functions. Current DNA sequencing technologies allows for the exploration of microbial communities in two principle ways: targeted rRNA gene surveys and shotgun metagenomics. For large study designs, it is often still prohibitively expensive to sequence metagenomes at both the breadth and depth necessary to statistically capture the true functional diversity of a community. Although rRNA gene surveys provide no direct evidence of function, they do provide a reasonable estimation of microbial diversity, while being a very cost effective way to screen samples of interestmore » for later shotgun metagenomic analyses. However, there is a great deal of 16S rRNA gene survey data currently available from diverse environments, and thus a need for tools to infer functional composition of environmental samples based on 16S rRNA gene survey data. As a result, we present a computational method called pangenome based functional profiles (PanFP), which infers functional profiles of microbial communities from 16S rRNA gene survey data for Bacteria and Archaea. PanFP is based on pangenome reconstruction of a 16S rRNA gene operational taxonomic unit (OTU) from known genes and genomes pooled from the OTU s taxonomic lineage. From this lineage, we derive an OTU functional profile by weighting a pangenome s functional profile with the OTUs abundance observed in a given sample. We validated our method by comparing PanFP to the functional profiles obtained from the direct shotgun metagenomic measurement of 65 diverse communities via Spearman correlation coefficients. These correlations improved with increasing sequencing depth, within the range of 0.8 0.9 for the most deeply sequenced Human Microbiome Project mock community samples. PanFP is very similar in performance to another recently released tool, PICRUSt, for almost all of survey data analysed here. But

  9. LanFP10-A, first functional fluorescent protein whose chromophore contains the elusive mutation G67A.

    PubMed

    Roldán-Salgado, Abigail; Sánchez-Barreto, Celidee; Gaytán, Paul

    2016-11-05

    Since Green Fluorescent Protein (GFP) was first successfully expressed in heterologous systems in 1994, many genes encoding other natural autofluorescent proteins (AFPs) have been cloned and subsequently modified by protein engineering to improve their physicochemical properties. Throughout this twenty-two-year period, glycine 67 (Gly67) has been regarded as the only amino acid in the entire protein family that is essential for the formation of the different reported chromophores. In this work, we demonstrate that a synthetic gene encoding LanFP10-A, a natural protein encoded in the genome of the lancelet Branchiostoma floridae containing the G67A mutation, produces a heterologous, functional yellow fluorescent protein when expressed in E. coli. In contrast to LanFP10-A, LanFP6-A, a second GFP-like protein found in the lancelet genome that also contains the natural G67A mutation, was non-fluorescent.

  10. Investigating FP Tau’s protoplanetary disk structure through modeling

    NASA Astrophysics Data System (ADS)

    Brinjikji, Marah; Espaillat, Catherine

    2017-01-01

    This project presents a study aiming to understand the structure of the protoplanetary disk around FP Tau, a very young, very low mass star in the Taurus star-forming region. We have gathered existing optical, Spitzer, Herschel and submillimeter observations to construct the spectral energy distribution (SED) of FP Tau. We have used the D’Alessio et al (2006) physically self-consistent irradiated accretion disk model including dust settling to model the disk of FP Tau. Using this method, the best fit for the SED of FP Tau is a model that includes a gap located 10-20 AU away from the star. This gap is filled with optically thin dust that separates the optically thick dust in the outer disk from the optically thick dust in the inner disk. These characteristics indicate that FP Tau’s protostellar system is best classified as a pre-transitional disk. Near-infrared interferometry in the K-Band from Willson et al 2016 indicates that FP Tau has a small gap located 10-20 AU from the star, which is consistent with the model we produced, lending further support to the pre-transitional disk interpretation. The most likely explanation for the existence of a gap in the disk is a forming planet.

  11. Recombinant mussel adhesive protein fp-5 (MAP fp-5) as a bulk bioadhesive and surface coating material.

    PubMed

    Choi, Yoo Seong; Kang, Dong Gyun; Lim, Seonghye; Yang, Yun Jung; Kim, Chang Sup; Cha, Hyung Joon

    2011-08-01

    Mussel adhesive proteins (MAPs) attach to all types of inorganic and organic surfaces, even in wet environments. MAP of type 5 (fp-5), in particular, has been considered as a key adhesive material. However, the low availability of fp-5 has hampered its biochemical characterization and practical applications. Here, soluble recombinant fp-5 is mass-produced in Escherichia coli. Tyrosinase-modified recombinant fp-5 showed ∼1.11 MPa adhesive shear strength, which is the first report of a bulk-scale adhesive force measurement for purified recombinant of natural MAP type. Surface coatings were also performed through simple dip-coating of various objects. In addition, complex coacervate using recombinant fp-5 and hyaluronic acid was prepared as an efficient adhesive formulation, which greatly improved the bulk adhesive strength. Collectively, it is expected that this work will enhance basic understanding of mussel adhesion and that recombinant fp-5 can be successfully used as a realistic bulk-scale bioadhesive and an efficient surface coating material.

  12. A comparison of Stirling engines for use with a 25 kW dish-electric conversion system

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.

    1987-01-01

    Two designs for an advanced Stirling conversion system (ASCS) are described. The objective of the ASCS is to generate about 25 kW of electric power to an electric utility grid at an engine/alternator target cost of $300.00/kW at the manufacturing rate of 10,000 unit/yr. Both designs contain a free-piston Stirling engine (FPSE), a heat transport system, solar receiver, a means to generate electric power, the necessary auxiliaries, and a control system. The major differences between the two concepts are: one uses a 25 kWe single-piston FPSE which incorporates a linear alternator to directly convert the energy to electricity on the utility grid; and in the second design, electrical power is generated indirectly using a hydraulic output to a ground based hydraulic motor coupled to a rotating alternator. Diagrams of the two designs are presented.

  13. Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin-interacting protein 2)

    SciTech Connect

    Wilson, Randall C.; Hughes, Ronny C.; Flatt, Justin W.; Meehan, Edward J.; Ng, Joseph D.; Twigg, Pamela D.

    2009-08-07

    The ubiquitin-conjugating enzyme E2-25K has been identified as a huntingtin (the key protein in Huntington's disease) interacting protein and has been shown to play a role in mediating the toxicity of A{beta}, the principal protein involved in Alzheimer's disease pathogenesis. E2-25K is a dual-domain protein with an ubiquitin-associated (UBA) domain as well as a conserved ubiquitin-conjugating (UBC) domain which catalyzes the formation of a covalent bond between the C-terminal glycine of an ubiquitin molecule and the {var_epsilon}-amine of a lysine residue on the acceptor protein as part of the ubiquitin-proteasome pathway. The crystal structures of E2-25K M172A mutant protein at pH 6.5 and pH 8.5 were determined to 1.9 and 2.2 {angstrom} resolution, respectively. Examination of the structures revealed domain-domain interactions between the UBC and UBA domains which have not previously been reported

  14. DoFP polarimeter based polarization microscope for biomedical applications

    NASA Astrophysics Data System (ADS)

    Chang, Jintao; He, Honghui; He, Chao; Ma, Hui

    2016-03-01

    Polarization microscope is a useful technique to observe the optical anisotropic nature of biomedical specimens and provide more microstructural information than the conventional microscope. In this paper, we present a division of focal plane (DoFP) polarimeter based polarization microscope which is capable of imaging both the Stokes vector and the 3×4 Mueller matrix. The Mueller matrix measurement can help us completely understand the polarization properties of the sample and the Stokes vector measurement is a simultaneous technology. First, we calibrate a DoFP polarimeter using the polarization data reduction method for accurate Stokes vector measurements. Second, as the Stokes vector computation for all pixels using the calibrated instrument matrix is usually time consuming, we develop a GPU acceleration algorithm for real time Stokes vector calculations. Third, based on the accurate and fast Stokes vector calculation, we present an optimal 4-states of polarization (4-SoP) illumination scheme for Mueller matrix measurement using the DoFP polarimeter. Finally, we demonstrate the biomedical applications of the DoFP polarimeter based polarization microscope. Experiment results show that the characteristic features of many biomedical samples can be observed in the "polarization staining" images using the circularly polarized light as illumination. In this way, combined with GPU acceleration algorithm, the DoFP polarization microscope has the capacity for real time polarization monitoring of dynamic processes in biological samples.

  15. Comparison of conceptual designs for 25 kWe advanced Stirling conversion systems for dish electric applications

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    1989-01-01

    The Advanced Stirling Conversion System (ASCS) Project is managed by NASA Lewis Research Center through a cooperative interagency agreement with DOE. Conceptual designs for the ASCS's were completed under parallel contracts in 1987 by Mechanical Technology Inc. (MTI) of Latham, NY, and Stirling Technology Company (STC) of Richland, WA. Each design features a free-piston Stirling engine, a liquid metal heat pipe receiver, and a means to provide about 25 kW of electric power to a utility grid while meeting DOE's long term performance and cost goals. An independent assessment showed that both designs are manufacturable and have the potential to easily meet DOE's long term cost goals.

  16. Comparison of conceptual designs for 25 kWe advanced Stirling conversion systems for dish electric application

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.; Schreiber, Jeffrey G.

    1989-01-01

    The Advanced Stirling Conversion System (ASCS) Project is managed by NASA Lewis Research Center through a cooperative interagency agreement with DOE. Conceptual designs for the ASCS's were completed under parallel contracts in 1987 by Mechanical Technology Inc. (MTI) of Latham, NY, and Stirling Technology Company (STC) of Richland, WA. Each design features a free-piston Stirling engine, a liquid metal heat pipe receiver, and a means to provide about 25 kW of electric power to a utility grid while meeting DOE's long term performance and cost goals. An independent assessment showed that both designs are manufacturable and have the potential to easily meet DOE's long term cost goals.

  17. 2.5 kWe dynamic isotope power system for the space exploration initiative including an Antarctic demonstration

    NASA Astrophysics Data System (ADS)

    Hunt, Maribeth E.; Rovang, Richard D.

    1992-01-01

    The current focus of the Dynamic Isotope Power Systems (DIPS) Demonstration Program is a standardized 2.5-kWe portable generator for multiple applications on the Lunar or Martian surface. A variety of potential remote and mobile applications has been identified by the National Aeronautics and Space Administration (NASA). Included among these are surface rovers for both short and extended duration missions, remote power to science packages, and backup to central base power. Several power levels were investigated to determine the optimum level for the identified applications. Operational concerns were of a primary concern. Recent work focused on refining the 2.5-kWe design to assure compatibility with the Martian environment while imposing only a minor mass penalty on Lunar operations. A plan and cycle schematic were generated for an early demonstration of a prototypic isotope powered Brayton system using the Antarctic as the test bed. This plan included a schedule and cost and a determination of the impact of such a program on the qualification of a DIPS.

  18. Different effects of 25-kDa amelogenin on the proliferation, attachment and migration of various periodontal cells

    SciTech Connect

    Li, Xiting; Shu, Rong; Liu, Dali; Jiang, Shaoyun

    2010-04-09

    Previous studies have assumed that amelogenin is responsible for the therapeutic effect of the enamel matrix derivative (EMD) in periodontal tissue healing and regeneration. However, it is difficult to confirm this hypothesis because both the EMD and the amelogenins are complex mixtures of multiple proteins. Further adding to the difficulties is the fact that periodontal tissue regeneration involves various types of cells and a sequence of associated cellular events including the attachment, migration and proliferation of various cells. In this study, we investigated the potential effect of a 25-kDa recombinant porcine amelogenin (rPAm) on primarily cultured periodontal ligament fibroblasts (PDLF), gingival fibroblasts (GF) and gingival epithelial cells (GEC). The cells were treated with 25-kDa recombinant porcine amelogenin at a concentration of 10 {mu}g/mL. We found that rPAm significantly promoted the proliferation and migration of PDLF, but not their adhesion. Similarly, the proliferation and adhesion of GF were significantly enhanced by treatment with rPAm, while migration was greatly inhibited. Interestingly, this recombinant protein inhibited the growth rate, cell adhesion and migration of GEC. These data suggest that rPAm may play an essential role in periodontal regeneration through the activation of periodontal fibroblasts and inhibition of the cellular behaviors of gingival epithelial cells.

  19. TLR4 antagonist FP7 inhibits LPS-induced cytokine production and glycolytic reprogramming in dendritic cells, and protects mice from lethal influenza infection

    PubMed Central

    Perrin-Cocon, Laure; Aublin-Gex, Anne; Sestito, Stefania E.; Shirey, Kari Ann; Patel, Mira C.; André, Patrice; Blanco, Jorge C.; Vogel, Stefanie N.; Peri, Francesco; Lotteau, Vincent

    2017-01-01

    Dysregulated Toll-like receptor (TLR)-4 activation is involved in acute systemic sepsis, chronic inflammatory diseases, such as atherosclerosis and diabetes, and in viral infections, such as influenza infection. Thus, therapeutic control of the TLR4 signalling pathway is of major interest. Here we tested the activity of the small-molecule synthetic TLR4 antagonist, FP7, in vitro on human monocytes and monocyte-derived dendritic cells (DCs) and in vivo during influenza virus infection of mice. Our results indicate that FP7 antagonized the secretion of proinflammatory cytokines (IL-6, IL-8, and MIP-1β) by monocytes and DCs (IC50 < 1 μM) and prevented DC maturation upon TLR4 activation by ultrapure lipopolysaccharide (LPS). FP7 selectively blocked TLR4 stimulation, but not TLR1/2, TLR2/6, or TLR3 activation. TLR4 stimulation of human DCs resulted in increased glycolytic activity that was also antagonized by FP7. FP7 protected mice from influenza virus-induced lethality and reduced both proinflammatory cytokine gene expression in the lungs and acute lung injury (ALI). Therefore, FP7 can antagonize TLR4 activation in vitro and protect mice from severe influenza infection, most likely by reducing TLR4-dependent cytokine storm mediated by damage-associated molecular patterns (DAMPs) like HMGB1. PMID:28106157

  20. Isospin-mixing correction for fp-shell Fermi transitions

    SciTech Connect

    Ormand, W.E.; Brown, B.A.

    1995-10-01

    Isospin-mixing corrections for superallowed Fermi transitions in fp-shell nuclei are computed within the framework of the shelf model. The study includes a re-evaluation of three nuclei that are part of the set of nine accurately measured transitions and five new cases that are expected to be measured in the future at radioactive-beam facilities. For the heavier fp-shell nuclei, both the configuration mixing term, {delta}{sub IM}, and the radial-overlap mis-match correction, {delta}{sub RO}, are much larger than in the case of the previous nine transitions. For the nine accurately measured transitions, excellent agreement with the CVC hypothesis is found. but the CKM matrix is found to violate the unitarity condition at the level of 3 {sigma}.

  1. Design of a pool boiler heat transport system for a 25 kWe advanced Stirling conversion system

    NASA Technical Reports Server (NTRS)

    Anderson, W. G.; Rosenfeld, J. H.; Noble, J.; Kesseli, J.

    1991-01-01

    The overall operating temperature and efficiency of solar-powered Stirling engines can be improved by adding a heat transport system to more uniformly supply heat to the heater head tubes. One heat transport system with favorable characteristics is an alkali metal pool boiler. An alkali metal pool boiler heat transport system was designed for a 25-kW advanced Stirling conversion system (ASCS). Solar energy concentrated on the absorber dome boils a eutectic mixture of sodium and potassium. The alkali metal vapors condense on the heater head tubes, supplying the Stirling engine with a uniform heat flux at a constant temperature. Boiling stability is achieved with the use of an enhanced boiling surface and noncondensible gas.

  2. Study on characteristics of high temperature superconducting magnetic thrust bearing for 25 kW h flywheel

    NASA Astrophysics Data System (ADS)

    Nagaya, S.; Kashima, N.; Minami, M.; Kawashima, H.; Unisuga, S.; Kakiuchi, Y.; Ishigaki, H.

    2001-09-01

    An axial air gap type thrust bearing of the outer diameter of 620 mm for 25 kW h flywheel which combined with the permanent magnet of Nd-Fe-B and 10 pieces of high temperature YBaCuO superconductors of the diameter of 150 mm directly cooled by the refrigerator was fabricated, and its performance tests were conducted. Load capacity which could support a planned rotor weight of 8.2 kN was confirmed, and also the stiffness of the radial direction and the axial direction were measured in case of several initial cooling conditions. Spring and damping coefficients in zero field cooling were also measured in the tapping test, and it was found that axial spring coefficients were about 10 times as large as radial spring coefficients, though damping coefficients were almost the same.

  3. A 2.5 kW cascaded Schwarz converter for 20 kHz power distribution

    NASA Astrophysics Data System (ADS)

    Shetler, Russell E.; Stuart, Thomas A.

    Because it avoids the high currents in a parallel loaded capacitor, the cascaded Schwarz converter should offer better component utilization than converters with sinusoidal output voltages. The circuit is relatively easy to protect, and it provides a predictable trapezoidal voltage waveform that should be satisfactory for 20-kHz distribution systems. Analysis of the system is enhanced by plotting curves of normalized variables vs. gamma(1), where gamma(1) is proportional to the variable frequency of the first stage. Light-load operation is greatly improved by the addition of a power recycling rectifier bridge that is back biased at medium to heavy loads. Operation has been verified on a 2.5-kW circuit that uses input and output voltages in the same range as those anticipated for certain future spacecraft power systems.

  4. Structural basis for bathochromic shift of fluorescence in far-red fluorescent proteins eqFP650 and eqFP670.

    PubMed

    Pletnev, Sergei; Pletneva, Nadya V; Souslova, Ekaterina A; Chudakov, Dmitry M; Lukyanov, Sergey; Wlodawer, Alexander; Dauter, Zbigniew; Pletnev, Vladimir

    2012-09-01

    The crystal structures of the far-red fluorescent proteins (FPs) eqFP650 (λ(ex)(max)/λ(em)(max) 592/650 nm) and eqFP670 (λ(ex)(max)/λ(em)(max) 605/670 nm), the successors of the far-red FP Katushka (λ(ex)(max)/λ(em)(max) 588/635 nm), have been determined at 1.8 and 1.6 Å resolution, respectively. An examination of the structures demonstrated that there are two groups of changes responsible for the bathochromic shift of excitation/emission bands of these proteins relative to their predecessor. The first group of changes resulted in an increase of hydrophilicity at the acylimine site of the chromophore due to the presence of one and three water molecules in eqFP650 and eqFP670, respectively. These water molecules provide connection of the chromophore with the protein scaffold via hydrogen bonds causing an ~15 nm bathochromic shift of the eqFP650 and eqFP670 emission bands. The second group of changes observed in eqFP670 arises from substitution of both Ser143 and Ser158 by asparagines. Asn143 and Asn158 of eqFP670 are hydrogen bonded with each other, as well as with the protein scaffold and with the p-hydroxyphenyl group of the chromophore, resulting in an additional ~20 nm bathochromic shift of the eqFP670 emission band as compared to eqFP650. The role of the observed structural changes was verified by mutagenesis.

  5. Bearing development program for a 25 kWe solar-powered organic Rankine-cycle engine

    NASA Technical Reports Server (NTRS)

    Nesmith, B.

    1985-01-01

    The bearing development program is summarized for a 25-kWe power conversion subsystem (PCS) consisting of an organic Rankine-cycle engine, and permanent magnetic alternator (PMA) and rectifier to be used in a 100-kWe point-focusing distributed receiver solar power plant. The engine and alternator were hermetically sealed and used toluene as the working fluid. The turbine, alternator, and feed pump (TAP) were mounted on a single shaft operating at speeds up to 60,000 rev/min. Net thermal-to-electric efficiencies in the range of 21 to 23% were demonstrated at the maximum working fluid temperature of 400 C (750 F). A chronological summary of the bearing development program is presented. The primary causes of bearing wear problems were traced to a combination of rotordynamic instability and electrodynamic discharge across the bearing surfaces caused by recirculating currents from the PMA. These problems were resolved by implementing an externally supplied, flooded-bearing lubrication system and by electrically insulating all bearings from the TAP housing. This program resulted in the successful development of a stable, high-speed, toluene-lubricated five-pad tilting-pad journal bearing and Rayleigh step thrust bearing system capable of operating at all inclinations between horizontal and vertical.

  6. Design and development of a prototype 25 kV, 10 A long pulse Marx modulator for high power klystron

    NASA Astrophysics Data System (ADS)

    Acharya, Mahesh; Shrivastava, Purushottam

    2016-02-01

    Research, design, and development of high average power modulators for the proposed Indian Spallation Neutron Source are in progress at Raja Ramanna Centre for Advanced Technology. With this objective, a prototype of 25 kV, 10 A, 1 ms Marx modulator at repetition rate of 1 Hz has been designed and developed which serves as a proof of principle and technology assessment stage for further development of high repetition rate high voltage high average power modulators. Insulated Gate Bipolar Transistor (IGBT) based modules of 2.8 kV switching capability have been used as main modules. The modulator had 8.2% droop in output voltage pulse without any droop compensation circuit. A droop compensation involving 15 corrector modules has been used to reduce the droop up to 1%. We have used IGBT based 250 V switches to realize the corrector module. A microcontroller based control unit was designed and developed for triggering the main and corrector modules. With this control unit, programmable output pulse has been achieved. Electrical isolation between high voltage circuits and control circuit has been achieved by the use of fiber optic based control signal transmission. Output pulses of 1 ms pulse width, 800 ns rise time, and 5 μs fall time have been achieved. The modulator has advantages of modular design, adjustable pulse width, adjustable rise time, and fall time.

  7. Design and production of a 2.5 kWe insulated metal substrate-based densely packed CPV assembly

    NASA Astrophysics Data System (ADS)

    Micheli, Leonardo; Sarmah, Nabin; Luo, Xichun; Reddy, K. S.; Mallick, Tapas K.

    2014-09-01

    The original design of a new 144-cell concentrating photovoltaic assembly is presented in this paper. It is conceived to work under 500 suns and to generate about 2.5 kWe. An insulated metal substrate was selected as baseplate, in order to get the best compromise between costs and thermal performances. It is based on a 2mm thick aluminum plate, which is in charge of removing the heat as quick as possible. The copper pattern and thickness has been designed accordingly to the IPC Generic Standard on Printed Board Design and to the restrictions of fit a reflective 125x primary optics and a 4x secondary refractive optics. The original outline of the conductive copper layer has been developed to minimize Joule losses by reducing the number of interconnections between the cells in series. Multijunction solar cells and Schottky bypass diodes have been soldered onto the board as surface mounted components. All the fabrication processes are described. This board represents a novelty for the innovative pattern of the conductive layer, which can be easily adapted to be coupled with different optics geometries and to allocate a different number of cells. The use of an IMS as baseplate will give an experimental contribution to the debate about the exploitability of this kind of substrates in CPV. This board is being characterized indoor and outdoor: the results will be used to improve the design and the reliability of the future receivers.

  8. Solid state nuclear magnetic resonance with magic-angle spinning and dynamic nuclear polarization below 25 K

    PubMed Central

    Thurber, Kent R.; Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert

    2012-01-01

    We describe an apparatus for solid state nuclear magnetic resonance (NMR) with dynamic nuclear polarization (DNP) and magic-angle spinning (MAS) at 20–25 K and 9.4 Tesla. The MAS NMR probe uses helium to cool the sample space and nitrogen gas for MAS drive and bearings, as described earlier (Thurber et al., J. Magn. Reson. 2008) [1], but also includes a corrugated waveguide for transmission of microwaves from below the probe to the sample. With a 30 mW circularly polarized microwave source at 264 GHz, MAS at 6.8 kHz, and 21 K sample temperature, greater than 25-fold enhancements of cross-polarized 13C NMR signals are observed in spectra of frozen glycerol/water solutions containing the triradical dopant DOTOPA-TEMPO when microwaves are applied. As demonstrations, we present DNP-enhanced one-dimensional and two-dimensional 13C MAS NMR spectra of frozen solutions of uniformly 13C-labeled L-alanine and melittin, a 26-residue helical peptide that we have synthesized with four uniformly 13C-labeled amino acids. PMID:23238592

  9. Design and development of a prototype 25 kV, 10 A long pulse Marx modulator for high power klystron.

    PubMed

    Acharya, Mahesh; Shrivastava, Purushottam

    2016-02-01

    Research, design, and development of high average power modulators for the proposed Indian Spallation Neutron Source are in progress at Raja Ramanna Centre for Advanced Technology. With this objective, a prototype of 25 kV, 10 A, 1 ms Marx modulator at repetition rate of 1 Hz has been designed and developed which serves as a proof of principle and technology assessment stage for further development of high repetition rate high voltage high average power modulators. Insulated Gate Bipolar Transistor (IGBT) based modules of 2.8 kV switching capability have been used as main modules. The modulator had 8.2% droop in output voltage pulse without any droop compensation circuit. A droop compensation involving 15 corrector modules has been used to reduce the droop up to 1%. We have used IGBT based 250 V switches to realize the corrector module. A microcontroller based control unit was designed and developed for triggering the main and corrector modules. With this control unit, programmable output pulse has been achieved. Electrical isolation between high voltage circuits and control circuit has been achieved by the use of fiber optic based control signal transmission. Output pulses of 1 ms pulse width, 800 ns rise time, and 5 μs fall time have been achieved. The modulator has advantages of modular design, adjustable pulse width, adjustable rise time, and fall time.

  10. Comparison of Stirling engines for use with a 25-kW disk-electric conversion system

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.

    1987-01-01

    Heat engines were evaluated for terrestrial solar heat receivers. The Stirling Engine was identified as one of the most promising engines for terrestrial applications. The potential to meet the Department of Energy (DOE) goals for performance and cost can be met by the free-piston Stirling engine. NASA Lewis is providing technical management for an Advanced Stirling Conversion System (ASCS) through a cooperative interagency agreement with DOE. Parallel contracts were awarded for conceptual designs of an ASCS. Each design will feature a free-piston Stirling engine, a liquid-metal heat pipe receiver, and a means to provide about 25 kW of electric power to a utility grid while meeting long-term performance and goals. The Mechanical Technology, Ins. (MTI) design incorporates a linear alternator to directly convert the solar energy to electricity while the Stirling Technology Company (STC) generates electrical power indirectly by using a hydraulic output to a ground-bases hydraulic pump/motor coupled to a rotating alternator. Both designs use technology which can reasonably be expected to be available in the 1980's. The ASCS designs using a free-piston Stirling engine, a heat transport system, a receiver, and the methods of providing electricity to the utility grid will be discussed.

  11. The vector-related influences of autophagic microRNA delivery by Lipofectamine 2000 and polyethylenimine 25K on mouse embryonic fibroblast cells.

    PubMed

    Lin, Chia-Wei; Jan, Ming-Shiou; Kuo, Jung-Hua Steven

    2017-04-01

    Despite the greater potential for clinical applications of autophagic microRNA (miRNA) delivery, the vector-related effects of such delivery on cells have not been fully explored. In this study, autophagic mmu-miR-494-3p (miR-494) in mouse embryonic fibroblast (MEF) cells was selected as a cargo miRNA, and two commonly used non-viral carriers (Lipofectamine 2000 (Lipo) and polyethylenimine 25K (PEI)), were used as delivery vectors to mechanistically elucidate its vector-related effects. The cellular uptake, nuclear localization, and quantitative miR-494 levels of the complexes of miR-494 with Lipo (miR-494 lipoplexes) were lower than those of the complexes of miR-494 with PEI (miR-494 polyplexes) in MEF cells. The indicator of autophagic activity (LC3 (microtubule-associated protein 1 light chain 3)-II/LC3-I ratio) in cells treated with miR-494 lipoplexes was higher than that in cells treated with miR-494 polyplexes. Lipo alone and PEI alone induced slight increases in the quantitative levels of miR-494 in cells, but Lipo resulted in higher gene and protein expressions of target Igf1, higher LC3-II/LC3-I ratios, and higher autophagosome formation than PEI. We also demonstrated that the delivery of miR-494 by Lipo was more involved in apoptotic caspase-3 pathways than such delivery by PEI. By applying knock-out atg5 gene in MEF cells, we found that autophagy played a protective role in cell survival and also affected cellular uptake, the quantitative level of miR-494, and target gene Igf1 regulation of delivery systems. Taken together, these results indicate that there are different degrees of responses in MEF cells for autophagic miR-494 delivery through the use of Lipo or PEI vectors that also induce autophagy in cells. Therefore, Lipo and PEI vectors cannot be treated as inert molecules, and their effects must be known and evaluated when they are used in autophagic miRNA delivery systems. Most importantly, understanding these vector-related effects on cells will

  12. The 25 kW power module evolution study. Part 3: Conceptual designs for power module evolutions. Volume 3: Cost estimates

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Cost data generated for the evolutionary power module concepts selected are reported. The initial acquisition costs (design, development, and protoflight unit test costs) were defined and modeled for the baseline 25 kW power module configurations. By building a parametric model of this initial building block, the cost of the 50 kW and the 100 kW power modules were derived by defining only their configuration and programmatic differences from the 25 kW baseline module. Variations in cost for the quantities needed to fulfill the mission scenarios were derived by applying appropriate learning curves.

  13. File Specification for GEOS-5 FP (Forward Processing)

    NASA Technical Reports Server (NTRS)

    Lucchesi, R.

    2013-01-01

    The GEOS-5 FP Atmospheric Data Assimilation System (GEOS-5 ADAS) uses an analysis developed jointly with NOAA's National Centers for Environmental Prediction (NCEP), which allows the Global Modeling and Assimilation Office (GMAO) to take advantage of the developments at NCEP and the Joint Center for Satellite Data Assimilation (JCSDA). The GEOS-5 AGCM uses the finite-volume dynamics (Lin, 2004) integrated with various physics packages (e.g, Bacmeister et al., 2006), under the Earth System Modeling Framework (ESMF) including the Catchment Land Surface Model (CLSM) (e.g., Koster et al., 2000). The GSI analysis is a three-dimensional variational (3DVar) analysis applied in grid-point space to facilitate the implementation of anisotropic, inhomogeneous covariances (e.g., Wu et al., 2002; Derber et al., 2003). The GSI implementation for GEOS-5 FP incorporates a set of recursive filters that produce approximately Gaussian smoothing kernels and isotropic correlation functions. The GEOS-5 ADAS is documented in Rienecker et al. (2008). More recent updates to the model are presented in Molod et al. (2011). The GEOS-5 system actively assimilates roughly 2 × 10(exp 6) observations for each analysis, including about 7.5 × 10(exp 5) AIRS radiance data. The input stream is roughly twice this volume, but because of the large volume, the data are thinned commensurate with the analysis grid to reduce the computational burden. Data are also rejected from the analysis through quality control procedures designed to detect, for example, the presence of cloud. To minimize the spurious periodic perturbations of the analysis, GEOS-5 FP uses the Incremental Analysis Update (IAU) technique developed by Bloom et al. (1996). More details of this procedure are given in Appendix A. The assimilation is performed at a horizontal resolution of 0.3125-degree longitude by 0.25- degree latitude and at 72 levels, extending to 0.01 hPa. All products are generated at the native resolution of the

  14. The 25 kW power module evolution study. Part 3: Conceptual designs for power module evolution. Volume 1: Power module evolution

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Candidate power module confugurations which will directly support an evolutionary scenario allowing growth from 25 kW to 100 kW are described. The growth rationale is structured to support a nominal scenario for sortie mission support to the POrbiter and to free-flying payloads during the 1983 to 1990 era.

  15. Effect of (Li,Ce) doping in Aurivillius phase material Na0.25K0.25Bi2.5Nb2O9

    NASA Astrophysics Data System (ADS)

    Gai, Zhi-Gang; Wang, Jin-Feng; Wang, Chun-Ming

    2007-01-01

    The effect of (Li,Ce) substitution for A site on the properties of Na0.25K0.25Bi2.5Nb2O9-based ceramics was investigated. The piezoelectric activity of Na0.25K0.25Bi2.5Nb2O9-based ceramics is significantly improved by the modification of lithium and cerium. The Curie temperature (TC) gradually increases from 668to684°C with increasing the (Li,Ce) modification. The piezoelectric coefficient d33 of the [(Na0.5K0.5)Bi]0.44(LiCe)0.03[]0.03Bi2Nb2O9 ceramic was found to be 28pC/N, the highest value among the Na0.25K0.25Bi2.5Nb2O9-based ceramics and also almost 50% higher than the reported d33 values of other bismuth layer-structured ferroelectric systems (˜5-19pC/N). The planar coupling factors kp and kt were found to be 8.0% and 23.0%, together with the high TC (˜670°C) and stable piezoelectric properties, demonstrating that the (Li,Ce) modified Na0.25K0.25Bi2.5Nb2O9-based material a promising candidate for high temperature applications.

  16. System Description for the K-25/K-27 D&D Project Polyurethane Foam Delivery System, East Tennessee Technology Park, Oak Ridge, Tennessee

    SciTech Connect

    Boris, G.

    2008-02-21

    The Foam Delivery System used in the decontamination and decommissioning (D&D) project for the K-25/K-27 Buildings at the East Tennessee Technology Park (ETTP) is comprised of a trailer-mounted Gusmer{reg_sign} H20/35 Pro-TEC Proportioning Unit and the associated equipment to convey electrical power, air, and foam component material to the unit. This high-pressure, plural-component polyurethane foam pouring system will be used to fill process gas and non-process equipment/piping (PGE/P) within the K-25/K-27 Buildings with polyurethane foam to immobilize contaminants prior to removal. The system creates foam by mixing isocyanate and polyol resin (Resin) component materials. Currently, the project plans to utilize up to six foaming units simultaneously during peak foaming activities. Also included in this system description are the foam component material storage containers that will be used for storage of the component material drums in a staging area outside of the K-25/K-27 Buildings. The Foam Delivery System and foam component material storage enclosures (i.e., Foaming Component Protective Enclosures) used to store polymeric methylene diphenyl diisocyanate (PMDI) component material are identified as Safety Significant (SS) Structures, Systems and Components (SSC) in the Documented Safety Analysis (DSA) for the project, Documented Safety Analysis for the K-25 and K-27 Facilities at the East Tennessee Technology Park, Oak Ridge, Tennessee, DSA-ET-K-25/K-27-0001.

  17. Field evaluations of the VD max approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

    NASA Astrophysics Data System (ADS)

    Kowalski, John B.; Herring, Craig; Baryschpolec, Lisa; Reger, John; Patel, Jay; Feeney, Mary; Tallentire, Alan

    2002-08-01

    The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD max for quarterly dose audits; Facility B compared VD max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment. The field evaluations of the VD max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD max experiments were consistent with the outcomes observed with Method 1. The VD max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.

  18. Synthesis of Air-Stable Cyclopentadienyl Fe(CO)2 (Fp) Polymers by a Host-Guest Interaction of Cyclodextrin with Air-Sensitive Fp Pendant Groups.

    PubMed

    Zhou, Na; Peng, Liao; Salgado, Shehan; Yuan, Jinying; Wang, Xiaosong

    2017-03-13

    Host-guest chemistry is used to address the challenge of the synthesis of air-stable polymers containing air-sensitive metal complexes. The complexation of the CpFe(CO)2 (Fp) pendent group with cyclodextrin (CD) molecules created air-stable poly(Fp-methylstyrene) P(CD/FpMSt). This CD complexation resulted in dimerization of the adjacent Fp groups, which was characterized by NMR, FTIR, and cyclic voltammetry (CV) analyses. P(CD/FpMSt) was soluble in DMSO and remained stable even the solution was exposed to air for months. The host-guest chemistry accounted for the improved stability, because the Fp groups decomposed upon removal of the CD molecules using competing guest molecules. The CD-complexed polymer showed light-trigged properties, including CO release and antimicrobial activity. Host-guest chemistry of air-sensitive organometallic complexes is therefore a promising technique that can be used to broaden the scope of metal-containing polymers (MCPs) with processable novel functions.

  19. Recent activities of the FP7-ESPaCE consortium

    NASA Astrophysics Data System (ADS)

    Thuillot, W.; Lainey, V.; Dehant, V.; Arlot, J.-E.; Gurvits, , L.; Hussmann, H.; Oberst, J.; Rosenblatt, P.; Marty, J. C.; Vermeersen, B.; Bauer, S.; De Cuyper, J.-P.; Dirkx, D.; Hestroffer, D.; Kudryashova, M.; Meunier, L. E.; Pasewaldt, A.; Rambaux, N.; Robert, V.; Tajeddine, R.; Willner, K.

    2014-12-01

    The consortium ESPaCE (European Satellite Partnership for Computing Ephemerides) is composed of seven European institutes: IMCCE ((Institut de Mécanique Céleste et de Calcul des Ephémérides, Paris Obs.), ROB (Royal Observatory of Belgium), TUB (Technical University of Berlin), JIVE (Joint Institute for VLBI in Europe), TUD (Delft University of Technology), French space agency (CNES) in France and German Aerospace Center (DLR) in Germany. The objective of this FP7 European project is to provide new accurate ephemerides of natural satellites and spacecraft. For this goal many astrometric data issued from ground-based observations as well as from space observations have been analyzed and reduced. On the other hand new technologies applied to the positioning of spacecraft are also studied. The ESPaCE project addresses also data related to gravity and shape modeling, control point network and rotational parameters of natural satellites. The accuracy improvement of these ephemerides makes them a powerful tool for the analysis of space missions or the preparation of future missions, or for the determination of some physical parameters.

  20. COST Action FP1005 ``Fibre suspension flow modelling''

    NASA Astrophysics Data System (ADS)

    Marchioli, Cristian

    2013-11-01

    Fibre suspensions are extremely complex solid-liquid systems since their components (fibres, flocs, air bubbles and additives) interact mutually in a complex way. The dynamics of fibre suspensions are crucial in many real-life applications, such as pulp and paper production. Current understanding of suspension flow dynamics remains poor and incomplete, resulting in conservative design of industrial equipments, low energy efficiency and equipment oversizing. In this paper, the most recent advancements in modelling and experimentation of fibre suspensions dynamics are presented. These advancements have been obtained in the framework of Action FP1005, funded by the COST Programme (European Cooperation in Science and Technology) to coordinate nationally-funded research on a European level. The Action aims at developing and validating numerical models for prediction of fibre suspensions as well as measurement techniques. The Action offers a forum to solve test cases and to compare simulated results to experiments, resulting in more reliable simulation tools to industry. Successfull introduction of such tool into industrial practice is crucial to innovate and increase competitivity of papermaking industry.

  1. Effect of oxygen breathing on micro oxygen bubbles in nitrogen-depleted rat adipose tissue at sea level and 25 kPa altitude exposures.

    PubMed

    Randsoe, Thomas; Hyldegaard, Ole

    2012-08-01

    The standard treatment of altitude decompression sickness (aDCS) caused by nitrogen bubble formation is oxygen breathing and recompression. However, micro air bubbles (containing 79% nitrogen), injected into adipose tissue, grow and stabilize at 25 kPa regardless of continued oxygen breathing and the tissue nitrogen pressure. To quantify the contribution of oxygen to bubble growth at altitude, micro oxygen bubbles (containing 0% nitrogen) were injected into the adipose tissue of rats depleted from nitrogen by means of preoxygenation (fraction of inspired oxygen = 1.0; 100%) and the bubbles studied at 101.3 kPa (sea level) or at 25 kPa altitude exposures during continued oxygen breathing. In keeping with previous observations and bubble kinetic models, we hypothesize that oxygen breathing may contribute to oxygen bubble growth at altitude. Anesthetized rats were exposed to 3 h of oxygen prebreathing at 101.3 kPa (sea level). Micro oxygen bubbles of 500-800 nl were then injected into the exposed abdominal adipose tissue. The oxygen bubbles were studied for up to 3.5 h during continued oxygen breathing at either 101.3 or 25 kPa ambient pressures. At 101.3 kPa, all bubbles shrank consistently until they disappeared from view at a net disappearance rate (0.02 mm(2) × min(-1)) significantly faster than for similar bubbles at 25 kPa altitude (0.01 mm(2) × min(-1)). At 25 kPa, most bubbles initially grew for 2-40 min, after which they shrank and disappeared. Four bubbles did not disappear while at 25 kPa. The results support bubble kinetic models based on Fick's first law of diffusion, Boyles law, and the oxygen window effect, predicting that oxygen contributes more to bubble volume and growth during hypobaric conditions. As the effect of oxygen increases, the lower the ambient pressure. The results indicate that recompression is instrumental in the treatment of aDCS.

  2. Research Progress on F-P Interference-Based Fiber-Optic Sensors.

    PubMed

    Huang, Yi Wen; Tao, Jin; Huang, Xu Guang

    2016-09-03

    We review our works on Fabry-Perot (F-P) interferometric fiber-optic sensors with various applications. We give a general model of F-P interferometric optical fiber sensors including diffraction loss caused by the beam divergence and the Gouy phase shift. Based on different structures of an F-P cavity formed on the end of a single-mode fiber, the F-P interferometric optical sensor has been extended to measurements of the refractive index (RI) of liquids and solids, temperature as well as small displacement. The RI of liquids and solids can be obtained by monitoring the fringe contrast related to Fresnel reflections, while the ambient temperature and small displacement can be obtained by monitoring the wavelength shift of the interference fringes. The F-P interferometric fiber-optic sensors can be used for many scientific and technological applications.

  3. Research Progress on F-P Interference—Based Fiber-Optic Sensors

    PubMed Central

    Huang, Yi Wen; Tao, Jin; Huang, Xu Guang

    2016-01-01

    We review our works on Fabry-Perot (F-P) interferometric fiber-optic sensors with various applications. We give a general model of F-P interferometric optical fiber sensors including diffraction loss caused by the beam divergence and the Gouy phase shift. Based on different structures of an F-P cavity formed on the end of a single-mode fiber, the F-P interferometric optical sensor has been extended to measurements of the refractive index (RI) of liquids and solids, temperature as well as small displacement. The RI of liquids and solids can be obtained by monitoring the fringe contrast related to Fresnel reflections, while the ambient temperature and small displacement can be obtained by monitoring the wavelength shift of the interference fringes. The F-P interferometric fiber-optic sensors can be used for many scientific and technological applications. PMID:27598173

  4. The 25 kW power module evolution study. Part 3: Conceptual design for power module evolution. Volume 6: WBS and dictionary

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Program elements of the power module (PM) system, are identified, structured, and defined according to the planned work breakdown structure. Efforts required to design, develop, manufacture, test, checkout, launch and operate a protoflight assembled 25 kW, 50 kW and 100 kW PM include the preparation and delivery of related software, government furnished equipment, space support equipment, ground support equipment, launch site verification software, orbital verification software, and all related data items.

  5. Tunable single frequency fiber laser based on FP-LD injection locking.

    PubMed

    Zhang, Aiqin; Feng, Xinhuan; Wan, Minggui; Li, Zhaohui; Guan, Bai-ou

    2013-05-20

    We propose and demonstrate a tunable single frequency fiber laser based on Fabry Pérot laser diode (FP-LD) injection locking. The single frequency operation principle is based on the fact that the output from a FP-LD injection locked by a multi-longitudinal-mode (MLM) light can have fewer longitudinal-modes number and narrower linewidth. By inserting a FP-LD in a fiber ring laser cavity, single frequency operation can be possibly achieved when stable laser oscillation established after many roundtrips through the FP-LD. Wavelength switchable single frequency lasing can be achieved by adjusting the tunable optical filter (TOF) in the cavity to coincide with different mode of the FP-LD. By adjustment of the drive current of the FP-LD, the lasing modes would shift and wavelength tunable operation can be obtained. In experiment, a wavelength tunable range of 32.4 nm has been obtained by adjustment of the drive current of the FP-LD and a tunable filter in the ring cavity. Each wavelength has a side-mode suppression ratio (SMSR) of at least 41 dB and a linewidth of about 13 kHz.

  6. Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer.

    PubMed

    Harding, Thomas C; Long, Li; Palencia, Servando; Zhang, Hongbing; Sadra, Ali; Hestir, Kevin; Patil, Namrata; Levin, Anita; Hsu, Amy W; Charych, Deborah; Brennan, Thomas; Zanghi, James; Halenbeck, Robert; Marshall, Shannon A; Qin, Minmin; Doberstein, Stephen K; Hollenbaugh, Diane; Kavanaugh, W Michael; Williams, Lewis T; Baker, Kevin P

    2013-03-27

    The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c, and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1-amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind the hormonal FGFs, because these ligands require a cell surface co-receptor, klotho or β-klotho, for high-affinity binding and signaling. Serum calcium and phosphate levels, which are regulated by FGF-23, are not altered by administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039 treatment confers antitumor efficacy without the toxicities associated with other FGF pathway inhibitors.

  7. Growth of electron plasma waves above and below f(p) in the electron foreshock

    NASA Technical Reports Server (NTRS)

    Cairns, Iver H.; Fung, Shing F.

    1988-01-01

    This paper investigates the conditions required for electron beams to drive wave growth significantly above and below the electron plasma frequency, f(p), by numerically solving the linear dispersion equation. It is shown that kinetic growth well below f(p) may occur over a broad range of frequencies due to the beam instability, when the electron beam is slow, dilute, and relatively cold. Alternatively, a cold or sharp feature at low parallel velocities in the distribution function may drive kinetic growth significantly below f(p). Kinetic broadband growth significantly above f(p) is explained in terms of faster warmer beams. A unified qualitative theory for the narrow-band and broad-band waves is proposed.

  8. Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB

    PubMed Central

    Attems, Johannes; Colloby, Sean J.; O'Brien, John T.; McKeith, Ian; Walker, Rodney; Lee, Lean; Burn, David; Lett, Debra J.; Walker, Zuzana

    2017-01-01

    Objective: To conduct a validation study of 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard. Methods: Patients >60 years of age with dementia who had undergone 123I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent 123I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria. Results: Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis, 123I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal 123I-FP-CIT imaging. Conclusions: This large autopsy analysis of 123I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal 123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement. Classification of evidence: This study provides Class I evidence that 123I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB

  9. Experimental research of high field pinning centers in 2% C doped MgB2 wires at 20 K and 25 K

    NASA Astrophysics Data System (ADS)

    Gajda, D.; Morawski, A.; Zaleski, A. J.; Häßler, W.; Nenkov, K.; Małecka, M.; Rindfleisch, M. A.; Hossain, M. S. A.; Tomsic, M.

    2016-09-01

    High field pinning centers in MgB2 doped with 2 at. % carbon under a low and a high hot isostatic pressures have been investigated by transport measurements. The field dependence of the transport critical current density was analyzed within the different pinning mechanisms: surface pinning, point pinning, and pinning due to spatial variation in the Ginzburg-Landau parameter (Δκ pinning). Research indicates that a pressure of 1 GPa allows similar pinning centers to Δκ pinning centers to be obtained. This pinning is very important, because it makes it possible to increase the critical current density in high magnetic fields at 20 K and 25 K. Our results indicate that the δTc and δl pinning mechanisms, which are due to a spatial variation in the critical temperature (Tc) and the mean free path, l, respectively, create dislocations. The high density of dislocations with inhomogeneous distribution in the structure of the superconducting material creates the δl pinning mechanism. The low density of dislocations with inhomogeneous distribution creates the δTc pinning mechanism. Research indicates that the hot isostatic pressure process makes it possible to obtain a high dislocation density with a homogeneous distribution. This allows us to obtain the δTc pinning mechanism in MgB2 wires. In addition, a high pressure increases the crossover field from the single vortex to the small vortex bundle regime (Bsb) and improves the δTc pinning mechanism. Our research has proved that a high pressure significantly increases the crossover field from the small bundle to the thermal regime (Bth), with only a modest decrease in Tc of 1.5 K, decreases the thermal fluctuations, increases the irreversibility magnetic field (Birr) and the upper critical field (Bc2) in the temperature range from 4.2 K to 25 K, and reduces Birr and Bc2 above 25 K.

  10. Preliminary results of the PREFER FP7 Project

    NASA Astrophysics Data System (ADS)

    Fusilli, Lorenzo; Laneve, Giovanni; De Bonis, Roberto; Sebastian, Ana; Ferrucci, Fabrizio; Oliveira, Sandra

    2014-05-01

    The need to improve the information and intelligence support for forest fire prevention is widely recognized. Fire prevention is still the most cost-effective strategy when compared to firefighting and extinguishing that are costly, local, and triggered only in response to already ongoing crises. PREFER project, funded under the EU FP7 (G.A. 312931), intends to contribute at responding to such a pragmatic need of southern Europe's forests by: providing timely information products based on the exploitation of all available spacecraft sensors, offering a portfolio of products focused on pre- and post-crisis forest fire emergency, suitable for the users in the different countries of the European Mediterranean area. The PREFER Service portfolio consists of two main services: 1. Information Support to Fire Preparedness/Prevention Phase" (ISP) Service 2. Information Support to Fire Recovery/Reconstruction Phase" (ISR) Service This service is already at an advanced stage having completed the first year of activity. During this time several products have been consolidated: seasonal fuel maps; daily and seasonal fire hazard maps; seasonal risk maps; prescribed fire maps. This paper aims at presenting the preliminary results of the research activity carried out in the framework of the PREFER project, focusing, in particular, on these recalled above. As for Fire Risk and Hazard assessment, many indexes have been developed in the last years. Hardly any of them uses data derived from satellite images. The FPI index is an exception to this rule which, in addition, makes use of meteorological data. In spite of being a very complete index, the FPI still allows room for improvement which justify the interest of PREFER in it. PREFER's innovative approach to FPI will allow taking into account the effect of solar illumination conditions in determining the humidity present in the dead vegetation, and therefore its proneness to burn. PREFER innovation also focus in allowing the index to

  11. Matching intermediate-term, multi-angle averages of CIRS FP1+FP3 observations for the He VMR and cloud in Saturn’s atmosphere

    NASA Astrophysics Data System (ADS)

    Serrano, Joshua; Orton, Glenn S.; Sinclair, James; Fletcher, Leigh N.

    2017-01-01

    IntroductionSaturn’s atmosphere is a complicated system that is affected by many internal and external variables. To better understand these variables and how they affect Saturn’s atmospheric system we rely on data obtained from spacecraft and Earth based observatories. For this particular study, we used data from Cassini’s Composite Infrared Spectrometer (CIRS) instrument.Currently we do not know the exact amount of helium (He) with respect to molecular hydrogen gas (H2) in Saturn’s atmosphere. This He and H2 volume mixing ratio (VMR) is extremely important in understanding the structure and evolution of Saturn’s atmosphere. The CIRS team was not able to identify reliable matching spectra with data obtained from Focal Plane 1 (FP1) and Focal Plane 3 (FP3) of the CIRS instrument.MethodsAll the data sets we have worked with range from the years 2005-2012. Each year’s data sets were organized into 6 month intervals spanning the months January-June and July-December with data for FP1 and FP3 being completely separate. Each data set is also binned by planetographic latitude.Each data point consists of a spectra wavenumber, radiance value, and an emission angle. The emission angle is then converted to the unit μ, the value of this unit is simply the cosine of the emission angle. Initially all data was binned by year, latitude, and calculated µ value. This data was then plotted as a function of radiance and wavenumber to identify areas of spectral overlap data overlap in corresponding FP1 and FP3 data sets. These data sets were then prepped to be processed by a radiative transfer retrieval algorithm called NEMESIS.ResultsFurther binning of the data sets by looking at abundance of spectra values at certain μ values allows us to increase our confidence that these data sets are populated with enough spectra for NEMESIS to work with. NEMESIS has been operating with assumed He and H2 values derived from results of other studies, this means that narrowing down a

  12. Evaluation of data from the Vaisala CT25K for Estimation of PM10 Concentration and Mixing Heights in an Urban Environment

    NASA Astrophysics Data System (ADS)

    Gunter, R. L.; Hosker, R. P.

    2005-12-01

    During the month of August, the Urban Dispersion Project was conducted in New York City. NOAA's Atmospheric and Turbulence Division (ATDD), Oak Ridge, TN operated a Vaisala CT25K Ceilometer for a two-week timeframe during the project. Typically, ceilometer measurements are used for cloud height determination. It has been found that during dry conditions, there is a good correlation between the ceilometer near- range backscatter and in situ PM10 concentration readings. In addition, it also has been determined that the ceilometer is a suitable instrument for determining the convective mixing height (MH). Aerosol concentrations are calculated and mixing heights are estimated using data from the ceilometer during dry conditions in Manhattan. Mixing heights are compared to radiosonde data taken during the project.

  13. X-ray intensity and source size characterizations for the 25 kV upgraded Manson source at Sandia National Laboratories

    NASA Astrophysics Data System (ADS)

    Loisel, G.; Lake, P.; Gard, P.; Dunham, G.; Nielsen-Weber, L.; Wu, M.; Norris, E.

    2016-11-01

    At Sandia National Laboratories, the x-ray generator Manson source model 5 was upgraded from 10 to 25 kV. The purpose of the upgrade is to drive higher characteristics photon energies with higher throughput. In this work we present characterization studies for the source size and the x-ray intensity when varying the source voltage for a series of K-, L-, and M-shell lines emitted from Al, Y, and Au elements composing the anode. We used a 2-pinhole camera to measure the source size and an energy dispersive detector to monitor the spectral content and intensity of the x-ray source. As the voltage increases, the source size is significantly reduced and line intensity is increased for the three materials. We can take advantage of the smaller source size and higher source throughput to effectively calibrate the suite of Z Pulsed Power Facility crystal spectrometers.

  14. X-ray intensity and source size characterizations for the 25 kV upgraded Manson source at Sandia National Laboratories.

    PubMed

    Loisel, G; Lake, P; Gard, P; Dunham, G; Nielsen-Weber, L; Wu, M; Norris, E

    2016-11-01

    At Sandia National Laboratories, the x-ray generator Manson source model 5 was upgraded from 10 to 25 kV. The purpose of the upgrade is to drive higher characteristics photon energies with higher throughput. In this work we present characterization studies for the source size and the x-ray intensity when varying the source voltage for a series of K-, L-, and M-shell lines emitted from Al, Y, and Au elements composing the anode. We used a 2-pinhole camera to measure the source size and an energy dispersive detector to monitor the spectral content and intensity of the x-ray source. As the voltage increases, the source size is significantly reduced and line intensity is increased for the three materials. We can take advantage of the smaller source size and higher source throughput to effectively calibrate the suite of Z Pulsed Power Facility crystal spectrometers.

  15. Measurement error analysis of Brillouin lidar system using F-P etalon and ICCD

    NASA Astrophysics Data System (ADS)

    Yao, Yuan; Niu, Qunjie; Liang, Kun

    2016-09-01

    Brillouin lidar system using Fabry-Pérot (F-P) etalon and Intensified Charge Coupled Device (ICCD) is capable of real time remote measuring of properties like temperature of seawater. The measurement accuracy is determined by two key parameters, Brillouin frequency shift and Brillouin linewidth. Three major errors, namely the laser frequency instability, the calibration error of F-P etalon and the random shot noise are discussed. Theoretical analysis combined with simulation results showed that the laser and F-P etalon will cause about 4 MHz error to both Brillouin shift and linewidth, and random noise bring more error to linewidth than frequency shift. A comprehensive and comparative analysis of the overall errors under various conditions proved that colder ocean(10 °C) is more accurately measured with Brillouin linewidth, and warmer ocean (30 °C) is better measured with Brillouin shift.

  16. Investigation on a fiber optic accelerometer based on FBG-FP interferometer

    NASA Astrophysics Data System (ADS)

    Lin, Chongyu; Luo, Hong; Xiong, Shuidong; Li, Haitao

    2014-12-01

    A fiber optic accelerometer based on fiber Bragg grating Fabry-Perot (FBG-FP) interferometer is presented. The sensor is a FBG-FP cavity which is formed with two weak fiber Bragg gratings (FBGs) in a single-mode fiber. The reflectivity of the two FBGs is 9.42% and 7.74% respectively, and the fiber between them is 10 meters long. An optical demodulation system was set up to analyze the reflected light of FBG-FP cavity. Acceleration signals of different frequencies and intensities were demodulated correctly and stably by the system. Based on analyzing the optical spectrum of weak FBG based FBG-FP cavity, we got the equivalent length of FBG-FP cavity. We used a path-matching Michelson interferometer (MI) to demodulate the acceleration signal. The visibility of the interference fringe we got was 41%~42% while the theory limit was 50%. This indicated that the difference of interferometer's two arms and the equivalent length of FBG-FP cavity were matched well. Phase generated carrier (PGC) technology was used to eliminate phase fading caused by random phase shift and Faraday rotation mirrors (FRMs) were used to eliminate polarization-induced phase fading. The accelerometer used a compliant cylinder design and its' sensitivity and frequency response were analyzed and simulated based on elastic mechanics. Experiment result showed that the accelerometer had a flat frequency response over the frequency range of 31-630Hz. The sensitivity was about 31dB (0dB=1rad/g) with fluctuation less than 1.5dB.

  17. Development of an embedded Fabry Perot Fiber Optic Strain Rosette Sensor (FP-FOSRS)

    NASA Technical Reports Server (NTRS)

    Carman, Gregory P.; Lesko, John J.; Case, Scott W.; Fogg, Brian; Claus, Richard O.

    1992-01-01

    We investigate the feasibility of utilizing a Fabry-Perot Fiber Optic Strain Rosette Sensor (FP-FOSRS) for the evaluation of the internal strain state of a material system. We briefly describe the manufacturing process for this sensor and point out some potential problem areas. Results of an embedded FP-FOSRS in an epoxy matrix with external resistance strain gauges applied for comparative purposes are presented. We show that the internal and external strain measurements are in close agreement. This work lays the foundation for embedding this sensor in actual composite laminas.

  18. Experimental study of upper sd shell nuclei and evolution of sd-fp shell gap

    SciTech Connect

    Sarkar, M. Saha

    2012-06-27

    The intruder orbitals from the fp shell play important role in the structure of nuclei around the line of stability in the upper sd shell. Experimentally we have studied {sup 35}Cl, {sup 30}P, {sup 36}Cl, {sup 37}Ar and {sup 34}Cl in this mass region using the INGA setup. Large basis cross-shell shell model calculations have indicated the need for change of the sd-fp energy gap for reliable reproduction of negative parity and high spin positive parity states. Indication of population of states of large deformation has been found in our data. Theoretical interpretation of these states has been discussed.

  19. Enhanced gene transfection performance and biocompatibility of polyethylenimine through pseudopolyrotaxane formation with α-cyclodextrin.

    PubMed

    Hu, Li-Zhong; Wan, Ning; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2017-03-24

    Polyethylenimine (PEI), a commercially available gene transfection reagent, is a promising nonviral vector due to its inherent ability to efficiently condense genetic materials and its successful transfection performance in vitro. However, its low transfection efficiency in vivo, along with its high cytotoxicity, limit any further applications in gene therapy. To enhance the gene transfection performance and reduce the cytotoxicity of linear polyethylenimine, pseudopolyrotaxane PEI25k/CD and the polyrotaxanes PEI25k/CD-PA and PEI25k/CD-PB were prepared and their transfection efficiencies were then evaluated. The pseudopolyrotaxane PEI25k/CD exhibited better transfection efficiency and lower cytotoxicity than the transfection reagent linear PEI25k, even in the presence of serum. It also showed a remarkably higher cell viability, similar DNA protecting capability, and better DNA decondensation and release ability, and could be useful for the development of novel and safe nonviral gene delivery vectors for gene therapy.

  20. Enhanced gene transfection performance and biocompatibility of polyethylenimine through pseudopolyrotaxane formation with α-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Hu, Li-Zhong; Wan, Ning; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2017-03-01

    Polyethylenimine (PEI), a commercially available gene transfection reagent, is a promising nonviral vector due to its inherent ability to efficiently condense genetic materials and its successful transfection performance in vitro. However, its low transfection efficiency in vivo, along with its high cytotoxicity, limit any further applications in gene therapy. To enhance the gene transfection performance and reduce the cytotoxicity of linear polyethylenimine, pseudopolyrotaxane PEI25k/CD and the polyrotaxanes PEI25k/CD-PA and PEI25k/CD-PB were prepared and their transfection efficiencies were then evaluated. The pseudopolyrotaxane PEI25k/CD exhibited better transfection efficiency and lower cytotoxicity than the transfection reagent linear PEI25k, even in the presence of serum. It also showed a remarkably higher cell viability, similar DNA protecting capability, and better DNA decondensation and release ability, and could be useful for the development of novel and safe nonviral gene delivery vectors for gene therapy.

  1. Simultaneous MMW generation and up-conversion for WDM-ROF systems based on FP laser

    NASA Astrophysics Data System (ADS)

    Zhang, Chan; Ning, TiGang; Li, Jing; Li, Chao; He, Xueqing; Pei, Li

    2016-10-01

    A new wavelength division multiplexing radio-over-fiber (WDM-ROF) scheme based on Fabry-Perot (FP) laser is proposed and demonstrated for simultaneous millimeter-wave (MMW) generation and up-conversion. The tunable optical comb generated by FP laser is served as a cost-effective WDM optical source in central station (CS) and it makes all-optical up-conversion process for all channels simple compared with using a DFB array. All modes from the FP laser are modulated simultaneously by a LiNbO3 Mach-Zehnder modulator (LN-MZM) then. We have systematically compared the performances of MMW generation and up-conversion using LN-MZM based on different modulation schemes. A reflective semiconductor optical amplifiers (RSOA) is used both for the downstream modulation of each channel and for the reduction of mode partition noise (MPN) induced from FP laser. In the scheme, the multiple optical carrier suppression (OCS) modulation shows the highest receiver sensitivity and smallest power penalty over long-distance delivery. In the numerical simulation, 7 WDM channels each carrying 2.5 Gb/s baseband signal have been up-converted to 60 GHz simultaneously with good performance over 25 km single mode fiber (SMF) transmission.

  2. Modification of FP-HIV activity by peptide sequences of GB virus C: a biophysical approach.

    PubMed

    Domènech, O; Ortiz, A; Pujol, M; Haro, I; Muñoz, M; Alsina, M A; Prat, J; Busquets, M A; Girona, V

    2014-05-01

    Three synthetic peptide sequences of 18 amino acid each, corresponding to different fragments of the E2 capsid protein of GB virus C (GBV-C): SDRDTVVELSEWGVPCAT (P45), GSVRFPFHRCGAGPKLTK (P58) and RFPFHRCGAGPKLTKDLE (P59) have been characterized in order to find a relationship between their physicochemical properties and the results obtained in cellular models. Experiments were performed in presence and absence of the HIV fusion peptide (FP-HIV) due to the evidences that GBV-C inhibits AIDS progression. P45 peptide showed lower surface activity and less extent of penetration into 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) (3:2, mol/mol) lipid monolayers than P58 and P59. However, P45 peptide presented higher capacity to inhibit FP-HIV induced cell-cell fusion than the other two sequences. These results were supported by fluorescence anisotropy measurements which indicated that P45 had a significant effect on the inhibition of FP-HIV perturbation of liposomes of the same lipid composition. Finally, atomic force microscopy (AFM) studies have evidenced the modification of the changes induced by the FP-HIV in the morphology of lipid bilayers when P45 was present in the medium.

  3. Comparison in gas media (absolute and gauge mode)in the range from 25 kPa TO 200 kPa (EURAMET.M.P-K8)

    NASA Astrophysics Data System (ADS)

    Wuethrich, C.; Alisic, S.; Altintas, A.; van Andel, I.; C, In­Mook; Eltawil, A. A.; Farár, P.; Hetherington, P.; Koçaş, I.; Lefkopoulos, A.; Otal, P.; Prazak, D.; Sabuga, W.; Salustiano, R.; Sandu, I.; Sardi, M.; Saxholm, S.; Setina, J.; Spohr, I.; Steindl, D.; Testa, N.; Vámossy, C.; Grgec Bermanec, L.

    2016-01-01

    It was decided at the EURAMET TC-M meeting in Torino in 2006 to realize a comparison in gauge and absolute pressure up to 200 kPa as it would allow a link to the CCM.P-K6 and CCM.P-K2 comparisons to be established. This project interested a lot of laboratories from the beginning with 23 participants, 22 of which have submitted results. The circulation of the transfer standard began in July 2009 and lasted until January 2012. No major problems occurred during the transport. The measurand of the comparison is the effective area of a piston-cylinder determined in gauge and absolute pressure from 25 kPa to 200 kPa with pressure steps of 25 kPa. The transfer standard is a gas lubricated tungsten carbide piston-cylinder with an effective area of ~9.8 cm2, fabricated by DH Instruments and compatible with a PG-7601 pressure balance. Some participants used their own pressure balance while a pressure balance with a reference vacuum sensor has been circulated for the participants not equipped with this system. One participant (SMU, Slovakia) has never provided the measurement results and another participant (FORCE Technology, Denmark) submitted a revised set of measurement results after the pilot laboratory mentioned that the equivalence was not met. After the determination of the reference value, all the 22 participants who delivered the results in gauge pressure demonstrated equivalence respective to the reference value on most of the range. In absolute pressure the equivalence is demonstrated, for all nominal pressures, by all 17 participants who submitted results. The comparison is linked to the CCM.P-K6 for gauge pressure and to CCM.P-K2 for absolute pressure. The link does not strongly affect the equivalence of the results and an excellent degree of equivalence is achieved in gauge and absolute pressure. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb

  4. Studies on the development and efficiency improvement of a 1.5 W at 25 K two stage pulse tube cooler

    NASA Astrophysics Data System (ADS)

    Kranthi Kumar, J.; Jacob, S.; Karunanithi, R.; Narasimham, GSVL

    2017-02-01

    A high frequency two stage pulse tube cooler (PTC) has been designed using Sage software for a JT-PTC hybrid helium recondensation system. The cold end of the first stage regenerator is anchored at 80 K using a liquid nitrogen supply. Such a thermally coupled design simplifies the design without the need for considering flow distribution between the stages and ensures that entire flow is available to produce cooling power at 25 K. The pulse tube cooler is designed for maximal utilization of the 900 W PV power provided by the Pressure Wave Generator (PWG). With the first prototype, a no load temperature of 40.4 K was achieved at a filling pressure of 24.1 bar. The effect of filling pressure on the acoustic matching of the PTC and PWG was investigated. It is observed that filling pressure has a significant effect on the PWG piston stroke amplitude. Using phasor analysis, it is shown that the phase relationship at different sections of the two stage PTC is detrimentally affected by the pulse tube volume. A scheme for achieving advantageous phasing by reducing the pulse tube volume is proposed. This involves maintaining the hot heat exchanger, inertance tube and buffer volume at 80 K. With the modification it is shown that a beneficial phase reversal across second stage Regenerator is achieved. The method is currently under experimental investigation.

  5. Development and testing of a 2.5 kW synchronous generator with a high temperature superconducting stator and permanent magnet rotor

    NASA Astrophysics Data System (ADS)

    Qu, Timing; Song, Peng; Yu, Xiaoyu; Gu, Chen; Li, Longnian; Li, Xiaohang; Wang, Dewen; Hu, Boping; Chen, Duxing; Zeng, Pan; Han, Zhenghe

    2014-04-01

    High temperature superconducting (HTS) armature windings have the potential for increasing the electric loading of a synchronous generator due to their high current transport capacity, which could increase the power density of an HTS rotating machine. In this work, a novel synchronous generator prototype with an HTS stator and permanent magnet rotor has been developed. It has a basic structure of four poles and six slots. The armature winding was constructed from six double-pancake race-track coils with 44 turns each. It was designed to deliver 2.5 kW at 300 rpm. A concentrated winding configuration was proposed, to prevent interference at the ends of adjacent HTS coils. The HTS stator was pressure mounted into a hollow Dewar cooled with liquid nitrogen. The whole stator could be cooled down to around 82 K by conduction cooling. In the preliminary testing, the machine worked properly and could deliver 1.8 kW power when the armature current was 14.4 A. Ic for the HTS coils was found to be suppressed due to the influence of the temperature and the leakage field.

  6. Characteristics of the MMPI-2 F(p) Scale as a Function of Diagnosis in an Inpatient Sample of Veterans.

    ERIC Educational Resources Information Center

    Arbisi, Paul A.; Ben-Porath, Yossef S.

    1997-01-01

    A new infrequent response indicator, frequency psychopathology [F(p)] was developed for the Minnesota Multiphasic Personality Inventory (MMPI) and tested with 308 male psychiatric inpatients (veterans). Findings support the F(p) as a sensitive index of profile invalidity in psychiatric populations. (SLD)

  7. Evaluating the Latent Structure of the MMPI-2 F(p) Scale in a Forensic Sample: A Taxometric Analysis

    ERIC Educational Resources Information Center

    Strong, David R.; Glassmire, David M.; Frederick, Richard I.; Greene, Roger L.

    2006-01-01

    P. A. Arbisi and Y. S. Ben-Porath (1995) originally proposed that the Infrequency Psychopathology scale, F(p), be used as the final step in an algorithm to determine the validity of a Minnesota Multiphasic Personality Inventory-2 (MMPI-2) protocol. The current study used taxometric procedures to determine the latent structure of F(p) among…

  8. Evaluation of pancreatic VMAT2 binding with active and inactive enantiomers of 18F-FP-DTBZ in baboons

    PubMed Central

    Lim, Keunpoong; Labaree, David; Ropchan, Jim; Harris, Paul; Huang, Yiyun; Ichise, Masanori; Carson, Richard E.; Cline, Gary W.

    2017-01-01

    Introduction 18F-Fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-(+)-DTBZ) is a vesicular monoamine transporter type 2 (VMAT2) radiotracer for positron emission tomography (PET) imaging to quantify human β-cell mass. Renal cortex and spleen have been suggested as reference regions, however, little is known about 18F-FP-(+)-DTBZ binding in these regions including the fraction of radiometabolite. We compared the kinetics of 18F-FP-(+)-DTBZ and its inactive enantiomer 18F-FP-(−)-DTBZ in baboons, estimated the non-displaceable binding (VND) of the tracers, and used ex vivo studies to measure radiometabolite fractions. Methods PET scans were conducted for up to 4 h with (+) and (−) enantiomers. Displacement experiments using unlabeled (+) and (−) enantiomers of FP-DTBZ and fluvoxamine (to evaluate sigma-1 receptor binding) were performed. SUV curves were used to calculate displacement values in the pancreas, renal cortex, and spleen. Distribution volumes (VT) were computed, and three approaches for calculation of VND were compared: (1) 18F-FP-(+)-DTBZ reference VT, (2) 18F-FP-(−)-DTBZ pancreatic VT, and (3) a scaled 18F-FP-(+)-DTBZ reference VT values. Ex vivo study was conducted to measure radiometabolite fraction in homogenized tissue samples from baboons at 90 min post-injection. Results Spleen uptake was lowest for both tracers. Highest uptake was in the pancreas with 18F-FP-(+)-DTBZ and renal cortex with 18F-FP-(−)-DTBZ. Substantial displacement effect was observed only with unlabeled FP-(+)-DTBZ in the 18F-FP-(+)-DTBZ studies. Radiometabolite fraction was higher in the renal cortex than the spleen. Approaches (1) and (3) with spleen to estimate VND provided lowest inter-subject variability of BPND. Conclusions VT differences among organs and between enantiomers indicated that scaling of reference region values is needed for quantification of VMAT2 binding in the pancreas with 18F-FP-(+)-DTBZ. Since the kidney PET signal has greater partial volume

  9. Space weather in the EU's FP7 Space Theme. Preface to the special issue on "EU-FP7 funded space weather projects"

    NASA Astrophysics Data System (ADS)

    Chiarini, Paola

    2013-11-01

    Technological infrastructures in space and on ground provide services on which modern society and economies rely. Space weather related research is funded under the 7th Framework Programme for Research and Innovation (FP7) of the European Union in response to the need of protecting such critical infrastructures from the damage which could be caused by extreme space weather events. The calls for proposals published under the topic "Security of space assets from space weather events" of the FP7 Space Theme aimed to improve forecasts and predictions of disruptive space weather events as well as identify best practices to limit the impacts on space- and ground-based infrastructures and their data provision. Space weather related work was also funded under the topic "Exploitation of space science and exploration data", which aims to add value to space missions and Earth-based observations by contributing to the effective scientific exploitation of collected data. Since 2007 a total of 20 collaborative projects have been funded, covering a variety of physical phenomena associated with space weather, from ionospheric disturbances and scintillation, to geomagnetically induced currents at Earth's surface, to coronal mass ejections and solar energetic particles. This article provides an overview of the funded projects, touching upon some results and referring to specific websites for a more exhaustive description of the projects' outcomes.

  10. Conjugal transfer of R68.45 and FP5 between Pseudomonas aeruginosa strains in a freshwater environment.

    PubMed Central

    O'Morchoe, S B; Ogunseitan, O; Sayler, G S; Miller, R V

    1988-01-01

    Recent concern over the release of genetically engineered organisms has resulted in a need for information about the potential for gene transfer in the environment. In this study, the conjugal transfer in Pseudomonas aeruginosa of the plasmids R68.45 and FP5 was demonstrated in the freshwater environment of Fort Loudoun Resevoir, Knoxville, Tenn. When genetically well defined plasmid donor and recipient strains were introduced into test chambers suspended in Fort Loudoun Lake, transfer of both plasmids was observed. Conjugation occurred in both the presence and absence of the natural microbial community. The number of transconjugants recovered was lower when the natural community was present. Transfer of the broad-host-range plasmid R68.45 to organisms other than the introduced recipient was not observed in these chambers but was observed in laboratory simulations when an organism isolated from lakewater was used as the recipient strain. Although the plasmids transferred in laboratory studies were genetically and physically stable, a significant number of transconjugants recovered from the field trials contained deletions and other genetic rearrangements, suggesting that factors which increase gene instability are operating in the environment. The potential for conjugal transfer of genetic material must be considered in evaluating the release of any genetically engineered microorganism into a freshwater environment. Images PMID:3140724

  11. Interface-induced superconductivity at ∼25 K at ambient pressure in undoped CaFe2As2 single crystals.

    PubMed

    Zhao, Kui; Lv, Bing; Deng, Liangzi; Huyan, Shu-Yuan; Xue, Yu-Yi; Chu, Ching-Wu

    2016-11-15

    Superconductivity has been reversibly induced/suppressed in undoped CaFe2As2 (Ca122) single crystals through proper thermal treatments, with Tc at ∼25 K at ambient pressure and up to 30 K at 1.7 GPa. We found that Ca122 can be stabilized in two distinct tetragonal (T) phases at room temperature and ambient pressure: PI with a nonmagnetic collapsed tetragonal (cT) phase at low temperature and PII with an antiferromagnetic orthorhombic (O) phase at low temperature, depending on the low-temperature annealing condition. Neither phase at ambient pressure is superconducting down to 2 K. However, systematic annealing for different time periods at 350 °C on the as-synthesized crystals, which were obtained by quenching the crystal ingot from 850 °C, reveals the emergence of superconductivity over a narrow time window. Whereas the onset Tc is insensitive to the anneal time, the superconductive volume fraction evolves with the time in a dome-shaped fashion. Detailed X-ray diffraction profile analyses further reveal mesoscopically stacked layers of the PI and the PII phases. The deduced interface density correlates well with the superconducting volume measured. The transport anomalies of the T-cT transition, which is sensitive to lattice strain, and the T-O transition, which is associated with the spin-density-wave (SDW) transition, are gradually suppressed over the superconductive region, presumably due to the interface interactions between the nonmagnetic metallic cT phase and the antiferromagnetic O phase. The results provide the most direct evidence to date for interface-enhanced superconductivity in undoped Ca122, consistent with the recent theoretical prediction.

  12. Identification and Characterization of a 25 kDa Protein That Is Indispensable for the Efficient Saccharification of Eisenia bicyclis in the Digestive Fluid of Aplysia kurodai

    PubMed Central

    Tsuji, Akihiko; Kuwamura, Shuji; Shirai, Akihiro; Yuasa, Keizo

    2017-01-01

    The digestive fluid of the sea hare Aplysia kurodai can liberate approximately 2.5 mg of glucose from 10 mg of dried Eisenia bicyclis powder. Although laminaran, a major storage polysaccharide in E. bicyclis, is easily digested to glucose by the synergistic action of the 110 and 210 kDa A. kurodai β-glucosidases (BGLs), glucose is not liberated from E. bicyclis by direct incubation with these BGLs. To clarify this discrepancy, we searched for an Eisenia hydrolysis enhancing protein (EHEP) in the digestive fluid of A. kurodai. A novel 25 kDa protein that enhances E. bicyclis saccharification by β-glucosidases was purified to a homogeneous state from the digestive fluid of A. kurodai, and its cDNA was cloned from total cDNAs reverse-transcribed from hepatopancreas total RNA. The E. bicyclis extract strongly inhibited BGLs, suggesting some compound within this brown alga functioned as a feeding deterrent. However, when E. bicyclis was incubated with BGLs in the presence of EHEP, glucose production was markedly increased. As E. bicyclis is rich in phlorotannin, which are only found in brown algae, our study suggested that these compounds are the main BGL inhibitors in E. bicyclis extract. EHEP protects BGLs from phlorotannin inhibition by binding to phlorotannins and forming an insoluble complex with phloroglucinol and phlorotannins. These findings indicated that EHEP plays a key role in the saccharification of brown seaweeds containing phlorotannins in the digestive fluid of A. kurodai. This is the first report of EHEP as a phlorotannin-binding protein that protects BGLs from inhibition. PMID:28129373

  13. Electronic structure of the oxygen evolving complex in photosystem II, as revealed by 55Mn Davies ENDOR studies at 2.5 K.

    PubMed

    Jin, Lu; Smith, Paul; Noble, Christopher J; Stranger, Rob; Hanson, Graeme R; Pace, Ron J

    2014-05-07

    We report the first (55)Mn pulsed ENDOR studies on the S2 state multiline spin ½ centre of the oxygen evolving complex (OEC) in Photosystem II (PS II), at temperatures below 4.2 K. These were performed on highly active samples of spinach PS II core complexes, developed previously in our laboratories for photosystem spectroscopic use, at temperatures down to 2.5 K. Under these conditions, relaxation effects which have previously hindered observation of most of the manganese ENDOR resonances from the OEC coupled Mn cluster are suppressed. (55)Mn ENDOR hyperfine couplings ranging from ∼50 to ∼680 MHz are now seen on the S2 state multiline EPR signal. These, together with complementary high resolution X-band CW EPR measurements and detailed simulations, reveal that at least two and probably three Mn hyperfine couplings with large anisotropy are seen, indicating that three Mn(III) ions are likely present in the functional S2 state of the enzyme. This suggests a low oxidation state paradigm for the OEC (mean Mn oxidation level 3.0 in the S1 state) and unexpected Mn exchange coupling in the S2 state, with two Mn ions nearly magnetically silent. Our results rationalize a number of previous ligand ESEEM/ENDOR studies and labelled water exchange experiments on the S2 state of the photosystem, in a common picture which is closely consistent with recent photo-assembly (Kolling et al., Biophys. J. 2012, 103, 313-322) and large scale computational studies on the OEC (Gatt et al., Angew. Chem., Int. Ed. 2012, 51, 12025-12028, Kurashige et al. Nat. Chem. 2013, 5, 660-666).

  14. Interface-induced superconductivity at ˜25 K at ambient pressure in undoped CaFe2As2 single crystals

    NASA Astrophysics Data System (ADS)

    Zhao, Kui; Lv, Bing; Deng, Liangzi; Huyan, Shu-Yuan; Xue, Yu-Yi; Chu, Ching-Wu

    2016-11-01

    Superconductivity has been reversibly induced/suppressed in undoped CaFe2As2 (Ca122) single crystals through proper thermal treatments, with Tc at ˜25 K at ambient pressure and up to 30 K at 1.7 GPa. We found that Ca122 can be stabilized in two distinct tetragonal (T) phases at room temperature and ambient pressure: PI with a nonmagnetic collapsed tetragonal (cT) phase at low temperature and PII with an antiferromagnetic orthorhombic (O) phase at low temperature, depending on the low-temperature annealing condition. Neither phase at ambient pressure is superconducting down to 2 K. However, systematic annealing for different time periods at 350 °C on the as-synthesized crystals, which were obtained by quenching the crystal ingot from 850 °C, reveals the emergence of superconductivity over a narrow time window. Whereas the onset Tc is insensitive to the anneal time, the superconductive volume fraction evolves with the time in a dome-shaped fashion. Detailed X-ray diffraction profile analyses further reveal mesoscopically stacked layers of the PI and the PII phases. The deduced interface density correlates well with the superconducting volume measured. The transport anomalies of the T-cT transition, which is sensitive to lattice strain, and the T-O transition, which is associated with the spin-density-wave (SDW) transition, are gradually suppressed over the superconductive region, presumably due to the interface interactions between the nonmagnetic metallic cT phase and the antiferromagnetic O phase. The results provide the most direct evidence to date for interface-enhanced superconductivity in undoped Ca122, consistent with the recent theoretical prediction.

  15. Experimental determination of the effects of steep front-short duration surges on 25 kVA pole mounted distribution transformers

    SciTech Connect

    Eichler, C.H.; Legro, J.R.; Barnes, P.R.

    1988-01-01

    Nineteen standard commercial, 7200-volt, 25-kVa distribution transformers were tested to determine vulnerability of their insulation systems to steep front-short duration (SFSD) surges. These transformers were tested both with and without surge arresters using the high voltage pulser at the Maxwell Laboratories, San Diego, CA. The open circuit pulser test voltages were 400 kV, 500 kV, 800kV, and 1000kV. These voltages exhibited an approximately 60 ns rise time and aproximately 2000 ns to half value. The voltage was applied to the transformer under test through a 400-Ohm series resistor. This series resistor represented the distribution line surge impedance. Standard lightning impulse tests for this voltage class of distribution transformers were conducted prior to the steep front surge tests to verify insulation integrity, and were repeated following the steep-front surge tests to ascertain if an insulation failure had occurred in the tested transformer due to the steep-front impulse. Failed transformers were disassembled to evaluate failure modes. It was determined that no insulation failures occurred on any transformers tested that were protected by surge arresters mounted directly on the transformer. An external flashover of the high voltage bushing occurred in some cases when the transformer was not protected by a surge arrester, but the bushing sparkover was not always sufficient to protect the transformer. Unprotected transformers failed at voltages around 250 kV to 300 kV peak. The failure mode was usually an internal flashover/puncture between the first few turns of the outer layer of the high voltage winding and the low voltage winding or, sometimes, to an inner layer of the high voltage winding. 10 refs., 10 figs., 1 tab.

  16. Thermal analysis for the HTS stator consisting of HTS armature windings and an iron core for a 2.5 kW HTS generator

    NASA Astrophysics Data System (ADS)

    Song, P.; Qu, T.-M.; Lai, L.-F.; Wu, M.-S.; Yu, X.-Y.; Han, Z.

    2016-05-01

    Most present demonstrations of high-temperature superconducting (HTS) synchronous motors/generators are partially superconducting, only installing HTS coils on the rotor as excitation windings. The possible applicability of HTS armature windings is an interesting research topic because these windings can certainly increase the power density attributed to a potentially high armature loading capacity. In this study, we analysed the thermal behaviours of a developed 2.5 kW-300 rpm synchronous generator prototype that consists of an HTS stator with Bi-2223-Ag armature windings on an iron core and a permanent magnet (PM) rotor. The entire HTS stator, including the iron core, is cooled with liquid nitrogen through conduction cooling. The rated frequency is set at 10 Hz to reduce AC loss. The properties of the HTS windings and the iron core are characterized, and the temperatures in the HTS stator under different operation conditions are measured. The estimated iron loss is 11.5 W under operation in 10 Hz at liquid nitrogen temperature. Conduction cooling through the silicon iron core is sufficient to cool the iron core and to compensate for the temperature increment caused by iron loss. The stable running capacity is limited to 1.6 kW when the armature current is 12.6 A (effective values) due to the increasing temperature in the slots as a result of the AC loss in the HTS coils. The thermal contact between the HTS coils and the cooling media should be improved in the future to take away the heat generated by AC loss.

  17. Theory for the 2f(p) radiation upstream of the earth's bow shock

    SciTech Connect

    Cairns, I.H.; Melrose, D.B.

    1985-07-01

    The mechanism responsible for the radiation observed near the earth bow shock at twice the plasma frequency f(p) is investigated theoretically. A model comprising two three-wave steps and involving Langmuir (L), ion-sound (S), and EM (t) waves is proposed: L + or - S yields L-prime; L + L-prime yields t. This model is shown to be consistent with observations of low-frequency S-like waves (Anderson et al., 1981), and further observational tests are suggested. A critical examination of the theory of Fung et al. (1982) is included, and it is found that an important term in the absorption coefficient was neglected. Correcting this error leads to an intrinsic theoretical brightness-temperature limit of 3 x 10 to the 9th K, well below the observed brightness temperature of the 2 f(p) radiation, about 10 to the 11th K. 18 references.

  18. 123I-FP-CIT and 99mTc-HMPAO in Pathologically Confirmed Progressive Supranuclear Palsy.

    PubMed

    Matesan, Manuela Cristina; Elojeimy, Saeed; Minoshima, Satoshi

    2016-12-01

    Molecular brain imaging I-FP-CIT SPECT is an important tool in evaluation of patients with parkinsonism. However, various neurodegenerative etiologies cannot be differentiated by I-FP-CIT SPECT alone. We present a case of progressive supranuclear palsy with abnormal I-FP-CIT SPECT and abnormal Tc-HMPAO SPECT depicted by quantitative analyses but unremarkable MRI 16 months after the onset of symptoms. Brain autopsy demonstrated presence of neuronal and glial tau pathology in both cortical and subcortical regions confirming the diagnosis of progressive supranuclear palsy. This case illustrates potential values of multimodal molecular brain imaging in conjunction with quantitative analysis in the evaluation of movement disorders.

  19. Isospin-mixing corrections for {ital fp}-shell Fermi transitions

    SciTech Connect

    Ormand, W.E. |; Brown, B.A.

    1995-11-01

    Isospin-mixing corrections for superallowed Fermi transitions in {ital fp}-shell nuclei are computed within the framework of the shell model. The study includes three nuclei that are part of the set of nine accurately measured transitions as well as five cases that are expected to be measured in the future at radioactive-beam facilities. We also include some new calculations for {sup 10}C. With the isospin-mixing corrections applied to the nine accurately measured {ital ft} values, the conserved-vector-current hypothesis and the unitarity condition of the Cabbibo-Kobayashi-Maskawa matrix are tested.

  20. File Specification for GEOS-5 FP-IT (Forward Processing for Instrument Teams)

    NASA Technical Reports Server (NTRS)

    Lucchesi, R.

    2013-01-01

    The GEOS-5 FP-IT Atmospheric Data Assimilation System (GEOS-5 ADAS) uses an analysis developed jointly with NOAA's National Centers for Environmental Prediction (NCEP), which allows the Global Modeling and Assimilation Office (GMAO) to take advantage of the developments at NCEP and the Joint Center for Satellite Data Assimilation (JCSDA). The GEOS-5 AGCM uses the finite-volume dynamics (Lin, 2004) integrated with various physics packages (e.g, Bacmeister et al., 2006), under the Earth System Modeling Framework (ESMF) including the Catchment Land Surface Model (CLSM) (e.g., Koster et al., 2000). The GSI analysis is a three-dimensional variational (3DVar) analysis applied in grid-point space to facilitate the implementation of anisotropic, inhomogeneous covariances (e.g., Wu et al., 2002; Derber et al., 2003). The GSI implementation for GEOS-5 FP-IT incorporates a set of recursive filters that produce approximately Gaussian smoothing kernels and isotropic correlation functions. The GEOS-5 ADAS is documented in Rienecker et al. (2008). More recent updates to the model are presented in Molod et al. (2011). The GEOS-5 system actively assimilates roughly 2 × 10(exp 6) observations for each analysis, including about 7.5 × 10(exp 5) AIRS radiance data. The input stream is roughly twice this volume, but because of the large volume, the data are thinned commensurate with the analysis grid to reduce the computational burden. Data are also rejected from the analysis through quality control procedures designed to detect, for example, the presence of cloud. To minimize the spurious periodic perturbations of the analysis, GEOS-5 FP-IT uses the Incremental Analysis Update (IAU) technique developed by Bloom et al. (1996). More details of this procedure are given in Appendix A. The analysis is performed at a horizontal resolution of 0.625-degree longitude by 0.5-degree latitude and at 72 levels, extending to 0.01 hPa. All products are generated at the native resolution of the

  1. A Magnetic Field Sensor Based on a Magnetic Fluid-Filled FP-FBG Structure.

    PubMed

    Xia, Ji; Wang, Fuyin; Luo, Hong; Wang, Qi; Xiong, Shuidong

    2016-04-29

    Based on the characteristic magnetic-controlled refractive index property, in this paper, a magnetic fluid is used as a sensitive medium to detect the magnetic field in the fiber optic Fabry-Perot (FP) cavity. The temperature compensation in fiber Fabry-Perot magnetic sensor is demonstrated and achieved. The refractive index of the magnetic fluid varies with the applied magnetic field and external temperature, and a cross-sensitivity effect of the temperature and magnetic field occurs in the Fabry-Perot magnetic sensor and the accuracy of magnetic field measurements is affected by the thermal effect. In order to overcome this problem, we propose a modified sensor structure. With a fiber Bragg grating (FBG) written in the insert fiber end of the Fabry-Perot cavity, the FBG acts as a temperature compensation unit for the magnetic field measurement and it provides an effective solution to the cross-sensitivity effect. The experimental results show that the sensitivity of magnetic field detection improves from 0.23 nm/mT to 0.53 nm/mT, and the magnetic field measurement resolution finally reaches 37.7 T. The temperature-compensated FP-FBG magnetic sensor has obvious advantages of small volume and high sensitivity, and it has a good prospect in applications in the power industry and national defense technology areas.

  2. The Easy Way of Finding Parameters in IBM (EWofFP-IBM)

    SciTech Connect

    Turkan, Nureddin

    2008-11-11

    E2/M1 multipole mixing ratios of even-even nuclei in transitional region can be calculated as soon as B(E2) and B(M1) values by using the PHINT and/or NP-BOS codes. The correct calculations of energies must be obtained to produce such calculations. Also, the correct parameter values are needed to calculate the energies. The logic of the codes is based on the mathematical and physical Statements describing interacting boson model (IBM) which is one of the model of nuclear structure physics. Here, the big problem is to find the best fitted parameters values of the model. So, by using the Easy Way of Finding Parameters in IBM (EWofFP-IBM), the best parameter values of IBM Hamiltonian for {sup 102-110}Pd and {sup 102-110}Ru isotopes were firstly obtained and then the energies were calculated. At the end, it was seen that the calculated results are in good agreement with the experimental ones. In addition, it was carried out that the presented energy values obtained by using the EWofFP-IBM are dominantly better than the previous theoretical data.

  3. Modeling trans-cis chromophore isomerization for the asFP595 kindling protein

    NASA Astrophysics Data System (ADS)

    Grigorenko, Bella L.; Nemukhin, Alexander V.

    2007-02-01

    We present the results of modeling properties of the chromophore, 2-acetyl-4-(p-hydroxybenzylidene)-1-methyl-5- imidazolone (AHBMI), from the newly discovered fluorescent protein asFP595 inside the protein environment by using the combined quantum mechanical - molecular mechanical (QM/MM) method. In this approach, the chromophore unit and the side chains of the nearest amino acid residues are assigned to the quantum subsystem. The starting coordinates of heavy atoms were taken from the relevant crystal structures of the protein. Hydrogen atoms were added manually, and the structure of the model protein system was optimized by using QM/MM energy minimization for the trans-form of the chromophore. The Hartree-Fock/6-31G quantum chemical approximation and the AMBER force field parameters were employed in geometry optimization. The points on potential energy surfaces of the ground and first and second excited electronic states were computed with the complete active space self-consistent field approximation in the quantum subsystem under different choices of the QM/MM partitioning. Possible pathways for the trans-cis photo isomerization presumably responsible for the kindling properties of asFP595 as well as other mechanisms of photo excitation are discussed.

  4. Hybrid wireless-over-fiber transmission system based on multiple injection-locked FP LDs.

    PubMed

    Li, Chung-Yi; Lu, Hai-Han; Chu, Chien-An; Ying, Cheng-Ling; Lu, Ting-Chien; Peng, Peng-Chun

    2015-07-27

    A hybrid wireless-over-fiber (WoF) transmission system based on multiple injection-locked Fabry-Perot laser diodes (FP LDs) is proposed and experimentally demonstrated. Unlike the traditional hybrid WoF transmission systems that require multiple distributed feedback (DFB) LDs to support different kinds of services, the proposed system employs multiple injection-locked FP LDs to provide different kinds of applications. Such a hybrid WoF transmission system delivers downstream intensity-modulated 20-GHz microwave (MW)/60-GHz millimeter-wave (MMW)/550-MHz cable television (CATV) signals and upstream phase-remodulated 20-GHz MW signal. Excellent bit error rate (BER), carrier-to-noise ratio (CNR), composite second-order (CSO), and composite triple-beat (CTB) are observed over a 40-km single-mode fiber (SMF) and a 4-m radio frequency (RF) wireless transport. Such a hybrid WoF transmission system has practical applications for fiber-wireless convergence to provide broadband integrated services, including telecommunication, data communication, and CATV services.

  5. Spectroscopy of Mirror Nuclei in the Upper-fp Shell Using GRETINA

    NASA Astrophysics Data System (ADS)

    Clark, Roderick; Henry, Thomas; Bentley, Michael; E11025 Gretina@Msu Collaboration

    2013-10-01

    Isospin symmetry breaking in nuclei of the upper-fp shell has been investigated in a recent experiment at the National Superconducting Cyclotron Laboratory (NSCL) at Michigan State University (MSU). A 78Kr primary beam (with energy 150 MeV.A) was fragmented on a Be target to produce a cocktail of secondary beams, including 66As, 65Ge, and 64Ga, which were selected with the A1900 separator. These secondary beams were in turn fragmented at the target position of S800 magnetic spectrograph, which was used to identify neutron-deficient reaction products including 62,63Ga, 63Ge, and 65As. Gamma-rays emitted from excited states in these nuclei were detected with GRETINA, which comprises 28 highly-segmented, tapered hexagonal, close-packed HPGe and is a first generation gamma-ray tracking array. Many new states and transitions have been identified in these nuclei of the upper-fp shell, including a candidate for the T = 1 2+ state in 62Ga. Preliminary results from the analysis of this data will be presented and the implications for our understanding of isospin-symmetry breaking effects will be discussed. This work supported in part by the United States Department of Energy under grant no. DE-AC02-05CH11231 (LBNL).

  6. A Magnetic Field Sensor Based on a Magnetic Fluid-Filled FP-FBG Structure

    PubMed Central

    Xia, Ji; Wang, Fuyin; Luo, Hong; Wang, Qi; Xiong, Shuidong

    2016-01-01

    Based on the characteristic magnetic-controlled refractive index property, in this paper, a magnetic fluid is used as a sensitive medium to detect the magnetic field in the fiber optic Fabry-Perot (FP) cavity. The temperature compensation in fiber Fabry-Perot magnetic sensor is demonstrated and achieved. The refractive index of the magnetic fluid varies with the applied magnetic field and external temperature, and a cross-sensitivity effect of the temperature and magnetic field occurs in the Fabry-Perot magnetic sensor and the accuracy of magnetic field measurements is affected by the thermal effect. In order to overcome this problem, we propose a modified sensor structure. With a fiber Bragg grating (FBG) written in the insert fiber end of the Fabry-Perot cavity, the FBG acts as a temperature compensation unit for the magnetic field measurement and it provides an effective solution to the cross-sensitivity effect. The experimental results show that the sensitivity of magnetic field detection improves from 0.23 nm/mT to 0.53 nm/mT, and the magnetic field measurement resolution finally reaches 37.7 T. The temperature-compensated FP-FBG magnetic sensor has obvious advantages of small volume and high sensitivity, and it has a good prospect in applications in the power industry and national defense technology areas. PMID:27136564

  7. Providing universal access. Malvar, province of Batangas. Community-based RH / FP.

    PubMed

    Villegas, P M

    1998-01-01

    Health development is a priority objective in Malvar, a town of 27,800 people, as of 1996, in the province of Batangas. Malvar's population lives in 4633 households. The Japanese Organization for International Cooperation in Family Planning (JOICFP)-supported Sustainable Community-based Reproductive Health (RH)/Family Planning (FP) Project Emphasizing Quality of Care is very important to the people of Malvar. The project is managed by the Interagency Community Organizing Committee (ICOC) established in December 1993. The author describes the many ways in which the RH/FP project has contributed to Malvar's goal of providing universal access to various services, including family planning information and services and reproductive health services. The project has increased the acceptance of family planning and resulted in an increase in the contraceptive prevalence rate from 13.3% in 1993 to 61.0% in 1997. Over the same period, the infant mortality rate per 1000 live births has fallen from 39.4 to 14.1.

  8. Singlet oxygen photosensitisation by the fluorescent protein Pp2FbFP L30M, a novel derivative of Pseudomonas putida flavin-binding Pp2FbFP.

    PubMed

    Torra, Joaquim; Burgos-Caminal, Andrés; Endres, Stephan; Wingen, Marcus; Drepper, Thomas; Gensch, Thomas; Ruiz-González, Rubén; Nonell, Santi

    2015-02-01

    Flavin-binding fluorescent proteins (FbFPs) are a class of fluorescent reporters that have been increasingly used as reporters in the study of cellular structures and dynamics. Flavin's intrinsic high singlet oxygen ((1)O2) quantum yield (ΦΔ = 0.51) provides a basis for the development of new FbFP mutants capable of photosensitising (1)O2 for mechanistic and therapeutic applications, as recently exemplified by the FbFP miniSOG. In the present work we report an investigation on the (1)O2 photoproduction by Pp2FbFP L30M, a novel derivative of Pseudomonas putida Pp2FbFP. Direct detection of (1)O2 through its phosphorescence at 1275 nm yielded the value ΦΔ = 0.09 ± 0.01, which is the highest (1)O2 quantum yield reported to date for any FP and is approximately 3-fold higher than the ΦΔ for miniSOG. Unlike miniSOG, transient absorption measurements revealed the existence of two independent triplet states each with a different ability to sensitise (1)O2.

  9. Effects of PGF{sub 2{alpha}} on human melanocytes and regulation of the FP receptor by ultraviolet radiation

    SciTech Connect

    Scott, Glynis . E-mail: Glynis_Scott@urmc.rochester.edu; Jacobs, Stacey; Leopardi, Sonya; Anthony, Frank A.; Learn, Doug; Malaviya, Rama; Pentland, Alice

    2005-04-01

    Prostaglandins are potent lipid hormones that activate multiple signaling pathways resulting in regulation of cellular growth, differentiation, and apoptosis. In the skin, prostaglandins are rapidly released by keratinocytes following ultraviolet radiation and are chronically present in inflammatory skin lesions. We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE{sub 2} receptors EP{sub 1} and EP{sub 3} and the PGF{sub 2{alpha}} receptor FP, and that PGF{sub 2{alpha}} stimulates melanocyte dendricity. We now show that PGF{sub 2{alpha}} stimulates the activity and expression of tyrosinase, the rate-limiting enzyme in melanin synthesis. Analysis of FP receptor regulation showed that the FP receptor is regulated by ultraviolet radiation in melanocytes in vitro and in human skin in vivo. We also show that ultraviolet irradiation stimulates production of PGF{sub 2{alpha}} by melanocytes. These results show that PGF{sub 2{alpha}} binding to the FP receptor activates signals that stimulate a differentiated phenotype (dendricity and pigmentation) in melanocytes. The regulation of the FP receptor and the stimulation of production of PGF{sub 2{alpha}} in melanocytes in response to ultraviolet radiation suggest that PGF{sub 2{alpha}} could act as an autocrine factor for melanocyte differentiation.

  10. Safety and immunogenicity of the malaria candidate vaccines FP9 CS and MVA CS in adult Gambian men.

    PubMed

    Imoukhuede, E B; Berthoud, T; Milligan, P; Bojang, K; Ismaili, J; Keating, S; Nwakanma, D; Keita, S; Njie, F; Sowe, M; Todryk, S; Laidlaw, S M; Skinner, M A; Lang, T; Gilbert, S; Greenwood, B M; Hill, A V S

    2006-10-30

    We assessed the safety and immunogenicity of prime-boost vectors encoding the Plasmodium falciparum circumsporozoite (CS) protein expressed either in the attenuated fowl-pox virus (FP9) or modified vaccinia virus Ankara (MVA). Thirty-two adult Gambians in groups of four to eight received one, two or three doses of FP9 CS and/or MVA CS. No serious adverse event was observed following vaccination. The most immunogenic regimen was two doses of FP9 followed by a single dose of MVA 4 weeks later (an average of 1000 IFN-gamma spot forming units/million PBMCs). This level of effector T-cell responses appears higher than that seen in previously reported studies of CS-based candidate malaria vaccines.

  11. [Measurement of the amino acid sequence for the fusion protein FP3 with LC-MS/MS].

    PubMed

    Li, Xiang; Gao, Xiang-Dong; Tao, Lei; Pei, De-Ning; Guo, Ying; Rao, Chun-Ming; Wang, Jun-Zhi

    2012-02-01

    The amino acid sequence of the fusion protein FP3 was measured by two types of LC-MS/MS and its primary structure was confirmed. After reduction and alkylation, the protein was digested with trypsin and glycosyl groups in glycopeptide were removed by PNGase F. The mixed peptides were separated by LC, then Q-TOF and Ion trap tandem mass spectrometry were used to measure b, y fragment ions of each peptide to analyze the amino acid sequence of fusion protein FP3. Seventy-six percent of full amino acid sequence of the fusion protein FP3 was measured by LC-ESI-Q-TOF with the remaining 24% completed by LC-ESI-Trap. As LC-MS and tandem mass spectrometry are rapid, sensitive, accurate to measure the protein amino acid sequence, they are important approach to structure analysis and identification of recombinant protein.

  12. Toward a reassessment of the 19F(p, α0)16O reaction rate at astrophysical temperatures

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Dell'Aquila, D.; Di Leva, A.; Indelicato, I.; La Cognata, M.; La Commara, M.; Ordine, A.; Rigato, V.; Romoli, M.; Rosato, E.; Spadaccini, G.; Spitaleri, C.; Tumino, A.; Vigilante, M.

    2015-09-01

    The 19F(p, α0)16O reaction at low energies plays an important role in fundamental physics. In particular in nuclear astrophysics it represents, together with the 19F(p, γ)20Ne reaction, the crossing point between the CNO and the NeNa cycles in stars. Further, in hydrogen-rich stellar environments, it is the most important fluorine destruction channel. In this paper we report new measurements on the 19F(p, α0)16O reaction at deeply sub-Coulomb energies (0.2-0.6 MeV), a region where, despite the key role of this reaction, very few and old data are reported. The deduced astrophysical S-factor is ≈ 1.5- 2 times larger than currently adopted extrapolations with possibly important astrophysical consequences.

  13. FP-180 Water Motor AFFF Proportioner First Article Procedure and Evaluation

    DTIC Science & Technology

    1989-07-20

    Fil E W Y. . Naval Research Laboratory Washington, DC 20375-500 NRL Memorandum Report 6507 FP-180 Water Motor AFFF Proportioner First Article...Procedure and Evaluation CI C.R. FULPER, R.L. GIPE, C.L. WmTEHuRST, R.E. BURNS,* R.J. OUELLET* E AND C.W. SEIGMANN* Navy Technology Center for Safety and...9-Z9-ZZ9 C C S C S Sd. 33 Li 3Li LL CCZCZCC oxd0 d00. ma’ i IALi L IA - 59 E ~ A in9- CEE CD Cj I- C. UIL 0- e cu z C- w - w~ w at z 40 0 I U W 0 IL

  14. The FP4026 Research Database on the fundamental period of RC infilled frame structures.

    PubMed

    Asteris, Panagiotis G

    2016-12-01

    The fundamental period of vibration appears to be one of the most critical parameters for the seismic design of buildings because it strongly affects the destructive impact of the seismic forces. In this article, important research data (entitled FP4026 Research Database (Fundamental Period-4026 cases of infilled frames) based on a detailed and in-depth analytical research on the fundamental period of reinforced concrete structures is presented. In particular, the values of the fundamental period which have been analytically determined are presented, taking into account the majority of the involved parameters. This database can be extremely valuable for the development of new code proposals for the estimation of the fundamental period of reinforced concrete structures fully or partially infilled with masonry walls.

  15. Test of IMME in fp shell via direct mass measurements of nuclides

    NASA Astrophysics Data System (ADS)

    Zhang, Y. H.; Xu, H. S.; Litvinov, Yu A.; Tu, X. L.; Yan, X. L.; Typel, S.; Blaum, K.; Wang, M.; Zhou, X. H.; Sun, Y.; Brown, B. A.; Yuan, Y. J.; Xia, J. W.; Yang, J. C.; Audi, G.; Chen, X. C.; Jia, G. B.; Hu, Z. G.; Ma, X. W.; Mao, R. S.; Mei, B.; Shuai, P.; Sun, Z. Y.; Wang, S. T.; Xiao, G. Q.; Xu, X.; Yamaguchi, T.; Yamaguchi, Y.; Zang, Y. D.; Zhao, H. W.; Zhao, T. C.; Zhang, W.; Zhan, W. L.

    2013-03-01

    Isochronous mass spectrometry has been applied to neutron-deficient 58Ni projectile fragments at the HIRFL-CSR facility in Lanzhou, China. Masses of four shortlived Tz = -3/2 nuclides 41Ti, 45Cr, 49Fe, and 53Ni have been measured with a precision of 20 — 40 keV. The new mass data enabled for the first time to test the isobaric multiplet mass equation (IMME) in fp-shell nuclei. We observed that the IMME is inconsistent with the generally accepted quadratic form for the A = 53, T = 3/2 quartet. We performed full space shell model calculations and compared them with the new experimental results. The main results were published in Y.H. Zhang et al., Physical Review Letters 109 (2012). Here we give details on the experiment and data analysis as well as summarize the main findings.

  16. The Comparison of Wading Measurement Discharge between ADC and FP111 in Shallow Flow

    NASA Astrophysics Data System (ADS)

    Yang, H. C.; Chiang, C. J.

    2012-04-01

    During the low water period, the water depth of streams in Taiwan is very shallow and the velocity is too slow; the discharge in the streams is relatively small. At this time, larger velocity measurement equipments such as Price Type AA cannot be completely submerged in water so that they are unable to be applied to measure the velocity. Discharge measurements using conventional methods, including Price Type AA suspended in the water from bridge, are therefore unusable. The discharge records during the low water period can provide required information for monitoring ecological reference flow and various related applications of water intake engineering design. Therefore, it is necessary to choose an appropriate equipment to measure the discharge in shallow water flow in order to continuously carry out the monitoring and recording the discharge. This study is conducted in Linbian river basin, selecting Laiyi Bridge in Linbian Township Pingtung County as the gauging station. The research uses Acoustic Digital Current Meter (ADC) and Digital water velocity meter (FP111 Global Flow Probe) to measure the discharge of river during the low water period in order to explore the applicability and deviation of the two equipments which have different features and measurement principles. There are 11 discharges conducted in this study. The method of calculating the discharge is to get the sum of the measured discharge of sub-section in each measurement. Furthermore, based on velocity-area principle in Mean-Section Method, the total discharge can be estimated from the velocity data obtained by using velocity equipment. The result of the study indicates that both equipments can be applied to measure the discharge on the condition that the measurement probe should be completely submerged in water. However, ADC is more applicable than FP111 to measure discharge in shallow water flow because the precision of ADC is 7.96% higher than that of FP111. Also, through the independent sample

  17. Social Franchising: A Blockbuster to Address Unmet Need for Family Planning and to Advance Toward the FP2020 Goal.

    PubMed

    2015-06-17

    Social franchising has scaled-up provision of voluntary family planning, especially long-acting reversible contraceptives, across Africa and Asia at a rapid and remarkable pace. The approach should be pursued vigorously, especially in countries with a significant private-sector presence, to advance the FP2020 goal of providing access to modern contraception to 120 million additional clients by 2020.

  18. Long-Acting Recombinant Fusion Protein Linking Coagulation Factor IX with Albumin (rIX-FP) in Children

    PubMed Central

    Chambost, Hervé; Male, Christoph; Lambert, Thierry; Halimeh, Susan; Chernova, Tatiana; Mancuso, Maria Elisa; Curtin, Julie; Voigt, Christine; Li, Yanyan; Jacobs, Iris; Santagostino, Elena

    2016-01-01

    Summary A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2% of bleeding episodes were successfully treated with one or two injections of rIX-FP (95% CI: 92% to 99%), 88.7% with one injection, and 96% of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531) PMID:27583313

  19. The highly antigenic 53/25 kDa Taenia solium protein fraction with cathepsin-L like activity is present in the oncosphere/cysticercus and induces non-protective IgG antibodies in pigs.

    PubMed

    Zimic, Mirko; Pajuelo, Mónica; Gilman, Robert H; Gutiérrez, Andrés H; Rueda, Luis D; Flores, Myra; Chile, Nancy; Verástegui, Manuela; Gonzalez, Armando; García, Héctor H; Sheen, Patricia

    2012-01-15

    Cathepsin L-like proteases are secreted by several parasites including Taenia solium. The mechanism used by T. solium oncospheres to degrade and penetrate the intestine and infect the host is incompletely understood. It is assumed that intestinal degradation is driven by the proteolytic activity of enzymes secreted by the oncosphere. Blocking the proteolytic activity by an antibody response would prevent the oncosphere penetration and further infection. Serine and cysteine proteases including chymotrypsin, trypsin, elastase, and cathepsin L, are secreted by T. solium and Taenia saginata oncospheres when cultured in vitro, being potential vaccine candidates. However, the purification of a sufficient quantity of proteases secreted by oncospheres to conduct a vaccine trial is costly and lengthy. A 53/25 kDa cathepsin L-like fraction partially purified from T. solium cyst fluid was described previously as an important antigen for immunodiagnostics. In this study we found that this antigen is present in the T. solium oncosphere and is also secreted by the cysticercus. This protein fraction was tested for its ability to protect pigs against an oral challenge with T. solium oncospheres in a vaccine trial. IgG antibodies against the 53/25 kDa cathepsin L-like protein fraction were elicited in the vaccinated animals but did not confer protection.

  20. Modeling the EUV/UV irradiance within the FP7 SOLID Project

    NASA Astrophysics Data System (ADS)

    Haberreiter, Margit; Delouille, Veronique; Del Zanna, Giulio; Dammasch, Ingolf; Dominique, Marie; Dudok de Wit, Thierry; Ermolli, Ilaria; Jones, Andrew; Kretzschmar, Matthieu; Mampaey, Benjamin; Schaefer, Robert; Schmidtke, Gerhard; Schoell, Micha; Thuillier, Gerard; Verbeeck, Cis; Wieman, Seth; Woods, Tom; Schmutz, Werner

    2015-04-01

    The solar EUV irradiance has strong effects on the Earth's ionosphere and thermosphere. Here we present latest results for the EUV spectral range carried out within the European FP7 Project SOLID. Specifically, we model the SSI variations in the EUV spectral range based on the analysis of images obtained with SOHO/EIT, PROBA2/SWAP, and SDO/AIA. These images are segmented to regions of solar activity using the SPoCA tool. Moreover, with the SOLar MODeling code (SOLMOD) we calculate intensity spectra representing the intensity emitted by these regions. We present the latest set of reconstructions and compare it to available data, such as SOHO/SEM, PROBA2/LYRA, ISS/SOLAR/SOLACES, and SDO/EVE. Furthermore, we will present a probabilistic method to obtain a consistent composite from the available data. These results are an important for understanding the spectral variability in the EUV/UV and as well as its effect on the Earth's upper atmosphere.

  1. The severe accident research programme PHEBUS F.P.: First results and future tests

    SciTech Connect

    Schwarz, M.; Hardt, P. von der

    1996-03-01

    PHEBUS FP is an international programme, managed by the French Institut de Protection et de Surete Nucleaire, Electricite de France and the European Commission in close collaboration with the USNRC (US), COG (Canada), NUPEC and JAERI (Japan) and KAERI (South Korea). Its objective is to investigate through a series of in-pile integral experiments, key phenomena involved in LWR severe accident such as the degradation of core materials up to molten pool, the subsequent release of fission products and of structural materials, their transport in the cooling system and their deposition in the containment with a special emphasis on the volatility of iodine. After a general programme description, the paper focuses on the status of analysis of the first test FPT-0, which involved trace irradiated fuel and which has shown some quite unexpected results regarding fuel degradation and iodine behaviour, and on the upcoming test FPT-1 which will use irradiated fuel. The status of the preparation of the remaining tests of the programme is also presented.

  2. APhoRISM FP7 project: the Multi-platform volcanic Ash Cloud Estimation (MACE) infrastructure

    NASA Astrophysics Data System (ADS)

    Merucci, Luca; Corradini, Stefano; Bignami, Christian; Stramondo, Salvatore

    2014-05-01

    APHORISM is an FP7 project that aims to develop innovative products to support the management and mitigation of the volcanic and the seismic crisis. Satellite and ground measurements will be managed in a novel manner to provide new and improved products in terms of accuracy and quality of information. The Multi-platform volcanic Ash Cloud Estimation (MACE) infrastructure will exploit the complementarity between geostationary, and polar satellite sensors and ground measurements to improve the ash detection and retrieval and to fully characterize the volcanic ash clouds from source to the atmosphere. The basic idea behind the proposed method consists to manage in a novel manner, the volcanic ash retrievals at the space-time scale of typical geostationary observations using both the polar satellite estimations and in-situ measurements. The typical ash thermal infrared (TIR) retrieval will be integrated by using a wider spectral range from visible (VIS) to microwave (MW) and the ash detection will be extended also in case of cloudy atmosphere or steam plumes. All the MACE ash products will be tested on three recent eruptions representative of different eruption styles in different clear or cloudy atmospheric conditions: Eyjafjallajokull (Iceland) 2010, Grimsvotn (Iceland) 2011 and Etna (Italy) 2011-2012. The MACE infrastructure will be suitable to be implemented in the next generation of ESA Sentinels satellite missions.

  3. Comparison of LECO FP-228 "nitrogen determinator" with AOAC copper catalyst Kjeldahl method for crude protein.

    PubMed

    Sweeney, R A; Rexroad, P R

    1987-01-01

    The LECO FP-228 "Nitrogen Determinator" was compared with the AOAC copper catalyst Kjeldahl method, 7.033-7.037, for the determination of crude protein in feed materials. The completely microprocessor-controlled instrument determines nitrogen by measuring the nitrogen gas following combustion of the sample; it was easy to operate and broadly applicable. A wide variety of feed materials of various nitrogen levels were analyzed in one mixed sequence. Results were precise, accurate, and rapid. Analysis time for one sample was approximately 3 min. Fourteen samples containing 2.5-15.5% N were selected for study and consisted of meals, grains, forages, and standard organic materials. The overall mean for the 14 samples by the LECO combustion method was 8.61% N compared with an overall mean of 8.58% N for the AOAC Kjeldahl method. Within-sample standard deviations for the LECO combustion method ranged from 0.013 to 0.052% N with a pooled standard deviation (SD) of 0.033% N for the 14 samples. Standard deviations for the AOAC Kjeldahl method ranged from 0.006 to 0.035% N with a pooled SD of 0.022% N. Combined average recovery of nitrogen from tryptophan, lysine-HCl, and EDTA determined by the LECO combustion method was 99.94% compared to 99.88% determined by the AOAC Kjeldahl method.

  4. Low power reconfigurable FP-FFT core with an array of folded DA butterflies

    NASA Astrophysics Data System (ADS)

    Beulet Paul, Augusta Sophy; Raju, Srinivasan; Janakiraman, Raja

    2014-12-01

    A variable length (32 ~ 2,048), low power, floating point fast Fourier transform (FP-FFT) processor is designed and implemented using energy-efficient butterfly elements. The butterfly elements are implemented using distributed arithmetic (DA) algorithm that eliminates the power-consuming complex multipliers. The FFT computations are scheduled in a quasi-parallel mode with an array of 16 butterflies. The nodes of the data flow graph (DFG) of the FFT are folded to these 16 butterflies for any value of N by the control unit. Register minimization is also applied after folding to decrease the number of scratch pad registers to (log 2 N - 1) × 16. The real and imaginary parts of the samples are represented by 32-bit single-precision floating point notation to achieve high precision in the results. Thus, each sample is represented using 64 bits. Twiddle factor ROM size is reduced by 25% using the symmetry of the twiddle factors. Reconfigurability based on the sample size is achieved by the control unit. This distributed floating point arithmetic (DFPA)-based design of FFT processor implemented in 45-nm process occupies an area of 0.973 mm2 and dissipates a power of 68 mW at an operating frequency of 100 MHz. When compared with FFT processor designed in the same technology with multiplier-based butterflies, this design shows 33% less area and 38% less power. The throughput for 2,048-point FFT is 222 KS/s and the energy spent per FFT is 7.4 to 14 nJ for 64 to 2,048 points being one among the most energy-efficient FFT processors.

  5. Evolution of clinical features in possible DLB depending on FP-CIT SPECT result

    PubMed Central

    Moreno, Emilio; Thomas, Alan; Inglis, Fraser; Tabet, Naji; Stevens, Tim; Whitfield, Tim; Aarsland, Dag; Rainer, Michael; Padovani, Alessandro

    2016-01-01

    Objective: To test the hypothesis that core and suggestive features in possible dementia with Lewy bodies (DLB) would vary in their ability to predict an abnormal dopamine transporter scan and therefore a follow-up diagnosis of probable DLB. A further objective was to assess the evolution of core and suggestive features in patients with possible DLB over time depending on the 123I-FP-CIT SPECT scan result. Methods: A total of 187 patients with possible DLB (dementia plus one core or one suggestive feature) were randomized to have dopamine transporter imaging or to follow-up without scan. DLB features were compared at baseline and at 6-month follow-up according to imaging results and follow-up diagnosis. Results: For the whole cohort, the baseline frequency of parkinsonism was 30%, fluctuations 29%, visual hallucinations 24%, and REM sleep behavior disorder 17%. Clinician-rated presence of parkinsonism at baseline was significantly (p = 0.001) more frequent and Unified Parkinson’s Disease Rating Scale (UPDRS) score at baseline was significantly higher (p = 0.02) in patients with abnormal imaging. There was a significant increase in UPDRS score in the abnormal scan group over time (p < 0.01). There was relatively little evolution of the rest of the DLB features regardless of the imaging result. Conclusions: In patients with possible DLB, apart from UPDRS score, there was no difference in the evolution of DLB clinical features over 6 months between cases with normal and abnormal imaging. Only parkinsonism and dopamine transporter imaging helped to differentiate DLB from non-DLB dementia. PMID:27511183

  6. High-spin structure of {sup 37}Cl, intruder excitations, and the sd-fp shell gap

    SciTech Connect

    Ionescu-Bujor, M.; Iordachescu, A.; Marginean, N.; Bucurescu, D.; Lenzi, S. M.; Bazzacco, D.; Della Vedova, F.; Farnea, E.; Menegazzo, R.; Lunardi, S.; Zilio, S.; Napoli, D. R.; De Angelis, G.; Gadea, A.; Medina, N. H.; Ur, C. A.; Otsuka, T.; Utsuno, Y.

    2009-09-15

    The structure of the N=20 nucleus {sup 37}Cl has been investigated in the {sup 24}Mg({sup 16}O,3p) reaction with a 70 MeV {sup 16}O beam. A complex level scheme extended up to an excitation energy of 17 MeV and spins (29/2{sup +}) and (27/2{sup -}) on positive and negative parity, respectively, has been established. Lifetimes for the new states have been investigated by the Doppler shift attenuation method. Large-scale shell-model calculations have been performed in a valence space involving orbitals in the sd and fp shells using the sdfp and SDPF-M effective interactions. The comparison with the experimental data indicates the need for slight changes of the sd-fp energy gaps produced by these interactions.

  7. Probing sd-fp Cross-Shell Interactions via Terminating Configurations in 42,43Sc

    SciTech Connect

    Chiara, C. J.; Devlin, M.; Ideguchi, E.; LaFosse, D.R.; Lerma, F.; Reviol, W.; Ryu, S. K.; Sarantites, D. G.; Pechenaya, O. L.; Baktash, Cyrus; Galindo-Uribarri, Alfredo {nmn}; Carpenter, M. P.; Janssens, R. V.F.; Lauritsen, T.; Lister, C. J.; Reiter, P.; Seweryniak, D.; Fallon, P.; Gorgen, A.; Macchiavelli, A. O.; Rudolph, D.; Stoitcheva, G.; Ormand, W. E.

    2007-01-01

    An experimental study of the lower fp-shell nuclei 42,43Sc was performed via {alpha}pn and {alpha}p evaporation, respectively, from 20Ne + 28Si and 24Mg + 24Mg fusion-evaporation reactions. The experiments were conducted with the Gammasphere and Microball detector arrays. The level schemes of both nuclei have been extended considerably. Terminating states associated with the fn7/2 and d−13/2fn+17/2 configurations were identified in each nuclide, and incorporated into detailed comparisons with neighboring nuclei and with shell model calculations. The energy differences between the terminating states provide a test of the sd−fp cross-shell interactions in these calculations.

  8. Long-term orbital period behaviour of low mass ratio contact binaries GR Vir and FP Boo

    NASA Astrophysics Data System (ADS)

    Ćetinkaya, Halil; Soydugan, Faruk

    2017-02-01

    In this study, we investigated orbital period variations of two low mass ratio contact binaries GR Vir and FP Boo based on published minima times. From the O-C analysis, it was found that FP Boo indicates orbital period decrease while the period of GR Vir is increasing. Mass transfer process was used to explain increase and decrease in the orbital periods. In the O-C diagrams of both systems periodic variations also exist. Cyclic changes can be explained as being the result of a light-travel time effect via a third component around the eclipsing binaries. In order to interpret of cyclic orbital period changes for GR Vir, which has late-type components, possible magnetic activity cycles of the components have been also considered.

  9. Constitutive and inducible pectinolytic enzymes from Aspergillus flavipes FP-500 and their modulation by pH and carbon source

    PubMed Central

    Martínez-Trujillo, Aurora; Aranda, Juan S.; Gómez-Sánchez, Carlos; Trejo-Aguilar, Blanca; Aguilar-Osorio, Guillermo

    2009-01-01

    Growth and enzymes production by Aspergillus flavipes FP-500 were evaluated on pectin, polygalacturonic acid, galacturonic acid, arabinose, rhamnose, xylose, glycerol and glucose at different initial pH values. We found that the strain produced exopectinases, endopectinases and pectin lyases. Exopectinases and pectin lyase were found to be produced at basal levels as constitutive enzymes and their production was modulated by the available carbon source and pH of culture medium and stimulated by the presence of inducer in the culture medium. Endo-pectinase was basically inducible and was only produced when pectin was used as carbon source. Our results suggest that pectinases in A. flavipes FP-500 are produced in a concerted way. The first enzyme to be produced was exopectinase followed by Pectin Lyase and Endo-pectinase. PMID:24031315

  10. Pulmonary nodule detection in PET/CT images: improved approach using combined nodule detection and hybrid FP reduction

    NASA Astrophysics Data System (ADS)

    Teramoto, Atsushi; Fujita, Hiroshi; Tomita, Yoya; Takahashi, Katsuaki; Yamamuro, Osamu; Tamaki, Tsuneo

    2012-03-01

    In this study, an automated scheme for detecting pulmonary nodules in PET/CT images has been proposed using combined detection and hybrid false-positive (FP) reduction techniques. The initial nodule candidates were detected separately from CT and PET images. FPs were then eliminated in the initial candidates by using support vector machine with characteristic values obtained from CT and PET images. In the experiment, we evaluated proposed method using 105 cases of PET/CT images that were obtained in the cancer-screening program. We evaluated true positive fraction (TPF) and FP / case. As a result, TPFs of CT and PET detections were 0.76 and 0.44, respectively. However, by integrating the both results, TPF was reached to 0.82 with 5.14 FPs/case. These results indicate that our method may be of practical use for the detection of pulmonary nodules using PET/CT images.

  11. 25K Halvorsen Loader Automation Report

    DTIC Science & Technology

    2013-01-02

    rate of 75 Hz with a field of view of 180° and a 0.25° angular resolution. The SICK LMS 291 relies on a spinning mirror and laser diode to perform...of up to 8 cameras (any combination up to 4 pan-tilt-zoom and 4 fixed). These cameras are connected to an internal multiplexer and the video is sent...Equipment Preparation Course. Section 3.2. 1 Jan 2011 4) SICK. “SICK LMS 291 LIDAR Sensor” in LMS 2000/211/221/291 Laser Measurement Systems: Technical

  12. Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft models of primary colon carcinoma and related lymphatic and hepatic metastases.

    PubMed

    Jin, Ketao; Lan, Huanrong; Xie, Bojian; He, Kuifeng; Xu, Zhenzhen; Li, Guangliang; Han, Na; Teng, Lisong; Cao, Feilin

    2012-07-01

    FP3 is an engineered protein which contains the extracellular domain 2 of VEGF receptor 1 (Flt-1) and extracellular domain 3 and 4 of VEGF receptor 2 (Flk-1, KDR) fused to the Fc portion of human immunoglobulin G 1. Previous studies demonstrated its antiangiogenic effects in vitro and in vivo, and its antitumor activity in vivo. In this study, patient-derived tumor tissue (PDTT) xenograft models of primary colon carcinoma and lymphatic and hepatic metastases were established for assessment of the antitumor activity of FP3 in combination with capecitabine. Xenografts were treated with FP3, capecitabine, alone or in combination. After tumor growth was confirmed, volume and microvessel density in tumors were evaluated. Levels of VEGF, and PCNA in the tumor were examined by immunohistonchamical staining, level of thymidine phosphorylase (TP) was examined by ELISA, and levels of related cell signaling pathways proteins expression were examined by western blotting. FP3 in combination with capecitabine showed significant antitumor activity in three xenograft models (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). The microvessel density in tumor tissues treated with FP3 in combination with capecitabine was lower than that of the control. Antitumor activity of FP3 in combination with capecitabine was significantly higher than that of each agent alone in three xenograft models (primary colon carcinoma, lymphatic metastasis, and hepatic metastasis). This study indicated that addition of FP3 to capecitabine significantly improved tumor growth inhibition in the PDTT xenograft models of primary colon carcinoma and lymphatic and hepatic metastases.

  13. The influence of HIP on the homogeneity, Jc, Birr, Tc and Fp in MgB2 wires

    NASA Astrophysics Data System (ADS)

    Gajda, D.; Morawski, A.; Zaleski, A.; Kurnatowska, M.; Cetner, T.; Gajda, G.; Presz, A.; Rindfleisch, M.; Tomsic, M.

    2015-01-01

    Unreacted MgB2 wires were made at Hyper Tech Research, USA by a continuous tube forming and filling method using mixtures of Mg and B with and without SiC powder additions. All of the wires underwent hot isostatic pressure (HIP) treatment at the Institute of High Pressure. The first part of the wire was annealed at a pressure of 1 GPa, and the second part was annealed at 0.1 MPa. In this work, we show the influence of high pressure on critical current density (Jc), pinning force (Fp), critical temperature (Tc), irreversible magnetic fields (Birr) and the Fp scaling and microstructure of MgB2 wires. The results obtained indicate that after annealing at high pressure, the MgB2 wires show increases of Jc and Fp in high magnetic fields (8 T-12 T); in SiC doped MgB2 wires, Fpmax shifts to higher magnetic fields. We also compared the Jc of the doped and undoped MgB2 wires (without HIP and with HIP). The scanning electron microscope (SEM) results show that HIP increases the density of MgB2 material and improves its uniformity.

  14. Applications research in ultrasonic testing of carbon fiber composite based on an optical fiber F-p sensor

    NASA Astrophysics Data System (ADS)

    Shan, Ning

    2016-10-01

    Carbon fiber composite is widely applied to the field of aerospace engineering because of its excellent performance. But it will be able to form more defects in the process of manufacturing inevitably on account of unique manufacturing process. Meanwhile it has sophisticated structure and services in the bad environment long time. The existence of defects will be able to cause the sharp decline in component's performance when the defect accumulates to a certain degree. So the reliability and safety test demand of carbon fiber composite is higher and higher. Ultrasonic testing technology is the important means used for characteristics of component inspection of composite materials. Ultrasonic information detection uses acoustic transducer generally. It need coupling agent and is higher demand for the surface of sample. It has narrow frequency band and low test precision. The extrinsic type optical fiber F-P interference cavity structure is designed to this problem. Its optical interference model is studied. The initial length of F-P cavity is designed. The realtime online detection system of carbon fiber composite is established based on optical fiber F-P Ultrasound sensing technology. Finally, the testing experiment study is conducted. The results show that the system can realize real-time online detection of carbon fiber composite's defect effectively. It operates simply and realizes easily. It has low cost and is easy to practical engineering.

  15. An FP7 "Space" project: Aphorism "Advanced PRocedures for volcanic and Seismic Monitoring"

    NASA Astrophysics Data System (ADS)

    Di Iorio, A., Sr.; Stramondo, S.; Bignami, C.; Corradini, S.; Merucci, L.

    2014-12-01

    APHORISM project proposes the development and testing of two new methods to combine Earth Observation satellite data from different sensors, and ground data. The aim is to demonstrate that this two types of data, appropriately managed and integrated, can provide new improved GMES products useful for seismic and volcanic crisis management. The first method, APE - A Priori information for Earthquake damage mapping, concerns the generation of maps to address the detection and estimate of damage caused by a seism. The use of satellite data to investigate earthquake damages is not an innovative issue. We can find a wide literature and projects concerning such issue, but usually the approach is only based on change detection techniques and classifications algorithms. The novelty of APE relies on the exploitation of a priori information derived by InSAR time series to measure surface movements, shake maps obtained from seismological data, and vulnerability information. This a priori information is then integrated with change detection map to improve accuracy and to limit false alarms. The second method deals with volcanic crisis management. The method, MACE - Multi-platform volcanic Ash Cloud Estimation, concerns the exploitation of GEO (Geosynchronous Earth Orbit) sensor platform, LEO (Low Earth Orbit) satellite sensors and ground measures to improve the ash detection and retrieval and to characterize the volcanic ash clouds. The basic idea of MACE consists of an improvement of volcanic ash retrievals at the space-time scale by using both the LEO and GEO estimations and in-situ data. Indeed the standard ash thermal infrared retrieval is integrated with data coming from a wider spectral range from visible to microwave. The ash detection is also extended in case of cloudy atmosphere or steam plumes. APE and MACE methods have been defined in order to provide products oriented toward the next ESA Sentinels satellite missions.The project is funded under the European Union FP7

  16. Identification of AcMNPV EXON0 (ac141) domains required for efficient production of budded virus, dimerization and association with BV/ODV-C42 and FP25.

    PubMed

    Fang, Minggang; Nie, Yingchao; Dai, Xiaojiang; Theilmann, David A

    2008-05-25

    The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) late gene exon0 (ac141) is required for the efficient production of budded virus (BV). EXON0 interacts with nucleopcapsid protein BV/ODV-C42 and FP25 and enables egress of nucleocapsids from the nucleus to the cytoplasm. This study examines the functional domains of EXON0 that play a role in BV production. Six putative domains of the 261 amino acid EXON0 were deleted and examined for functionality by determining their ability to rescue an AcMNPV exon0 knockout bacmid. Domain mapping results showed that all the six domains were required but deletion of the N-terminal acidic region and the leucine zipper domains had the greatest impact on BV production. Yeast 2-hybrid and co-immunoprecipitation demonstrated that EXON0 formed dimers. Point mutation analysis demonstrated that the leucine zipper was required for dimer formation and interaction with BV/ODV-C42 and FP25. The charged domain was also required for BV/ODV-C42 interaction.

  17. The 559-to-600 nm shift observed in red fluorescent protein eqFP611 is attributed to cis-trans isomerization of the chromophore in an anionic protein pocket.

    PubMed

    Yan, Weizhong; Xie, Daiqian; Zeng, Jun

    2009-08-07

    Fluorescent proteins are commonly used as molecular labels, noninvasive markers of gene expression, and reporters of environmental conditions in live cells. We investigate the structural and spectroscopic properties of the chromophore of a far-red fluorescent protein eqFP611. Both the cis and trans isomers of the chromophore are examined within the protein for which both anionic and neutral states of protonation are considered. Spectroscopic properties are examined using time-dependent density functional theory (TDDFT), employing the B3LYP, PBE and B3PW91 density functionals. Intermolecular and long-range contributions to the structure and spectroscopy were treated using the own n-layered integrated molecular orbital and molecular mechanics (ONIOM) approach. The results indicated that the chromophore before excitation is in an anionic, protonated state, with the long-range contributions inducing a blue shift in the absorption and fluorescence maxima of the chromophore. Moreover, the calculated changes of the lowest pi-pi* excitation energy upon isomerization match the observed shift from 559 to 600 nm in the absorption maximum of the system following prolonged irradiation. Furthermore, decomposition analysis of the electrostatic contributions from individual residues indicated that the interactions from four residues Arg92, Lys67, Glu145, and His197 to the chromophore play a key role in the absorption and fluorescence spectra of eqFP611, suggesting that mutations at these sites should provide very useful mechanistic information.

  18. Crystallographic study of red fluorescent protein eqFP578 and its far-red variant Katushka reveals opposite pH-induced isomerization of chromophore

    SciTech Connect

    Pletneva, Nadya V.; Pletnev, Vladimir Z.; Shemiakina, Irina I.; Chudakov, Dmitriy M.; Artemyev, Igor; Wlodawer, Alexander; Dauter, Zbigniew; Pletnev, Sergei

    2012-08-10

    The wild type red fluorescent protein eqFP578 (from sea anemone Entacmaea quadricolor, {lambda}{sub ex} = 552 nm, {lambda}{sub em} = 578 nm) and its bright far-red fluorescent variant Katushka ({lambda}{sub ex} = 588 nm, {lambda}{sub em} = 635 nm) are characterized by the pronounced pH dependence of their fluorescence. The crystal structures of eqFP578f (eqFP578 with two point mutations improving the protein folding) and Katushka have been determined at the resolution ranging from 1.15 to 1.85 {angstrom} at two pH values, corresponding to low and high level of fluorescence. The observed extinguishing of fluorescence upon reducing pH in eqFP578f and Katushka has been shown to be accompanied by the opposite trans-cis and cis-trans chromophore isomerization, respectively. Asn143, Ser158, His197 and Ser143, Leu174, and Arg197 have been shown to stabilize the respective trans and cis fluorescent states of the chromophores in eqFP578f and Katushka at higher pH. The cis state has been suggested as being primarily responsible for the observed far-red shift of the emission maximum of Katushka relative to that of eqFP578f.

  19. Genes

    MedlinePlus

    ... Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Customer Support Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Genes URL of this page: //medlineplus.gov/ency/article/ ...

  20. Influence of CT-based attenuation correction on dopamine transporter SPECT with [(123)I]FP-CIT.

    PubMed

    Lapa, Constantin; Spehl, Timo S; Brumberg, Joachim; Isaias, Ioannis U; Schlögl, Susanne; Lassmann, Michael; Herrmann, Ken; Meyer, Philipp T

    2015-01-01

    Dopamine transporter (DAT) imaging using single-photon emission computed tomography (SPECT) and (123)I-labelled radiopharmaceuticals like [(123)I]FP-CIT is an established part in the diagnostic work-up of parkinsonism. Guidelines recommend attenuation correction (AC), either by a calculated uniform attenuation matrix (calAC) or by a measured attenuation map (nowadays done by low-dose CT; CTAC). We explored the impact of CTAC compared to conventional calAC on diagnostic accuracy and the use of DAT availability as a biomarker of nigrostriatal integrity.Integrated SPECT/CT studies with [(123)I]FP-CIT were performed in patients with Parkinson's disease (PD; n = 15) and essential tremor (ET; n = 15). SPECT data was reconstructed with calAC, CTAC and without AC (noAC). Regional DAT availability was assessed by uniform volume-of-interest analyses providing striatal binding potential (BP ND) estimates. BP ND values were compared among methods and correlated with clinical parameters. Compared to calAC, both CTAC and noAC provided significantly lower, but highly linearly correlated BP ND estimates (R (2) = 0.96). Diagnostic performance to distinguish between patients with PD and those with ET was very high and did not differ between AC methods. CTAC and noAC data tended so show a stronger correlation with severity and duration of disease in PD and age in ET than did calAC. Defining the reference region on low-dose CT instead of SPECT did not consistently alter findings. [(123)I]FP-CIT SPECT provides a very high diagnostic accuracy for differentiation between PD and ET that is not dependent on the employed AC method. Preliminary correlations analyses suggest that BP ND estimates derived from CTAC represent a superior biomarker of nigrostriatal integrity.

  1. Photoactivation in green to red converting EosFP and other fluorescent proteins from the GFP family

    NASA Astrophysics Data System (ADS)

    Wiedenmann, Jörg; Nienhaus, G. Ulrich

    2006-02-01

    The green fluorescent protein (GFP) from the hydromedusa Aequorea victoria and its derivatives have become indispensable imaging devices in cell biology. In previous years, a wide variety of GFP-like proteins were discovered in non-bioluminescent anthozoa. Some of them displayed exciting new properties, including photoactivated changes of the fluorescence emission intensity and wavelength. Photoactivatable proteins offer a high potential as tools for regional optical marking in live cells and tissues. This review aims to give an overview of photoactivatable marker proteins, focusing on the molecular basis of light-induced green to red photoconversion in EosFP.

  2. Intermediate-energy inverse-kinematics one-proton pickup reactions on neutron-deficient fp-shell nuclei

    NASA Astrophysics Data System (ADS)

    McDaniel, S.; Gade, A.; Tostevin, J. A.; Baugher, T.; Bazin, D.; Brown, B. A.; Cook, J. M.; Glasmacher, T.; Grinyer, G. F.; Ratkiewicz, A.; Weisshaar, D.

    2012-01-01

    Background: Thick-target-induced nucleon-adding transfer reactions onto energetic rare-isotope beams are an emerging spectroscopic tool. Their sensitivity to single-particle structure complements one-nucleon removal reaction capabilities in the quest to reveal the evolution of nuclear shell structure in very exotic nuclei. Purpose: Our purpose is to add intermediate-energy, carbon-target-induced one-proton pickup reactions to the arsenal of γ-ray-tagged direct reactions applicable in the regime of low beam intensities and to apply these for the first time to fp-shell nuclei. Methods: Inclusive and partial cross sections were measured for the 12C(48Cr,49Mn+γ)X and 12C(50Fe,51Co+γ)X proton pickup reactions at 56.7 and 61.2 MeV/nucleon, respectively, using coincident particle-γ spectroscopy at the National Superconducting Cyclotron Laboratory. The results are compared to reaction theory calculations using fp-shell-model nuclear structure input. For comparison with our previous work, the same reactions were measured on 9Be targets. Results: The measured partial cross sections confirm the specific population pattern predicted by theory, with pickup into high-ℓ orbitals being strongly favored, driven by linear and angular momentum matching. Conclusion: Carbon-target-induced pickup reactions are well suited, in the regime of modest beam intensity, to study the evolution of nuclear structure, with specific sensitivities that are well described by theory.

  3. Assessment of core damage models in SCDAP/RELAP5 during OECD LOFT LP-FP-2

    SciTech Connect

    Coryell, E.W.

    1991-12-31

    The US Nuclear Regulatory Commission has sponsored a program to apply the SCDAP/RELAP5 code to analysis of the transient and reflood phases of the OECD LOFT LP-FP-2 Experiment. The principal objectives of the LP-FP-2 experiment were to determine the fission product release from the fuel during the early phases of a severe fuel damage scenario and to examine the phenomena controlling fission product transport in a vapor/aerosol environment. Calculations with the SCDAP/RELAP5 code, developed at the INEL with NRC support, have been performed to (1) examine the phenomena controlling the progression of both transient and reflood phases of the experiment, (2) enhance our understanding of the phenomena occurring during reflood and add credence to the postulated phenomenological sequence, (3) assess the ability of SCDAP/RELAP5 to examine severe fuel damage issues and phenomena, and (4) identify code strengths and deficiencies with the intent of prioritizing code improvements. Results indicate that the code is able to analyze the early phases of severe fuel damage reasonably well, with potential deficiencies in modelling interaction between molten control rod material and intact fuel.

  4. Assessment of core damadge models in SCDAP/RELAP5 during OECD LOFT LP-FP-2

    SciTech Connect

    Coryell, E.W.

    1991-01-01

    The US Nuclear Regulatory Commission has sponsored a program to apply the SCDAP/RELAP5 code to analysis of the transient and reflood phases of the OECD LOFT LP-FP-2 Experiment. The principal objectives of the LP-FP-2 experiment were to determine the fission product release from the fuel during the early phases of a severe fuel damage scenario and to examine the phenomena controlling fission product transport in a vapor/aerosol environment. Calculations with the SCDAP/RELAP5 code, developed at the INEL with NRC support, have been performed to (1) examine the phenomena controlling the progression of both transient and reflood phases of the experiment, (2) enhance our understanding of the phenomena occurring during reflood and add credence to the postulated phenomenological sequence, (3) assess the ability of SCDAP/RELAP5 to examine severe fuel damage issues and phenomena, and (4) identify code strengths and deficiencies with the intent of prioritizing code improvements. Results indicate that the code is able to analyze the early phases of severe fuel damage reasonably well, with potential deficiencies in modelling interaction between molten control rod material and intact fuel.

  5. Surface behavior of peptides from E1 GBV-C protein: Interaction with anionic model membranes and importance in HIV-1 FP inhibition.

    PubMed

    Galatola, R; Cruz, A; Gómara, M J; Prat, J; Alsina, M A; Haro, I; Pujol, M

    2015-02-01

    The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural analogs (E1P8-12), (E1P8-13), and (E1P8-21) with anionic lipid membranes (POPG vesicles and POPG, DPPG or DPPC/DPPG (2:1) monolayers) and their association with HIV-1 fusion peptide (HIV-1 FP) inhibition at the membrane level were studied using biophysical methods. All peptides showed surface activity but leakage experiments in vesicles as well as insertion kinetics in monolayers and lipid/peptide miscibility indicated a low level of interaction: neither E1P8 nor its analogs induced the release of vesicular content and the exclusion pressure values (πe) were clearly lower than the biological membrane pressure (24-30 mN m(-1)) and the HIV-1 FP (35 mN m(-1)). Miscibility was elucidated in terms of the additivity rule and excess free energy of mixing (GE). E1P8, E1P8-12 and E1P8-21 (but not E1P8-13) induced expansion of the POPG monolayer. The mixing process is not thermodynamically favored as the positive GE values indicate. To determine how E1 peptides interfere in the action of HIV-1 FP at the membrane level, mixed monolayers of HIV-1 FP/E1 peptides (2:1) and POPG were obtained. E1P8 and its derivative E1P8-21 showed the greatest HIV-1 FP inhibition. The LC-LE phase lipid behavior was morphologically examined via fluorescence microscopy (FM) and atomic force microscopy (AFM). Images revealed that the E1 peptides modify HIV-1 FP-lipid interaction. This fact may be attributed to a peptide/peptide interaction as indicated by AFM results. Finally, hemolysis assay demonstrated that E1 peptides inhibit HIV-1 FP activity.

  6. High and compact formation of baculoviral polyhedrin-induced inclusion body by co-expression of baculoviral FP25 in Escherichia coli.

    PubMed

    Li, Lin; Kim, Young Soo; Hwang, Dong Soo; Seo, Jeong Hyun; Jung, Hee Jung; Du, Juan; Cha, Hyung Joon

    2007-04-15

    Previously, we found that baculoviral polyhedrin (Polh) can successfully be used in Escherichia coli as a fusion partner for the expression of special foreign proteins as inclusion bodies, and the resulting, easily isolatable Polh-induced fusion inclusion bodies had almost the same characteristics as the native Polh. Here, we investigated the effects of co-expression of baculoviral FP25 protein on Polh-induced inclusion-body production in an E. coli expression system, as FP25 is known to be involved specifically in polyhedra formation. Using several analytical tools, including SDS-PAGE, pronase proteolysis, solubilization under alkaline conditions, and electron microscopy, we found that co-expressed FP25 was associated with Polh-induced inclusion bodies and that its co-expression led to formation of compact inclusion bodies as well as high production levels. We confirmed that FP25 co-expression induced higher production levels of other heterologous protein, antimicrobial peptide Hal18, fused with aggregation-prone Polh. Therefore, co-expression of baculoviral FP25 can be promisingly used to increase the levels of baculoviral Polh-fused foreign proteins, especially harmful proteins, expressed as inclusion bodies in an E. coli expression system.

  7. Localized surface plasmon resonance enhanced ultraviolet emission and F-P lasing from single ZnO microflower

    SciTech Connect

    Lin, Yi; Li, Jitao; Xu, Chunxiang Fan, Xuemei; Wang, Baoping

    2014-10-06

    In this work, monodispersed ZnO microflowers are fabricated by a vapor phase transport method, and Au nanoparticles (NPs) are directly decorated on the surface of the ZnO microflowers. The micro-photoluminescence of a single ZnO microflower demonstrates that the near band-edge emission is tremendously enhanced while the defect-related emission is completely suppressed after Au decoration. The average enhancement factor reaches up to 65 fold. The enhancement mechanism is assumed to be the electron transfer from excited Au NPs to the ZnO microflower induced by the localized surface plasmon resonance based on the time-resolved photoluminescence. The enhanced F-P lasing from a single ZnO sample is further realized.

  8. Making Use of the Latest Earth Observation Datasets from Copernicus Programme: The SAFI EU-FP7 Project

    NASA Astrophysics Data System (ADS)

    Vincent, Chloe; Mangin, Antoine; Bryere, Philippe; Serra, Romain; Sicard, Pierre; Lesne, Olivia; Scarrott, Rory; Dunne, Declan; Gault, Jeremy; Lecouffe, Catherine; Rougier, Antoine; Jarry, Etienne; Morales, Jesus; Moreno, Oscar; Duque Perea, Raquel; Jimenez, Carlos; Martinez, Ines; Gaspar, Miguel; Rufino, Marta; Santos, Miguel A.; Garrido, Susana; Bugalho, Lourdes; Marques, Vitor; Shorten, Marc; Smith, Catherine; Maguire, Julie; Amine Taji, Mohamed

    2016-08-01

    The EU-FP7 funded project SAFI ("Supporting our Aquaculture and Fisheries Industries", www.safiservices.eu) is primary focused on the exploitation of Earth Observation (EO) data resources, is specifically targeting the support of fisheries and aquaculture industries in our ocean and near-shore areas. The initiative aims at providing information assistance for marine aquaculture deployment (optimization of cage location with respect to environmental and ecological context) and environmental monitoring during operations. It also targets supporting fisheries providing informative indicator products developed through exploitation of Ocean Colour and Sea Surface Temperature data to derive correlations between the environmental situation and the biological status (maturation stage, recruitment and abundance rates) of the fish and shellfish studied. Developed in close collaboration with key stakeholders in the aquaculture and fishery sectors, the SAFI project proposes synthetic indicators for the species of critical importance to regional fisheries and aquaculture sectors.

  9. Study of the electronic and magnetic properties of EuAlO{sub 3} using FP-LAPW method

    SciTech Connect

    Sandeep, Shankar, A.; Rai, D. P.; Thapa, R. K.; Ghimire, M. P.

    2015-05-15

    The electronic and magnetic properties of EuAlO{sub 3} is calculated by first-principles full-potential linearized augmented plane wave (FP-LAPW) method based on density functional theory (DFT). Density of states (DOS), magnetic moments and band structures of the systems are presented. For the exchange and correlation energy, local spin density approximation (LSDA+U) with the inclusion of Hubbard potential U is used. Our calculation showed an indirect band gap of the order of 4 eV for EuAlO{sub 3} in the spin down channel of the DOS and band structures supporting HMF nature of the system. The effective magnetic moment of 6.00 µ{sub B} also supported the above conclusion with an integral value. The DOS of Eu were found responsible for the HMF nature of the system.

  10. An Integrated Data-Driven Strategy for Safe-by-Design Nanoparticles: The FP7 MODERN Project.

    PubMed

    Brehm, Martin; Kafka, Alexander; Bamler, Markus; Kühne, Ralph; Schüürmann, Gerrit; Sikk, Lauri; Burk, Jaanus; Burk, Peeter; Tamm, Tarmo; Tämm, Kaido; Pokhrel, Suman; Mädler, Lutz; Kahru, Anne; Aruoja, Villem; Sihtmäe, Mariliis; Scott-Fordsmand, Janeck; Sorensen, Peter B; Escorihuela, Laura; Roca, Carlos P; Fernández, Alberto; Giralt, Francesc; Rallo, Robert

    2017-01-01

    The development and implementation of safe-by-design strategies is key for the safe development of future generations of nanotechnology enabled products. The safety testing of the huge variety of nanomaterials that can be synthetized is unfeasible due to time and cost constraints. Computational modeling facilitates the implementation of alternative testing strategies in a time and cost effective way. The development of predictive nanotoxicology models requires the use of high quality experimental data on the structure, physicochemical properties and bioactivity of nanomaterials. The FP7 Project MODERN has developed and evaluated the main components of a computational framework for the evaluation of the environmental and health impacts of nanoparticles. This chapter describes each of the elements of the framework including aspects related to data generation, management and integration; development of nanodescriptors; establishment of nanostructure-activity relationships; identification of nanoparticle categories; hazard ranking and risk assessment.

  11. Coating Proteins: Structure and Cross-Linking in fp-1 from the Green Shell Mussel Perna canaliculus†‡

    PubMed Central

    Zhao, Hua; Waite, J. Herbert

    2007-01-01

    The protein family known as fp-1 provides mussel byssus with a protective outer coating and has drawn much attention for its water resistant bioadhesive properties in vitro. A new fp-l isolated from the green shell mussel Perna canaliculus (pcfp-1) reveals a composition dominated by only four amino acids: 3,4-dihydroxyphenyl-L-alanine (dopa), lysine, proline, and valine at ~20 mol % each. SDS–PAGE and MALDI-TOF mass spectrometry detected size variants at 48 and 52 kDa in preparations of purified Pcfp-1. The N-terminal sequence enabled construction of oligonucleotide primers for PCR and RACE-derived cDNAs from which the complete sequence of four variants was deduced. pcfp-1 deviates from all known homologues in other mussels in several notable respects: its mass is half, most of its sequence is represented by 75 tandem repeats of a tetrapeptide, i.e., PY*VK, in which Y* is dopa, prolines are not hydroxylated, and thiolate cysteines are clustered in homologous sequences at both the amino and carboxy termini. Amino acids in the repeat sequence show a striking resemblance to proline-rich cell wall proteins with tandemly repeated PPVYK pentapeptides [Hong, J. C., Nagao, R. T., and Key, J. L. (1987) J. Biol. Chem. 262, 8367–8376]. Cysteine plays a key role in cross-linking pcfp-1 by forming adducts with dopaquinone. Significant 5-S-cysteinyldopa and smaller amounts of 2-S-cysteinyldopa were detected in hydrolysates of the byssal threads of P. canaliculus. The cross-links could also be formed by oxidation of pcfp-1 in vitro using mushroom tyrosinase. Cysteinyldopa cross-links were present in trace amounts only in the byssus of other mussel species. PMID:16313194

  12. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients

    PubMed Central

    Negrier, Claude; Klamroth, Robert; Tiede, Andreas; Pabinger-Fasching, Ingrid; Voigt, Christine; Jacobs, Iris; Morfini, Massimo

    2012-01-01

    A recombinant fusion protein linking coagulation factor IX (FIX) with human albumin (rIX-FP) has been developed to facilitate hemophilia B treatment by less frequent FIX dosing. This first-in-human dose-escalation trial in 25 previously treated subjects with hemophilia B (FIX ≤ 2 IU/dL) examined the safety and pharmacokinetics of 25, 50, and 75 IU/kg rIX-FP. Patients in the 50-IU/kg cohort underwent a comparative pharmacokinetics assessment with their previous FIX product (plasma-derived or recombinant). No allergic reactions or inhibitors were observed. Four mild, possibly treatment-related adverse events were reported. In the 50-IU/kg cohort (13 subjects), the mean half-life of rIX-FP was 92 hours, more than 5 times longer than the subjects' previous FIX product. After 25 or 50 IU/kg rIX-FP administration, the baseline-corrected mean FIX activity remained elevated at day 7 (7.4 IU/dL and 13.4 IU/dL, respectively) and day 14 (2.5 IU/dL and 5.5 IU/dL, respectively). The incremental recovery of rIX-FP was higher than both recombinant and plasma-derived FIX (1.4 vs 0.95 and 1.1 IU/dL per IU/kg, respectively). These results demonstrated both the safety and improved pharmacokinetics of rIX-FP, thus indicating this new product with extended half-life as possibly able to control and prevent bleeding with less frequent injection. The trial was registered at www.clinicaltrials.gov as no. NCT01233440. PMID:22859609

  13. Radiosynthesis and validation of 18F-FP-CMT, a phenyltropane with superior properties for imaging the dopamine transporter in living brain

    PubMed Central

    Cumming, Paul; Maschauer, Simone; Riss, Patrick J; Tschammer, Nuska; Fehler, Stefanie K; Heinrich, Markus R; Kuwert, Torsten; Prante, Olaf

    2014-01-01

    To date there is no validated, 18F-labeled dopamine transporter (DAT) radiotracer with a rapid kinetic profile suitable for preclinical small-animal positron emission tomography (PET) studies in rodent models of human basal ganglia disease. Herein we report radiosynthesis and validation of the phenyltropane 18F-FP-CMT. Dynamic PET recordings were obtained for 18F-FP-CMT in six untreated rats, and six rats pretreated with the high-affinity DAT ligand GBR 12909; mean parametric maps of binding potential (BPND) relative to the cerebellum reference region, and maps of total distribution volume (VT) relative to the metabolite-corrected arterial input were produced. 18F-FP-CMT BPND maps showed peak values of ∼4 in the striatum, versus ∼0.4 in the vicinity of the substantia nigra. Successive truncation of the PET recordings indicated that stable BPND estimates could be obtained with recordings lasting only 45 minutes, reflecting rapid kinetics of 18F-FP-CMT. Pretreatment with GBR 12909 reduced the striatal binding by 72% to 76%. High-performance liquid chromatography analysis revealed rapid metabolism of 18F-FP-CMT to a single, non-brain penetrant hydrophilic metabolite. Total distribution of volume calculated relative to the metabolite-corrected arterial input was 4.4 mL/g in the cerebellum. The pharmacological selectivity of 18F-FP-CMT, rapid kinetic profile, and lack of problematic metabolites constitute optimal properties for quantitation of DAT in rat, and may also predict applicability in human PET studies. PMID:24714035

  14. MZF-1 and DbpA interact with DNase I hypersensitive sites that correlate with expression of the human MUC1 mucin gene

    SciTech Connect

    Shiraga, Toshiyuki; Winpenny, John P.; Carter, Emma J.; McCarthy, Victoria A.; Hollingsworth, Michael A.; Harris, Ann . E-mail: ann.harris@paediatrics.ox.ac.uk

    2005-08-01

    The MUC1 mucin is a large membrane-tethered glycoprotein that shows differential expression in many adenocarcinomas, where it contributes to their invasive and metastatic properties. We previously identified DNase I hypersensitive sites at -750 and -250 bp in the human MUC1 gene promoter and showed concordance between the -250 site and MUC1 mRNA levels in vivo. Transient expression assays using promoter constructs, in which the core DHS was deleted, to drive reporter gene expression revealed in vivo evidence for their activity. DNase I footprinting using nuclear extracts from HPAF human pancreatic carcinoma cells and MCF7 breast carcinoma cells identified three protein-binding elements in these regions (-250FP1, FP2 and -750FP). Electrophoretic mobility shift assays detected several complexes between HPAF nuclear proteins and labeled FP DNA probes. Southwestern blots and UV cross-linking experiments identified myeloid zinc finger-1 (MZF-1) as a candidate transcription factor among proteins binding to the -250FP1 and FP2 sequences. Another candidate that was identified by screening an HPAF cDNA expression library with the -250FP1 probe is DNA binding protein A (DbpA). Exogenous DbpA expression in COS-7 cells was accompanied by upregulation of MUC1 promoter activity via the -250 DHS, suggesting that DbpA binding to the -250 DHS can influence human MUC1 gene expression.

  15. Impact of fowlpox-vectored Mycoplasma gallisepticum vaccine Vectormune® FP MG on layer hen egg production and egg quality parameters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was conducted to determine the impact of vaccination with Vectormune®FP MG on egg production and egg quality characteristics of white leghorn hens. Due to questions of the efficacy of this vaccine in preventing M. gallisepticum mediated pathology, the ability of this vaccine to protect a...

  16. ENVIRONMENTAL TECHNOLOGY VERIFICATION, TEST REPORT OF CONTROL OF BIOAEROSOLS IN HVAC SYSTEMS, FILTRATION GROUP, AEROSTAR FP-98 MINIPLEAT V-BLANK FILTER

    EPA Science Inventory

    The Environmental Technology Verification report discusses the technology and performance of the AeroStar FP-98 Minipleat V-Bank Filter air filter for dust and bioaerosol filtration manufactured by Filtration Group. The pressure drop across the filter was 137 Pa clean and 348 Pa ...

  17. Fuzzy-PI-based centralised control of semi-isolated FP-SEPIC/ZETA BDC in a PV/battery hybrid system

    NASA Astrophysics Data System (ADS)

    Mahendran, Venmathi; Ramabadran, Ramaprabha

    2016-11-01

    Multiport converters with centralised controller have been most commonly used in stand-alone photovoltaic (PV)/battery hybrid system to supply the load smoothly without any disturbances. This study presents the performance analysis of four-port SEPIC/ZETA bidirectional converter (FP-SEPIC/ZETA BDC) using various types of centralised control schemes like Fuzzy tuned proportional integral controller (Fuzzy-PI), fuzzy logic controller (FLC) and conventional proportional integral (PI) controller. The proposed FP-SEPIC/ZETA BDC with various control strategy is derived for simultaneous power management of a PV source using distributed maximum power point tracking (DMPPT) algorithm, a rechargeable battery, and a load by means of centralised controller. The steady state and the dynamic response of the FP-SEPIC/ZETA BDC are analysed using three different types of controllers under line and load regulation. The Fuzzy-PI-based control scheme improves the dynamic response of the system when compared with the FLC and the conventional PI controller. The power balance between the ports is achieved by pseudorandom carrier modulation scheme. The response of the FP-SEPIC/ZETA BDC is also validated experimentally using hardware prototype model of 500 W system. The effectiveness of the control strategy is validated using simulation and experimental results.

  18. 18F-FP-PEG2-β-Glu-RGD2: A Symmetric Integrin αvβ3-Targeting Radiotracer for Tumor PET Imaging

    PubMed Central

    Tang, Ganghua; Yao, Shaobo; Yao, Baoguo; Wang, Hongliang; Nie, Dahong; Liang, Xiang; Tang, Caihua; He, Shanzhen

    2015-01-01

    Radiolabeled cyclic arginine-glycine-aspartic (RGD) peptides can be used for noninvasive determination of integrin αvβ3 expression in tumors. In this study, we performed radiosynthesis and biological evaluation of a new 18F-labeled RGD homodimeric peptide with one 8-amino-3,6-dioxaoctanoic acid (PEG2) linker on the glutamate β-amino group (18F-FP-PEG2-β-Glu-RGD2) as a symmetric PET tracer for tumor imaging. Biodistribution studies showed that radioactivity of 18F-FP-PEG2-β-Glu-RGD2 was rapidly cleared from blood by predominately renal excretion. MicroPET-CT imaging with 18F-FP-PEG2-β-Glu-RGD2 revealed high tumor contrast and low background in A549 human lung adenocarcinoma-bearing mouse models, PC-3 prostate cancer-bearing mouse models, and orthotopic transplanted C6 brain glioma models. 18F-FP-PEG2-β-Glu-RGD2 exhibited good stability in vitro and in vivo. The results suggest that this tracer is a potential PET tracer for tumor imaging. PMID:26397833

  19. An FP-CIT PET comparison of the differences in dopaminergic neuronal loss between idiopathic Parkinson disease with dementia and without dementia.

    PubMed

    Song, In-Uk; Kim, Young-Do; Cho, Hyun-Ji; Chung, Sung-Woo; Chung, Yong-An

    2013-01-01

    Previous studies have demonstrated a decreased density of dopamine transporters (DAT) in basal ganglia in patients with idiopathic Parkinson disease (IPD) using I-n-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (FP-CIT), and the reductions in striatal DAT levels were inversely correlated with the severity of motor dysfunction in IPD. However, there has been no study on the correlation of DAT levels between IPD patients with and without cognitive dysfunction. Thus, we evaluated the differences in regional DAT density in the brain of patients with IPD without dementia and those with dementia using FP-CIT positron emission tomography. We recruited 24 consecutive patients with IPD, including 7 with IPD without dementia and 17 with IPD with dementia, and 18 healthy controls. FP-CIT positron emission tomography scans were acquired 90 and 210 minutes after the FP-CIT injection. The DAT density did not differ in the caudate nucleus or the putamen between patients with IPD without dementia and those with dementia. However, the DAT density between the 2 groups with IPD demonstrated a significantly decreased density compared with that of healthy controls in the putamen. We cautiously suggest that there is no relationship between DAT density and cognitive severity because there were no significant differences in the DAT density between IPD with dementia and those without dementia.

  20. Combined visual and semi-quantitative assessment of (123)I-FP-CIT SPECT for the diagnosis of dopaminergic neurodegenerative diseases.

    PubMed

    Ueda, Jun; Yoshimura, Hajime; Shimizu, Keiji; Hino, Megumu; Kohara, Nobuo

    2017-04-07

    Visual and semi-quantitative assessments of (123)I-FP-CIT single-photon emission computed tomography (SPECT) are useful for the diagnosis of dopaminergic neurodegenerative diseases (dNDD), including Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. However, the diagnostic value of combined visual and semi-quantitative assessment in dNDD remains unclear. Among 239 consecutive patients with a newly diagnosed possible parkinsonian syndrome who underwent (123)I-FP-CIT SPECT in our medical center, 114 patients with a disease duration less than 7 years were diagnosed as dNDD with the established criteria or as non-dNDD according to clinical judgment. We retrospectively examined their clinical characteristics and visual and semi-quantitative assessments of (123)I-FP-CIT SPECT. The striatal binding ratio (SBR) was used as a semi-quantitative measure of (123)I-FP-CIT SPECT. We calculated the sensitivity and specificity of visual assessment alone, semi-quantitative assessment alone, and combined visual and semi-quantitative assessment for the diagnosis of dNDD. SBR was correlated with visual assessment. Some dNDD patients with a normal visual assessment had an abnormal SBR, and vice versa. There was no statistically significant difference between sensitivity of the diagnosis with visual assessment alone and semi-quantitative assessment alone (91.2 vs. 86.8%, respectively, p = 0.29). Combined visual and semi-quantitative assessment demonstrated superior sensitivity (96.7%) to visual assessment (p = 0.03) or semi-quantitative assessment (p = 0.003) alone with equal specificity. Visual and semi-quantitative assessments of (123)I-FP-CIT SPECT are helpful for the diagnosis of dNDD, and combined visual and semi-quantitative assessment shows superior sensitivity with equal specificity.

  1. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial.

    PubMed

    Santagostino, Elena; Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-04-07

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P< .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274.

  2. Long-acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: results of a phase 3 trial

    PubMed Central

    Martinowitz, Uri; Lissitchkov, Toshko; Pan-Petesch, Brigitte; Hanabusa, Hideji; Oldenburg, Johannes; Boggio, Lisa; Negrier, Claude; Pabinger, Ingrid; von Depka Prondzinski, Mario; Altisent, Carmen; Castaman, Giancarlo; Yamamoto, Koji; Álvarez-Roman, Maria-Teresa; Voigt, Christine; Blackman, Nicole; Jacobs, Iris

    2016-01-01

    A global phase 3 study evaluated the pharmacokinetics, efficacy, and safety of recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 63 previously treated male patients (12-61 years) with severe hemophilia B (factor IX [FIX] activity ≤2%). The study included 2 groups: group 1 patients received routine prophylaxis once every 7 days for 26 weeks, followed by either 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively; group 2 patients received on-demand treatment of bleeding episodes for 26 weeks and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. The mean terminal half-life of rIX-FP was 102 hours, 4.3-fold longer than previous FIX treatment. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg weekly and 75 IU/kg every 2 weeks, respectively. There was 100% reduction in median annualized spontaneous bleeding rate (AsBR) and 100% resolution of target joints when subjects switched from on-demand to prophylaxis treatment with rIX-FP (P < .0001). The median AsBR was 0.00 for all prophylaxis regimens. Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection. No patient developed an inhibitor, and no safety concerns were identified. These results indicate rIX-FP is safe and effective for preventing and treating bleeding episodes in patients with hemophilia B at dosing regimens of 40 IU/kg weekly and 75 IU/kg every 2 weeks. This trial was registered at www.clinicaltrials.gov as #NCT0101496274. PMID:26755710

  3. VAMDC FP7 project and STARK-B database: C II Stark broadening parameters for white dwarf atmospheres research

    NASA Astrophysics Data System (ADS)

    Larbi-Terzi, Neila; Sahal-Bréchot, Sylvie; Ben Nessib, Nebil; Dimitrijević, Milan S.

    2010-11-01

    Stark broadening parameters of C II lines were determined within 3s-np spectral series within the semiclassical perturbation method. The atomic energy levels needed for calculations were taken from TOPBASE as well as the oscillator strengths, calculated additionally using the Coulomb approximation (the method of Bates and Damgaard). The both results were compared and the disagreement is found only in one case where the configuration mixing allows a forbidden transition to a close perturbing energy level. Calculations were performed for plasma conditions relevant for atmospheres of DQ white dwarfs and for a new type of white dwarfs, with surface composed mostly of carbon, discovered in 2007 by Dufour et al.. The aim of this work is to provide accurate C II Stark broadening data, which are crucial for this type of white dwarf atmosphere modellisation. Obtained results will be included in STARK-B database (http://stark-b.obspm.fr/), entering in the FP7 project of European Virtual Atomic and Molecular Data Center VAMDC aiming at building an interoperable e-Infrastructure for the exchange of atomic and molecular data (http://www.vamdc.org/).

  4. FP-LAPW investigation of electronic, magnetic, elastic and thermal properties of Fe-doped zirconium nitride

    SciTech Connect

    Sirajuddeen, M. Mohamed Sheik Banu, I. B. Shameem

    2014-05-15

    Full Potential- Linear Augmented Plane Wave (FP-LAPW) method has been employed to study the electronic, magnetic, elastic and thermal properties of Fe-doped Zirconium nitride. In this work, Fe-atoms were doped into the super cell of ZrN in doping concentrations of 12.5%, 25% and 37.5% to replace Zr atoms. Electronic properties such as band structure and DOS were plotted and compared for the doped compounds. Charge density contours were plotted for all the doped compounds. The non-magnetic ZrN doped in different Fe concentrations were found to be ferromagnetic. Magnetic moments have been calculated and compared. Elastic properties have been studied and compared with electronic properties. Appearance of magnetic ordering and its influence with the elastic properties have been reported. Impact of 3d states of Fe in DOS plot on the elastic nature of the compounds has been highlighted. Thermal properties such as Debye temperature and molar heat capacities at low temperature have been determined. Debye temperature is found to decrease with higher doping concentrations. Molar heat capacities are found to increase with higher concentrations of Fe atoms.

  5. Identification and Characterization of the Cr_2O3 (0001) Surface by DFT FP-LAPW Calculations

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Scheffler, Matthias

    2000-03-01

    The physical and chemical properties of Cr_2O3 play an important role in a wide variety of industrial applications (e.g. catalysis and corrosion prevention). Though much has been learned about the Cr-oxide surfaces in recent years, the understanding of how and why this system behaves as it does, is still very shallow. In fact, even with respect to the surface composition and geometry the controversy is significant. Using density-functional theory (DFT) together with the full-potential linearized augmented plane wave (FP-LAPW) method, we investigated the structural, electronic, and magnetic properties of the Cr_2O3 (0001) surface. Our results reveal that the surface structures depend crucially on the environment, i.e. on the partial pressure of oxygen. Under oxygen poor conditions (e.g. at low pressure), the Cr-terminated surface is the most stable one. However, with increasing oxygen pressure, a chromyl (O=Cr) terminated and a O_3-terminated surfaces become energetically favorable. They exhibit pronounced differences in their surface relaxations and surface chemical properties. The differences to Fe_2O3 [1] are significant and explained in terms of the different number of d-electrons. We also studied the adsorption and dissociation of O2 molecules. ^* Present address:Delphi Research and Development Center, Warren, MI 48090-9055, U.S.A. [1] X.G. Wang et al. Phys. Rev. Lett. 81, 1038 (1998).

  6. Summary of important results and SCDAP/RELAP5 analysis for OECD LOFT experiment LP-FP-2

    SciTech Connect

    Coryell, E.W.

    1994-04-01

    This report summarizes significant technical findings from the LP-FP-2 Experiment sponsored by the Organization of Economic Cooperation and Development (OECD). It was the second, and final, fission product experiment conducted in the Loss-of-Fluid Test (LOFT) facility at the Idaho National Engineering Laboratory. The overall technical objective of the test was to contribute to the understanding of fuel rod behavior, hydrogen generation, and fission product release, transport, and deposition during a V-sequence accident scenario that resulted in severe core damage. An 11 by 11 test bundle, comprised of 100 prepressurized fuel rods, 11 control rods, and 10 instrumented guide tubes, was surrounded by an insulating shroud and contained in a specially designed central fuel module, that was inserted into the LOFT reactor. The simulated transient was a V-sequence loss-of-coolant accident scenario featuring a pipe break in the low pressure injection system line attached to the hot leg of the LOFT broken loop piping. The transient was terminated by reflood of the reactor vessel when the outer wall shroud temperature reached 1517 K. With sustained fission power and heat from oxidation and metal-water reactions, elevated temperatures resulted in zircaloy melting, fuel liquefaction, material relocation, and the release of hydrogen, aerosols, and fission products. A description and evaluation of the major phenomena, based upon the response of on line instrumentation, analysis of fission product data, postirradiation examination of the fuel bundle, and calculations using the SCDAP/RELAP5 computer code, are presented.

  7. Large Scale Modeling of Floodplain Inundation; Calibration and Forecast Based on Lisflood-FP Model and Remotely Sensed Data

    NASA Astrophysics Data System (ADS)

    Najafi, M.; Durand, M. T.; Neal, J. C.; Moritz, M.

    2013-12-01

    The Logone floodplain located in the Chad basin in north Cameroon, Africa experiences seasonal flooding as the result of Logone River overbank flow. The seasonal and inter-annual variability of flood depths and extents have significant impacts on the socio-economic as well as eco-hydrology of the basin. Recent human interventions on the hydraulic characteristics of the basin have caused serious concerns for the future behavior of the system. Construction of the Maga dam and hundreds of fish canals along with the impact of climate change are potential factors which alternate the floodplain characteristics. To understand the hydraulics of the basin and predict future changes in flood inundation we calibrate the LISFLOOD-FP numerical model using the historical records of river discharge as well as satellite observations of flood depths and extents. LISFLOOD is a distributed 2D model which efficiently simulates large basins. Because of data limitations the Shuttle Radar Topography Mission (SRTM) is considered to extract the DEM data. LISFLOOD subgrid 2D model is applied which allows for defining river channel widths smaller than the DEM resolution. River widths are extracted from Landsat 4 image obtained on Feb-1999. Model parameters including roughness coefficient and river bathymetry are then calibrated. The results demonstrate the potential application of the proposed model to simulate future changes in the floodplain. The sub-grid model has shown to improve hydraulic connectivity within the inundated area. DEM errors are major sources of uncertainty in model prediction.

  8. Thermal degradation of the tensile properties of undirectionally reinforced FP-Al2O3/EZ 33 magnesium composites

    NASA Technical Reports Server (NTRS)

    Bhatt, R.T.; Grimes, H. H.

    1983-01-01

    The effects of isothermal and cyclic exposure on the room temperature axial and transverse tensile strength and dynamic flexural modulus of 35 volume percent and 55 volume percent FP-Al203/EZ 33 magnesium composites were studied. The composite specimens were continuously heated in a sand bath maintained at 350 C for up to 150 hours or thermally cycled between 50 and 250 C or 50 and 350 C for up to 3000 cycles. Each thermal cycle lasted for a total of six minutes with a hold time of two minutes at the maximum temperature. Results indicate no significant loss in the room temperature axial tensile strength and dynamic flexural modulus of composites thermally cycled between 50 and 250 C or of composites isothermally heated at 350 C for up to 150 hours from the strength and modulus data for the untreated, as-fabricated composites. In contrast, thermal cycling between 50 and 350 C caused considerable loss in both room temperature strength and modulus. Fractographic analysis and measurement of composite transverse strength and matrix hardness of thermally cycled and isothermally heated composites indicated matrix softening and fiber/matrix debonding due to void growth at the interface and matrix cracking as the likely causes of the strength and modulus loss behavior. Previously announced in STAR as N82-21260

  9. Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230

    PubMed Central

    Ganji, Gopinath; Barnette, Mary; Hoang, Bao; Tunstead, James; Skedzielewski, Tina; Alsaid, Hasan; Jucker, Beat M.; Minthorn, Elisabeth; Kumar, Rakesh; DeYoung, M. Phillip

    2016-01-01

    Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of mesothelioma, a tumor type shown to express high levels of FGF2 and FGFR1. GSK3052230 demonstrated antiproliferative activity across a panel of mesothelioma cell lines and inhibited growth of tumor xenografts in mice. High expression of FGF2 and FGFR1 correlated well with response to FGF pathway inhibition. GSK3052230 inhibited MAPK signaling as evidenced by decreased phospho-ERK and phospho-S6 levels in vitro and in vivo. Additionally, dose-dependent and statistically-significant reductions in tumor vessel density were observed in GSK3052230-treated tumors compared to vehicle-treated tumors. These data support the role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma, demonstrate its impact on tumor growth and angiogenesis, and provide a rationale for the current clinical evaluation of this molecule in mesothelioma patients. PMID:27223434

  10. EUTEMPE-RX, an EC supported FP7 project for the training and education of medical physics experts in radiology.

    PubMed

    Bosmans, H; Bliznakova, K; Padovani, R; Christofides, S; Van Peteghem, N; Tsapaki, V; Caruana, C J; Vassileva, J

    2015-07-01

    The core activity of the medical physics expert (MPE) is to ensure optimal use of ionising radiation in healthcare. It is essential that these healthcare professionals are trained to the highest level, defined as European Qualifications Framework for Lifelong Learning (EQF) level 8 by the European Commission's Radiation Protection Report 174 'Guidelines on the MPE'. The main objective of the EUTEMPE-RX project is to provide a model training scheme that allows the medical physicist in diagnostic and interventional radiology (D&IR) to reach this high level. A European network of partners was brought together in this FP7 EC project to ensure sufficient expertise in all aspects of the subject and to create a harmonised course programme. Targeted participants are medical physicists in D&IR in hospitals, engineers and scientists in medical device industries and officers working in regulatory authorities. Twelve course modules will be developed at EQF level 8, with radiation safety and diagnostic effectiveness being prevalent subjects. The modules will combine online with face-to-face teaching using a blended learning approach.

  11. The implementation of the Open Access paradigm to the EC-FP7 MED-SUV (Mediterranean Supersite Volcanoes) project

    NASA Astrophysics Data System (ADS)

    Puglisi, Giuseppe; Brito, Fabrice; Caumont, Hervé; D'Auria, Luca; Fernandez, José; Mazzetti, Paolo; Mathieu, Pierre Philippe; Nativi, Stefano; Papeschi, Fabrizio; Pepe, Antonio; Reitano, Danilo; Sangianantoni, Agata; Scarpato, Giovanni; Spampinato, Letizia

    2016-04-01

    The overall goal of the EC-FP7 Mediterranean Supersite Volcanoes (MED-SUV) project is to apply the rationale of the Supersites GEO initiative to Campi Flegrei/Vesuvius and Mt. Etna to reduce the volcanic risk, by improving the understanding of the underlying geophysical processes, through the integration and sharing of the in-situ and Earth Observation (EO) data sets and the implementation of new instruments and monitoring systems. The project involves 24 EU and no-EU partners, including research and academic institutions, space agencies and SMEs. In this framework, the application of the Open Access paradigm has offered the opportunity to study and apply practical solutions concerning the data management (i.e. data polices, foreground exploitation and sustainability), intellectual property rights (i.e., ownership, licences, agreements) and technical issues (i.e., design and implementation of an interoperability e-infrastructure, access systems, etc.). This contribution presents pro and cons encountered in the project, as well as the main outcomes of the implementation of the Open Access to the Italian Supersites. This experience will be exploited in the building of international research infrastructures, such as EPOS, and the outcomes of the project will contribute to foster the Open Access to the research data in a wide context, as the GEO-GEOSS framework.

  12. FP7 project MyWater - Merging hydrologic models and EO data for reliable information on Water

    NASA Astrophysics Data System (ADS)

    Araujo, Antonio; Chambel, Pedro; Silva, Adélio; Velickov, Slavco; van Andel, Schalk; Toth, Gergely; Almeida, Waldenio; Mako, Andras; Alexandridis, Thomas; Cugala, Domigos

    2013-04-01

    21st century reality already sees 2.5 billion people without adequate access to water, whilst climate changes lead to dramatically changing water resources availability and needs. These changes will influence all citizens, and authorities will need more reliable information to adapt to the new situation. The MyWater project responds to these challenges, implementing a new information platform which integrates data from three scientific research areas - earth observation, catchment modelling and meteorology - to better access hydrological processes. This platform will allow a quasi-automatic service chains which output user tailored results like: drinking water needs (quantity and quality), agriculture water needs, water health related indicators, flood scenarios, etc. Overall, MyWater will provide reliable information on water quantity, quality and usage for appropriate water management, improving knowledge and creating the forecasting capabilities necessary to catchment managers, and at the same time optimizing the ratio cost/benefit of water resources monitoring. The work presented regards to the FP7-EU project "Merging hydrological models and Earth observation data for reliable information on water - MyWater".

  13. VAMDC FP7 project and STARK-B database: C II Stark broadening parameters for white dwarf atmospheres research

    SciTech Connect

    Larbi-Terzi, Neila; Ben Nessib, Nebil; Sahal-Brechot, Sylvie; Dimitrijevic, Milan S.

    2010-11-23

    Stark broadening parameters of C II lines were determined within 3s-np spectral series within the semiclassical perturbation method. The atomic energy levels needed for calculations were taken from TOPBASE as well as the oscillator strengths, calculated additionally using the Coulomb approximation (the method of Bates and Damgaard). The both results were compared and the disagreement is found only in one case where the configuration mixing allows a forbidden transition to a close perturbing energy level. Calculations were performed for plasma conditions relevant for atmospheres of DQ white dwarfs and for a new type of white dwarfs, with surface composed mostly of carbon, discovered in 2007 by Dufour et al.. The aim of this work is to provide accurate C II Stark broadening data, which are crucial for this type of white dwarf atmosphere modellisation. Obtained results will be included in STARK-B database (http://stark-b.obspm.fr/), entering in the FP7 project of European Virtual Atomic and Molecular Data Center VAMDC aiming at building an interoperable e-Infrastructure for the exchange of atomic and molecular data (http://www.vamdc.org/).

  14. Batch and Pulsed Fed-Batch Cultures of Aspergillus flavipes FP-500 Growing on Lemon Peel at Stirred Tank Reactor.

    PubMed

    Wolf-Márquez, V E; García-García, E; García-Rivero, M; Aguilar-Osorio, G; Martínez Trujillo, M A

    2015-11-01

    Aspergillus flavipes FP-500 grew up on submerged cultures using lemon peel as the only carbon source, developing several batch and pulsed fed-batch trials on a stirred tank reactor. The effect of carbon source concentration, reducing sugar presence and initial pH on exopectinase and endopectinase production, was analyzed on batch cultures. From this, we observed that the highest substrate concentration favored biomass (X max) but had not influence on the corresponding specific production (q p) of both pectinases; the most acid condition provoked higher endopectinase-specific productions but had not a significant effect on those corresponding to exopectinases; and reducing sugar concentrations higher than 1.5 g/L retarded pectinase production. On the other hand, by employing the pulsed fed-batch operation mode, we observed a prolonged growth phase, and an increase of about twofold on endopectinase production without a significant raise on biomass concentration. So, pulsed fed-batch seems to be a good alternative for obtaining higher endopectinase titers by using high lemon peel quantities without having mixing and repression problems to the system. The usefulness of unstructured kinetic models for explaining, under a theoretic level, the behavior of the fungus along the batch culture with regard to pectinase production was evident.

  15. Preliminary calculational analysis of the actinide samples from FP-4 exposed in the Dounreay Prototype Fast Reactor

    SciTech Connect

    Murphy, B.D.; Raman, S.; Newton, T.D.

    1996-12-01

    This report discusses the current status of results from an extensive experiment on the irradiation of selected actinides in a fast reactor. These actinides ranged from thorium to curium. They were irradiated in the core of the Dounreay Prototype Fast Reactor. Rates for depletion, transmutation, and fission-product generation were experimentally measured, and, in turn, were calculated using current cross-section and fission-yield data. Much of the emphasis is on the comparison between experimental and calculated values for both actinide and fission-product concentrations. Some of the discussion touches on the adequacy of current cross-section and fission-yield data. However, the main purposes of the report are: to collect in one place the most recent yield data, to discuss the comparisons between the experimental and calculated results, to discuss each sample that was irradiated giving details of any adjustments needed or specific problems encountered, and to give a chronology of the analysis as it pertained to the set of samples (referred to as FP-4 samples) that constitutes the most extensively irradiated and final set. The results and trends reported here, together with those discussions touching on current knowledge about cross sections and fission yields, are intended to serve as a starting point for further analysis. In general, these results are encouraging with regard to the adequacy of much of the currently available nuclear data in this region of the periodic table. But there are some cases where adjustments and improvements can be suggested. However, the application of these results in consolidating current cross-section and fission-yield data must await further analysis.

  16. An optical pulse width modulation generator based on the injection-locking property of single mode FP-LD

    NASA Astrophysics Data System (ADS)

    Tran, Quoc Hoai; Nakarmi, Bikash; Won, Yong Hyub

    2013-03-01

    A novel simple optical pulse width modulation generator (OPWMG) based on injection-locking property of a single mode FP-LD (SMFP-LD) has been proposed and experimentally verified. The OPWMG consists of a SMFP-LD (which acts as comparator), an optical sinusoidal wave source (analog input), and a continuous optical beam (control signal). The power required for fully injection-locking the SMFP-LD acts as the referent power whereas the combination power of continuous optical beam and analog optical sinusoidal signals work as control signals for changing the duty cycle of the proposed OPWMG. The presence of only continuous optical beam is not sufficient to suppress the dominant mode of SMFP-LD with high ON/OFF contrast ratio; however, the application of additional sinusoidal wave of constant amplitude and frequency, the dominant mode of SMFP-LD can be suppressed for the certain time window. Since, injection-locking power is dependent with the combined power of input injected continuous beam and sinusoidal optical wave, the time window of injection-locking can be varied by changing input beam power which provides different duty cycle of 13% to 68% at the output. Current available schemes for generating PWM signals are in electrical domain, hence, they need to convert electrical signals into optical domain by using expensive O/E converters for application in optical control and signal processing. The proposed OPWMG scheme has several advantages, such as low cost, low power consumption (~0.5 mW) which can be used for various applications where the effect of EMI/EMR is considered as an important factor such as control circuit for high voltage converters in power plant and electrical vehicles.

  17. Experiment study of bio-tissue's temperature irradiated by laser based on optical fiber F-P sensor

    NASA Astrophysics Data System (ADS)

    Shan, Ning; Liu, Xia

    2014-08-01

    Laser has several advantages, such as strong anti-interference ability, quick speed, high power, agility and precision. It is widely applied in military and medicine fields. When laser acts on human body, biological tissue of human body will appear the phenomenon of ablation and carbonization and solidification. In order to effectively defend excess damage by laser, the thermal effect research of skin tissue should be carried out. Temperature is a key parameter in the processing between laser and bio-tissue. It is the mostly foundation using analyze size of thermal damage area and forecast thermal damage degree. In this paper, the low fineness optical fiber F-P sensing system for temperature measurement is designed and established. The real-time measurement system of temperature generated by laser irradiating bio-tissue is build based on the sensing system. The temperature distributing generated by laser in the bio-tissue is studied through experiment when the spot diameter of emission laser is difference with the same energy density and the energy density is difference with the same spot diameter of emission laser. The experimental results show that the sensing system can be used to the real-time temperature measurement of bio-tissue efficiency. It has small bulk. Its outer diameter is 250μm. And the hurt for bio-tissue is small. It has high respond speed. The respond time of temperature is less than 1s. These can be satisfied with practice demand. When the energy density of laser is same, the temperature rising in the same location is low along the spot diameter of emission laser increasing. When the spot diameter of emission laser is same, the temperature rising in the same location is increasing along with the energy density of laser increasing.

  18. Hypoxia monitoring activities within the FP7 EU-project HYPOX: diverse approaches to understand a complex phenomenon

    NASA Astrophysics Data System (ADS)

    Janssen, F.; Waldmann, C.; Boetius, A.

    2012-04-01

    Hypoxic conditions in aquatic systems and the occurrence of 'dead zones' increase worldwide due to man-made eutrophication and global warming with consequences for biodiversity, ecosystem functions and services such as fisheries, aquaculture and tourism. Monitoring of hypoxia and its consequences has to (1) account for the appropriate temporal and spatial scales, (2) separate anthropogenic from natural drivers and long-term trends from natural variations, (3) assess ecosystem response, (4) use modeling tools for generalization and prediction, and (5) share data and obtained knowledge. In 2009 the EU FP7 project HYPOX (www.hypox.net) started out as a pioneering attempt to improve and integrate hypoxia observation capacities addressing these requirements. Target ecosystems selected for HYPOX cover a broad range of settings (e.g., hydrography, oxygenation status, biological activity, anthropogenic impact) and differ in their sensitivity towards change. Semi-enclosed basins with permanent anoxia (Black Sea, Baltic Sea), are included as well as seasonally or locally hypoxic land-locked systems (fjords, lagoons, lakes) and open ocean systems with high sensitivity to global warming (North Atlantic - Arctic transition). Adopted monitoring approaches involve autonomous, cabled, and shipboard instruments and include static and profiling moorings, benthic observatories, drifters, as well as classical CTD surveys. In order to improve observatory performance, project activities encompass developments of oxygen sensors as well as calibration procedures and technologies to reduce biofouling. Modeling and data assimilation are used to synthesize findings, to obtain an in-depth understanding of hypoxia causes and consequences, and to improve forecasting capacities. For integration of the collected information into a global oxygen observing system, results are disseminated through the HYPOX portal following GEOSS data sharing principles. This presentation will give an overview of

  19. Neutralization of improvised explosive devices by high-power lasers: research results from the FP7 project ENCOUNTER

    NASA Astrophysics Data System (ADS)

    Osterholz, J.; Lueck, M.; Lexow, B.; Wickert, M.

    2016-10-01

    The development of reliable techniques for the safe neutralization of improvised explosive devices (IEDs) is an active field of research. Recently, innovative approaches for the neutralization of IEDs were developed and tested within the FP7 project ENCOUNTER ("Explosive Neutralisation and Mitigation Countermeasures for IEDs in Urban/Civil Environment") and were compared to existing, established technologies. Here, the ENCOUNTER project is presented with a special focus on the neutralization of IEDs by high-power lasers. The working principle of the application of high-power lasers for the neutralization of explosive devices is based on thermal effects. Heating of the IEDs main charge may occur either by direct irradiation of the explosive material or by heat transfer through the main charge's confinement. The aim of the application of the laser is to achieve a low order burning reaction of the explosive charge and thus a controlled neutralization of the IED. Since laser beams allow for the directed transport of energy, this technique can be applied over long stand-off distances and has thus potential for an increase of the safety of clearing forces and population in the case of terroristic attacks in a civilian environment. Within the ENCOUNTER project, a laboratory environment has been set up which allows for the irradiation of IEDs with a laser power of up to 10 kW. Experiments have been carried out on a broad spectrum of different types of IEDs. The processes during neutralization were studied in detail with high-speed diagnostics. On the basis of these experimental data, the safety and the reliability of the application of the laser was analyzed, and recommendations to end users were given. In addition to the results of the ENCOUNTER project, approaches for the numerical simulation of the neutralization of IEDs are discussed.

  20. 123I-FP-CIT SPECT imaging in early diagnosis of dementia in patients with and without a vascular component

    PubMed Central

    Garriga, Marina; Milà, Marta; Mir, Manzoor; Al-Baradie, Raid; Huertas, Sonia; Castejon, Cesar; Casas, Laura; Badenes, Dolors; Giménez, Nuria; Font, M. Angels; Gonzalez, Jose M.; Ysamat, Maria; Aguilar, Miguel; Slevin, Mark; Krupinski, Jerzy

    2015-01-01

    Alzheimer’s disease (AD) and vascular dementia (VaD) are the most common cause of dementia. Cerebral ischemia is a major risk factor for development of dementia. 123I-FP-CIT SPECT (DaTScan) is a complementary tool in the differential diagnoses of patients with incomplete or uncertain Parkinsonism. Additional application of DaTScan enables the categorization of Parkinsonian disease with dementia (PDD), and its differentiation from pure AD, and may further contribute to change the therapeutic decision. The aim of this study was to analyze the vascular contribution towards dementia and mild cognitive impairment (MCI). We evaluated the utility of DaTScan for the early diagnosis of dementia in patients with and without a clinical vascular component, and the association between neuropsychological function, vascular component and dopaminergic function on DaTScan. One-hundred and five patients with MCI or the initial phases of dementia were studied prospectively. We developed an initial assessment using neurologic examination, blood tests, cognitive function tests, structural neuroimaging and DaTScan. The vascular component was later quantified in two ways: clinically, according to the Framingham Risk Score (FRS) and by structural neuroimaging using Wahlund Scale Total Score (WSTS). Early diagnosis of dementia was associated with an abnormal DaTScan. A significant association was found between a high WSTS and an abnormal DaTScan (p < 0.01). Mixed AD was the group with the highest vascular component, followed by the VaD group, while MCI and pure AD showed similar WSTS. No significant associations were found between neuropsychological impairment and DaTScan independently of associated vascular component. DaTScan seems to be a good tool to discriminate, in a first clinical assessment, patients with MCI from those with established dementia. There was bigger general vascular affectation observable in MRI or CT in patients with abnormal dopaminergic uptake seen on Da

  1. The FP7 ULTimateCO2 project: a study of the long term fate of CO2

    NASA Astrophysics Data System (ADS)

    Audigane, Pascal; Waldmann, Svenja; Pearce, Jonathan; Dimier, Alain; Le Gallo, Yann; Frykman, Peter; Maurand, Nicolas; Gherardi, Fabrizio; Yalamas, Thierry; Cremer, Holger; Spiers, Chris; Nussbaum, Christophe

    2014-05-01

    The objectives of the European FP7 ULTimateCO2 project are to study specific processes that could influence the long-term fate of geologically stored CO2, mainly: the trapping mechanisms occurring in the storage reservoir, the influence of fluid-rock interactions on mechanical integrity of caprock and well vicinity, and also the modifications induced at the regional scale (brine displacement, fault reactivation, hydrogeology changes...). A comprehensive approach combining laboratory experiments, numerical modeling and natural analogue studies is developed to assess all the processes mentioned above. A collection of data has been generated from natural and industrial (oil industry) analogues on the fluid flow and mechanical properties, structure, and mineralogy of faults and fractures that could affect the long-term storage capacity of underground CO2 storage sites. To address geochemical trapping at reservoir scale, an experimental approach is developed using sandstone core materials in batch reactive mode with CO2 and impurities at reservoir pressure and temperature conditions. Three inter-related lines of laboratory experiments investigate the long-term evolution of the mechanical properties and sealing integrity of fractured and faulted caprocks using Opalinus clay of Mont Terri Gallery (Switzerland), an analogue for caprock well investigated in the past for nuclear waste disposal purpose. To evaluate the interactions between CO2 (and formation fluid) and the well environment (formation, cement, casing) and to assess the consequences of these interactions on the transport properties of well materials, a 1 to 1 scale experiment has been set in the Mont Terri Gallery Opalinus clay to reproduce classical well objects (cemented annulus, casing and cement plug) perforating caprock formations. An extensive program of numerical modeling is also developed to calibrate, to reproduce and to extrapolate the experimental results at longer time scales including uncertainty

  2. Brain MRI, Tc-99m HMPAO SPECT and F-18 FP-CIT PET/CT Findings in a Patient with Wilson Disease: A Case Report.

    PubMed

    Kim, Seungyoo; Song, In Uk; Chung, Yong An; Choi, Eun Kyung; Oh, Jin Kyoung

    2014-12-01

    A 34-year-old female had experienced head and hand tremors with a dystonic component for 8 months. Brain MRI showed T2 high signal intensity in the periaqueductal region, dorsal midbrain and dorsal upper pons. No abnormal uptake was noted on Tc-99m HMPAO SPECT or F-18 FP-CIT PET/CT. Wilson disease was diagnosed according to the 2008 consensus guideline from the American Association for the Study of Liver Disease and 2012 guideline from the European Association for the Study of the Liver. This case demonstrates T2 signal change in the basal ganglia, excluding the putamen, in a Wilson disease patient with relatively severe clinical findings, but normal Tc-99m HMPAO SPECT and F-18 FP-CIT PET/CT.

  3. Evaluating a LARC Expansion Program in 14 Sub-Saharan African Countries: A Service Delivery Model for Meeting FP2020 Goals.

    PubMed

    Ngo, Thoai D; Nuccio, Olivia; Pereira, Shreya K; Footman, Katharine; Reiss, Kate

    2016-05-06

    Objectives In many sub-Saharan African countries, the use of long-acting reversible contraceptives (LARCs) is low while unmet need for family planning (FP) remains high. We evaluated the effectiveness of a LARC access expansion initiative in reaching young, less educated, poor, and rural women. Methods Starting in 2008, Marie Stopes International (MSI) has implemented a cross-country expansion intervention to increase access to LARCs through static clinics, mobile outreach units, and social franchising of private sector providers. We analyzed routine service statistics for 2008-2014 and 2014 client exit interview data. Indicators of effectiveness were the number of LARCs provided and the percentages of LARC clients who had not used a modern contraceptive in the last 3 months ("adopters"); switched from a short-term contraceptive to a LARC ("switchers"); were aged <25; lived in extreme poverty; had not completed primary school; lived in rural areas; and reported satisfaction with their overall experience at the facility/site. Results Our annual LARC service distribution increased 1037 % (from 149,881 to over 1.7 million) over 2008-2014. Of 3816 LARC clients interviewed, 46 % were adopters and 46 % switchers; 37 % were aged 15-24, 42 % had not completed primary education, and 56 % lived in a rural location. Satisfaction with services received was rated 4.46 out of 5. Conclusions The effectiveness of the LARC expansion in these 14 sub-Saharan African FP programs demonstrates vast untapped potential for wider use of LARC methods, and suggests that this service delivery model is a plausible way to support FP 2020 goals of reaching those with an unmet need for FP.

  4. PEI grafted hyperbranched polymers with polyglycerol as a core for gene delivery.

    PubMed

    Zhang, Lei; Hu, Chao-Hua; Cheng, Si-Xue; Zhuo, Ren-Xi

    2010-04-01

    Hyperbranched polymers, PG6-PEI25k and PG6-PEI800, were synthesized through grafting branched polyethylenimines (PEIs) with molecular weights of 25 kDa and 800 Da to a polyglycerol core (PG6), respectively. The structure of the polymers was characterized by 1H NMR and FTIR. Through agarose gel electrophoresis retardation assay, PG6-PEI25k and PG6-PEI800 were demonstrated to have capability for DNA binding. PG6-PEI/DNA complexes with different weight ratios were characterized by TEM and particle size analysis. The activity of PG6-PEIs to mediate transfection of reporter plasmids pEGFP-C1 and pGL3-Luc was evaluated on 293T and HeLa cell lines. PG6-PEI25k and PG6-PEI800 showed enhanced levels in transgene expression and decreased cytotoxicities as compared with PEI25k and PEI800, respectively. The results indicated potential applications of PG6-PEIs for efficient gene delivery.

  5. The genome of Chelonid herpesvirus 5 harbors atypical genes

    USGS Publications Warehouse

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within thealphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of “atypical” DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis

  6. Multilaboratory evaluation of 15 bioassays for (eco)toxicity screening and hazard ranking of engineered nanomaterials: FP7 project NANOVALID

    PubMed Central

    Bondarenko, Olesja M.; Heinlaan, Margit; Sihtmäe, Mariliis; Ivask, Angela; Kurvet, Imbi; Joonas, Elise; Jemec, Anita; Mannerström, Marika; Heinonen, Tuula; Rekulapelly, Rohit; Singh, Shashi; Zou, Jing; Pyykkö, Ilmari; Drobne, Damjana; Kahru, Anne

    2016-01-01

    Abstract Within EU FP7 project NANOVALID, the (eco)toxicity of 7 well-characterized engineered nanomaterials (NMs) was evaluated by 15 bioassays in 4 laboratories. The highest tested nominal concentration of NMs was 100 mg/l. The panel of the bioassays yielded the following toxicity order: Ag > ZnO > CuO > TiO2 > MWCNTs > SiO2 > Au. Ag, ZnO and CuO proved very toxic in the majority of assays, assumingly due to dissolution. The latter was supported by the parallel analysis of the toxicity of respective soluble metal salts. The most sensitive tests/species were Daphnia magna (towards Ag NMs, 24-h EC50 = 0.003 mg Ag/l), algae Raphidocelis subcapitata (ZnO and CuO, 72-h EC50 = 0.14 mg Zn/l and 0.7 mg Cu/l, respectively) and murine fibroblasts BALB/3T3 (CuO, 48-h EC50 = 0.7 mg Cu/l). MWCNTs showed toxicity only towards rat alveolar macrophages (EC50 = 15.3 mg/l) assumingly due to high aspect ratio and TiO2 towards R. subcapitata (EC50 = 6.8 mg Ti/l) due to agglomeration of TiO2 and entrapment of algal cells. Finally, we constructed a decision tree to select the bioassays for hazard ranking of NMs. For NM testing, we recommend a multitrophic suite of 4 in vitro (eco)toxicity assays: 48-h D. magna immobilization (OECD202), 72-h R. subcapitata growth inhibition (OECD201), 30-min Vibrio fischeri bioluminescence inhibition (ISO2010) and 48-h murine fibroblast BALB/3T3 neutral red uptake in vitro (OECD129) representing crustaceans, algae, bacteria and mammalian cells, respectively. Notably, our results showed that these assays, standardized for toxicity evaluation of “regular” chemicals, proved efficient also for shortlisting of hazardous NMs. Additional assays are recommended for immunotoxicity evaluation of high aspect ratio NMs (such as MWCNTs). PMID:27259032

  7. Astrobiology Road Mapping (AstRoMap) - A project within FP7 of the European Commission: First results

    NASA Astrophysics Data System (ADS)

    Gomez-Gomez, Felipe; Capria, Maria Teresa; Palomba, Ernesto; Walter, Nicolas; Rettberg, Petra; Muller, Christian; Horneck, Gerda

    AstRoMap (Astrobiology and Planetary Exploration Road Mapping) is a funded project formulated in the 5th Call of the European Commission FP7 framework. The main objectives of the AstRoMap are: 1. Identify the main astrobiology issues to be addressed by Europe in the next decades in relation with space exploration 2. Identify potential mission concepts that would allow addressing these issues 3. Identify the technology developments required to enable these missions 4. Provide a prioritized roadmap integrating science and technology activities as well as ground-based approach 5. Map scientific knowledge related to astrobiology in Europe To reach those objectives, AstRoMap is executed within the following steps: 1. Community consultation. In order to map the European astrobiology landscape and to provide a collaborative networking platform for this community, the AstRoMap project hosts a database of scientists (European and beyond) interested in astrobiology and planetary exploration (see: http://www.astromap.eu/database.html). It reflects the demography and the research and teaching activities of the astrobiology community, as well as their professional profiles and involvement in astrobiology projects. Considering future aspects of astrobiology in Europe, the need for more astrobiology-dedicated funding programmes at the EU level, especially for cross-disciplinary groups, was stressed. This might eventually lead to the creation of a European laboratory of Astrobiology, or even of a European Astrobiology Institute. 2. Workshops organisation. On the basis of the feedbacks from the community consultation, the potential participants and interesting topics are being identified to take part in the following workshops: 1-. Origin of organic compounds, steps to life; 2. Physico-chemical boundary conditions for habitability 3. Biosignatures as facilitating life detection 4. Origin of the Solar system 3. Astrobiology road-mapping. Based on the results and major conclusions

  8. HCHO and NO2 MAXDOAS retrieval strategies harmonization: Recent results from the EU FP7 project QA4ECV

    NASA Astrophysics Data System (ADS)

    Pinardi, Gaia; Peters, Enno; Hendrick, François; Gielen, Clio; Van Roozendael, Michel; Richter, Andreas; Piters, Ankie; Wagner, Thomas; Wang, Yang; Drosoglou, Theano; Bais, Alkis; Wang, Shanshan; Saiz-Lopez, Alfonso

    2016-04-01

    During the last decade, it has been extensively demonstrated that MAXDOAS is a useful and reliable technique to retrieve integrated column amounts of tropospheric trace gases and aerosols, as well as information on their vertical distributions. Since it is based on optical remote-sensing in the UV-visible region like nadir backscatter space-borne sensors, MAXDOAS is also increasingly recognized as a reference technique for validating satellite nadir observations of air quality species like NO2 and HCHO. However, building up an harmonized network of MAXDOAS spectrometers requires significant efforts in terms of common retrieval strategies and best-practices definitions. Within the EU FP7 project QA4ECV (Quality Assurance for Essential Climate Variables; see http://www.qa4ecv.eu/), harmonization activities have been initiated focusing on the two main steps of the MAXDOAS retrieval, i.e. the DOAS spectral fit providing the so-called differential slant column densities (DSCDs) and the conversion of the retrieved DSCDs to vertical profiles and/or vertical column densities (VCDs). Regarding the first step, the DOAS settings for HCHO and NO2 are optimized through an intercomparison exercise of slant column retrievals involving 15 groups of the MAXDOAS community including the QA4ECV partners, and based on the radiance spectra acquired during the MAD-CAT campaign held in Mainz (Germany) in June-July 2013 (see http://joseba.mpch-mainz.mpg.de/mad_cat.htm). The harmonization of the second step is done through the application of an AMF (aim mass factor) look-up table (LUT) approach on the optimized NO2 and HCHO DSCDs. The AMF LUTs depend on entry parameters like SZA, elevation and relative azimuth angles, wavelength, boundary layer height, AOD, and surface albedo. The advantages and drawbacks of the LUT approach are illustrated at several stations through comparison of the derived VCDs with those retrieved using the more sophisticated Optimal-Estimation-based profiling method

  9. The ISS SOLAR payload data preservation in the frame of the PERICLES FP-7 project: metadata aspects.

    NASA Astrophysics Data System (ADS)

    Muller, Christian; Pandey, Praveen

    2016-04-01

    PERICLES (Promoting and Enhancing the Reuse of Information throughout the Content Lifecycle exploiting Evolving Semantics) is an FP7 project started on February 2013. It aims at preserving by design large and complex data sets. PERICLES is coordinated by King's College London, UK and its partners are University of Borås (Sweden), CERTH- ITI (Greece), DotSoft (Greece), Georg-August-Universität Göttingen (Germany), University of Liverpool (UK), Space Application Services (Belgium), XEROX France and University of Edinburgh (UK). Two additional partners provide the two case studies: Tate Gallery (UK) brings the digital art and media case study and B.USOC (Belgian Users Support and Operations Centre) brings the space science case study . PERICLES addresses the life-cycle of large and complex data sets in order to cater for the evolution of context of data sets and user communities, including groups unanticipated when the data was created. Semantics of data sets are thus also expected to evolve and the project includes elements which could address the reuse of data sets at periods where the data providers and even their institutions are not available any more. PERICLES uses the Linked Resources Model (LRM) which will be compared with the OAIS standard. In this study we present the space science case associated with PERICLES. B.USOC supports experiments on the International Space Station and is the curator of the collected data and operations history. B.USOC has chosen to analyse the SOLAR payload flying since 2008 on the ESA COLUMBUS module of the ISS as the PERICLES prime space science case. Solar observation data are prime candidates for long term data preservation as variabilities of the solar spectral irradiance have an influence on earth climate. The nature of the data to be preserved for the reuse of the current SOLAR series is much more extended than a simple set of time tagged tables of spectral irradiances, it is an important inventory of more than 50 classes

  10. Unification and Enhancement of Planetary Robotic Vision Ground Processing: The EC FP7 Project PRoVisG

    NASA Astrophysics Data System (ADS)

    Paar, G.

    2009-04-01

    At present, mainly the US have realized planetary space missions with essential robotics background. Joining institutions, companies and universities from different established groups in Europe and two relevant players from the US, the EC FP7 Project PRoVisG started in autumn 2008 to demonstrate the European ability of realizing high-level processing of robotic vision image products from the surface of planetary bodies. PRoVisG will build a unified European framework for Robotic Vision Ground Processing. State-of-art computer vision technology will be collected inside and outside Europe to better exploit the image data gathered during past, present and future robotic space missions to the Moon and the Planets. This will lead to a significant enhancement of the scientific, technologic and educational outcome of such missions. We report on the main PRoVisG objectives and the development status: - Past, present and future planetary robotic mission profiles are analysed in terms of existing solutions and requirements for vision processing - The generic processing chain is based on unified vision sensor descriptions and processing interfaces. Processing components available at the PRoVisG Consortium Partners will be completed by and combined with modules collected within the international computer vision community in the form of Announcements of Opportunity (AOs). - A Web GIS is developed to integrate the processing results obtained with data from planetary surfaces into the global planetary context. - Towards the end of the 39 month project period, PRoVisG will address the public by means of a final robotic field test in representative terrain. The European tax payers will be able to monitor the imaging and vision processing in a Mars - similar environment, thus getting an insight into the complexity and methods of processing, the potential and decision making of scientific exploitation of such data and not least the elegancy and beauty of the resulting image products

  11. Multiple-address radio systems, allocation of forty-eight 25 kHz channels in the 900 MHz range; and establishment of a new standard for frequency tolerance in the 952-960 MHz band: Federal Communications Commission. Third notice of proposed rulemaking.

    PubMed

    1981-02-04

    In response to a petition, the Commission proposes the reallocation of forty-eight 25 kHz channels in the 928-929 and 952-960 MHz band segments to the Private Operational-Fixed Microwave Service and the Domestic Public Land Mobile Radio Service for distribution automation and wide-area control and repeater operations, respectively. The spectrum from 928 to 929 MHz is presently reserved for Land Mobile. The 952-950 MHz band is currently allocated to the Private Operational-Fixed Microwave Service and the International Control Services.

  12. The Mechanism of E2F/P130 Mediated Repression and Its Potential Tumor Suppressor Function in Breast Cancer

    DTIC Science & Technology

    2000-07-01

    of genes that are necessary for a cell cycle progression into S phase. During times of cellular quiescence when expression of S phase genes would be...CtBP corepressor" was presented at the Keystone Symposia, Cancer, Cell Cycle and Therapeutics in January of 2000. 9 Conclusions As described by the...retinoblastoma- binding protein. Genomics 51, 351-358 (1998). 7. Xin, Y., and Baer, R. Nuclear localization and cell cycle -specific expression of CtIP, a

  13. EC FP6 Enviro-RISKS project outcomes in area of Earth and Space Science Informatics applications

    NASA Astrophysics Data System (ADS)

    Gordov, E. P.; Zakarin, E. A.

    2009-04-01

    exploit completely huge potential of web bases technologies. In particular, development of a region devoted web portal using approached suggested by the Open Geospatial Consortium has been started recently. The state of the art of the information-computational infrastructure in the targeted region is quite a step in the process of development of a distributed collaborative information-computational environment to support multidisciplinary investigations of Earth regional environment, especially those required meteorology, atmospheric pollution transport and climate modeling. Established in process of the Project carrying out cooperative links, new Partners initiatives, and gained expertise allow us to hope that this infrastructure rather soon will make significant input into understanding regional environmental processes in their relationships with Global Change. In particular, this infrastructure will play a role of the 'underlying mechanics' of the research work, leaving the earth scientists to concentrate on their investigations as well as providing the environment to make research results available and understandable to everyone. Additionally to the core FP6 Enviro-RISKS project (INCO-CT-2004-013427) support this activity was partially supported by SB RAS Integration Project 34, SB RAS Basic Program Project 4.5.2.2 and APN Project CBA2007-08NSY. Valuable input into the expert group work and elaborated outcomes of Profs. V. Lykosov and A. Starchenko, Drs. D. Belikov, , M. Korets, S. Kostrykin, B. Mirkarimova, I. Okladnikov, , A. Titov and A. Tridvornov is acknowledged.

  14. InSAR analysis of ground deformation over the Istanbul Area in the framework of the FP7 MARsite Project

    NASA Astrophysics Data System (ADS)

    Salvi, Stefano; Bonano, Manuela; Nobile, Adriano; Merryman Boncori, John Peter; Manzo, Mariarosaria; Solaro, Giuseppe; Moro, Marco; Saroli, Michele

    2015-04-01

    The FP7 MARsite project (New Directions in Seismic Hazard assessment through Focused Earth Observation in Marmara Supersite), is aiming at providing complete geodetic records of crustal deformation for major continental earthquake occurring in the Marmara region through repeated GPS, InSAR, gravity and seismological observations. One of the goals of the project is the long-term continuous geodetic monitoring of the crustal deformation affecting the Istanbul area using large archives of X-band satellite SAR data, made available through the GEO Supersites Initiative. To this aim, we processed the available SAR datasets by exploiting the multi-temporal and multi-scale InSAR techniques known as Small BAseline Subset (SBAS, Berardino et al., 2002) and StaMPS (Persistent Scatterer Interferometry, Hooper et al., 2007), which have the potential of providing new insights into the spatial and temporal patterns of the investigated phenomena. The results achieved in the first 2 years of the MARsite project over the megacity of Istanbul are presented. IREA-CNR applied the SBAS technique to a dataset of 101 SAR images acquired by the TerraSAR-X constellation over descending orbits, spanning the interval from November 2010 to August 2014. 312 differential interferograms were generated. INGV applied the StaMPS PSI approach (Hooper et al., 2007) to COSMO-SkyMed SAR images acquired from two different ascending tracks, consisting of 29 and 64 image strips for the Eastern and the Western tracks respectively, and covering the period between 2011 and 2013. Two sets of 28 and 63 differential interferograms were generated for the two tracks. The resulting ground velocity maps show several localized deformation sources in the urban area, due to subsidence and/or slope deformation. No clear long spatial wavelength tectonic patterns are visible, possibly due to the limited extent of the X-band satellite swaths (~40 km). We identified a displacement pattern related to the Istanbul airport

  15. Biscarbamate cross-linked low molecular weight PEI for delivering IL-1 receptor antagonist gene to synoviocytes for arthritis therapy.

    PubMed

    Xiang, Shengnan; Su, Jing; Tong, Haijun; Yang, Fei; Tong, Wenxue; Yuan, Weien; Wu, Fei; Wang, Chuandong; Jin, Tuo; Dai, Kerong; Zhang, Xiaoling

    2012-09-01

    Cytoxicity is an essential concern for polyethyleneimine 25 kDa (PEI 25 kDa), a widely reported, highly effective transfection agent used in gene delivery. In our recent experiments, Small molecular weight cross-linked poly(ethylene imine) by biscarbamate linkage (PEI-Bu) (Mn: 3278, Mw: 4289) can reduce target cell apoptosis induced by polycationic transfection, and has almost the same DNA condensation capability as PEI 25 kDa. PEI-Bu showed significantly higher activity and lower cytotoxicity than PEI 25 kDa in transfecting the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) gene to rat synoviocytes, an optimal target for arthritis treatment. The expression of IL-1Ra in synoviocytes then suppresses the expression of metalloproteases 13 (MMP13) gene, which is responsible for cartilage destruction regulated by IL-1β in arthritis. In conclusion, PEI-Bu is a promising tool for delivering IL-1Ra gene to synoviocytes for arthritis therapy.

  16. The Validation Activities of the APhoRISM EC 7FP Project, Aimed at Post Seismic Damage Mapping, Through a Combined Use of EOS and Ground Data

    NASA Astrophysics Data System (ADS)

    Devanthery, N.; Luzi, G.; Stramondo, S.; Bignami, C.; Pierdicca, N.; Wegmuller, U.; Romaniello, V.; Anniballe, R.; Piscini, A.; Albano, M.; Moro, M.; Crosetto, M.

    2016-08-01

    The estimate of damage after an earthquake using spaceborne remote sensing data is one of the main application of the change detection methodologies widely discussed in literature. APhoRISM - Advanced PRocedures for volcanIc and Seismic Monitoring is a collaborative European Commission project (FP7-SP ACE- 2013-1) addressing the development of innovative methods, using space and ground sensors to support the management and mitigation of the seismic and the volcanic risk. In this paper a novel approach aimed at damage assessment based on the use of a priori information derived by different sources in a preparedness phase is described and a preliminary validation is shown.

  17. Health monitoring of engine blades by using an in-line fiber-optic F-P strain sensor based on hollow-core photonic crystal fiber

    NASA Astrophysics Data System (ADS)

    Rao, Yunjiang; Fan, Yanen; Li, Hong; Zhu, Tao

    2009-10-01

    We present the application of a fiber-optic F-P strain sensor based on hollow-core photonic crystal fiber (HCPCF) to measurement of stress of engine blades. The blade stress under different rotating speeds is tested by detecting the reflected wavelength shift of the HCPCF sensor. The experimental results show that the strain has a quadratic relationship with the rotating speed, which agrees well with the theoretical analysis. As such a HCPCF sensor with short cavity length can stand high temperature of up to 600°C and has low temperature sensitivity, it would be possible to realize real-time health monitoring of engine blades during operation.

  18. High-molecular-weight polyethyleneimine conjuncted pluronic for gene transfer agents.

    PubMed

    Liang, Wenqing; Gong, Haiyang; Yin, Dongfeng; Lu, Shiyong; Fu, Qiang

    2011-01-01

    In order to enhance the gene delivery efficiency and decrease cytotoxicity of polyplexes, copolymers consisting of branched polyethyleneimine (PEI) 25 kDa grafted with Pluronic (F127, F68, P105) were successfully synthesized using a simple two-step procedure. The copolymers were tested for cytotoxicity and DNA condensation and complexation properties. Their polyplexes with plasmid DNA were characterized in terms of DNA size and surface charge and transfection efficiency. The complex sizes were below 300 nm, which implicated their potential for intracellular delivery. The Pluronic-g-PEI exhibited better condensation and complexation properties than PEI 25 kDa. The cytotoxicity of PEI was strongly reduced after copolymerization. The Pluronic-g-PEI showed lower cytotoxicity in three different cell lines (Hela, MCF-7, and HepG2) than PEI 25 kDa. pGL3-lus was used as a reporter gene, and the transfection efficiency was in vitro measured in HeLa cells. Compared with unmodified PEI 25 kDa Pluronic-g-PEI showed much higher transfection efficiency. These results demonstrate that polyplexes prepared using a combined strategy of surface crosslinking and grafted with Pluronic seem to provide promising properties as stable, high transfection efficiency vectors.

  19. Automatic on-line detection system design research on internal defects of metal materials based on optical fiber F-P sensing technology

    NASA Astrophysics Data System (ADS)

    Xia, Liu; Shan, Ning; Chao, Ban; Caoshan, Wang

    2016-10-01

    Metal materials have been used in aerospace and other industrial fields widely because of its excellent characteristics, so its internal defects detection is very important. Ultrasound technology is used widely in the fields of nondestructive detection because of its excellent characteristic. But the conventional detection instrument for ultrasound, which has shortcomings such as low intelligent level and long development cycles, limits its development. In this paper, the theory of ultrasound detection is analyzed. A computational method of the defects distributional position is given. The non-contact type optical fiber F-P interference cavity structure is designed and the length of origin cavity is given. The real-time on-line ultrasound detecting experiment devices for internal defects of metal materials is established based on the optical fiber F-P sensing system. The virtual instrument of automation ultrasound detection internal defects is developed based on LabVIEW software and the experimental study is carried out. The results show that this system can be used in internal defect real-time on-line locating of engineering structures effectively. This system has higher measurement precision. Relative error is 6.7%. It can be met the requirement of engineering practice. The system is characterized by simple operation, easy realization. The software has a friendly interface, good expansibility, and high intelligent level.

  20. Analysis of the 19F(p, α0)16O reaction at low energies and the spectroscopy of 20Ne

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Dell'Aquila, D.; Campajola, L.; Rosato, E.; Spadaccini, G.; Vigilante, M.

    2013-12-01

    The investigation of the 19F(p, α0) reaction at low bombarding energies allows the study of the spectroscopy of the 20Ne compound nucleus in an energy region where the existence of quartet excitations has been suggested in the literature. Moreover, this reaction plays a major role in the fourth branch of the CNO cycle since it is relevant for the correct description of the hydrogen burning of fluorine in stars. For these reasons, we decided to investigate the 19F(p, α0) reaction in the Ep ≃ 0.6-1 MeV energy range. The analysis of angular distributions and excitation functions allows one to improve the 20Ne spectroscopy in an excitation energy region where some ambiguities concerning Jπ assignments exist in the literature. In particular, the present data suggest a Jπ = 0+ assignment to the Ex = 13.642 MeV resonance. For this state, both partial and reduced widths for the α0 channel have been deduced. The trend of the astrophysical factor has been obtained from the integrated cross section. A comparison of the present results with data reported in the literature is also discussed.

  1. Reduction of mode partition noise of FP-LD by using Mach-Zehnder interferometer for RSOA-based DWDM applications.

    PubMed

    Yoo, Sang-Hwa; Moon, Sang-Rok; Kye, Myeonggyun; Lee, Chang-Hee

    2016-06-27

    We investigate reduction of mode partition noise of a spectrally sliced Fabry-Perot laser diode (FP-LD) for application to seeded DWDM systems. The proposed scheme for the noise reduction incorporates a fiber-based Mach-Zehnder interferometer (MZI) and a reflective semiconductor optical amplifier (RSOA). The MZI enables to reduce a relative intensity noise (RIN) more than 3 dB with better noise distributions. Experimental results of 10-Gb/s signal transmission exhibit a considerable bit-error-rate (BER) reduction by three orders of magnitude at the given received power. After the noise reduction, the FP-LD is applied to a 10-Gb/s DWDM system as a seed-light-source. In a local-seeding scheme, return-to-zero (RZ) and carrier-suppressed (CS)-RZ signal formats are compared as a function of transmission distance. Furthermore, a back-reflection induced impairment is evaluated in a remote-seeding scheme. We also count the number of useable channels to show the feasibility of DWDM transmission.

  2. Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss).

    PubMed

    Kutyrev, Ivan; Cleveland, Beth; Leeds, Timothy; Wiens, Gregory D

    2016-11-01

    Flavobacterium psychrophilum (Fp) is the causative agent of bacterial cold water disease (BCWD) which causes appreciable economic losses in rainbow trout aquaculture. We previously reported development of a genetic line, designated ARS-Fp-R that exhibits higher survival relative to a susceptible line, designated ARS-Fp-S, following either laboratory or natural on-farm challenge. The objectives of this study were to determine the temporal kinetics of gene expression between experimentally-challenged ARS-Fp-R and ARS-Fp-S fish and the correlation between gene expression and pathogen load. We developed a GeXP multiplex RT-PCR assay to simultaneously examine expression of immune-relevant genes, concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. Spleen tissue was sampled at 6 h, 24 h, 48 h and 144 h post-challenge and pathogen load quantified by qPCR. Transcript abundance of cytokine genes tnfa1, tnfa2, tnfa3, il1b1, il1b2, il11a; acute phase response genes saa and drtp1; and putative cytokine receptors il1r1-like-b, il1r2, tnfrsf1a, tnfrsf9, tnfrsf1a-like-b increased following challenge while the transcript abundance of il1r-like-1 and tnfrsf1a-like-a decreased compared to PBS-injected line-matched control fish. Principal component analysis identified transcript levels of genes il1r-like-1 and tnfrsf1a-like-a as exhibiting differential expression between genetic lines. In summary, Fp i.p. injection challenge elicited a proinflammatory cytokine gene expression response in the spleen, with ARS-Fp-R line fish exhibiting modestly higher basal expression levels of several putative cytokine receptors. This study furthers the understanding of the immune response following Fp challenge and differences in gene expression associated with selective breeding for disease resistance.

  3. Effect of long-term treatment with pramipexole or levodopa on presynaptic markers assessed by longitudinal [123I]FP-CIT SPECT and histochemistry.

    PubMed

    Depboylu, Candan; Maurer, Lukas; Matusch, Andreas; Hermanns, Guido; Windolph, Andrea; Béhé, Martin; Oertel, Wolfgang H; Höglinger, Günter U

    2013-10-01

    A previous clinical trial studied the effect of long-term treatment with levodopa (LD) or the dopamine agonist pramipexole (PPX) on disease progression in Parkinson disease using SPECT with the dopamine transporter (DAT)-radioligand [(123)I]β-CIT as surrogate marker. [(123)I]β-CIT binding declined to significantly lower levels in patients receiving LD compared to PPX. However, the interpretation of this difference as LD-induced neurotoxicity, PPX-induced neuroprotection/-regeneration, or only drug-induced regulatory changes of DAT-availability remained controversial. To address this question experimentally, we induced a subtotal lesion of the substantia nigra in mice by bilateral injection of the neurotoxin 6-hydroxydopamine. After 4 weeks, mice were treated for 20 weeks orally with LD (100mg/kg/day) or PPX (3mg/kg/day), or water (vehicle) only. The integrity of nigrostriatal projections was assessed by repeated [(123)I]FP-CIT SPECT in vivo and by immunostaining for DAT and the dopamine-synthesizing enzyme tyrosine hydroxylase (TH) after sacrifice. In sham-lesioned mice, we found that both LD and PPX treatment significantly decreased the striatal FP-CIT binding (LD: -21%; PPX: -14%) and TH-immunoreactivity (LD: -42%; PPX: -45%), but increased DAT-immunoreactivity (LD: +42%; PPX: +33%) compared to controls without dopaminergic treatment. In 6-hydroxydopamine-lesioned mice, however, neither LD nor PPX significantly influenced the stably reduced FP-CIT SPECT signal (LD: -66%; PPX: -66%; controls -66%), TH-immunoreactivity (LD: -70%; PPX: -72%; controls: -77%) and DAT-immunoreactivity (LD: -70%; PPX: -75%; controls: -75%) in the striatum or the number of TH-positive cells in the substantia nigra (LD: -88%; PPX: -88%; controls: -86%), compared to lesioned mice without dopaminergic treatment. In conclusion, chronic dopaminergic stimulation with LD or PPX induced similar adaptive presynaptic changes in healthy mice, but no discernible changes in severely lesioned mice

  4. H-H, C-H, and C-C NMR spin-spin coupling constants calculated by the FP-INDO method for aromatic hydrocarbons

    NASA Technical Reports Server (NTRS)

    Long, S. A. T.; Memory, J. D.

    1978-01-01

    The FP-INDO (finite perturbation-intermediate neglect of differential overlap) method is used to calculate the H-H, C-H, and C-C coupling constants in hertz for molecules of six different benzenoid hydrocarbons: benzene, naphthalene, biphenyl, anthracene, phenanthrene, and pyrene. The calculations are based on both the actual and the average molecular geometries. It is found that only the actual molecular geometries can always yield the correct relative order of values for the H-H coupling constants. For the calculated C-C coupling constants, as for the calculated C-H coupling constants, the signs are positive (negative) for an odd (even) number of bonds connecting the two nuclei. Agreements between the calculated and experimental values of the coupling constants for all six molecules are comparable to those reported previously for other molecules.

  5. Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise

    PubMed Central

    Jäger, Ralf; Purpura, Martin; Stone, Jason D.; Turner, Stephanie M.; Anzalone, Anthony J.; Eimerbrink, Micah J.; Pane, Marco; Amoruso, Angela; Rowlands, David S.; Oliver, Jonathan M.

    2016-01-01

    Probiotics have immunomodulatory effects. However, little is known about the potential benefit of probiotics on the inflammation subsequent to strenuous exercise. In a double-blind, randomized, placebo controlled, crossover design separated by a 21-day washout, 15 healthy resistance-trained men ingested an encapsulated probiotic Streptococcus (S.) thermophilus FP4 and Bifidobacterium (B.) breve BR03 at 5 bn live cells (AFU) concentration each, or a placebo, daily for 3 weeks prior to muscle-damaging exercise (ClinicalTrials.gov NCT02520583). Isometric strength, muscle soreness, range of motion and girth, and blood interleukin-6 (IL-6) and creatine kinase (CK) concentrations were measured from pre- to 72 h post-exercise. Statistical analysis was via mixed models and magnitude-based inference to the standardized difference. Probiotic supplementation resulted in an overall decrease in circulating IL-6, which was sustained to 48 h post-exercise. In addition, probiotic supplementation likely enhanced isometric average peak torque production at 24 to 72 h into the recovery period following exercise (probiotic–placebo point effect ±90% CI: 24 h, 11% ± 7%; 48 h, 12% ± 18%; 72 h, 8% ± 8%). Probiotics also likely moderately increased resting arm angle at 24 h (2.4% ± 2.0%) and 48 h (1.9% ± 1.9%) following exercise, but effects on soreness and flexed arm angle and CK were unclear. These data suggest that dietary supplementation with probiotic strains S. thermophilus FP4 and B. breve BR03 attenuates performance decrements and muscle tension in the days following muscle-damaging exercise. PMID:27754427

  6. Bivariate distributions in statistical spectroscopy studies: IV. Interacting particle Gamow-Teller strength densities and β-decay rates of fp-shell nuclei for presupernova stars

    NASA Astrophysics Data System (ADS)

    Kota, V. K. B.; Majumdar, D.

    1995-12-01

    A method to calculate temperature dependent β-decay rates is developed by writing the expression for the rates explicitly in terms of bivariate GT strength densities ( I {/O H } ( GT)) for a given hamiltonian H=h+V and state densities of the parent nucleus besides having the usual phase space factors. The theory developed in the preceding paper (III) for constructing NIP strength densities is applied for generating I {/O h } ( GT) and then I {/O H } ( GT) is constructed using the bivariate convolution form I {/O H } ( GT)=Σ S I {/O(GT) h,S }⊗ρ{/O(GT) V, S }; BIV-G . The spreading bivariate Gaussian ρ{/O(GT) V}; BIV-G, for fp-shell nuclei, is constructed by assuming that the marginal centroids are zero, the marginal variances are same as the corresponding state density variances and fixing the bivariate correlation coefficientbar ζ using experimental β-decay half lifes. With the deduced values ofbar ζ bar ζ ˜ 0.67, β-S-decay rates for61,62Fe and62 64Co isotopes are calculated at presupernova matter densities ρ=107 109 gm/cc, temperatures T=(3 5)×109 ∘K and electron fractions Ye=0.43 0.5. The convolution form for I {O(GT)/ H } led to a simple expression for calculating GT non-energy weighted sum rule strength and it describes (within 10%) the shell model results of fp-shell nuclei.

  7. Genes and Gene Therapy

    MedlinePlus

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  8. The planetary hydraulics analysis based on a multi-resolution stereo DTMs and LISFLOOD-FP model: Case study in Mars

    NASA Astrophysics Data System (ADS)

    Kim, J.; Schumann, G.; Neal, J. C.; Lin, S.

    2013-12-01

    Earth is the only planet possessing an active hydrological system based on H2O circulation. However, after Mariner 9 discovered fluvial channels on Mars with similar features to Earth, it became clear that some solid planets and satellites once had water flows or pseudo hydrological systems of other liquids. After liquid water was identified as the agent of ancient martian fluvial activities, the valley and channels on the martian surface were investigated by a number of remote sensing and in-suit measurements. Among all available data sets, the stereo DTM and ortho from various successful orbital sensor, such as High Resolution Stereo Camera (HRSC), Context Camera (CTX), and High Resolution Imaging Science Experiment (HiRISE), are being most widely used to trace the origin and consequences of martian hydrological channels. However, geomorphological analysis, with stereo DTM and ortho images over fluvial areas, has some limitations, and so a quantitative modeling method utilizing various spatial resolution DTMs is required. Thus in this study we tested the application of hydraulics analysis with multi-resolution martian DTMs, constructed in line with Kim and Muller's (2009) approach. An advanced LISFLOOD-FP model (Bates et al., 2010), which simulates in-channel dynamic wave behavior by solving 2D shallow water equations without advection, was introduced to conduct a high accuracy simulation together with 150-1.2m DTMs over test sites including Athabasca and Bahram valles. For application to a martian surface, technically the acceleration of gravity in LISFLOOD-FP was reduced to the martian value of 3.71 m s-2 and the Manning's n value (friction), the only free parameter in the model, was adjusted for martian gravity by scaling it. The approach employing multi-resolution stereo DTMs and LISFLOOD-FP was superior compared with the other research cases using a single DTM source for hydraulics analysis. HRSC DTMs, covering 50-150m resolutions was used to trace rough

  9. Effect of fish oil on lateral mobility of prostaglandin F2α (FP) receptors and spatial distribution of lipid microdomains in bovine luteal cell plasma membrane in vitro.

    PubMed

    Plewes, M R; Burns, P D; Graham, P E; Hyslop, R M; Barisas, B G

    2017-01-01

    Lipid microdomains are ordered regions on the plasma membrane of cells, rich in cholesterol and sphingolipids, ranging in size from 10 to 200 nm in diameter. These lipid-ordered domains may serve as platforms to facilitate colocalization of intracellular signaling proteins during agonist-induced signal transduction. It is hypothesized that fish oil will disrupt the lipid microdomains, increasing spatial distribution of these lipid-ordered domains and lateral mobility of the prostaglandin (PG) F2α (FP) receptors in bovine luteal cells. The objectives of this study were to examine the effects of fish oil on (1) the spatial distribution of lipid microdomains, (2) lateral mobility of FP receptors, and (3) lateral mobility of FP receptors in the presence of PGF2α on the plasma membrane of bovine luteal cells in vitro. Bovine ovaries were obtained from a local abattoir and corpora lutea were digested using collagenase. In experiment 1, lipid microdomains were labeled using cholera toxin subunit B Alexa Fluor 555. Domains were detected as distinct patches on the plasma membrane of mixed luteal cells. Fish oil treatment decreased fluorescent intensity in a dose-dependent manner (P < 0.01). In experiment 2, single particle tracking was used to examine the effects of fish oil treatment on lateral mobility of FP receptors. Fish oil treatment increased microdiffusion and macrodiffusion coefficients of FP receptors as compared to control cells (P < 0.05). In addition, compartment diameters of domains were larger, and residence times were reduced for receptors in fish oil-treated cells (P < 0.05). In experiment 3, single particle tracking was used to determine the effects of PGF2α on lateral mobility of FP receptors and influence of fish oil treatment. Lateral mobility of receptors was decreased within 5 min following the addition of ligand for control cells (P < 0.05). However, lateral mobility of receptors was unaffected by addition of ligand for fish oil-treated cells

  10. Intranasal Dopamine Reduces In Vivo [123I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

    PubMed Central

    de Souza Silva, Maria A.; Mattern, Claudia; Decheva, Cvetana; Huston, Joseph P.; Sadile, Adolfo G.; Beu, Markus; Müller, H.-W.; Nikolaus, Susanne

    2016-01-01

    Purpose: Dopamine (DA), which does not cross the blood-brain barrier, has central and behavioral effects when administered via the nasal route. Neither the mechanisms of central action of intranasal dopamine (IN-DA), nor its mechanisms of diffusion and transport into the brain are well understood. We here examined whether IN-DA application influences dopamine transporter (DAT) binding in the dorsal striatum and assessed the extent of binding in relation to motor and exploratory behaviors. We hypothesized that, based on the finding of increased extracellular DA in the striatum induced by application of IN-DA, binding of [123I]FP-CIT to the DAT should be decreased due to competition at the receptor. Methods: Rats were administered 3 mg/kg IN-DA and vehicle (VEH), with IN-DA injection either preceding or following VEH. Then motor and exploratory behaviors (traveled distance, velocity, center time, sitting, rearing, head-shoulder motility, grooming) were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. DAT binding after IN-DA and VEH was measured with small animal SPECT 2 h following administration of the radioligand. Results: (1) After IN-DA application, striatal DAT binding was significantly lower as compared to VEH, indicating that the nasally delivered DA had central action and increased DA levels comparable to that found previously with L-DOPA administration; and (2) DAT binding in response to intranasal VEH was lower when IN-DA application preceded VEH treatment. This finding is suggestive of Pavlovian conditioning of DA at the level of the DAT, since the DA treatment modified (decreased) the binding in response to the subsequent VEH treatment. VEH treatment also reduced motor and exploratory behaviors more when applied before, as compared to when it followed IN-DA application, also indicative of behavioral Pavlovian conditioning akin to that found upon application of various psychostimulant drugs. Conclusions: The results: (a

  11. Exploring (NH2F)2, H2FP:NFH2, and (PH2F)2 potential surfaces: hydrogen bonds or pnicogen bonds?

    PubMed

    Alkorta, Ibon; Sánchez-Sanz, Goar; Elguero, José; Del Bene, Janet E

    2013-01-10

    An ab initio MP2/aug'-cc-pVTZ study has been carried out to identify local minima on the (NH(2)F)(2), H(2)FP:NFH(2), and (PH(2)F)(2) potential surfaces, to characterize the types of interactions which stabilize the complexes found at these minima, and to evaluate their binding energies. With one exception, (NH(2)F)(2) complexes are stabilized by N-H···N or N-H···F hydrogen bonds. Only one complex, that with the smallest binding energy, has a pnicogen N···N bond. In contrast, (PH(2)F)(2) complexes are stabilized by P···P or P···F pnicogen bonds or by an antiparallel alignment of the dipole moment vectors of the two monomers, but not by hydrogen bonds. The most stable complex has an F-P···P-F alignment which approaches linearity. Both hydrogen-bonded and pnicogen-bonded complexes exist on the H(2)FP:NFH(2) surface, with the most stable being the pnicogen-bonded complex with F-P···N-F approaching a linear arrangement. Charge transfer transitions from a lone pair on a P, N, or F atom in one molecule to an antibonding σ* orbital of the other stabilize these complexes. These transitions are most important for complexes with pnicogen bonds. Although net charge transfer occurs in complexes in which the two monomers are inequivalent, charges on N and P do not correlate with N and P absolute chemical shieldings. Rather, these shieldings also reflect charge distributions and overall bonding patterns. EOM-CCSD two-bond spin-spin coupling constants (2h)J(X-Y) across X-H···Y hydrogen bonds tend to be small, due in part to the nonlinearity of many of the hydrogen bonds. (1p)J values across a particular kind of pnicogen bond are relatively large and vary significantly but do not correlate with corresponding distances.

  12. Broadband finite-pulse radio-frequency-driven recoupling (fp-RFDR) with (XY8)4(1) super-cycling for homo-nuclear correlations in very high magnetic fields at fast and ultra-fast MAS frequencies.

    PubMed

    Shen, Ming; Hu, Bingwen; Lafon, Oliver; Trébosc, Julien; Chen, Qun; Amoureux, Jean-Paul

    2012-10-01

    We demonstrate that inter-residue (13)C-(13)C proximities (of about 380 pm) in uniformly (13)C-labeled proteins can be probed by applying robust first-order recoupling during several milliseconds in single-quantum single-quantum dipolar homo-nuclear correlation (SQ-SQ D-HOMCOR) 2D experiments. We show that the intensity of medium-range homo-nuclear correlations in these experiments is enhanced using broadband first-order finite-pulse radio-frequency-driven recoupling (fp-RFDR) NMR sequence with a nested (XY8)4(1) super-cycling. The robustness and the efficiency of the fp-RFDR-(XY8)4(1) method is demonstrated at high magnetic field (21.1T) and high Magic-Angle Spinning (MAS) speeds (up to 60 kHz). The introduced super-cycling, formed by combining phase inversion and a global four-quantum phase cycle, improves the robustness of fp-RFDR to (i) chemical shift anisotropy (CSA), (ii) spread in isotropic chemical shifts, (iii) rf-inhomogeneity and (iv) hetero-nuclear dipolar couplings for long recoupling times. We show that fp-RFDR-(XY8)4(1) is efficient sans (1)H decoupling, which is beneficial for temperature-sensitive biomolecules. The efficiency and the robustness of fp-RFDR-(XY8)4(1) is investigated by spin dynamics numerical simulations as well as solid-state NMR experiments on [U-(13)C]-L-histidine·HCl, a tetra-peptide (Fmoc-[U-(13)C,(15)N]-Val-[U-(13)C,(15)N]-Ala-[U-(13)C,(15)N]-Phe-Gly-t-Boc) and Al(PO(3))(3).

  13. Identification of the Core Set of Carbon-Associated Genes in a Bioenergy Grassland Soil

    PubMed Central

    Howe, Adina; Yang, Fan; Williams, Ryan J.; Meyer, Folker; Hofmockel, Kirsten S.

    2016-01-01

    Despite the central role of soil microbial communities in global carbon (C) cycling, little is known about soil microbial community structure and even less about their metabolic pathways. Efforts to characterize soil communities often focus on identifying differences in gene content across environmental gradients, but an alternative question is what genes are similar in soils. These genes may indicate critical species or potential functions that are required in all soils. Here we identified the “core” set of C cycling sequences widely present in multiple soil metagenomes from a fertilized prairie (FP). Of 226,887 sequences associated with known enzymes involved in the synthesis, metabolism, and transport of carbohydrates, 843 were identified to be consistently prevalent across four replicate soil metagenomes. This core metagenome was functionally and taxonomically diverse, representing five enzyme classes and 99 enzyme families within the CAZy database. Though it only comprised 0.4% of all CAZy-associated genes identified in FP metagenomes, the core was found to be comprised of functions similar to those within cumulative soils. The FP CAZy-associated core sequences were present in multiple publicly available soil metagenomes and most similar to soils sharing geographic proximity. In soil ecosystems, where high diversity remains a key challenge for metagenomic investigations, these core genes represent a subset of critical functions necessary for carbohydrate metabolism, which can be targeted to evaluate important C fluxes in these and other similar soils. PMID:27855202

  14. Arginine-conjugated polypropylenimine dendrimer as a non-toxic and efficient gene delivery carrier.

    PubMed

    Kim, Tae-Il; Baek, Jung-Un; Zhe Bai, Cheng; Park, Jong-Sang

    2007-04-01

    We synthesized arginine-conjugated polypropylenimine dendrimer G2 (DAB-8), PPI2-R for gene delivery systems. Synthesized PPI2-R could retard plasmid DNA at a weight ratio of 4 completely and PPI2-R polyplexes showed a fluorescence of less than 10% over a charge ratio of 2 by PicoGreen reagent assay, suggesting its good DNA condensing ability. The size of PPI2-R polyplex was measured to about 200nm at a charge ratio of 150. PPI2-R displayed 80-90% cell viability at even a 150microg/mL concentration. Transfection efficiency of PPI2-R was found to be high comparable to that of PEI25kD and to be 8-214 times higher than that of unmodified PPI2 on HeLa and 293 cells. Moreover, PPI2-R showed 4 times higher transfection efficiency than PEI25kD, treating with 10microg pDNA because of its low cytotoxicity on HeLa cells. Finally, PPI2-R showed a transfection efficiency 2-3 times higher than PEI25kD on HUVECs, showing its potency as a gene delivery carrier for primary cells. These results demonstrate that arginine-conjugation of PPI2 is successful in developing a low toxic and highly transfection efficient gene delivery carrier.

  15. The fast-spectrum transmutation experimental facility FASTEF: Main design achievements (Part 1: Core and primary system) within the FP7-CDT collaborative project of the European Commission

    SciTech Connect

    De Bruyn, D.; Fernandez, R.; Mansani, L.; Woaye-Hune, A.; Sarotto, M.; Bubelis, E.

    2012-07-01

    MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) is the flexible experimental accelerator-driven system (ADS) in development at SCK CEN in replacement of its material testing reactor BR2. SCK CEN in association with 17 European partners from industry, research centres and academia, responded to the FP7 (Seventh Framework Programme) call from the European Commission to establish a Central Design Team (CDT) for the design of a Fast Spectrum Transmutation Experimental Facility (FASTEF) able to demonstrate efficient transmutation and associated technology through a system working in subcritical and/or critical mode. The project has started on April 01, 2009 for a period of three years. In this paper, we present the latest configuration of the reactor core and primary system. The FASTEF facility has evolved quite a lot since the intermediate reporting done at the ICAPP'10 and ICAPP'11 conferences 1 2. If it remains a small-scale facility, the core power amounts now up to 100 MWth in critical mode. In a companion paper 3, we present the concept of the reactor building and the plant layout. (authors)

  16. Identification and characterization of the ocular hypotensive efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist, and AL-6598, a DP prostaglandin receptor agonist.

    PubMed

    Hellberg, Mark R; McLaughlin, Marsha A; Sharif, Naj A; DeSantis, Louis; Dean, Tom R; Kyba, Evan P; Bishop, John E; Klimko, Peter G; Zinke, Paul W; Selliah, Robert D; Barnes, George; DeFaller, Joseph; Kothe, Angela; Landry, Theresa; Sullivan, E Kenneth; Andrew, Russell; Davis, Alberta A; Silver, Lewis; Bergamini, Michael V W; Robertson, Stella; Weiner, Alan L; Sallee, Verney L

    2002-08-01

    The structure-activity studies that led to the identification of travoprost, a highly selective and potent FP prostaglandin analog, and AL-6598, a DP prostaglandin analog, are detailed. In both series, the 1-alcohol analogs are very effective and are thought to be acting as prodrugs for the biologically active carboxylic acids. The efficacy of amide prodrugs depends on the degree of substitution and the size of the substituents. Selected compounds are profiled in vitro and in vivo preclinically. Clinical studies show that travoprost 0.004% (isopropyl ester) provided intraocular pressure control superior to timolol 0.5% when used as monotherapy in patients with open-angle glaucoma or ocular hypertension. In clinical studies, AL-6598 0.01% provided a sustained intraocular pressure reduction with q.d. application; b.i.d. provided greater intraocular pressure control. The acute and, apparently, conjunctival hyperemia associated with topical ocular AL-6598 can be attenuated while maintaining intraocular pressure-lowering efficacy by formulating with brimonidine.

  17. Tropical Forest Remote Sensing Services for the Democratic Republic of Congo inside the EU FP7 ReCover Project (Final Results 2000-2012)

    NASA Astrophysics Data System (ADS)

    Haarpaintner, J.; de la Fuente Blanco, D.; Enssle, F.; Datta, P.; Mazinga, A.; Singa, C.; Mane, L.

    2015-04-01

    'ReCover' was a 3-year EU-FP7 project (Nov. 2010 - Dec. 2013), aiming to develop and improve science based remote sensing services to support tropical forest management and activities to reduce emission from deforestation and forest degradation (REDD) in the tropical region (Hame et al., 2012). This is an overview of the final ReCover service delivery of 2000-2012 single-year optical (Landsat, ALOS AVNIR-2, RapidEye) and C-and L-band SAR (Envisat ASAR and ALOS Palsar, respectively) image mosaics, their derived forest/non-forest maps, a multi-sensor forest change map (2000-2010) and a biomass map (based on 2003-2009 ICESat GLAS) o he user of he De ocr ic Repub ic of Congo DRC), he Observatoir Satellitale des Fore s d'Afrique Cen r e OSFAC). The results are an improvement from a first iteration service delivery in 2012 after a critical review and validation process by both, the user and service providers, further method development and research, like a prior statistical data analysis considering temporal/seasonal variability, improved data pre-processing, and through the use of ground reference data collected in March 2013 for classification training. Validation with Kompsat-2 VHR data for the 2010 forest/non-forest maps revealed accuracies of 87% and 88% for optical and radar sensors, respectively.

  18. Characterization of the native form and the carboxy-terminally truncated halotolerant form of α-amylases from Bacillus subtilis strain FP-133.

    PubMed

    Takenaka, Shinji; Miyatake, Ayaka; Tanaka, Kosei; Kuntiya, Ampin; Techapun, Charin; Leksawasdi, Noppol; Seesuriyachan, Phisit; Chaiyaso, Thanongsak; Watanabe, Masanori; Yoshida, Ken-ichi

    2015-06-01

    Two amylases, amylase I and amylase II from Bacillus subtilis strain FP-133, were purified to homogeneity and characterized. Their stabilities toward temperature, pH, and organic solvents, and their substrate specificities toward polysaccharides and oligosaccharides were similar. Under moderately high salt conditions, both amylases were more stable than commercial B. licheniformis amylase, and amylase I retained higher amylase activity than amylase II. The N-terminal amino acid sequence, genomic southern blot analysis, and MALDI-TOFF-MS analysis indicated that the halotolerant amylase I was produced by limited carboxy-terminal truncation of the amylase II peptide. The deduced amino acid sequence of amylase II was >95% identical to that of previously reported B. subtilis α-amylases, but their carboxy-terminal truncation points differed. Three recombinant amylases--full-length amylase corresponding to amylase II, an artificially truncated amylase corresponding to amylase I, and an amylase with a larger artificial C-terminal truncation--were expressed in B. subtilis. The artificially truncated recombinant amylases had the same high amylase activity as amylase I under moderately high salt conditions. Sequence comparisons indicated that an increased ratio of Asp/Glu residues in the enzyme may be one factor responsible for increasing halotolerance.

  19. Modelling the flood-risk extent using LISFLOOD-FP in a complex watershed: case study of Mundeni Aru River Basin, Sri Lanka

    NASA Astrophysics Data System (ADS)

    Amarnath, G.; Umer, Y. M.; Alahacoon, N.; Inada, Y.

    2015-06-01

    Flood management is adopting a more risk-based approach, whereby flood risk is the product of the probability and consequences of flooding. Two-dimensional flood inundation modeling is a widely used tool to aid flood-risk management. The aim of this study is to develop a flood inundation model that uses historical flow data to produce flood-risk maps, which will help to identify flood protection measures in the rural areas of Sri Lanka. The LISFLOOD-FP model was developed at the basin scale using available historical data, and also through coupling with a hydrological modelling system, to map the inundation extent and depth. Results from the flood inundation model were evaluated using Synthetic Aperture Radar (SAR) images to assess product accuracy. The impacts of flooding on agriculture and livelihoods were analyzed to assess the flood risks. It was identified that most of the areas under paddy cultivation that were located near the middle and downstream part of the river basin are more susceptible to flood risks. This paper also proposes potential countermeasures for future natural disasters to prevent and mitigate possible damages.

  20. Electronic structure and optical properties of Sr{sub 2}SnO{sub 4} studied with FP-LAPW method in density functional theory

    SciTech Connect

    Prijamboedi, B. Umar, S.; Failamani, F.

    2015-04-16

    Oxide material of Sr{sub 2}SnO{sub 4}, when it is doped with Ti becomes a phosphor material that can emit intense blue light at room temperature. It is important to study the electronic structure of this material in order to determine the optical processes that occur in Ti-doped Sr{sub 2}SnO{sub 4}. Electronic structure and optical properties of Sr{sub 2}SnO{sub 4} is studied using density functional theory framework with full potential linearized augmented plane waves plus local orbitals (FP-LAPW+lo) method. We use modified Becke-Johnson (mBJ) exchange-correlation potential to calculate the energy gap. Our calculation showed that Sr{sub 2}SnO{sub 4} has indirect band gap with band gap energy of around 4.2 eV. The experimental absorption spectra of Sr{sub 2}SnO{sub 4} indicated that this oxide has band gap of around 4.6 eV and it is closer to the results given by mBJ exchange-correlation potential. We also studied other optical properties of Sr{sub 2}SnO{sub 4} and it is found in agreement with the experimental results.

  1. FP-LAPW calculations of the elastic, electronic and thermoelectric properties of the filled skutterudite CeRu{sub 4}Sb{sub 12}

    SciTech Connect

    Shankar, A.; Rai, D.P.; Chettri, Sandeep; Khenata, R.; Thapa, R.K.

    2016-08-15

    We have investigated the electronic structure, elastic and thermoelectric properties of the filled skutterudite CeRu{sub 4}Sb{sub 12} using the density functional theory (DFT). The full potential linearized augmented plane wave (FP-LAPW) method within a framework of the generalized gradient approximation (GGA) approach is used to perform the calculations presented here. The electronic structure calculation suggests an indirect band gap semiconducting nature of the material with energy band gap of 0.08 eV. The analysis of the elastic constants at relaxed positions reveals the ductile nature of the sample material with covalent contribution in the inter-atomic bonding. The narrow band gap semiconducting nature with high value of Seebeck coefficient suggests the possibility of the thermoelectric application of the material. The analysis of the thermal transport properties confirms the result obtained from the energy band structure of the material with high thermopower and dimensionless figure of merit 0.19 at room temperature.

  2. Analysis of the chemical behavior of iodine in the suppression tank of the LOFT facility during experiment LP-FP-2 with IODE and IMPAIR-2/M

    SciTech Connect

    Herranz, L.E.; Polo, J. . Centro de Investigaciones Energeticas Medioambientales y Tecnologicas)

    1994-05-01

    The significance of iodine for source term quantification has been studied by investigating its chemical behavior under the prototypical conditions of a hypothetical severe accident within the containment. As a result, some computer codes were developed and their validation is currently under way. The loss-of-fluid test (LOFT) program was one of the most relevant research projects in the area of nuclear safety. Its last experiment, LP-FP-2, simulated a V-sequence. A great deal of information was recorded on the fission product release, transport, and deposition. A theoretical approach to the chemical behavior of iodine in the blowdown suppression tank (BST) of the LOFT facility was attempted with the IODE and IMPAIR-2/M codes. The comparison of the predictions with the existing experimental data led to the conclusion that the BST system behaved as a low-volatility system, with most of the iodine in the form of the soluble nonvolatile species iodide. Only a partial conversion to volatile molecular iodine was observed due to the presence of radiation. However, the intensity of the [gamma] field was so weak that this transformation was not quantitatively meaningful.

  3. Dynamic Assessment of Seismic Risk (DASR) by Multi-parametric Observations: Preliminary Results of PRIME experiment within the PRE-EARTHQUAKES EU-FP7 Project

    NASA Astrophysics Data System (ADS)

    Tramutoli, V.; Inan, S.; Jakowski, N.; Pulinets, S. A.; Romanov, A.; Filizzola, C.; Shagimuratov, I.; Pergola, N.; Ouzounov, D. P.; Papadopoulos, G. A.; Parrot, M.; Genzano, N.; Lisi, M.; Alparlsan, E.; Wilken, V.; Tsybukia, K.; Romanov, A.; Paciello, R.; Zakharenkova, I.; Romano, G.

    2012-12-01

    The integration of different observations together with the refinement of data analysis methods, is generally expected to improve our present knowledge of preparatory phases of earthquakes and of their possible precursors. This is also the main goal of PRE-EARTHQUAKES (Processing Russian and European EARTH observations for earthQUAKE precursors Studies) the FP7 Project which, to this aim, committed together, different international expertise and observational capabilities, in the last 2 years. In the learning phase of the project, different parameters (e.g. thermal anomalies, total electron content, radon concentration, etc.), measured from ground and satellite systems and analyzed by using different data analysis approaches, have been studied for selected geographic areas and specific seismic events in the past. Since July 2012 the PRIME (PRE-EARTHQUAKES Real-time Integration and Monitoring Experiment) started attempting to perform, on the base of independent observations collected and integrated in real-time through the PEG (PRE-EARTHQUAKES Geo-portal), a Dynamic Assessment of Seismic Risk (DASR) on selected geographic areas of Europe (Italy-Greece-Turkey) and Asia (Kamchatka, Sakhalin, Japan). In this paper, results so far achieved as well as the potential and opportunities they open for a worldwide Earthquake Observation System (EQuOS) - as a dedicated component of GEOSS (Global Earth Observation System of Systems) - will be presented.

  4. EU-FP7-iMARS: analysis of Mars multi-resolution images using auto-coregistration, data mining and crowd source techniques

    NASA Astrophysics Data System (ADS)

    Ivanov, Anton; Muller, Jan-Peter; Tao, Yu; Kim, Jung-Rack; Gwinner, Klaus; Van Gasselt, Stephan; Morley, Jeremy; Houghton, Robert; Bamford, Steven; Sidiropoulos, Panagiotis; Fanara, Lida; Waenlish, Marita; Walter, Sebastian; Steinkert, Ralf; Schreiner, Bjorn; Cantini, Federico; Wardlaw, Jessica; Sprinks, James; Giordano, Michele; Marsh, Stuart

    2016-07-01

    Understanding planetary atmosphere-surface and extra-terrestrial-surface formation processes within our Solar System is one of the fundamental goals of planetary science research. There has been a revolution in planetary surface observations over the last 15 years, especially in 3D imaging of surface shape. This has led to the ability to be able to overlay different epochs back in time to the mid 1970s, to examine time-varying changes, such as the recent discovery of mass movement, tracking inter-year seasonal changes and looking for occurrences of fresh craters. Within the EU FP-7 iMars project, UCL have developed a fully automated multi-resolution DTM processing chain, called the Co-registration ASP-Gotcha Optimised (CASP-GO), based on the open source NASA Ames Stereo Pipeline (ASP), which is being applied to the production of planetwide DTMs and ORIs (OrthoRectified Images) from CTX and HiRISE. Alongside the production of individual strip CTX & HiRISE DTMs & ORIs, DLR have processed HRSC mosaics of ORIs and DTMs for complete areas in a consistent manner using photogrammetric bundle block adjustment techniques. A novel automated co-registration and orthorectification chain has been developed and is being applied to level-1 EDR images taken by the 4 NASA orbital cameras since 1976 using the HRSC map products (both mosaics and orbital strips) as a map-base. The project has also included Mars Radar profiles from Mars Express and Mars Reconnaissance Orbiter missions. A webGIS has been developed for displaying this time sequence of imagery and a demonstration will be shown applied to one of the map-sheets. Automated quality control techniques are applied to screen for suitable images and these are extended to detect temporal changes in features on the surface such as mass movements, streaks, spiders, impact craters, CO2 geysers and Swiss Cheese terrain. These data mining techniques are then being employed within a citizen science project within the Zooniverse family

  5. Calibration of channel depth and friction parameters in the LISFLOOD-FP hydraulic model using medium-resolution SAR data and identifiability techniques

    NASA Astrophysics Data System (ADS)

    Wood, Melissa; Hostache, Renaud; Neal, Jeffrey; Wagener, Thorsten; Giustarini, Laura; Chini, Marco; Corato, Giovani; Matgen, Patrick; Bates, Paul

    2016-12-01

    Single satellite synthetic aperture radar (SAR) data are now regularly used to estimate hydraulic model parameters such as channel roughness, depth and water slope. However, despite channel geometry being critical to the application of hydraulic models and poorly known a priori, it is not frequently the object of calibration. This paper presents a unique method to simultaneously calibrate the bankfull channel depth and channel roughness parameters within a 2-D LISFLOOD-FP hydraulic model using an archive of moderate-resolution (150 m) ENVISAT satellite SAR-derived flood extent maps and a binary performance measure for a 30 × 50 km domain covering the confluence of the rivers Severn and Avon in the UK. The unknown channel parameters are located by a novel technique utilising the information content and dynamic identifiability analysis (DYNIA) (Wagener et al., 2003) of single and combinations of SAR flood extent maps to find the optimum satellite images for model calibration. Highest information content is found in those SAR flood maps acquired near the peak of the flood hydrograph, and improves when more images are combined. We found that model sensitivity to variation in channel depth is greater than for channel roughness and a successful calibration for depth could only be obtained when channel roughness values were confined to a plausible range. The calibrated reach-average channel depth was within 0.9 m (16 % error) of the equivalent value determined from river cross-section survey data, demonstrating that a series of moderate-resolution SAR data can be used to successfully calibrate the depth parameters of a 2-D hydraulic model.

  6. Progress on the calibration of channel geometry and friction parameters of the LISFLOOD-FP hydraulic model using time series of SAR flood images

    NASA Astrophysics Data System (ADS)

    Wood, M.; Neal, J. C.; Hostache, R.; Corato, G.; Bates, P. D.; Chini, M.; Giustarini, L.; Matgen, P.; Wagener, T.

    2014-12-01

    The objective of this work is to calibrate channel depth and roughness parameters of the LISFLOOD-FP Sub-Grid 2D hydraulic model using SAR image-derived flood extent maps. The aim is to reduce uncertainty in flood model predictions for those rivers where channel geometry is unknown and/or cannot be easily measured. In particular we consider the effectiveness of using real SAR data for calibration and whether the number and timings of SAR acquisitions is of benefit to the final result. Terrain data are processed from 2m LiDAR images and inflows to the model are taken from gauged data. As a test case we applied the method to the River Severn between Worcester and Tewkesbury. We firstly applied the automatic flood mapping algorithm of Giustarini[1] et al. (2013) to ENVISAT ASAR (wide swath mode) flood images; generating a series of flood maps. We then created an ensemble of flood extent maps with the hydraulic model (each model representing a unique parameter set). Where there is a favourable comparison between the modelled flood map and the SAR obtained flood map we may suggest an optimal parameter set. Applying the method to a sequence of SAR acquisitions provides insight into the advantages, disadvantages and limitations of using series of acquired images. To complete the investigation we simultaneously explore parameter 'identifiabilty' within a sequence of available satellite observations by adopting the DYNIA method proposed by Wagener[2] et al. (2003). We show where we might most easily detect the depth and roughness parameters within the SAR acquisition sequence. [1] Giustarini. 2013. 'A Change Detection Approach to Flood Mapping in Urban Areas Using TerraSAR-X'. IEEE Transactions on Geoscience and Remote Sensing, vol. 51, no. 4. [2] Wagener. 2003. 'Towards reduced uncertainty in conceptual rainfall-runoff modelling: Dynamic identifiability analysis'. Hydrol. Process. 17, 455-476.

  7. EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

    PubMed Central

    Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

    2016-01-01

    Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

  8. Prediction of phase transition, mechanical and electronic properties of inverse Heusler compound Y2RuPb, via FP-LMTO method

    NASA Astrophysics Data System (ADS)

    Labair, M.; Rached, H.; Rached, D.; Benalia, S.; Abidri, B.; Khenata, R.; Ahmed, R.; Omran, S. Bin; Bouhemadou, A.; Syrotyuk, S. V.

    2016-03-01

    Topological insulators (TI) are immensely investigated due to their promising characteristics for spintronics and quantum computing applications. In this regard, although bismuth, telluride, selenide and antimony containing compounds are typically considered as topological insulators, materials with Hg2CuTi-type structure have also shown their potential for TIs as well. Here, we present first principles study of the Y2RuPb compound, pertaining to its structural, mechanical, electrical and the optical properties. Calculations are executed at the level of the parameterized Perdew-Burke-Ernzerhof (PBE) generalized gradient approximation (GGA), employing the full-potential (FP) linearized muffin-tin orbital (LMTO) approach, as designed within the density functional theory (DFT). The study is carried out on the Hg2CuTi-type and Cu2MnAl-type structures of the Y2RuPb compound. From our structural calculations, it is found that Y2RuPb is more stable in its Hg2CuTi-type structure; however, the analysis of the mechanical properties reveals its stability in both phases against any kind of elastic deformation. Similarly, Dirac cone shaped surface energy levels found in the predicted electronic band structure of the Y2RuPb compound, and good agreement of the obtained results with Zhang et al., demonstrates that it is a topological insulating material. Additionally, the real and imaginary parts of the dielectric function ɛ (ω) and refractive index n (ω), for an energy range up to 14eV, are analyzed as well.

  9. Structural, mechanical, electronic and thermal properties of KZnF3 and AgZnF3 Perovskites: FP-(L)APW+lo calculations

    NASA Astrophysics Data System (ADS)

    Hiadsi, S.; Bouafia, H.; Sahli, B.; Abidri, B.; Bouaza, A.; Akriche, A.

    2016-08-01

    This study presents a theoretical prediction of the structural, mechanical, electronic and thermal properties of the zinc-based Perovskites (AgZnF3 and KZnF3) within the framework of Density Functional Theory (DFT) using All-electron self consistent Full Potential Augmented Plane Waves plus local orbital FP-(L)APW + lo method. To make our work comparable and reliable, several functional were used for the exchange-correlation potential. Also, this study intends to provide a basis and an improvement for updating either the values already predicted by other previous work (by using obsolete functional) or to predict them for the first time. GGA-PBE and GGA-PBEsol were used to predict the structural properties of AgZnF3 and KZnF3 Perovskites such as lattice parameter, bulk modulus and its pressure derivative and the cohesive energy. For these properties, the found values are in very good agreement; also those found by GGA-PBEsol are closer to other available previous and experimental results. The electronic properties of these materials are investigated and compared to provide a consolidated prediction by using the modified Becke Johnson potential TB-mBJ with other functional; the values found by this potential are closer to the available proven results and show that these materials exhibit an indirect gap from R to Γ point. The charge densities plot for [110] direction and QTAIM (Quantum Theory of Atoms in Molecules) theory indicate that ionic character is predominate for (K, Ag, Zn)sbnd F bonds. Finally, the effect of temperature and pressure on the unit cell volume, the heat capacity CV and entropy were studied using the quasi-harmonic Debye model.

  10. The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease.

    PubMed

    Yamada, Yoshiyuki; Rothenberg, Marc E; Lee, Andrew W; Akei, Hiroko Saito; Brandt, Eric B; Williams, David A; Cancelas, Jose A

    2006-05-15

    Dysregulated tyrosine kinase activity by the Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene has been identified as a cause of clonal hypereosinophilic syndrome (HES), called F/P-positive chronic eosinophilic leukemia (CEL) in humans. However, transplantation of F/P-transduced hematopoietic stem cells/progenitors (F/P(+) HSCs/Ps) into mice results in a chronic myelogenous leukemia-like disease, which does not resemble HES. Because a subgroup of patients with HES show T-cell-dependent interleukin-5 (IL-5) overexpression, we determined if expression of the F/P fusion gene in the presence of transgenic T-cell IL-5 overexpression in mice induces HES-like disease. Mice that received a transplant of CD2-IL-5-transgenic F/P(+) HSC/Ps (IL-5Tg-F/P) developed intense leukocytosis, strikingly high eosinophilia, and eosinophilic infiltration of nonhematopoietic as well as hematopoietic tissues, a phenotype resembling human HES. The disease phenotype was transferable to secondary transplant recipients of a high cell dose, suggesting involvement of a short-term repopulating stem cell or an early myeloid progenitor. Induction of significant eosinophilia was specific for F/P since expression of another fusion oncogene, p210-BCR/ABL, in the presence of IL-5 overexpression was characterized by a significantly lower eosinophilia than IL-5Tg-F/P recipients. These results suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires a second event associated with IL-5 overexpression.

  11. Rate constant for the reaction H + NO2 from 195 to 400 K with FP-RF and DF-RF techniques. [Flash Photolysis and Discharge Flow-Resonance Fluorescence

    NASA Technical Reports Server (NTRS)

    Michael, J. V.; Nava, D. F.; Payne, W. A.; Lee, J. H.; Stief, L. J.

    1979-01-01

    Measurements are made of the rate constant for the reaction H + NO2 yielding OH + NO over significant temperature ranges with the flash photolysis-resonance fluorescence (FP-RF) technique and also with the discharge flow-resonance fluorescence (DF-RF) technique. Since it is important to study chemical reactions with more than one technique, the above reaction is investigated with the FP-RF technique over the temperature range 230-400 K. The results reported do not agree with earlier determinations. Accordingly, a separate set of measurements is made with the DF-RF technique over the temperature range 195-368 K; the results are also reported. The reaction is also considered theoretically, especially with regard to the question of temperature dependence and absolute magnitude of the rate constant.

  12. Linear topology confers in vivo gene transfer activity to polyethylenimines.

    PubMed

    Brissault, B; Leborgne, C; Guis, C; Danos, O; Cheradame, H; Kichler, A

    2006-01-01

    Although polyethylenimines (PEIs) are frequently used transfection agents, it is still unclear which of their properties are required for efficient gene delivery. This is even more striking when working in vivo since some PEIs are able to generate significant gene expression, whereas others are not. To facilitate a rational development of compounds with improved transfection activities, studies aimed at identifying the properties involved in the transfection process seem indispensable. In the present work, we investigated how transfection with linear PEI of 22 kDa allows for high reporter gene expression in lungs after intravenous injection, whereas the branched PEI of 25 kDa does not. To this end, we synthesized L-PEI derivatives that are intermediates between linear and branched PEIs. Our results show that the topology plays a crucial role in obtaining in vivo reporter gene expression, whereas the content of primary, secondary, and tertiary amines is only of minor importance.

  13. Biodegradable Poly(aminoester)-Mediated p53 Gene Delivery for Cancer Therapy.

    PubMed

    Shen, He; Liu, Min; Zhang, Zhijun

    2016-03-01

    Gene therapy is a promising strategy in cancer treatment. However, efficient gene translation still remains challenging. In the previous work, a hydrolytically degradable poly(aminoester) with good biocompatibility was synthesized. Herein, the poly(aminoester) was explored as a vector for gene delivery and cancer therapy. The experiments revealed that the poly(aminoester) condensed plasmid DNA into nanosized particles via electrostatic interaction. The pEGFP-N1 and pGL-3 were first used as two reporter genes to study intracellular transfection. The poly(aminoester) showed higher GFP expression (33%) than PEI 25 kDa (21%). Intracellular trafficking of Cy3-labelled pGL-3 also indicated that the poly(aminoester) showed superior DNA delivery ability to nucleus compared to PEI 25 kDa. Furthermore, the therapeutic gene (p53) was translated into the breast cancer cell line (MCF-7), and then induced cell apoptosis. These results suggested that the degradable poly(aminoester) is a promising and efficient gene delivery vector for gene therapeutic applications.

  14. Polyethylenimine600-β-cyclodextrin: a promising nanopolymer for nonviral gene delivery of primary mesenchymal stem cells

    PubMed Central

    Tong, Haijun; Wang, Chuandong; Huang, Yan; Shi, Qin; Fernandes, Julio C; Dai, Kerong; Tang, Guping; Zhang, Xiaoling

    2013-01-01

    Genetically modified mesenchymal stem cells (MSCs) have great potential in the application of regenerative medicine and molecular therapy. In the present manuscript, we introduce a nanopolymer, polyethylenimine600-β-cyclodextrin (PEI600-β-CyD), as an efficient polyplex-forming plasmid delivery agent with low toxicity and ideal transfection efficiency on primary MSCs. PEI600-β-CyD causes significantly less cytotoxicity and apoptosis on MSCs than 25 kDa high-molecular-weight PEI (PEI25kDa). PEI600-β-CyD also exhibits similar transfection efficiency as PEI25kDa on MSCs, which is higher than that of PEI600Da. Quantum dot-labeled plasmids show that PEI600-β-CyD or PEI25kDa delivers the plasmids in a more scattered manner than PEI600Da does. Further study shows that PEI600-β-CyD and PEI25kDa are more capable of delivering plasmids into the cell lysosome and nucleus than PEI600Da, which correlates well with the results of their transfection-efficiency assay. Moreover, among the three vectors, PEI600-β-CyD has the most capacity of enhancing the alkaline phosphatase activity of MSCs by transfecting bone morphogenetic protein 2, 7, or special AT-rich sequence-binding protein 2. These results clearly indicate that PEI600-β-CyD is a safe and effective candidate for the nonviral gene delivery of MSCs because of its ideal inclusion ability and proton sponge effect, and the application of this nanopolymer warrants further investigation. PMID:23737665

  15. Computer-aided detection of clustered microcalcifications on full-field digital mammograms: A two-view information fusion scheme for FP reduction

    NASA Astrophysics Data System (ADS)

    Ge, Jun; Sahiner, Berkman; Chan, Heang-Ping; Hadjiiski, Lubomir M.; Helvie, Mark A.; Zhou, Chuan; Wei, Jun; Zhang, Yiheng

    2006-03-01

    We are developing new techniques to improve the performance of our computer-aided detection (CAD) system for clustered microcalcifications on full-field digital mammograms (FFDMs). In this study, we designed an information fusion scheme by using joint two-view information on craniocaudal (CC) and mediolateral-oblique (MLO) views. After cluster candidates were detected using a single-view detection technique, candidates on CC and MLO views were paired using their geometrical information. Candidate pairs were classified as true and false pairs with a similarity classifier that used the joint information from both views. Each cluster candidate was also characterized by its single-view features. The outputs of the similarity classifier and the single-view classifier were fused and the cluster candidate was classified as a true microcalcification cluster or a false-positive (FP) using the fused two-view information. A data set of 192 FFDM images was collected from 96 patients at the University of Michigan. All patients had two mammographic views. This data set contained 96 microcalcification clusters, of which 28 clusters were proven by biopsy to be malignant and 68 were proven to be benign. For training and testing the classifiers, the data set was partitioned into two independent subsets with the malignant cases equally distributed to the two subsets. One subset was used for training and the other subset was used for testing. We compared three computerized methods for geometrically pairing cluster candidates on two mammographic views. The areas under the fitted ROC curves were 0.75+/-0.01, 0.74+/-0.01, and 0.76+/-0.01 for the three methods, respectively. The difference between any two methods measured by the area under the fitted ROC curve, A z, was not statistically significant (p > 0.05). We also evaluated a new hybrid pairing scheme that used two different sensitivity levels for defining cluster pairs based on the single-view scores. The single-view CAD system

  16. Combination of 'idiopathic' REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT.

    PubMed

    Stiasny-Kolster, K; Doerr, Y; Möller, J C; Höffken, H; Behr, T M; Oertel, W H; Mayer, G

    2005-01-01

    REM sleep behaviour disorder (RBD) and olfactory dysfunction are common and very early features of alpha-synucleinopathies, in particular Parkinson's disease. To investigate the hypothesis that these two clinical features in combination are an indicator of evolving alpha-synucleinopathy, olfactory function was assessed in RBD. We studied 30 patients (18 male, 12 female; mean age 48 +/- 14 years, range 19-78 years) with clinical (idiopathic, n = 6; symptomatic, n = 13, mostly associated with narcolepsy) or subclinical (n = 11, associated with narcolepsy) RBD according to standard criteria and 30 age- and gender-matched healthy control subjects using standardized 'Sniffin' Sticks'. RBD patients had a significantly higher olfactory threshold (P = 0.0001), lower discrimination score (P = 0.003), and lower identification score (P = 0.001). Compared with normative data, 97% of the RBD patients had a pathologically increased olfactory threshold, 63% an impaired odour discrimination score, and 63% a decreased identification score. On neurological examination, signs of parkinsonism were newly found in five patients with clinical RBD (not associated with narcolepsy), who usually had a long history of 'idiopathic' RBD. Four of the five patients fulfilled the UK Brain Bank criteria for the clinical diagnosis of Parkinson's disease. The underlying nigrostriatal degeneration of clinical Parkinson's disease was confirmed by I-123-FP-CIT SPECT in one patient and early nigrostriatal degeneration was identified by SPECT in a further two patients with 'idiopathic' clinical RBD out of 11 RBD patients who agreed to undergo SPECT studies. Our study shows that RBD patients have a profound impairment of olfactory function. Five patients with clinical RBD not associated with narcolepsy had clinical or imaging signs of nigrostriatal degeneration. This new clinical finding correlates with the neuropathological staging of Parkinson's disease (stages 1-3) as proposed by Braak. In stage 1, the

  17. Multiple short-lived stellar prominences on O stars: The O6.5I(n)fp star λ Cephei

    NASA Astrophysics Data System (ADS)

    Sudnik, N. P.; Henrichs, H. F.

    2016-10-01

    Context. Most O-type stars and many B stars show unexplained cyclical variability in their spectral lines, i.e., modulation on the rotational timescale, but not strictly periodic. The variability occurs in the so-called discrete absorption components (DACs) that accelerate through the UV-wind line profiles and also in many optical lines. For such OB stars no dipolar magnetic fields have been detected with upper limits of ~300 G. Aims: We investigate whether multiple magnetic loops on the surface rather than non-radial pulsations or a dipolar magnetic field can explain the observed cyclical UV and optical spectral line variability. Methods: We present time-resolved, high-resolution optical spectroscopy of the O6.5I(n)fp star λ Cephei. We apply a simplified phenomenological model in which multiple spherical blobs attached to the surface represent magnetic-loop structures, which we call stellar prominences, by analogy with solar prominences. We compare the calculated line profiles as a function of rotational phase, adopting a rotation period of 4.1 d, with observed relative changes in subsequent quotient spectra. Results: We identify many periodicities in spectral lines, almost none of which is stable over timescales from months to years. We show that the relative changes in various optical absorption and emission lines are often very similar. Our proposed model applied to the He ii λ4686 line can typically be fitted with 2-5 equatorial blobs with lifetimes between ~1 and 24 h. Conclusions: Given the irregular timescales involved, we propose that the azimuthal distribution of DACs correspond to the locations of stellar prominences attached to the surface. This could explain the observed variability of optical and UV lines, and put constraints on the strength and lifetime of these structures, which can be compared with recent theoretical predictions, in which bright magnetic surface spots are formed by the action of the subsurface convection zone. Based on

  18. EU-FP7-iMARS: analysis of Mars multi-resolution images using auto-coregistration, data mining and crowd source techniques: A Status Report

    NASA Astrophysics Data System (ADS)

    Muller, Jan-Peter; Sidiropoulos, Panagiotis; Tao, Yu; Gwinner, Klaus; Willner, Konrad; Fanara, Lida; Waehlisch, Marita; Walter, Sebastian; Schreiner, Bjoern; Steikert, Ralf; Ivanov, Anton B.; Cantini, Federico; Wardlaw, Jessica; Sprinks, James Christopher; Giordano, Michele; Kim, Jungrack; Houghton, Robert; Bamford, Steven

    2016-10-01

    al., EPSC16; [11] Campbell, J.et al., EPSC16;[12] Kim, J-R., et al., EPSC16 AcknowledgementsThis research has received funding from the EU's FP7 Programme under iMars 607379. Partial support is also provided from the STFC Grant ST/K000977/1

  19. The European FP7 ULTimateCO2 project: A comprehensive approach to study the long term fate of CO2 geological storage sites

    NASA Astrophysics Data System (ADS)

    Audigane, P.; Brown, S.; Dimier, A.; Pearce, J.; Frykman, P.; Maurand, N.; Le Gallo, Y.; Spiers, C. J.; Cremer, H.; Rutters, H.; Yalamas, T.

    2013-12-01

    The European FP7 ULTimateCO2 project aims at significantly advance our knowledge of specific processes that could influence the long-term fate of geologically stored CO2: i) trapping mechanisms, ii) fluid-rock interactions and effects on mechanical integrity of fractured caprock and faulted systems and iii) leakage due to mechanical and chemical damage in the well vicinity, iv) brine displacement and fluid mixing at regional scale. A realistic framework is ensured through collaboration with two demonstration sites in deep saline sandstone formations: the onshore former NER300 West Lorraine candidate in France (ArcelorMittal GeoLorraine) and the offshore EEPR Don Valley (former Hatfield) site in UK operated by National Grid. Static earth models have been generated at reservoir and basin scale to evaluate both trapping mechanisms and fluid displacement at short (injection) and long (post injection) time scales. Geochemical trapping and reservoir behaviour is addressed through experimental approaches using sandstone core materials in batch reactive mode with CO2 and impurities at reservoir pressure and temperature conditions and through geochemical simulations. Collection of data has been generated from natural and industrial (oil industry) analogues on the fluid flow and mechanical properties, structure, and mineralogy of faults and fractures that could affect the long-term storage capacity of underground CO2 storage sites. Three inter-related lines of laboratory experiments investigate the long-term evolution of the mechanical properties and sealing integrity of fractured and faulted caprocks using Opalinus clay of Mont Terri Gallery (Switzerland) (OPA), an analogue for caprock well investigated in the past for nuclear waste disposal purpose: - Characterization of elastic parameters in intact samples by measuring strain during an axial experiment, - A recording of hydraulic fracture flow properties by loading and shearing samples in order to create a 'realistic

  20. Reducible Poly(Oligo-D-Arginine) as an Efficient Carrier of the Thymidine Kinase Gene in the Intracranial Glioblastoma Animal Model.

    PubMed

    Kim, Hyun Ah; Lee, Hyun-Lin; Choi, Eunji; Kim, Yong-Hee; Lee, Minhyung

    2015-11-01

    Gene therapy has been considered as an alternative treatment for glioblastoma therapy. In this study, a glioblastoma-specific suicide gene, pEpo-NI2-SV-TK, was delivered into the intracranial glioblastoma model using reducible poly(oligo-d-arginines) (rPOA). pEpo-NI2-SV-TK has the erythropoietin (Epo) enhancer and the nestin intron 2 (NI2) for glioblastoma specific gene expression. The in vitro studies showed that the rPOA formed stable complexes with pEpo-NI2-SV-TK. In the MTT and TUNEL assays, rPOA showed lower cytotoxicity than polyethylenimine (25 kDa, PEI25k). In addition, the rPOA/pEpo-NI2-SV-TK complex induced higher glioblastoma cell death under hypoxic condition than normoxic condition, suggesting that pEpo-NI2-SV-TK induced gene expression in the hypoxic tumor tissue. For in vivo therapeutic efficacy evaluation, the rPOA/pEpo-NI2-SV-TK complex was injected into the brains of an intracranial glioblastoma rat model. The rPOA/pEpo-NI2-SV-TK injected group had a significantly reduced tumor size, compared with the control and the PEI25k/pEpo-NI2-SV-TK injected group. The TUNEL assay showed that the rPOA-pEpo-NI2-SV-TK complex had more apoptotic cells than the control and PEI25k/pEpo-NI2-SV-TK injected groups. These results suggest that the rPOA is an efficient carrier for pEpo-NI2-SV-TK and increased the therapeutic efficacy in the intracranial glioblastoma models. Therefore, the rPOA/pEpo-NI2-SV-TK complex may be useful for glioblastoma specific gene therapy.

  1. In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production.

    PubMed

    Yasugi, Mayo; Sugahara, Yuki; Hoshi, Hidenobu; Kondo, Kaori; Talukdar, Prabhat K; Sarker, Mahfuzur R; Yamamoto, Shigeki; Kamata, Yoichi; Miyake, Masami

    2015-08-01

    Clostridium perfringens type A is a common source of food poisoning (FP) and non-food-borne (NFB) gastrointestinal diseases in humans. In the intestinal tract, the vegetative cells sporulate and produce a major pathogenic factor, C. perfringens enterotoxin (CPE). Most type A FP isolates carry a chromosomal cpe gene, whereas NFB type A isolates typically carry a plasmid-encoded cpe. In vitro, the purified CPE protein binds to a receptor and forms pores, exerting a cytotoxic activity in epithelial cells. However, it remains unclear if CPE is indispensable for C. perfringens cytotoxicity. In this study, we examined the cytotoxicity of cpe-harboring C. perfringens isolates co-cultured with human intestinal epithelial Caco-2 cells. The FP strains showed severe cytotoxicity during sporulation and CPE production, but not during vegetative cell growth. While Caco-2 cells were intact during co-culturing with cpe-null mutant derivative of strain SM101 (a FP strain carrying a chromosomal cpe gene), the wild-type level cytotoxicity was observed with cpe-complemented strain. In contrast, both wild-type and cpe-null mutant derivative of the NFB strain F4969 induced Caco-2 cell death during both vegetative and sporulation growth. Collectively, the Caco-2 cell cytotoxicity caused by C. perfringens strain SM101 is considered to be exclusively dependent on CPE production, whereas some additional toxins should be involved in F4969-mediated in vitro cytotoxicity.

  2. Failure of a recombinant fowl poxvirus vaccine containing an avian influenza hemagglutinin gene to provide consistent protection against influenza in chickens preimmunized with a fowl pox vaccine.

    PubMed

    Swayne, D E; Beck, J R; Kinney, N

    2000-01-01

    Vaccines against mildly pathogenic avian influenza (AI) have been used in turkeys within the United States as part of a comprehensive control strategy. Recently, AI vaccines have been used in control programs against highly pathogenic (HP) AI of chickens in Pakistan and Mexico. A recombinant fowl pox-AI hemagglutinin subtype (H) 5 gene insert vaccine has been shown to protect specific-pathogen-free chickens from HP H5 AI virus (AIV) challenge and has been licensed by the USDA for emergency use. The ability of the recombinant fowl pox vaccine to protect chickens preimmunized against fowl pox is unknown. In the current study, broiler breeders (BB) and white leghorn (WL) pullets vaccinated with a control fowl poxvirus vaccine (FP-C) and/or a recombinant fowl poxvirus vaccine containing an H5 hemagglutinin gene insert (FP-HA) were challenged with a HP H5N2 AIV isolated from chickens in Mexico. When used alone, the FP-HA vaccine protected BB and WL chickens from lethal challenge, but when given as a secondary vaccine after a primary FP-C immunization, protection against a HP AIV challenge was inconsistent. Both vaccines protected against virulent fowl pox challenge. This lack of consistent protection against HPAI may limit use to chickens without previous fowl pox vaccinations. In addition, prior exposure to field fowl poxvirus could be expected to limit protection induced by this vaccine.

  3. InSAR analysis of the crustal deformation affecting the megacity of Istanbul: the results of the FP7 Marsite Project as a GEO Supersite Initiative

    NASA Astrophysics Data System (ADS)

    Solaro, Giuseppe; Bonano, Manuela; Manzo, Mariarosaria

    2016-04-01

    The North Anatolian Fault (NAF) is one of the most active faults worldwide, extending approximately 1,200 km from Eastern Turkey to the Northern Aegean Sea. During the 20th century series of damaging earthquakes occurred along the NAF, generally propagated westward towards Istanbul; the last one occurred in 1999 at Izmit, a city 80 km away from Istanbul. Within this scenario, the FP7 MARsite project (New Directions in Seismic Hazard assessment through Focused Earth Observation in Marmara Supersite), supported by EU, intends to collect, share and integrate multidisciplinary data (seismologic, geochemical, surveying, satellite, etc.) in order to carry out assessment, mitigation and management of seismic risk in the region of the Sea of Marmara. In the framework of the MARsite project, we performed the analysis and monitoring of the surface deformation affecting the Istanbul mega city by exploiting the large archives of X-band satellite SAR data, made available through the Supersites Initiatives, and by processing them via the advanced multi-temporal and multi-scale InSAR technique, known as the Small BAseline Subset (SBAS) approach. In particular, we applied the SBAS technique to a dataset of 101 SAR images acquired by the TerraSAR-X constellation of the German Space Agency (DLR) over descending orbits and spanning the November 2010 - August 2014 time interval. From,these images, we generated 312 differential interferograms with a maximum spatial separation (perpendicular baseline) between the acquisition orbits of about 500 m., that were used to generate, via the SBAS approach, mean deformation velocity map and corresponding ground time series of the investigated area. The performed InSAR analysis reveals a generalized stability over the Istanbul area, except for some localized displacements, related to subsidence and slope instability phenomena. In particular, we identified: (i) a displacement pattern related to the Istanbul airport, showing a mostly linear

  4. Development of a flood early warning system and communication with end-users: the Vipava/Vipacco case study in the KULTURisk FP7 project

    NASA Astrophysics Data System (ADS)

    Grossi, Giovanna; Caronna, Paolo; Ranzi, Roberto

    2014-05-01

    Within the framework of risk communication, the goal of an early warning system is to support the interaction between technicians and authorities (and subsequently population) as a prevention measure. The methodology proposed in the KULTURisk FP7 project aimed to build a closer collaboration between these actors, in the perspective of promoting pro-active actions to mitigate the effects of flood hazards. The transnational (Slovenia/ Italy) Soča/Isonzo case study focused on this concept of cooperation between stakeholders and hydrological forecasters. The DIMOSHONG_VIP hydrological model was calibrated for the Vipava/Vipacco River (650 km2), a tributary of the Soča/Isonzo River, on the basis of flood events occurred between 1998 and 2012. The European Centre for Medium-Range Weather Forecasts (ECMWF) provided the past meteorological forecasts, both deterministic (1 forecast) and probabilistic (51 ensemble members). The resolution of the ECMWF grid is currently about 15 km (Deterministic-DET) and 30 km (Ensemble Prediction System-EPS). A verification was conducted to validate the flood-forecast outputs of the DIMOSHONG_VIP+ECMWF early warning system. Basic descriptive statistics, like event probability, probability of a forecast occurrence and frequency bias were determined. Some performance measures were calculated, such as hit rate (probability of detection) and false alarm rate (probability of false detection). Relative Opening Characteristic (ROC) curves were generated both for deterministic and probabilistic forecasts. These analysis showed a good performance of the early warning system, in respect of the small size of the sample. A particular attention was spent to the design of flood-forecasting output charts, involving and inquiring stakeholders (Alto Adriatico River Basin Authority), hydrology specialists in the field, and common people. Graph types for both forecasted precipitation and discharge were set. Three different risk thresholds were identified

  5. EU-FP7-iMars: Analysis of Mars Multi-Resolution Images using Auto-Coregistration, Data Mining and Crowd Source Techniques

    NASA Astrophysics Data System (ADS)

    Ivanov, Anton; Oberst, Jürgen; Yershov, Vladimir; Muller, Jan-Peter; Kim, Jung-Rack; Gwinner, Klaus; Van Gasselt, Stephan; Morley, Jeremy; Houghton, Robert; Bamford, Steven; Sidiropoulos, Panagiotis

    information employed to generate a time series of terrain relief with corrected ORIs back to 1977. Web-GIS using OGC protocols will be employed to allow visual exploration of changes to the surface. Data mining processing chains are being developed to search for changes in the Martian surface from 1971-2015 and the output of this data mining will be compared against the results from citizen scientists’ measurements in a specialized Zooniverse implementation. The final co-registered data sets will be distributed through both European and US channels in a manner to be decided towards the end of the project. Acknowledgements: The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under iMars grant agreement n ̊ 607379.

  6. New results on ground deformation in the Upper Silesian Coal Basin (southern Poland) obtained during the DORIS Project (EU-FP 7)

    NASA Astrophysics Data System (ADS)

    Graniczny, Marek; Colombo, Davide; Kowalski, Zbigniew; Przyłucka, Maria; Zdanowski, Albin

    2015-11-01

    This paper presents application of satellite interferometric methods (persistent scatterer interferometric synthetic aperture radar (PSInSAR™) and differential interferometric synthetic aperture radar (DInSAR)) for observation of ground deformation in the Upper Silesian Coal Basin (USCB) in Southern Poland. The presented results were obtained during the DORIS project (EC FP 7, Grant Agreement n. 242212, www.doris-project.eu). Several InSAR datasets for this area were analysed. Most of them were processed by Tele-Rilevamento Europa - T.R.E. s.r.l. Italy. Datasets came from different SAR satellites (ERS 1 and 2, Envisat, ALOS- PALSAR and TerraSAR-X) and cover three different SAR bands (L, C and X). They were processed using both InSAR techniques: DInSAR, where deformations are presented as interferometric fringes on the raster image, and PSInSAR, where motion is indentified on irregular set of persistent scatterer (PS) points. Archival data from the C-band European Space Agency satellites ERS and ENVISAT provided information about ground movement since 1992 until 2010 in two separate datasets (1992-2000 and 2003-2010). Two coal mines were selected as examples of ground motion within inactive mining areas: Sosnowiec and Saturn, where mining ceased in 1995 and 1997, respectively. Despite well pumping after closure of the mines, groundwater rose several dozen meters, returning to its natural horizon. Small surface uplift clearly indicated on satellite interferometric data is related to high permeability of the hydrogeological subregion and insufficient water withdrawal from abandoned mines. The older 1992-2000 PSInSAR dataset indicates values of ground motion ranging from -40.0 to 0.0 mm. The newer 2003-2010 dataset shows values ranging from -2.0 to +7.0 mm. This means that during this period of time subsidence was less and uplift greater in comparison to the older dataset. This is even more evident in the time series of randomly selected PS points from both coal

  7. Efficient inhibition of C-26 colon carcinoma by VSVMP gene delivered by biodegradable cationic nanogel derived from polyethyleneimine.

    PubMed

    Gou, MaLing; Men, Ke; Zhang, Juan; Li, YuHua; Song, Jia; Luo, Shan; Shi, HuaShan; Wen, YanJun; Guo, Gang; Huang, MeiJuan; Zhao, Xia; Qian, ZhiYong; Wei, YuQuan

    2010-10-26

    Biodegradable cationic nanoparticles have promising application as a gene delivery system. In this article, heparin-polyethyleneimine (HPEI) nanogels were prepared, and these nanogels were developed as a nonviral gene vector. The transfection efficiency of HPEI nanogels was comparable with that of PEI25K, while the cytotoxicity was lower than that of PEI2K and much lower than that of PEI25K in vitro. These HPEI nanogels also had better blood compatibility than PEI25K. After intravenous administration, HPEI nanogels degraded, and the degradation products were excreted through urine. The plasmid expressing vesicular stomatitis virus matrix protein (pVSVMP) could be efficiently transfected into C-26 colon carcinoma cells by HPEI nanogels in vitro, inhibiting the cell proliferation through apoptosis induction. Intraperitoneal injection of pVSVMP/HPEI complexes efficiently inhibited the abdominal metastases of C-26 colon carcinoma through apoptosis induction (mean tumor weight in mice treated with pVSVMP/HPEI complex = 0.93 g and in control mice = 3.28 g, difference = 2.35 g, 95% confidence interval [CI] = 1.75-2.95 g, P < 0.001) and prolonged the survival of treated mice. Moreover, intravenous application of pVSVMP/HPEI complexes also inhibited the growth of pulmonary metastases of C-26 colon carcinoma through apoptosis induction. The HPEI nanogels delivering pVSVMP have promising application in treating colon carcinoma.

  8. Genetic Diversity of Candidatus Liberibacter asiaticus Based on Two Hypervariable Effector Genes in Thailand

    PubMed Central

    Puttamuk, Thamrongjet; Zhou, Lijuan; Thaveechai, Niphone; Zhang, Shouan; Armstrong, Cheryl M.; Duan, Yongping

    2014-01-01

    Huanglongbing (HLB), also known as citrus greening, is one of the most destructive diseases of citrus worldwide. HLB is associated with three species of ‘Candidatus Liberibacter’ with ‘Ca. L. asiaticus’ (Las) being the most widely distributed around the world, and the only species detected in Thailand. To understand the genetic diversity of Las bacteria in Thailand, we evaluated two closely-related effector genes, lasAI and lasAII, found within the Las prophages from 239 infected citrus and 55 infected psyllid samples collected from different provinces in Thailand. The results indicated that most of the Las-infected samples collected from Thailand contained at least one prophage sequence with 48.29% containing prophage 1 (FP1), 63.26% containing prophage 2 (FP2), and 19.38% containing both prophages. Interestingly, FP2 was found to be the predominant population in Las-infected citrus samples while Las-infected psyllids contained primarily FP1. The multiple banding patterns that resulted from amplification of lasAI imply extensive variation exists within the full and partial repeat sequence while the single band from lasAII indicates a low amount of variation within the repeat sequence. Phylogenetic analysis of Las-infected samples from 22 provinces in Thailand suggested that the bacterial pathogen may have been introduced to Thailand from China and the Philippines. This is the first report evaluating the genetic variation of a large population of Ca. L. asiaticus infected samples in Thailand using the two effector genes from Las prophage regions. PMID:25437428

  9. Genetic diversity of Candidatus Liberibacter asiaticus based on two hypervariable effector genes in Thailand.

    PubMed

    Puttamuk, Thamrongjet; Zhou, Lijuan; Thaveechai, Niphone; Zhang, Shouan; Armstrong, Cheryl M; Duan, Yongping

    2014-01-01

    Huanglongbing (HLB), also known as citrus greening, is one of the most destructive diseases of citrus worldwide. HLB is associated with three species of 'Candidatus Liberibacter' with 'Ca. L. asiaticus' (Las) being the most widely distributed around the world, and the only species detected in Thailand. To understand the genetic diversity of Las bacteria in Thailand, we evaluated two closely-related effector genes, lasAI and lasAII, found within the Las prophages from 239 infected citrus and 55 infected psyllid samples collected from different provinces in Thailand. The results indicated that most of the Las-infected samples collected from Thailand contained at least one prophage sequence with 48.29% containing prophage 1 (FP1), 63.26% containing prophage 2 (FP2), and 19.38% containing both prophages. Interestingly, FP2 was found to be the predominant population in Las-infected citrus samples while Las-infected psyllids contained primarily FP1. The multiple banding patterns that resulted from amplification of lasAI imply extensive variation exists within the full and partial repeat sequence while the single band from lasAII indicates a low amount of variation within the repeat sequence. Phylogenetic analysis of Las-infected samples from 22 provinces in Thailand suggested that the bacterial pathogen may have been introduced to Thailand from China and the Philippines. This is the first report evaluating the genetic variation of a large population of Ca. L. asiaticus infected samples in Thailand using the two effector genes from Las prophage regions.

  10. Non-Invasive Gene Therapy of Experimental Parkinson’s Disease

    DTIC Science & Technology

    2005-09-01

    delivery system. Mol. Ther., 6: 67-72. 5. Zhang, Y., Boado, R.J., and Pardridge, W.M. (2003): Marked enhancement in gene expression by targeting the human...1999. 6. McMenamin MM, Bymes AP, Charlton HM, Coffin RS, Latchman show no chromosomal integration of the plasmid DS, Wood MJ. A y34.5 mutant of...1091-1095, 2001. Imaging of dopamine transporters with [1231]FP-CIT SPECT does 23. Zhang Y, Boado RJ, Pardridge WM. Marked enhancement in gene

  11. Computer-aided diagnosis of Parkinson’s disease based on [123I]FP-CIT SPECT binding potential images, using the voxels-as-features approach and support vector machines

    NASA Astrophysics Data System (ADS)

    Oliveira, Francisco P. M.; Castelo-Branco, Miguel

    2015-04-01

    Objective. The aim of the present study was to develop a fully-automated computational solution for computer-aided diagnosis in Parkinson syndrome based on [123I]FP-CIT single photon emission computed tomography (SPECT) images. Approach. A dataset of 654 [123I]FP-CIT SPECT brain images from the Parkinson’s Progression Markers Initiative were used. Of these, 445 images were of patients with Parkinson’s disease at an early stage and the remainder formed a control group. The images were pre-processed using automated template-based registration followed by the computation of the binding potential at a voxel level. Then, the binding potential images were used for classification, based on the voxel-as-feature approach and using the support vector machines paradigm. Main results. The obtained estimated classification accuracy was 97.86%, the sensitivity was 97.75% and the specificity 98.09%. Significance. The achieved classification accuracy was very high and, in fact, higher than accuracies found in previous studies reported in the literature. In addition, results were obtained on a large dataset of early Parkinson’s disease subjects. In summation, the information provided by the developed computational solution potentially supports clinical decision-making in nuclear medicine, using important additional information beyond the commonly used uptake ratios and respective statistical comparisons. (ClinicalTrials.gov Identifier: NCT01141023)

  12. Beta Decay Study of the T{sub z}=−2{sup 56}Zn Nucleus and the Determination of the Half-Lives of a Few fp-shell Nuclei

    SciTech Connect

    Rubio, B.; Orrigo, S.E.A.; Kucuk, L.; Montaner-Pizá, A.; Fujita, Y.; Fujita, H.; Blank, B.; Adachi, T.; Agramunt, J.; Algora, A.; Ascher, P.; Cáceres, L.; France, G. de; Gerbaux, M.; Giovinazzo, J.; Grevy, S. [CENBG, Université Bordeaux 1, UMR 5797 CNRS and others

    2014-06-15

    This paper concerns the experimental study of the β decay properties of few proton-rich fp-shell nuclei. The nuclei were produced at GANIL in fragmentation reactions, separated with the LISE spectrometer and stopped in an implantation detector surrounded by Ge detectors. The β-delayed gammas, β-delayed protons and the exotic β-delayed gamma-proton emission have been studied. Preliminary results are presented. The decay of the T{sub z}=−2 nucleus {sup 56}Zn has been studied in detail. Information from the β-delayed protons and β-delayed gammas has been used to deduce the decay scheme. The exotic beta-delayed gamma-proton decay has been observed for the first time in the fp-shell. The interpretation of the data was made possible thanks to the detailed knowledge of the mirror Charge Exchange (CE) process and the gamma de-excitation of the states in {sup 56}Co, the mirror nucleus of {sup 56}Cu.

  13. Studying Genes

    MedlinePlus

    ... Area What are genes? Genes are sections of DNA that contain instructions for making the molecules—many ... material in an organism. This includes genes and DNA elements that control the activity of genes. Does ...

  14. Chitosan based oligoamine polymers: synthesis, characterization, and gene delivery.

    PubMed

    Lu, Bo; Wang, Chang-Fang; Wu, De-Qun; Li, Cao; Zhang, Xian-Zheng; Zhuo, Ren-Xi

    2009-07-01

    A series of chitosan-based oligoamine polymers was synthesized from N-maleated chitosan (NMC) via Michael addition with diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and linear polyethylenimine (M(n) 423), respectively. The resulted polymers exhibited well binding ability to condense plasmid DNA to form complexes with size ranging from 200 to 600 nm when the polymer/DNA weight ratio was above 7. The polymer/DNA complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The cytotoxicity assay showed that the synthesized polymers were less toxic than that of PEI(25 K). The gene transfection effect of resulted polymers was evaluated in 293T and HeLa cells, and the results showed that the gene transfection efficiency of these polymers was better than that of chitosan. Moreover, the transfection efficiency was dependent on the length of the oligoamine side chains and the molecular weight of the chitosan derivatives.

  15. Low molecular weight PEIs modified by hydrazone-based crosslinker and betaine as improved gene carriers.

    PubMed

    Fang, Gang; Zeng, Fang; Yu, Changmin; Wu, Shuizhu

    2014-10-01

    Low-molecular-weight polyethyleneimine (LMW PEI) exhibits poorer transfection efficiency but lower cytotoxicity compared to high-molecular-weight polyethyleneimine (such as PEI 25kDa). To enhance the gene transfection performance of LMW PEI, we herein demonstrate a new strategy for modifying LMW PEI. A crosslinker containing an acid-labile hydrazone bond (hydrazone-based crosslinker) was synthesized and used to crosslink PEI 1.8kDa and convert it into higher-molecular-weight polycations. And the crosslinked polycations were further modified by incorporating a betaine monomer [N,N-dimethyl(acrylamidopropyl)ammonium propane sulfonate, DMAAPS] onto their surfaces. The molar percentages of the incorporated betaine molecules to amino groups on the polycations were determined as 21.2%, 36.0% and 77.2%, respectively. Molecular weights of the modified polycations were measured using capillary viscometry at pH 7.4 and 5.0, respectively, and the degradation of the polymers in acidic solution was confirmed. The PEIs modified with hydrazone and betaine (PEI-Hdz-DMAAPS) exhibit much lower cytotoxicity than PEI 25K, and they also show no or little hemolytic effect with their hemolysis rates around 5%. PEI-Hdz-DMAAPS21.2%/DNA and PEI-Hdz-DMAAPS36.0%/DNA complexes exhibit high transfection efficiencies, which are comparable to or higher than that of PEI 25K/DNA complex in the absence or presence of 10% serum. With these improved gene delivery properties, the PEI-Hdz-DMAAPS samples have great potential for serving as efficient gene carriers. This strategy may provide some insights for constructing some other biocompatible materials.

  16. Cross sections for proton induced high energy γ -ray emission (PIGE) in reaction 19 F(p, αγ)16 O at incident proton energies between 1.5 and 4 MeV

    NASA Astrophysics Data System (ADS)

    Cabanelas, P.; Cruz, J.; Fonseca, M.; Henriques, A.; Lourenço, F.; Luís, H.; Machado, J.; Pires Ribeiro, J.; Sánchez-Benítez, A. M.; Teubig, P.; Velho, P.; Zarza-Moreno, M.; Galaviz, D.; Jesus, A. P.

    2016-08-01

    We have studied the high energy gamma-rays produced in the reaction 19 F(p, αγ)16 O for incident proton energies from 1.5 to 4.0 MeV over NaF/Ag and CaF2/Ag thin targets in two different sets of data. Gamma-rays were detected with a High Purity Ge detector with an angle of 130° with respect to the beam axis. The cross-sections for the high energy gamma-rays of 6.129, 6.915 and 7.115 MeV have been measured for the whole group between 5 and 7.2 MeV with accuracy better than 10%. A new energy range was covered and more points are included in the cross-sections data base expanding the existing set of data. Results are in agreement with previous measurements in similar conditions.

  17. A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and biocompatible gene delivery vector

    NASA Astrophysics Data System (ADS)

    Zeng, Xin; Pan, Shirong; Li, Jie; Wang, Chi; Wen, Yuting; Wu, Hongmei; Wang, Cuifeng; Wu, Chuanbin; Feng, Min

    2011-09-01

    Non-viral gene delivery systems based on cationic polymers have faced limitations related to their relative low gene transfer efficiency, cytotoxicity and system instability in vivo. In this paper, a flexible and pompon-like dendrimer composed of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid) grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to combine the merits of size-controlled PAMAM G4.0 and the low toxicity and flexible chains of PLGE. In phosphate-buffered saline dispersions the well-defined DNA/MGI complex above a N/P ratio of 30 showed good stability with particle sizes of approximately 200 nm and a comparatively low polydispersity index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI 25K) complex was larger than 700 nm under the same salt conditions. The shielding of the compact amino groups at the periphery of flexible PAMAM and biocompatible PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained the same high levels of transfection efficiency as in serum-free medium, while the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000 were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into balloon-injured rabbit carotid arteries resulted in significant inhibition of restenosis by increasing VEGF165 expression in local vessels. Therefore, the pompon-like MGI dendrimer may be a promising vector candidate for efficient gene delivery in vivo.

  18. Development and application of a rat ovarian gene expression database.

    PubMed

    Jo, Misung; Gieske, Mary C; Payne, Charles E; Wheeler-Price, Sarah E; Gieske, Joseph B; Ignatius, Ignatius V; Curry, Thomas E; Ko, Chemyong

    2004-11-01

    The pituitary gonadotropins play a key role in follicular development and ovulation through the induction of specific genes. To identify these genes, we have constructed a genome-wide rat ovarian gene expression database (rOGED). The database was constructed from total RNA isolated from intact ovaries, granulosa cells, or residual ovarian tissues collected from immature pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin-treated rats at 0 h (no PMSG), 12 h, and 48 h post PMSG, as well as 6 and 12 h post human chorionic gonadotropin. The total RNA was used for DNA microarray analysis using Affymetrix Rat Expression Arrays 230A and 230B (Affymetrix, Santa Clara, CA). The microarray data were compiled and used for display of individual gene expression profiles through specially developed software. The final rOGED provides immediate analysis of temporal gene expression profiles for over 28,000 genes in intact ovaries, granulosa cells, and residual ovarian tissue during follicular growth and the preovulatory period. The accuracy of the rOGED was validated against the gene profiles for over 20 known genes. The utility of the rOGED was demonstrated by identifying six genes that have not been described in the rat periovulatory ovary. The mRNA expression patterns and cellular localization for each of these six genes (estrogen sulfotransferase, synaptosomal-associated protein 25 kDa, runt-related transcription factor, calgranulin B, alpha1-macroglobulin, and MAPK phosphotase-3) were confirmed by Northern blot analyses and in situ hybridization, respectively. The current findings demonstrate that the rOGED can be used as an instant reference for ovarian gene expression profiles, as well as a reliable resource for identifying important yet, to date, unknown ovarian genes.

  19. Evidence for increased recombination near the human insulin gene: implication for disease association studies.

    PubMed Central

    Chakravarti, A; Elbein, S C; Permutt, M A

    1986-01-01

    Haplotypes for four new restriction site polymorphisms (detected by Rsa I, Taq I, HincII, and Sac I) and a previously identified DNA length polymorphism (5' FP), all at the insulin locus, have been studied in U.S. Blacks, African Blacks, Caucasians, and Pima Indians. Black populations are polymorphic for all five markers, whereas the other groups are polymorphic for Rsa I, Taq I, and 5' FP only. The data suggest that approximately equal to 1 in 550 base pairs is variant in this region. The polymorphisms, even though located within 20 kilobases, display low levels of nonrandom association. Population genetic analysis suggests that recombination within this 20-kilobase segment occurs 24 times more frequently than expected if crossing-over occurred uniformly throughout the human genome. These findings suggest that population associations between DNA polymorphisms and disease susceptibility genes near the insulin gene or structural mutations in the insulin gene will be weak. Thus, population studies would probably require large sample sizes to detect associations. However, the low levels of nonrandom association increase the information content of the locus for linkage studies, which is the best alternative for discovering disease susceptibility genes. PMID:3006026

  20. The EU FP6 EpiGenChlamydia Consortium: contribution of molecular epidemiology and host-pathogen genomics to understanding Chlamydia trachomatis-related disease.

    PubMed

    Morré, S A; Ouburg, S; Peña, A S; Brand, A

    2009-11-01

    Chlamydia trachomatis infections are responsible for the world's leading cause of blindness (trachoma) and its most prevalent sexually transmitted disease, which is strongly associated with pelvic inflammatory disease, ectopic pregnancy and tubal infertility. Twin study-based findings of members of EpiGenChlamydia Consortium estimate that there is a 40% genetic predisposition to C. trachomatis infections. It is likely that the advances in human genomics will help to unravel the genetic predisposition at the gene level and will help to define a genetic fingerprint that can be used as a marker for this predisposition. The information gathered to date suggests that this predisposition and the factors contributing to prognosis are multifactorial. The EpiGenChlamydia Consortium aims to structure transnational research to such a degree that comparative genomics and genetic epidemiology can be performed in large numbers of unrelated individuals. Biobanking and data-warehouse building are the most central deliverables of the Coordination Action of the Consortium in Functional Genomics Research. In addition, the collective synergy acquired in this Coordination Action will allow for the generation of scientific knowledge on the C. trachomatis-host interaction, knowledge on the genetic predisposition to C. trachomatis infection and the development of tools for early detection of a predisposition to C. trachomatis infection and its complications. This review summarizes the consortium aims and progress, and future perspectives and directions.

  1. GWA analysis for milk production traits in dairy sheep and genetic support for a QTN influencing milk protein percentage in the LALBA gene.

    PubMed

    García-Gámez, Elsa; Gutiérrez-Gil, Beatriz; Sahana, Goutam; Sánchez, Juan-Pablo; Bayón, Yolanda; Arranz, Juan-José

    2012-01-01

    In this study, we used the Illumina OvineSNP50 BeadChip to conduct a genome-wide association (GWA) analysis for milk production traits in dairy sheep by analyzing a commercial population of Spanish Churra sheep. The studied population consisted of a total of 1,681 Churra ewes belonging to 16 half-sib families with available records for milk yield (MY), milk protein and fat yields (PY and FY) and milk protein and fat contents (PP and FP). The most significant association identified reached experiment-wise significance for PP and FP and was located on chromosome 3 (OAR3). These results confirm the population-level segregation of a previously reported QTL affecting PP and suggest that this QTL has a significant pleiotropic effect on FP. Further associations were detected at the chromosome-wise significance level on 14 other chromosomal regions. The marker on OAR3 showing the highest significant association was located at the third intron of the alpha-lactalbumin (LALBA) gene, which is a functional and positional candidate underlying this association. Sequencing this gene in the 16 Churra rams of the studied resource population identified additional polymorphisms. One out of the 31 polymorphisms identified was located within the coding gene sequence (LALBA_g.242T>C) and was predicted to cause an amino acid change in the protein (Val27Ala). Different approaches, including GWA analysis, a combined linkage and linkage disequilibrium study and a concordance test with the QTL segregating status of the sires, were utilized to assess the role of this mutation as a putative QTN for the genetic effects detected on OAR3. Our results strongly support the polymorphism LALBA_g.242T>C as the most likely causal mutation of the studied OAR3 QTL affecting PP and FP, although we cannot rule out the possibility that this SNP is in perfect linkage disequilibrium with the true causal polymorphism.

  2. Gene Therapy

    MedlinePlus

    ... cells in an effort to treat or stop disease. Genes contain your DNA — the code that controls much of your body's form and function, from making you grow taller to regulating your body systems. Genes that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds ...

  3. A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release

    NASA Astrophysics Data System (ADS)

    Yang, Yi; Zhao, Hang; Jia, Yanpeng; Guo, Qingfa; Qu, Ying; Su, Jing; Lu, Xiaoling; Zhao, Yongxiang; Qian, Zhiyong

    2016-02-01

    Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release.

  4. A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release.

    PubMed

    Yang, Yi; Zhao, Hang; Jia, YanPeng; Guo, QingFa; Qu, Ying; Su, Jing; Lu, XiaoLing; Zhao, YongXiang; Qian, ZhiYong

    2016-02-17

    Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release.

  5. A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release

    PubMed Central

    Yang, Yi; Zhao, Hang; Jia, YanPeng; Guo, QingFa; Qu, Ying; Su, Jing; Lu, XiaoLing; Zhao, YongXiang; Qian, ZhiYong

    2016-01-01

    Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate-poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA-PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate-poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release. PMID:26883682

  6. Reference gene for primary culture of prostate cancer cells.

    PubMed

    Souza, Aline Francielle Damo; Brum, Ilma Simoni; Neto, Brasil Silva; Berger, Milton; Branchini, Gisele

    2013-04-01

    Selection of reference genes to normalize mRNA levels between samples is critical for gene expression studies because their expression can vary depending on the tissues or cells used and the experimental conditions. We performed ten cell cultures from samples of prostate cancer. Cells were divided into three groups: control (with no transfection protocol), cells transfected with siRNA specific to knockdown the androgen receptor and cells transfected with inespecific siRNAs. After 24 h, mRNA was extracted and gene expression was analyzed by Real-time qPCR. Nine candidates to reference genes for gene expression studies in this model were analyzed (aminolevulinate, delta-, synthase 1 (ALAS1); beta-actin (ACTB); beta-2-microglobulin (B2M); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); hypoxanthine phosphoribosyltransferase 1 (HPRT1); succinate dehydrogenase complex, subunit A, flavoprotein (Fp) (SDHA); TATA box binding protein (TBP); ubiquitin C (UBC); tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ)). Expression stability was calculated NormFinder algorithm to find the most stable genes. NormFinder calculated SDHA as the most stable gene and the gene with the lowest intergroup and intragroup variation, and indicated GAPDH and SDHA as the best combination of two genes for the purpose of normalization. Androgen receptor mRNA expression was evaluated after normalization by each candidate gene and showed statistical difference in the transfected group compared to control group only when normalized by combination of GAPDH and SDHA. Based on the algorithm analysis, the combination of SDHA and GAPDH should be used to normalize target genes mRNA levels in primary culture of prostate cancer cells submitted to transfection with siRNAs.

  7. Gene Positioning

    PubMed Central

    Ferrai, Carmelo; de Castro, Inês Jesus; Lavitas, Liron; Chotalia, Mita; Pombo, Ana

    2010-01-01

    Eukaryotic gene expression is an intricate multistep process, regulated within the cell nucleus through the activation or repression of RNA synthesis, processing, cytoplasmic export, and translation into protein. The major regulators of gene expression are chromatin remodeling and transcription machineries that are locally recruited to genes. However, enzymatic activities that act on genes are not ubiquitously distributed throughout the nucleoplasm, but limited to specific and spatially defined foci that promote preferred higher-order chromatin arrangements. The positioning of genes within the nuclear landscape relative to specific functional landmarks plays an important role in gene regulation and disease. PMID:20484389

  8. The Caulobacter crescentus flaFG region regulates synthesis and assembly of flagellin proteins encoded by two genetically unlinked gene clusters.

    PubMed Central

    Schoenlein, P V; Lui, J; Gallman, L; Ely, B

    1992-01-01

    At a specific time in the Caulobacter crescentus cell cycle, a single flagellar filament and multiple receptor sites for the swarmer-specific phage phi Cbk are assembled at one pole of the predivisional cell. One cluster of genes required for this morphogenesis, the flaYG region, includes the flgJKL genes, which encode structural proteins of the flagellar filament. These flagellin genes are flanked by genes required for filament assembly, the flaYE genes at one end and the flaF-flbT-flbA-flaG genes at the other. In this study, we characterized mutants carrying large chromosomal deletions within this region. Several of these strains are phi CbK resistant and produce a novel 22-kDa flagellin that is not assembled into flagella. Merodiploid strains containing either the entire flaFG region or individual fla transcription units from this region were constructed. These strains were used to correlate the presence or absence of specific gene products to changes in flagellin synthesis, filament assembly, or phage sensitivity. As a result of these studies, we were able to conclude that (i) the production of the 22-kDa flagellin results from the absence of the flbA and flaG gene products, which appear to be components of a flagellin-processing pathway common to the 25-, 27-, and 29-kDa flagellins; (ii) flbT negatively modulates the synthesis of the 27- and 25-kDa flagellins from two genetically unlinked gene clusters; (iii) flgL is the only flagellin gene able to encode the 27-kDa flagellin, and this flagellin appears to be required for the efficient assembly of the 25-kDa flagellins; (iv) flaF is required for filament assembly; and (v) phi CbK resistance results from the deletion of at least two genes in the flaFG region. Images PMID:1400155

  9. Induction of apoptosis in cancer cells through N-acetyl-l-leucine-modified polyethylenimine-mediated p53 gene delivery.

    PubMed

    Li, Zhiyuan; Zhang, Liu; Li, Quanshun

    2015-11-01

    Herein, N-acetyl-L-leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine(2000). Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.

  10. Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

    PubMed

    Bousquet, J; Anto, J M; Akdis, M; Auffray, C; Keil, T; Momas, I; Postma, D S; Valenta, R; Wickman, M; Cambon-Thomsen, A; Haahtela, T; Lambrecht, B N; Lodrup Carlsen, K C; Koppelman, G H; Sunyer, J; Zuberbier, T; Annesi-Maesano, I; Arno, A; Bindslev-Jensen, C; De Carlo, G; Forastiere, F; Heinrich, J; Kowalski, M L; Maier, D; Melén, E; Palkonen, S; Smit, H A; Standl, M; Wright, J; Asarnoj, A; Benet, M; Ballardini, N; Garcia-Aymerich, J; Gehring, U; Guerra, S; Hohman, C; Kull, I; Lupinek, C; Pinart, M; Skrindo, I; Westman, M; Smagghe, D; Akdis, C; Albang, R; Anastasova, V; Anderson, N; Bachert, C; Ballereau, S; Ballester, F; Basagana, X; Bedbrook, A; Bergstrom, A; von Berg, A; Brunekreef, B; Burte, E; Carlsen, K H; Chatzi, L; Coquet, J M; Curin, M; Demoly, P; Eller, E; Fantini, M P; Gerhard, B; Hammad, H; von Hertzen, L; Hovland, V; Jacquemin, B; Just, J; Keller, T; Kerkhof, M; Kiss, R; Kogevinas, M; Koletzko, S; Lau, S; Lehmann, I; Lemonnier, N; McEachan, R; Mäkelä, M; Mestres, J; Minina, E; Mowinckel, P; Nadif, R; Nawijn, M; Oddie, S; Pellet, J; Pin, I; Porta, D; Rancière, F; Rial-Sebbag, A; Saeys, Y; Schuijs, M J; Siroux, V; Tischer, C G; Torrent, M; Varraso, R; De Vocht, J; Wenger, K; Wieser, S; Xu, C

    2016-11-01

    MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

  11. FP-LAPW methodology based theoretical investigation of structural, electronic and optical properties of MgxPb1-xS, MgxPb1-xSe and MgxPb1-xTe ternary alloys

    NASA Astrophysics Data System (ADS)

    Chattopadhyaya, Surya; Bhattacharjee, Rahul

    2017-01-01

    The structural, electronic and optical properties of MgxPb1-xS, MgxPb1-xSe and MgxPb1-xTe alloys for 0≤ x≤1 in their rock-salt (B1) crystallographic phase have been calculated using the full-potential linearized augmented plane wave (FP-LAPW) method under the framework of density functional theory (DFT). Using the Wu-Cohen generalized-gradient approximation (WC-GGA) induced exchange-correlation potential scheme, the ground state structural parameters such as equilibrium lattice constants, bulk modulus and its pressure derivatives are calculated and deviations of the lattice constants from Vegard's law and the bulk modulus from linear concentration dependence have been observed for the alloys. Electronic band structures and density of states have been calculated using Tran-Blaha modified Becke-Johnsoexit3b2tex.batn (TB-mBJ) parameterization scheme to study the electronic properties of the binary compounds and their ternary alloys. Using the approach of Zunger and co-workers, the microscopic origins of band gap bowing have been discussed in term of volume deformation, charge exchange and structural relaxation. Optical properties of the binary compounds and their ternary alloys have been calculated in terms of their respective dielectric function, refractive index, reflectivity and optical conductivity. Few calculated results are compared with available experimental and other theoretical data.

  12. Chitosan-graft-polyethylenimine/DNA nanoparticles as novel non-viral gene delivery vectors targeting osteoarthritis.

    PubMed

    Lu, Huading; Dai, Yuhu; Lv, Lulu; Zhao, Huiqing

    2014-01-01

    The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. The present study was designed to develop and evaluate the chitosan-graft-polyethylenimine (CP)/DNA nanoparticles as novel non-viral gene vectors for gene therapy of osteoarthritis. The CP/DNA nanoparticles were produced through a complex coacervation of the cationic polymers with pEGFP after grafting chitosan (CS) with a low molecular weight (Mw) PEI (Mw = 1.8 kDa). Particle size and zeta potential were related to the weight ratio of CP:DNA, where decreases in nanoparticle size and increases in surface charge were observed as CP content increased. The buffering capacity of CP was significantly greater than that of CS. The transfection efficiency of CP/DNA nanoparticles was similar with that of the Lipofectamine™ 2000, and significantly higher than that of CS/DNA and PEI (25 kDa)/DNA nanoparticles. The transfection efficiency of the CP/DNA nanoparticles was dependent on the weight ratio of CP:DNA (w/w). The average cell viability after the treatment with CP/DNA nanoparticles was over 90% in both chondrocytes and synoviocytes, which was much higher than that of PEI (25 kDa)/DNA nanoparticles. The CP copolymers efficiently carried the pDNA inside chondrocytes and synoviocytes, and the pDNA was detected entering into nucleus. These results suggest that CP/DNA nanoparticles with improved transfection efficiency and low cytotoxicity might be a safe and efficient non-viral vector for gene delivery to both chondrocytes and synoviocytes.

  13. Gene doping.

    PubMed

    Azzazy, Hassan M E

    2010-01-01

    Gene doping abuses the legitimate approach of gene therapy. While gene therapy aims to correct genetic disorders by introducing a foreign gene to replace an existing faulty one or by manipulating existing gene(s) to achieve a therapeutic benefit, gene doping employs the same concepts to bestow performance advantages on athletes over their competitors. Recent developments in genetic engineering have contributed significantly to the progress of gene therapy research and currently numerous clinical trials are underway. Some athletes and their staff are probably watching this progress closely. Any gene that plays a role in muscle development, oxygen delivery to tissues, neuromuscular coordination, or even pain control is considered a candidate for gene dopers. Unfortunately, detecting gene doping is technically very difficult because the transgenic proteins expressed by the introduced genes are similar to their endogenous counterparts. Researchers today are racing the clock because assuring the continued integrity of sports competition depends on their ability to develop effective detection strategies in preparation for the 2012 Olympics, which may mark the appearance of genetically modified athletes.

  14. Gene therapy.

    PubMed

    Williamson, B

    1982-07-29

    Gene therapy is not yet possible, but may become feasible soon, particularly for well understood gene defects. Although treatment of a patient raises no ethical problems once it can be done well, changing the genes of an early embryo is more difficult, controversial and unlikely to be required clinically.

  15. Gene discovery for Mendelian conditions via social networking: de novo variants in KDM1A cause developmental delay and distinctive facial features

    PubMed Central

    Chong, Jessica X.; Yu, Joon-Ho; Lorentzen, Peter; Park, Karen M.; Jamal, Seema M.; Tabor, Holly K.; Rauch, Anita; Saenz, Margarita Sifuentes; Boltshauser, Eugen; Patterson, Karynne E.; Nickerson, Deborah A.; Bamshad, Michael J.

    2015-01-01

    Purpose The pace of Mendelian gene discovery is slowed by the “n-of-1 problem” – the difficulty of establishing causality of a putatively pathogenic variant in a single person or family. Identification of an unrelated person with an overlapping phenotype and suspected pathogenic variant in the same gene can overcome this barrier but is often impeded by lack of a convenient or widely-available way to share data on candidate variants / genes among families, clinicians and researchers. Methods Social networking among families, clinicians and researchers was used to identify three children with variants of unknown significance in KDM1A and similar phenotypes. Results De novo variants in KDM1A underlie a new syndrome characterized by developmental delay and distinctive facial features. Conclusion Social networking is a potentially powerful strategy to discover genes for rare Mendelian conditions, particularly those with non-specific phenotypic features. To facilitate the efforts of families to share phenotypic and genomic information with each other, clinicians, and researchers, we developed the Repository for Mendelian Genomics Family Portal (RMD-FP). Design and development of a web-based tool, MyGene2, that enables families, clinicians and researchers to search for gene matches based on analysis of phenotype and exome data deposited into the RMD-FP is underway. PMID:26656649

  16. Tropospheric NO2 and HCHO columns derived from ground-based MAX-DOAS system in Guangzhou, China and comparison with satellite observations: First results within the EU FP7 project MarcoPolo

    NASA Astrophysics Data System (ADS)

    Drosoglou, Theano; Kouremeti, Natalia; Bais, Alkis; Zyrichidou, Irene; Li, Shu; Balis, Dimitris; Huang, Zhonghui

    2016-04-01

    A miniature MAX-DOAS system, Phaethon, has been developed at the Laboratory of Atmospheric Physics of the Aristotle University of Thessaloniki, Greece, for ground-based monitoring of column densities of atmospheric gases. Simultaneous measurements with two Phaethon systems at the city centre of Thessaloniki and at a rural location about 30 km away have shown that Phaethon provides NO2 and HCHO tropospheric column measurements of acceptable accuracy under both low and high air-pollution levels. Currently three systems have been deployed in areas with different pollution patterns to support air quality and satellite validation studies. In the framework of the EU FP7 Monitoring and Assessment of Regional air quality in China using space Observations, Project Of Long-term sino-european co-Operation, MarcoPolo project, one of the Phaethon systems has been installed since April 2015 in the Guangzhou region in China. Tropospheric NO2 and HCHO columns derived at Guangzhou during the first 10 months of operation are compared with corresponding retrievals from OMI/Aura and GOME-2/Metop-A and /Metop-B satellite sensors. The area is characterized by humid subtropical monsoon climate and cloud-free conditions are rather rare from early March to mid-October. Despite this limitation and the short period of operation of Phaethon in Guangzhou, the agreement between ground-based and satellite observations is generally good for both NO2 and HCHO. It appears that GOME-2 sensors seem to underestimate the tropospheric NO2, possibly due to their large pixel size, whereas the comparison with OMI data is better, especially when a small cloud fraction (< 0.2) is used for cloud screening.

  17. High-power and 2.5 kW advanced-technology ion thruster

    NASA Technical Reports Server (NTRS)

    Poeschel, R. L.

    1977-01-01

    Investigations for improving ion thruster components in the 30 cm engineering model thruster (EMT) resulted in the demonstration of useful techniques for grid short removal and discharge chamber erosion monitoring, establishment of relationships between double ion production and thruster operating parameters, verification of satisfactory specifications on porous tungsten vaporizer material and barium impregnated porous tungsten inserts, demonstration of a new hollow cathode configuration, and specification of magnetic circuit requirements for reproducing desired magnetic mappings. The capacity of a 30 cm EMT to operate at higher beam voltages and currents (higher power) was determined. Operation at 2 A beam current and higher beam voltage is shown to be essentially equivalent to operation at 1.1 kV with regard to efficiency, lifetime and operating conditions. The only additional requirement is an improvement in high voltage insulation and propellant isolator capacity. Operation at minimum voltage and higher beam currents is shown to increase thruster discharge chamber erosion in proportion to beam current. Studies to find alternatives to molybdenum for manufacturing ion optics grids are also reported.

  18. Permanent-magnet Faraday isolator with the field intensity of 25 kOe

    SciTech Connect

    Mironov, E A; Snetkov, I L; Voitovich, A V; Palashov, O V

    2013-08-31

    A Faraday isolator with a single magneto-optical element is constructed and experimentally tested. It provides the isolation ratio of 30 dB at an average laser radiation power of 650 W. These parameters are obtained by increasing the field intensity in the magnetic system of the isolator and employing a low-absorption magneto-optical element. (elements of laser devices)

  19. Test Results for the 2.5-kVA Ground Fault Detector.

    DTIC Science & Technology

    1986-01-01

    Officer. Code 60 Williamsburg , VA NAVCOASTSYSCEN CO. Panama City, FL; Code 223(0 (J. Quirk) Panama City. FL; Code 423, Panama City. FL; Code 630...Twentynine Plams, CA; ROICC/AROICC, Brooklyn , NY. ROICC/AROICC. Colts Neck. NJ; ROICC/OICC, SPA, Norfolk, VA; SW Pac, Dir. Engr Div, Mania. RP; SW Pac. OICC...Supt (Code 453). Vallejo. CA NAVSTA A. Sugihara, Pearl Harbor. HI; CO. Brooklyn , NY; CO, Long Beach. CA; CO. Roosevelt Roads. PR; Code 18. Midway

  20. The 2.5 kW advanced technology ion thruster. [design analysis and performance tests

    NASA Technical Reports Server (NTRS)

    Poeschel, R. L.

    1976-01-01

    A representative thruster was extensively documented with respect to performance parameters and characteristics at selected ion beam currents in the 0.5 to 2.75 A range, including measurements of thrust losses resulting from doubly-charged ions and ion beam divergence. Corrected total efficiency was shown to be relatively insensitive to operating parameter selection at any given power level. Factors affecting doubly-charged ionization were studied and it was found that the fraction of doubly-charged ions is directly proportional to the discharge chamber propellant utilization. The parameter that most affects this proportionality is the accel aperture diameter (which controls neutral atom loss). Thruster-power conditioner interactions were studied with the result that previous power supply specifications remain satisfactory. Options for reducing the number of power supplies required were demonstrated to be feasible. Gimbal actuator designs were studied with the goal of selecting a particular approach for design and development. The conclusion drawn was that optimum gimbal actuator design depends heavily on the thruster application and consequently the effort was concluded by developing a computer program to aid in specifying the gimbal requirements for the thrust vectoring required in a specific application.

  1. Low Molecular Weight Oligomers with Aromatic Backbone as Efficient Nonviral Gene Vectors.

    PubMed

    Luan, Chao-Ran; Liu, Yan-Hong; Zhang, Ji; Yu, Qing-Ying; Huang, Zheng; Wang, Bing; Yu, Xiao-Qi

    2016-05-04

    A series of oligomers were synthesized via ring-opening polymerization. Although the molecular weights of these oligomers are only ∼2.5 kDa, they could efficiently bind and condense DNA into nanoparticles. These oligomers gave comparable transfection efficiency (TE) to PEI 25 kDa, while their TE could even increase with the presence of serum, and up to 65 times higher TE than PEI was obtained. The excellent serum tolerance was also confirmed by TEM, flow cytometry, and BSA adsorption assay. Moreover, structure-activity relationship studies revealed some interesting factors. First, oligomers containing aromatic rings in the backbone showed better DNA binding ability. These materials could bring more DNA cargo into the cells, leading to much better TE. Second, the isomerism of the disubstituted phenyl group on the oligomer backbone has large effect on the transfection. The ortho-disubstituted ones gave at least 1 order of magnitude higher TE than meta- or para-disubstituted oligomers. Gel electrophoresis involving DNase and heparin indicated that the difficulty to release DNA might contribute to the lower TE of the latter. Such clues may help us to design novel nonviral gene vectors with high efficiency and biocompatibility.

  2. Gene dispensability.

    PubMed

    Korona, Ryszard

    2011-08-01

    Genome-wide mutagenesis studies indicate that up to about 90% of genes in bacteria and 80% in eukaryotes can be inactivated individually leaving an organism viable, often seemingly unaffected. Several strategies are used to learn what these apparently dispensable genes contribute to fitness. Assays of growth under hundreds of physical and chemical stresses are among the most effective experimental approaches. Comparative studies of genomic DNA sequences continue to be valuable in discriminating between the core bacterial genome and the more variable niche-specific genes. The concept of the core genome appears currently unfeasible for eukaryotes but progress has been made in understanding why they contain numerous gene duplicates.

  3. Nano-carrier for gene delivery and bioimaging based on carbon dots with PEI-passivation enhanced fluorescence.

    PubMed

    Liu, Changjun; Zhang, Peng; Zhai, Xinyun; Tian, Feng; Li, Wenchen; Yang, Jianhai; Liu, Yuan; Wang, Hongbo; Wang, Wei; Liu, Wenguang

    2012-05-01

    Polyethylenimine (PEI) functionalized carbon dots (CD-PEI) were fabricated by one-step microwave assisted pyrolysis of glycerol and branched PEI25k mixture where the formation of carbon nanoparticles and the surface passivation were accomplished simultaneously. In this hybrid C-dot, PEI molecule played two key roles in the system - as a nitrogen-rich compound to passivate surface to enhance the fluorescence and as a polyelectrolyte to condense DNA. This CD-PEI was shown to be water soluble and emit stable bright multicolor fluorescence relying on excitation wavelength. The DNA condensation capability and cytotoxicity of CD-PEI could be regulated by pyrolysis time possibly due to the somewhat destruction of PEI during the formation of carbon dots. CD-PEI obtained at an appropriate pyrolysis time exhibited lower toxicity, higher or comparable gene expression of plasmid DNA in COS-7 cells and HepG2 cells relative to control PEI25k. Intriguingly, the CD-PEIs internalized into cells displayed tunable fluorescent emission under varying excitation wavelength, suggesting the potential application of CD-PEI in gene delivery and bioimaging.

  4. Cyclen-based lipidic oligomers as potential gene delivery vehicles.

    PubMed

    Yi, Wen-Jing; Zhang, Qin-Fang; Zhang, Ji; Liu, Qiang; Ren, Laifeng; Chen, Qian-Ming; Guo, Liandi; Yu, Xiao-Qi

    2014-03-01

    A series of cyclen-based linear oligomers bearing hydrophobic long chains (lipopolymers Cy-LC, where Cy and LC represent cyclen-based linear backbone and hydrophobic long chain substituents, respectively) were designed and synthesized. The effects of type and degree of substitution (DS) of hydrophobic long chains on the transfection efficiency were systematically studied. The nitrogen atoms with relatively strong basicity on the cyclen ensure their good DNA binding ability, which was confirmed by gel retardation and ethidium bromide exclusion assays. Lipopolyplexes could be formed as nanoparticles with suitable sizes and zeta potentials for gene transfection. In vitro gene delivery experiments revealed that the linoleic acid (LIN) substituted material Cy-LIN has better transfection efficiency than 25 kDa polyethylenimine in the absence or in the presence of serum. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and hemolysis assays showed low cytotoxicity and good biocompatibility of the lipopolyplexes. Fluorescent labeled DNA was used to study the cellular uptake and intracellular distribution of transfected DNA. Flow cytometry results suggested that a long chain is necessary for efficient cellular uptake, and images from confocal laser scanning microscopy showed that after 4h transfection, most of the fluorescent labeled DNA accumulated in the perinuclear region, which was required for efficient gene expression. Moreover, it was also found that the DS of the hydrophobic moiety can adjust the balance between DNA binding ability and dissociation of polyplexes, significantly affecting the transfection efficiency.

  5. Trichoderma genes

    DOEpatents

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  6. Gene therapy.

    PubMed

    Drugan, A; Miller, O J; Evans, M I

    1987-01-01

    Severe genetic disorders are potentially correctable by the addition of a normal gene into tissues. Although the technical problems involving integration, stable expression, and insertional damage to the treated cell are not yet fully solved, enough scientific progress has already been made to consider somatic cell gene therapy acceptable from both the ethical and scientific viewpoints. The resolutions to problems evolving from somatic cell gene therapy will help to overcome the technical difficulties encountered presently with germ line gene manipulation. This procedure would then become morally permissible as it will cause, in time, a reduction in the pool of abnormal genes in the population. Enhancement genetic engineering is technically feasible but morally unacceptable. Eugenic genetic engineering is not technically possible or ethically permissible in the foreseeable future.

  7. Synthesis of a new potential biodegradable disulfide containing poly(ethylene imine)-poly(ethylene glycol) copolymer cross-linked with click cluster for gene delivery.

    PubMed

    Zhao, Nan; Roesler, Susanne; Kissel, Thomas

    2011-06-15

    Poly(ethylene glycol)-grafted-polyethylenimine (PEG-PEI) are promising non-viral gene delivery systems. Herein, we aimed to synthesize a biodegradable disulfide containing PEGylated PEI to attempt to reduce its cytotoxicity and enhance the gene transfer activity. Using click chemistry, low Mw PEI (br. 2 kDa) and short chain length PEG (tetraethylene glycol, TEG) were cross-linked to a high Mw PEG-PEI copolymer (∼ 22 kDa). The chemical structure of the copolymer was characterized using (1)H NMR and GPC. The degradation behavior was investigated under in vitro conditions in the presence of 1,4-dithiothreitol (DTT). The gel retardation assay, dynamic light scattering and atomic force microscopy showed good DNA condensation ability by forming polyplexes with small particle size and positive zeta potential. In particular, MTT assay indicated that this PEG-PEI polymer is about 22-fold less toxic than PEI 25k and only 2-fold more toxic than PEI 2k in L929 cell line. After coupling of small PEG chains and cross-linking by disulfide bridges, the transfection efficiency is increased approximately 6-fold in comparison to PEI 2k and still reaches approximately 17% of PEI 25k. Hence, this click cluster cross-linked disulfide containing PEG-PEI copolymer could be an attractive cationic polymer for non-viral gene delivery.

  8. [Gene and gene sequence patenting].

    PubMed

    Bergel, S D

    1998-01-01

    According to the author, the patenting of elements isolated or copied from the human body boils down to the issue of genes and gene sequences. He describes the current situation from the comparative law standpoint (U.S. and Spanish law mainly) and then esamines the biotechnology industry's position.

  9. EU-FP7-iMARS: Analysis of Mars Multi-Resolution Images Using Auto-Coregistration Data Mining and Crowd Source Techniques: Processed Results - a First Look

    NASA Astrophysics Data System (ADS)

    Muller, Jan-Peter; Tao, Yu; Sidiropoulos, Panagiotis; Gwinner, Klaus; Willner, Konrad; Fanara, Lida; Waehlisch, Marita; van Gasselt, Stephan; Walter, Sebastian; Steikert, Ralf; Schreiner, Bjoern; Ivanov, Anton; Cantini, Federico; Wardlaw, Jessica; Morley, Jeremy; Sprinks, James; Giordano, Michele; Marsh, Stuart; Kim, Jungrack; Houghton, Robert; Bamford, Steven

    2016-06-01

    Understanding planetary atmosphere-surface exchange and extra-terrestrial-surface formation processes within our Solar System is one of the fundamental goals of planetary science research. There has been a revolution in planetary surface observations over the last 15 years, especially in 3D imaging of surface shape. This has led to the ability to overlay image data and derived information from different epochs, back in time to the mid 1970s, to examine changes through time, such as the recent discovery of mass movement, tracking inter-year seasonal changes and looking for occurrences of fresh craters. Within the EU FP-7 iMars project, we have developed a fully automated multi-resolution DTM processing chain, called the Coregistration ASP-Gotcha Optimised (CASP-GO), based on the open source NASA Ames Stereo Pipeline (ASP) [Tao et al., this conference], which is being applied to the production of planetwide DTMs and ORIs (OrthoRectified Images) from CTX and HiRISE. Alongside the production of individual strip CTX & HiRISE DTMs & ORIs, DLR [Gwinner et al., 2015] have processed HRSC mosaics of ORIs and DTMs for complete areas in a consistent manner using photogrammetric bundle block adjustment techniques. A novel automated co-registration and orthorectification chain has been developed by [Sidiropoulos & Muller, this conference]. Using the HRSC map products (both mosaics and orbital strips) as a map-base it is being applied to many of the 400,000 level-1 EDR images taken by the 4 NASA orbital cameras. In particular, the NASA Viking Orbiter camera (VO), Mars Orbiter Camera (MOC), Context Camera (CTX) as well as the High Resolution Imaging Science Experiment (HiRISE) back to 1976. A webGIS has been developed [van Gasselt et al., this conference] for displaying this time sequence of imagery and will be demonstrated showing an example from one of the HRSC quadrangle map-sheets. Automated quality control [Sidiropoulos & Muller, 2015] techniques are applied to screen for

  10. Ab-initio DFT FP-LAPW GGA and LDA TB-mBJ and SO theoretical study of structural and elastic properties of Zinc-Blende crystal phase GaAs1-xBix alloys

    NASA Astrophysics Data System (ADS)

    Menezla, S.; Kadri, A.; Zitouni, K.; Djelal, A.; Djermouni, M.; Hallouche, A.; Zaoui, A.

    2015-12-01

    We present an ab-initio theoretical study of structural and elastic properties of GaAs1-xBix alloys in the Zinc-Blende (ZB) phase. We use a recent version of Wien2k package code based on Density Functional Theory (DFT) Full Potential and Linearized Augmented Plane Waves (FP-LAPW) method including recent Tran-Blaha modified Becke-Johnson correction of the exchange potential (TB-mBJ) and the spin-orbit interaction (SO). The calculations are performed within the Local Density Approximation (LDA) as well as the Generalized Gradient Approximation (GGA). We study first the structural properties of GaAs1-xBix alloys by solving Murnaghan equation of state. Our results show that the ZB phase is the lowest equilibrium crystal structure of GaAs1-xBix in the whole alloy composition range, in agreement with previous theoretical predictions. The variations versus Bi contents of the ZB GaAs1-xBix lattice constant a0, bulk modulus B0 and its pressure derivative B0‧ are also found very close to other theoretical and experimental data, but with much smaller bowing effects indicating a better resolution thanks to TB-mBJ correction. The variations of B0 versus the reverse equilibrium volume of the unit cell (1/V0) are found to be described by the simple linear empirical expression B0 = -0.21068 + 0.16695/V0 which is close to the theoretical prediction for III-V semiconductors with, however, somewhat lower linear coefficients values, suggesting a more metallic behavior. In a second part of this work, we use Birch-Murnaghan approach to study the elastic properties of GaAs1-xBix alloys. The elastic stiffness coefficients, C11, C12 and C44, and their variations versus alloy composition were determined for ZB GaAs1-xBix alloy. Their values in GaAs and GaBi binary compounds are found in very good agreement with available experimental and/or theoretical data. Their variations in GaAs1-xBix alloy show a monotonic decrease with increasing Bi contents, indicating a softening behavior as is

  11. Characterization of tailor-made copolymers of oligo(ethylene glycol) methyl ether methacrylate and N,N-dimethylaminoethyl methacrylate as nonviral gene transfer agents: influence of macromolecular structure on gene vector particle properties and transfection efficiency.

    PubMed

    Uzgün, Senta; Akdemir, Ozgür; Hasenpusch, Günther; Maucksch, Christof; Golas, Monika M; Sander, Bjoern; Stark, Holger; Imker, Rabea; Lutz, Jean-François; Rudolph, Carsten

    2010-01-11

    Oligo(ethylene glycol) methyl ether methacrylates (OEGMA) of various chain lengths (i.e., 9, 23, or 45 EG units) and N,N-dimethylaminoethyl methacrylate (DMAEMA) were copolymerized by atom transfer radical polymerization (ATRP), yielding well-defined P(DMAEMA-co-OEGMA) copolymers with increasing OEGMA molar fractions (F(OEGMA)) but a comparable degree of polymerization (DP approximately 120). Increase of both F(OEGMA) and OEGMA chain lengths correlated inversely with gene vector size, morphology, and zeta potential. P(DMAEMA-co-OEGMA) copolymers prevented gene vector aggregation at high plasmid DNA (pDNA) concentrations in isotonic solution and did not induce cytotoxicity even at high concentrations. Transfection efficiency of the most efficient P(DMAEMA-co-OEGMA) copolymers was found to be >10-fold lower compared with branched polyethylenimine (PEI) 25 kDa. Although OEGMA copolymerization largely reduced gene vector binding with the cell surface, cellular internalization of the bound complexes was less affected. These observations suggest that inefficient endolysosomal escape limits transfection efficiency of P(DMAEMA-co-OEGMA) copolymer gene vectors. Despite this observation, optimized p(DMAEMA-co-OEGMA) gene vectors remained stable under conditions for in vivo application leading to 7-fold greater gene expression in the lungs compared with PEI. Tailor-made P(DMAEMA-co-OEGMA) copolymers are promising nonviral gene transfer agents that fulfill the requirements for successful in vivo gene delivery.

  12. Dataset of proinflammatory cytokine and cytokine receptor gene expression in rainbow trout (Oncorhynchus mykiss) measured using a novel GeXP multiplex, RT-PCR assay.

    PubMed

    Kutyrev, Ivan; Cleveland, Beth; Leeds, Timothy; Wiens, Gregory D

    2017-04-01

    A GeXP multiplex, RT-PCR assay was developed and optimized that simultaneously measures expression of a suite of immune-relevant genes in rainbow trout (Oncorhynchus mykiss), concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. The dataset includes expression values for drpt, il11a, il1b1, il1b2, il1b3, il1r-like-1(e3-5), il1r-like-1(e9-11), il1r1-like-a, il1r1-like-b, il1r2, saa, tnfa1, tnfa2, tnfa3, tnfrsf1a, tnfrsf1a-like-a, tnfrsf1a-like-b, tnfrsf5, and tnfrsf9. Gene expression was measured at four time-points post-challenge in both a resistant line (ARS-Fp-R) and a susceptible line (ARS-Fp-S) of rainbow trout. In addition, fish body weight, spleen index and the Flavobacterium psychrophilum load are reported. These data are an extension of information presented and discussed in "Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss)" (Kutyrev et al., 2016) [1].

  13. Genes V.

    SciTech Connect

    Lewin, B.

    1994-12-31

    This fifth edition book encompasses a wide range of topics covering 1,272 pages. The book is arranged into nine parts with a total of 36 chapters. These nine parts include Introduction; DNA as a Store of Information; Translation; Constructing Cells; Control of Prokaryotypic Gene Expression; Perpetuation of DNA; Organization of the Eukaryotypic Genome; Eukaryotypic Transcription and RNA Processing; The Dynamic Genome; and Genes in Development.

  14. TACN-based cationic lipids with amino acid backbone and double tails: materials for non-viral gene delivery.

    PubMed

    Wang, Bing; Yi, Wen-Jing; Zhang, Ji; Zhang, Qin-Fang; Xun, Miao-Miao; Yu, Xiao-Qi

    2014-04-01

    Cationic lipids have become an efficient type of non-viral vectors for gene delivery. In this Letter, four cationic lipids containing 1,4,7-triazacyclononane (TACN) headgroup, glutamic/aspartic acid backbone and dioleyl tails were designed and synthesized. The TACN headgroup gives these lipids excellent pH buffering capacities, which were higher than branched 25 kDa PEI. Cationic liposomes prepared from these lipids and DOPE showed good DNA affinity, and full DNA condensation was found at N/P ratio of 3 via agarose gel electrophoresis. The lipoplexes were characterized by dynamic light scattering (DLS) assay, which gave proper particle sizes and zeta-potentials for transfection. In vitro gene transfection results in two cell lines reveal that TAN (with aspartic acid and amide bond in the structure) shows the best transfection efficiency, which is close to commercially available transfection agent Lipofectamine 2000.

  15. The RNase PD2 gene of almond (Prunus dulcis) represents an evolutionarily distinct class of S-like RNase genes.

    PubMed

    Ma, R C; Oliveira, M M

    2000-07-01

    A cDNA for an S-like RNase (RNase PD2) has been isolated from a pistil cDNA library of Prunus dulcis cv. Ferragnés. The cDNA encodes an acidic protein of 226 amino acid residues with a molecular weight of 25 kDa. A potential N-glycosylation site is present at the N-terminus in RNase PD2. A signal peptide of 23 amino acid residues and a transmembrane domain are predicted. The two active-site histidines present in enzymes of the T2/S RNase superfamily were detected in RNase PD2. Its amino acid sequence shows 71.2% similarity to RNSI of Arabidopsis and RNase T2 of chickpea, respectively. Northern blotting and RT-PCR analyses indicate that PD2 is expressed predominantly in petals, pistils of open flowers and leaves of the almond tree. Analyses of shoots cultured in vitro suggested that the expression of RNase PD2 is associated with phosphate starvation. Southern analysis detected two sequences related to RNase PD2 in the P. dulcis genome. RFLP analysis showed that S-like RNase genes are polymorphic in different almond cultivars. The PD2 gene sequence was amplified by PCR and two introns were shown to interrupt the coding region. Based on sequence analysis, we have defined three classes of S-like RNase genes, with the PD2 RNase gene representing a distinct class. The significance of the structural divergence of S-like RNase genes is further discussed.

  16. Poly(ethylene glycol) analogs grafted with low molecular weight poly(ethylene imine) as non-viral gene vectors.

    PubMed

    Zhang, Zhenfang; Yang, Cuihong; Duan, Yajun; Wang, Yanming; Liu, Jianfeng; Wang, Lianyong; Kong, Deling

    2010-07-01

    A novel class of non-viral gene vectors consisting of low molecular weight poly(ethylene imine) (PEI) (molecular weight 800 Da) grafted onto degradable linear poly(ethylene glycol) (PEG) analogs was synthesized. First, a Michael addition reaction between poly(ethylene glycol) diacrylates (PEGDA) (molecular weight 258 Da) and d,l-dithiothreitol (DTT) was carried out to generate a linear polymer (PEG-DTT) having a terminal thiol, methacrylate and pendant hydroxyl functional groups. Five PEG-DTT analogs were synthesized by varying the molar ratio of diacrylates to thiols from 1.2:1 to 1:1.2. Then PEI (800 Da) was grafted onto the main chain of the PEG-DTTs using 1,1'-carbonyldiimidazole as the linker. The above reaction gave rise to a new class of non-viral gene vectors, (PEG-DTT)-g-PEI copolymers, which can effectively complex DNA to form nanoparticles. The molecular weights and structures of the copolymers were characterized by gel permeation chromatography, (1)H nuclear magnetic resonance and Fourier transform infrared spectroscopy. The size of the nanoparticles was<200 nm and the surface charge of the nanoparticles, expressed as the zeta potential, was between+20 and+40 mV. Cytotoxicity assays showed that the copolymers exhibited much lower cytotoxicities than high molecular weight PEI (25 kDa). Transfection was performed in cultured HeLa, HepG2, MCF-7 and COS-7 cells. The copolymers showed higher transfection efficiencies than PEI (25 kDa) tested in four cell lines. The presence of serum (up to 30%) had no inhibitory effect on the transfection efficiency. These results indicate that this new class of non-viral gene vectors may be a promising gene carrier that is worth further investigation.

  17. Peptide-Mediated Tumor Targeting by a Degradable Nano Gene Delivery Vector Based on Pluronic-Modified Polyethylenimine

    NASA Astrophysics Data System (ADS)

    Wu, Zhaoyong; Zhan, Shuyu; Fan, Wei; Ding, Xueying; Wu, Xin; Zhang, Wei; Fu, Yinghua; Huang, Yueyan; Huang, Xuan; Chen, Rubing; Li, Mingjuan; Xu, Ningyin; Zheng, Yongxia; Ding, Baoyue

    2016-03-01

    Polyethylenimine (PEI) is considered to be a promising non-viral gene delivery vector. To solve the toxicity versus efficacy and tumor-targeting challenges of PEI used as gene delivery vector, we constructed a novel non-viral vector DR5-TAT-modified Pluronic-PEI (Pluronic-PEI-DR5-TAT), which was based on the attachment of low-molecular-weight polyethylenimine (LMW-PEI) to the amphiphilic polymer Pluronic to prepare Pluronic-modified LMW-PEI (Pluronic-PEI). This was then conjugated to a multifunctional peptide containing a cell-penetrating peptide (TAT) and a synthetic peptide that would bind to DR5—a receptor that is overexpressed in cancer cells. The vector showed controlled degradation, favorable DNA condensation and protection performance. The Pluronic-PEI-DR5-TAT/DNA complexes at an N/P ratio of 15:1 were spherical nanoparticles of 122 ± 11.6 nm and a zeta potential of about 22 ± 2.8 mV. In vitro biological characterization results indicated that Pluronic-PEI-DR5-TAT/DNA complexes had a higher specificity for the DR5 receptor and were taken up more efficiently by tumor cells than normal cells, compared to complexes formed with PEI 25 kDa or Pluronic-PEI. Thus, the novel complexes showed much lower cytotoxicity to normal cells and higher gene transfection efficiency in tumor cells than that exhibited by PEI 25 kDa and Pluronic-PEI. In summary, our novel, degradable non-viral tumor-targeting vector is a promising candidate for use in gene therapy.

  18. ETINDE. Improving the role of a methodological approach and ancillary ethnoarchaeological data application for place vulnerability and resilience to a multi-hazard environment: Mt. Cameroon volcano case study [MIA-VITA project -FP7-ENV-2007-1

    NASA Astrophysics Data System (ADS)

    Ilaria Pannaccione Apa, Maria; Kouokam, Emmanuel; Mbe Akoko, Robert; Peppoloni, Silvia; Fabrizia Buongiorno, Maria; Thierry, Pierre

    2013-04-01

    The FP7 MIA-VITA [Mitigate and assess risk from volcanic impact on terrain and human activities] project has been designed to address multidisciplinary aspects of volcanic threat assessment and management from prevention to crisis management recovery. In the socio-economic analysis carried out at Mt. Cameroon Bakweri and Bakossi ethnic groups, ancillary ethnoarchaeological information has been included to point out the cultural interaction between the volcano and its residents. In 2009-2011, ethnoanthropological surveys and interviews for data collection were carried out at Buea, Limbe, West Coast, Tiko and Muyuka sub-divisions adjacent to Mt. Cameroon. One of the outstanding, results from the Bakweri and Bakossi cultural tradition study: natural hazards are managed and produced by supernatural forces, as: Epasa Moto, God of the Mountain (Mt. Cameroon volcano) and Nyango Na Nwana , Goddess of the sea (Gulf of Guinea). In the case of Mount Cameroon, people may seek the spirit or gods of the mountain before farming, hunting and most recently the undertaking of the Mount Cameroon annual race are done. The spirit of this mountain must be seek to avert or stop a volcanic eruption because the eruption is attributed to the anger of the spirit. Among the Northern Bakweri, the association of spirits with the mountain could also be explained in terms of the importance of the mountain to the people. Most of their farming and hunting is done on the Mountain. Some forest products, for instance, wood for building and furniture is obtained from the forest of the mountain; this implies that the people rely on the Mountain for food, game and architecture/furniture etc. In addition, the eruption of the mountain is something which affects the people. It does not only destroy property, it frustrates people and takes away human lives when it occurs. Because of this economic importance of the Mountain and its unexpected and unwanted eruption, the tendency is to believe that it has some

  19. Natural and Anthropogenic Geohazards in Greater London Observed from Geological and ERS-1/2 and ENVISAT Persistent Scatterers Ground Motion Data: Results from the EC FP7-SPACE PanGeo Project

    NASA Astrophysics Data System (ADS)

    Cigna, Francesca; Jordan, Hannah; Bateson, Luke; McCormack, Harry; Roberts, Claire

    2015-11-01

    We combine geological data and ground motion estimates from satellite ERS-1/2 and ENVISAT persistent scatterer interferometry (PSI) to delineate areas of observed natural and anthropogenic geohazards in the administrative area of Greater London (United Kingdom). This analysis was performed within the framework of the EC FP7-SPACE PanGeo project, and by conforming to the interpretation and geohazard mapping methodology extensively described in the Production Manual (cf. http://www.pangeoproject.eu). We discuss the results of the generation of the PanGeo digital geohazard mapping product for Greater London, and analyse the potential of PSI, geological data and the PanGeo methodology to identify areas of observed geohazards. Based on the analysis of PSI ground motion data sets for the years 1992-2000 and 2002-2010 and geology field campaigns, we identify 25 geohazard polygons, covering a total of ~650 km2. These include not only natural processes such as compaction of deposits on the River Thames flood plain and slope instability, but also anthropogenic instability due to groundwater management and changes in the Chalk aquifer, recent engineering works such as those for the Jubilee Line Extension project and electricity tunnelling in proximity to the River Thames, and the presence of made ground. In many instances, natural and anthropogenic observed geohazards overlap, therefore indicating interaction of different processes over the same areas. In terms of ground area covered, the dominant geohazard is anthropogenic land subsidence caused by groundwater abstraction for a total of ~300 km2, followed by natural compression of River Thames sediments over ~105 km2. Observed ground motions along the satellite line-of-sight are as high as +29.5 and -25.3 mm/year, and indicate a combination of land surface processes comprising ground subsidence and uplift, as well as downslope movements. Across the areas of observed geohazards, urban land cover types from the Copernicus

  20. Cloning, expression and molecular analysis of Iranian Brucella melitensis Omp25 gene for designing a subunit vaccine

    PubMed Central

    Yousefi, Soheil; Tahmoorespur, Mojtaba; Sekhavati, Mohammad Hadi

    2016-01-01

    Brucellosis is a well-known domestic animal infectious disease, which is caused by Brucella bacterium. The outer membrane protein 25 kDa (Omp25) gene plays an important role in simulating of TNF-α, IFN-α, macrophage, and cytokines cells. In the current study molecular cloning and expression analysis of Omp25 gene for designing a subunit vaccine against Brucella was investigated. Amplifying the full length of candidate gene was performed using specific primers. Sub-cloning of this gene conducted using pTZ57R/T vector in TOP10F strain of Escherichia coli(E.coli) as the host. Also, pET32(a)+ vector used for expression in BL21 (DE3) strain of E.coli. Omp25 gene with 642 bp size was amplified and cloned successfully. The expression results were confirmed by sequencing and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analyses which showed 42 kDa protein band correctly. Also, phylogenic analysis showed this gene has a near genetic relation with other Brucella strains. According to our results we can propose this gene as a candidate useful for stimulation of cell-mediated and humoral immunity system in future study. PMID:27920824

  1. Treating colon cancer with a suicide gene delivered by self-assembled cationic MPEG-PCL micelles

    NASA Astrophysics Data System (ADS)

    Duan, Xingmei; Wang, Pan; Men, Ke; Gao, Xiang; Huang, Meijuan; Gou, Maling; Chen, Lijuan; Qian, Zhiyong; Wei, Yuquan

    2012-03-01

    Biodegradable cationic micelles show promise for applications in gene delivery. In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL, MP) micelles in one step, creating novel cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP). These micelles had a mean particle size of 46 +/- 5.6 nm and a zeta potential of 41.8 +/- 0.5 mV, and had the capacity to bind DNA. Compared with PEI25K (the gold standard), DMP micelles had higher transfection efficiency and lower cytotoxicity. Moreover, we used DMP to deliver the Survivin-T34A gene (S-T34A, a suicide gene) to treat colon cancer. DMP delivered the Survivin-T34A gene (DMP/S-T34A) and could induce apoptosis in cancer cells, resulting in inhibition of the growth of C-26 colon cancer cells in vitro. An in vivo study indicated that intraperitoneal administration of DMP micelles delivered the Survivin-T34A gene and efficiently inhibited the growth of abdominal metastatic C-26 colon cancer and the malignant ascites. These data suggest that DMP may be a novel gene carrier, and its delivery of the S-T34A gene may have promising applications in the treatment of colon cancer.

  2. Attention Genes

    ERIC Educational Resources Information Center

    Posner, Michael I.; Rothbart, Mary K.; Sheese, Brad E.

    2007-01-01

    A major problem for developmental science is understanding how the cognitive and emotional networks important in carrying out mental processes can be related to individual differences. The last five years have seen major advances in establishing links between alleles of specific genes and the neural networks underlying aspects of attention. These…

  3. Designer Genes.

    ERIC Educational Resources Information Center

    Miller, Judith; Miller, Mark

    1983-01-01

    Genetic technologies may soon help fill some of the most important needs of humanity from food to energy to health care. The research of major designer genes companies and reasons why the initial mad rush for biotechnology has slowed are reviewed. (SR)

  4. Developmental regulation of insulin-like growth factor-I and growth hormone receptor gene expression.

    PubMed

    Shoba, L; An, M R; Frank, S J; Lowe, W L

    1999-06-25

    During development, the insulin-like growth factor I (IGF-I) gene is expressed in a tissue specific manner; however, the molecular mechanisms governing its developmental regulation remain poorly defined. To examine the hypothesis that expression of the growth hormone (GH) receptor accounts, in part, for the tissue specific expression of the IGF-I gene during development, the developmental regulation of IGF-I and GH receptor gene expression in rat tissues was examined. The level of IGF-I and GH receptor mRNA was quantified in RNA prepared from rats between day 17 of gestation (E17) and 17 months of age (17M) using an RNase protection assay. Developmental regulation of IGF-I gene expression was tissue specific with four different patterns of expression seen. In liver, IGF-I mRNA levels increased markedly between E17 and postnatal day 45 (P45) and declined thereafter. In contrast, in brain, skeletal muscle and testis, IGF-I mRNA levels decreased between P5 and 4M but were relatively unchanged thereafter. In heart and kidney, a small increase in IGF-I mRNA levels was observed between the early postnatal period and 4 months, whereas in lung, minimal changes were observed during development. The changes in GH receptor mRNA levels were, in general, coordinate with the changes in IGF-I mRNA levels, except in skeletal muscle. Interestingly, quantification of GH receptor levels by Western blot analysis in skeletal muscle demonstrated changes coordinate with IGF-I mRNA levels. The levels of the proteins which mediate GH receptor signaling (STAT1, -3, and -5, and JAK2) were quantified by Western blot analysis. These proteins also are expressed in a tissue specific manner during development. In some cases, the pattern of expression was coordinate with IGF-I gene expression, whereas in others it was discordant. To further define molecular mechanisms for the developmental regulation of IGF-I gene expression, protein binding to IGFI-FP1, a protein binding site that is in the major

  5. Nucleotide sequence and expression of the gene encoding the major 25-kilodalton outer membrane protein of Brucella ovis: Evidence for antigenic shift, compared with other Brucella species, due to a deletion in the gene.

    PubMed Central

    Cloeckaert, A; Verger, J M; Grayon, M; Zygmunt, M S; Grépinet, O

    1996-01-01

    The nucleotide sequences encoding the major 25-kDa outer membrane protein (OMP) (omp25 genes) of Brucella ovis 63/290, Brucella melitensis 16M, Brucella suis 1330, Brucella canis RM6/66, and Brucella neotomae 5K33 (all reference strains) were determined and compared with that of Brucella abortus 544 (P. de Wergifosse, P. Lintermans, J. N. Limet, and A. Cloeckaert, J. Bacteriol. 177:1911-1914, 1995). The major difference found was between the omp25 gene of B. ovis and those of the other Brucella species; the B. ovis gene had a 36-bp deletion located at the 3' end of the gene. The corresponding regions of other Brucella species contain two 8-bp direct repeats and two 4-bp inverted repeats, which could have been involved in the genesis of the deletion. The mechanism responsible for the genesis of the deletion appears to be related to the "slipped mispairing" mechanism described in the literature. Expression of the 25-kDa outer membrane protein (Omp25) in Brucella spp. or expression from the cloned omp25 gene in Escherichia coli cells was studied with a panel of anti-Omp25 monoclonal antibodies (MAbs). As shown by enzyme-linked immunosorbent assay (ELISA) and immunoelectron microscopy, Omp25 was exported to the outer membrane in E. coli expressing either the truncated omp25 gene of B. ovis or the entire omp25 genes of the other Brucella species. Size and antigenic shifts due to the 36-bp deletion were demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting and by the differences in binding patterns in ELISA of the anti-Omp25 MAbs at the cell surface of E. coli cells harboring the appropriate gene and of cells of B. ovis and other Brucella species. In particular, MAbs directed against discontinuous epitopes of the entire Omp25 showed the absence of, or a significant reduction in, antibody reactivity with the B. ovis truncated Omp25. The results indicated that, as defined by the MAbs, exported Omp25 probably presents similar

  6. Cationized bovine serum albumin as gene carrier: Influence of specific secondary structure on DNA complexibility and gene transfection.

    PubMed

    Du, Jianwei; Li, Bangbang; Zhang, Peng; Wang, Youxiang

    2016-07-01

    In this research, BSA, one of the natural rigid globular proteins with ca. 51% of α-helix secondary structure, was utilized to prepare cationized BSA (cBSA) as gene carrier. Tetraethylenepentamine (TEPA) or polyethylenimine (PEI1800) was grafted to BSA with different grafting levels. Based on the circular dichoism (CD) spectra, all cBSA remained α-helical structure to some degree. This was exciting to endow cBSA with quite different DNA complexibility and cellular biology behavior from the random coiled and flexible polycations such as PEI and poly-l-lysine (PLL). Strangely, the DNA condensability decreased with the increment of TEPA or PEI1800 grafting level. Also, the cBSA could condense DNA effectively to form irregular nanoparticles around 50-200nm above N/P ratio of 10. On account of the excellent hydration of BSA, the cBSA/DNA complexes revealed good colloidal stability under physiological salt condition. Cell culture experiments indicated this BSA-based gene carrier possessed good cellular compatibility. Surprisingly, cBSA/DNA complexes could be uptaken excellently by up to 90% cells. This might be owing to the agitation effect of α-helical structure and the positive potential of these complexes. BSA-PEI1800/DNA complexes with quick endosome escape even had transfection efficiency as high as PEI25k/DNA complexes. Overall, this paper provided us the potential of cBSA as gene carrier and might have some instructions in the design of protein-based gene delivery system.

  7. Endothelial Genes

    DTIC Science & Technology

    2005-06-01

    Suppression subtractive hybridization re- Cancer: principles and practice of oncology. Philadelphia: Lippincott- vealed an RNA sequence (GenBank accession...Lau YC, Campbell AP, et al. Suppression subtractive hybridization : A method for generating differentially regulated or tissue-tissues, EG-1 appears to...this gene, we investigated its interaction with Src and members of the called suppression subtractive hybridization (12). In human mitogen-activated

  8. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila.

    PubMed

    Nagarkar-Jaiswal, Sonal; Lee, Pei-Tseng; Campbell, Megan E; Chen, Kuchuan; Anguiano-Zarate, Stephanie; Gutierrez, Manuel Cantu; Busby, Theodore; Lin, Wen-Wen; He, Yuchun; Schulze, Karen L; Booth, Benjamin W; Evans-Holm, Martha; Venken, Koen J T; Levis, Robert W; Spradling, Allan C; Hoskins, Roger A; Bellen, Hugo J

    2015-03-31

    Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstrate reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates.

  9. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

    SciTech Connect

    Nagarkar-Jaiswal, Sonal; Lee, Pei-Tseng; Campbell, Megan E.; Chen, Kuchuan; Anguiano-Zarate, Stephanie; Cantu Gutierrez, Manuel; Busby, Theodore; Lin, Wen-Wen; He, Yuchun; Schulze, Karen L.; Booth, Benjamin W.; Evans-Holm, Martha; Venken, Koen J.T.; Levis, Robert W.; Spradling, Allan C.; Hoskins, Roger A.; Bellen, Hugo J.

    2015-03-31

    Here, we document a collection of ~7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstrate reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates.

  10. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

    DOE PAGES

    Nagarkar-Jaiswal, Sonal; Lee, Pei-Tseng; Campbell, Megan E.; ...

    2015-03-31

    Here, we document a collection of ~7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstratemore » reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates.« less

  11. Dependence of PEI and PAMAM Gene Delivery on Clathrin- and Caveolin-Dependent Trafficking Pathways

    PubMed Central

    Hwang, Mark E.; Keswani, Rahul K.; Pack, Daniel W.

    2014-01-01

    Purpose Non-viral gene delivery vehicles such as polyethylenimine and polyamidoamine dendrimer effectively condense plasmid DNA, facilitate endocytosis, and deliver nucleic acid cargo to the nucleus in vitro. Better understanding of intracellular trafficking mechanisms involved in polymeric gene delivery is a prerequisite to clinical application. This study investigates the role of clathrin and caveolin endocytic pathways in cellular uptake and subsequent vector processing. Methods We formed 25-kD polyethylenimine (PEI) and generation 4 (G4) polyamidoamine (PAMAM) polyplexes at N/P 10 and evaluated internalization pathways and gene delivery in HeLa cells. Clathrin- and caveolin-dependent endocytosis inhibitors were used at varying concentrations to elucidate the roles of these important pathways. Results PEI and PAMAM polyplexes were internalized by both pathways. However, the amount of polyplex internalized poorly correlated with transgene expression. While the caveolin-dependent pathway generally led to effective gene delivery with both polymers, complete inhibition of the clathrin-dependent pathway was also deleterious to transfection with PEI polyplexes. Inhibition of one endocytic pathway may lead to an overall increase in uptake via unaffected pathways, suggesting the existence of compensatory endocytic mechanisms. Conclusions The well-studied clathrin- and caveolin-dependent endocytosis pathways are not necessarily independent, and perturbing one mechanism of trafficking influences the larger trafficking network. PMID:25511918

  12. ModObs: Atmospheric modelling for wind energy, climate and environment applications: exploring added value from new observation technique. Work in progress within a FP6 Marie Curie Research Training Network

    NASA Astrophysics Data System (ADS)

    Sempreviva, A. M.

    2009-09-01

    The EC FP6 Marie Curie Training Network "ModObs” http://www.modobs.windeng.net addresses the improvement of atmospheric boundary layer (ABL) models to investigate the interplay of processes at different temporal and spatial scales, and to explore the added value from new observation techniques. The overall goal is to bring young scientists to work ogether with experienced researchers in developing a better interaction amongst scientific communities of modelers and experimentalists, using a comprehensive approach to "Climate Change”, "Clean Energy assessment” and "Environmental Policies”, issues. This poster describes the work in progress of ten students, funded by the network, under the supervision of a team of scientists within atmospheric physics, engineering and satellite remote sensing and end-users such as companies in the private sector, all with the appropriate expertise to integrate the most advanced research methods and techniques in the following topics. MODELING: GLOBAL-TO-MESO SCALE: Analytical and process oriented numerical models will be used to study the interaction between the atmosphere and the ocean on a regional scale. Initial results indicate an interaction between the intensity of polar lows and the subsurface warm core often present in the Nordic Seas (11). The presence of waves, mainly swell, influence the MABL fluxes and turbulence structure. The regional and global wave effect on the atmosphere will be also studied and quantified (7) MESO-SCALE: Applicability of the planetary boundary layer (PBL) parametrizations in the meso-scale WRF model to marine atmospheric boundary layer (MABL) over the North Sea is investigated. The most suitable existing PBL parametrization will be additionally improved and used for downscaling North Sea past and future climates (2). Application of the meso-scale model (MM5 and WRF) for the wind energy in off-shore and coastal area. Set-up of the meso-scale model, post-processing and verification of the data

  13. EU-FP7-iMars: Analysis of Mars Multi-Resolution Images using Auto-Coregistration, Data Mining and Crowd Source Techniques: an overview and a request for scientific inputs.

    NASA Astrophysics Data System (ADS)

    Muller, Jan-Peter; Gwinner, Klaus; van Gasselt, Stephan; Ivanov, Anton; Morley, Jeremy; Houghton, Robert; Bamford, Steven; Yershov, Vladimir; Sidirpoulos, Panagiotis; Kim, Jungrack

    2014-05-01

    '. Acknowledgements: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under iMars grant agreement n° 607379. References: [1] Orloff et al. (2011) Boulder movement at high northern latitudes of Mars. J Geophys Res-Planet, 116: E11006-1-12; [2] Byrne et al. (2009) Distribution of mid-latitude ground ice on Mars from new impact craters. Science, 325: 1674-1676; [3] Gwinner, K., F. et al. (2010) Topography of Mars from global mapping by HRSC high-resolution digital terrain models and orthoimages: characteristics and performance. Earth and Planetary Science Letters 294, 506-519, doi:10.1016/j.epsl.2009.11.007, 2010.

  14. EU-FP7-iMars: Analysis of Mars Multi-Resolution Images using Auto-Coregistration, Data Mining and Crowd Source Techniques: One year on with a focus on auto-DTM, auto-coregistration and citizen science.

    NASA Astrophysics Data System (ADS)

    Muller, Jan-Peter; Sidiropoulos, Panagiotis; Yershov, Vladimir; Gwinner, Klaus; van Gasselt, Stephan; Walter, Sebastian; Ivanov, Anton; Morley, Jeremy; Sprinks, James; Houghton, Robert; Bamford, Stephen; Kim, Jung-Rack

    2015-04-01

    datasets will represent the best possible capture of changes and evolutions in the Martian surface. A workshop is planned to be held during the EPSC time period to demonstrate the first science results on these different types of changes based on initial results . Acknowledgements: The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under iMars grant agreement n˚ 607379. Partial support is also provided from the STFC "MSSL Consolidated Grant" ST/K000977/1. References: Gwinner, K., F. et al. (2010) Topography of Mars from global mapping by HRSC high-resolution digital terrain models and orthoimages: characteristics and performance. Earth and Planetary Science Letters 294, 506-519, doi:10.1016/j.epsl.2009.11.007, 2010; Gwinner, K., F. et al. (2015) MarsExpress High Resolution Stereo Camera (HRSC) Multi-orbit Data Products: Methodology, Mapping Concepts and Performance for the first Quadrangle (MC-11E). This conference.

  15. Supramolecular Aggregate as a High-Efficiency Gene Carrier Mediated with Optimized Assembly Structure.

    PubMed

    Zhang, Yi; Duan, Junkun; Cai, Lingguang; Ma, Dong; Xue, Wei

    2016-11-02

    For cancer gene therapy, a safe and high-efficient gene carrier is a must. To resolve the contradiction between gene transfection efficiency and cytotoxicity, many polymers with complex topological structures have been synthesized, although their synthesis processes and structure control are difficult as well as the high molecular weight also bring high cytotoxicity. We proposed an alternative strategy that uses supramolecular inclusion to construct the aggregate from the small molecules for gene delivery, and to further explore the relationship between the topological assembly structure and their ability to deliver gene. Herein, PEI-1.8k-conjugating β-CD through 6-hydroxyl (PEI-6-CD) and 2-hydroxyl (PEI-2-CD) have been synthesized respectively and then assembled with diferrocene (Fc)-ended polyethylene glycol (PEG-Fc). The obtained aggregates were then used to deliver MMP-9 shRNA plasmid for MCF-7 cancer therapy. It was found that the higher gene transfection efficiency can be obtained by selecting PEI-2-CD as the host and tuning the host/guest molar ratios. With the rational modulation of supramolecular architectures, the aggregate played the functions similar to macromolecules which exhibit higher transfection efficiency than PEI-25k, but show much lower cytotoxicity because of the nature of small/low molecules. In vitro and in vivo assays confirmed that the aggregate could deliver MMP-9 shRNA plasmid effectively into MCF-7 cells and then downregulate MMP-9 expression, which induced the significant MCF-7 cell apoptosis, as well inhibit MCF-7 tumor growth with low toxicity. The supramolecular aggregates maybe become a promising carrier for cancer gene therapy and also provided an alternative strategy for designing new gene carriers.

  16. Molecular cloning of Taenia taeniaeformis oncosphere antigen genes.

    PubMed

    Cougle, W G; Lightowlers, M W; Bogh, H O; Rickard, M D; Johnson, K S

    1991-03-01

    Infection of mice with the cestode Taenia taeniaeformis exhibits several important features common to other cestode infections, including the ability to vaccinate with crude antigen mixtures. Partial purification of the protective oncosphere antigens has been reported with a cutout from deoxycholate (DOC) acrylamide gels; this cutout was called fraction II (FII), and comprises approximately 10% of total DOC-soluble oncosphere antigen. Western blots of DOC gels probed with anti-FII antisera revealed a series of 3-5 discrete bands within the FII region. Further fractionation of the FII antigens on DOC gels was impractical due to limitations in supply of oncospheres, so a cDNA library was constructed from 150 ng of oncosphere mRNA and screened with alpha-FII antisera. Two distinct clone families were identified, oncA and oncB. Antibodies affinity-purified on either of two representative members, oncA1 and oncB1, recognised all the FII bands. Individual FII bands excised from a DOC gel resolved into an overlapping series of molecules when re-run on SDS-PAGE, indicating that each FII band consisted of several polypeptides of differing molecular weight. Immunoprecipitates resolved on SDS-PAGE revealed that alpha-FII recognised 3 major oncosphere antigens, of 62, 34 and 25 kDa; antisera against oncB precipitated both the 34- and 25-kDa antigens, whereas alpha-oncA antisera precipitated the 62-kDa antigen. We conclude that oncA and oncB encode the major antigens in the FII complex. The 62-kDa antigen encoded by oncA1 was the only common antigen precipitated by anti-FII and two other antisera raised against different protective extracts, suggesting that it may be a protective component in all three. Southern blot results indicate that oncA and oncB are distinct genes present at low copy number in the genome. Evidence is also presented suggesting that some cestode mRNAs, including oncA, may use variant polyadenylation signals.

  17. Transcriptome changes in foxtail millet genotypes at high salinity: identification and characterization of a PHGPX gene specifically upregulated by NaCl in a salt-tolerant line.

    PubMed

    Sreenivasulu, Nese; Miranda, Manoela; Prakash, Harischandra Sripathy; Wobus, Ulrich; Weschke, Winfriede

    2004-04-01

    Using a macro array filter with 711 cDNA inserts representing 620 unigenes selected from a barley EST collection, we identified transcripts differentially expressed in salt (NaCl)-treated tolerant (cv. Prasad) and sensitive (cv. Lepakshi) seedlings of foxtail millet (Setaria italica L.). Transcripts of hydrogen peroxide scavenging enzymes such as phospholipid hydroperoxide glutathione peroxidase (PHGPX), ascorbate peroxidase (APX) and catalase 1 (CAT1) in addition to some genes of cellular metabolism were found to be especially up-regulated at high salinity in the tolerant line. To analyse this process at the protein level we examined protein expression patterns under various stress conditions. A 25 kD protein with a pI of 4.8 was found to be induced prominently under high salt concentrations (250 mmol/L). This salt-induced 25 kD protein has been purified and identified by peptide sequencing as PHGPX protein. The increase of the PHGPX protein level under salt stress in the tolerant line parallels the PHGPX mRNA results of array analysis but was more pronounced. We cloned and characterized the foxtail millet PHGPX cDNA, which shows 85% and 95% homology at the DNA and protein level, respectively, to one stress-induced member of the small barley PHGPX gene family encoding non-selenium glutathione peroxidases. As shown by Southern blot analysis, a small family of PHGPX genes exists in foxtail millet, too. The specific expression pattern of the PHGPX gene in salt-induced tolerant millet seedlings suggests that its product plays an important role in the defense reaction against salt-induced oxidative damage and that the characterized glutathione peroxidase is one of the components conferring resistance against salt to the tolerant foxtail millet cultivar.

  18. Gene Therapy for Leber Hereditary Optic Neuropathy

    PubMed Central

    Feuer, William J.; Schiffman, Joyce C.; Davis, Janet L.; Porciatti, Vittorio; Gonzalez, Phillip; Koilkonda, Rajeshwari D.; Yuan, Huijun; Lalwani, Anil; Lam, Byron L.; Guy, John

    2015-01-01

    Purpose Leber hereditary optic neuropathy (LHON) is a disorder characterized by severe and rapidly progressive visual loss when caused by a mutation in the mitochondrial gene encoding NADH:ubiquinone oxidoreductase subunit 4 (ND4). We have initiated a gene therapy trial to determine the safety and tolerability of escalated doses of an adeno-associated virus vector (AAV) expressing a normal ND4 complementary DNA in patients with a G to A mutation at nucleotide 11778 of the mitochondrial genome. Design In this prospective open-label trial (NCT02161380), the study drug (self-complementary AAV [scAAV]2(Y444,500,730F)-P1ND4v2) was intravitreally injected unilaterally into the eyes of 5 blind participants with G11778A LHON. Four participants with visual loss for more than 12 months were treated. The fifth participant had visual loss for less than 12 months. The first 3 participants were treated at the low dose of vector (5 × 109 vg), and the fourth participant was treated at the medium dose (2.46 × 1010 vg). The fifth participant with visual loss for less than 12 months received the low dose. Treated participants were followed for 90 to 180 days and underwent ocular and systemic safety assessments along with visual structure and function examinations. Participants Five legally blind patients with G11778A LHON. Main Outcome Measures Loss of visual acuity. Results Visual acuity as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart remained unchanged from baseline to 3 months in the first 3 participants. For 2 participants with 90-day follow-up, acuity increased from hand movements to 7 letters in 1 and by 15 letters in 1, representing an improvement equivalent to 3 lines. No one lost vision, and no serious adverse events were observed. Minor adverse events included a transient increase of intraocular pressure (IOP), exposure keratitis, subconjunctival hemorrhage, a sore throat, and a transient increase in neutralizing antibodies (NAbs) against

  19. Molecular cloning, characterization and differential expression of novel phytocystatin gene during tropospheric ozone stress in maize (Zea mays) leaves.

    PubMed

    Ahmad, Rafiq; Zuily-Fodil, Yasmine; Passaquet, Chantal; Ali Khan, Sabaz; Repellin, Anne

    2015-03-01

    In this study, a full-length cDNA encoding a novel phytocystatin gene, designated CC14, was identified in maize leaves. The CC14 gene sequence reported in this study has been deposited in the GenBank database (accession number JF290478). The CC14 gene was cloned into an expression vector pET30 EK/LIC and was then transformed into Escherichia coli strain BL21 (DE3) pLysS to produce a recombinant CC14 protein. The recombinant protein was purified by nickel nitrilotriacetic acid affinity chromatography after induction with 1 mM IPTG. The purified CC14 protein was electrophoresed on SDS-PAGE and a protein 25 kDa in size was observed. Antiprotease activities of the purified recombinant CC14 protein against cysteine proteases and commercially available papain were tested. The results showed that CC14 purified protein suppressed 100% activity of papain and 57-86% plant cysteine protease activity. Moreover, an upregulation of CC14 gene expression was observed after 20 days of ozone stress in maize leaves. Together, these observations concurred to conclude that CC14 gene could potentially be used as a basis for the development of transgenic crops and natural pesticides that resist biotic and abiotic stresses.

  20. One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell

    PubMed Central

    Cong, Yue; Shi, Bingyang; Lu, Yiqing; Wen, Shihui; Chung, Roger; Jin, Dayong

    2016-01-01

    Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,1H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy. PMID:26902258

  1. Compare Gene Profiles

    SciTech Connect

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linux environment in serial or parallel mode.

  2. Efficient gene delivery with osmotically active and hyperbranched poly(ester amine)s.

    PubMed

    Arote, Rohidas B; Lee, Eun-Sun; Jiang, Hu-Lin; Kim, You-Kyoung; Choi, Yun-Jaie; Cho, Myung-Haing; Cho, Chong-Su

    2009-12-01

    Degradable and hyperbranched poly (ester amine)s (PEAs) were successfully synthesized by Michael addition reaction between hydrophilic glycerol triacrylate (GTA) and low-molecular-weight polyethylenimine (LMW-PEI) and evaluated as nonviral gene carriers. PEAs effectively condensed DNA with particle sizes below 200 nm and suitable surface charges (15-45 mV), suitable for intracellular delivery. PEAs degraded in a controlled fashion showing half-lives of more than 12 days and were essentially nontoxic in three different cell lines. Elevated transfection levels by luciferase assay revealed the superiority of PEAs over PEI 25K and Lipofectamine. PEAs synthesized using 1:4 mol ratio of GTA to PEI [GTA/PEI-1.2(1:4)] showed highest transfection efficiency in HepG2 cells. PEAs showed significant gene expression in vitro as well as in vivo through aerosol administration. Reduction in packed cell volume (PCV) of cells when treated with polyplexes supported the hyperosmotic effect of PEAs. Effect of bafilomycin A1 on transfection efficiency of PEAs on 293T cells indicated its endosomal buffering capacity. High transfection efficiency was attributed to the synergism from hyperosmotic glycerol backbone in the PEAs and endosomal buffering capacity of PEI amine groups. Therefore, this convergence of osmotically active biodegradable PEAs suggests their potential as a safe and efficient gene delivery vector.

  3. Efficient gene delivery to human umbilical cord mesenchymal stem cells by cationized Porphyra yezoensis polysaccharide nanoparticles.

    PubMed

    Yu, Qingtong; Cao, Jin; Chen, Baoding; Deng, Wenwen; Cao, Xia; Chen, Jingjing; Wang, Yan; Wang, Shicheng; Yu, Jiangnan; Xu, Ximing; Gao, Xiangdong

    2015-01-01

    This study centered on an innovative application of Porphyra yezoensis polysaccharide (PPS) with cationic modification as a safe and efficient nonviral gene vector to deliver a plasmid encoding human Wnt3a (pWnt3a) into human umbilical cord mesenchymal stem cells (HUMSCs). After modification with branched low-molecular-weight (1,200 Da) polyethylenimine, the cationized PPS (CPPS) was combined with pWnt3a to form spherical nanoscale particles (CPPS-pWnt3a nanoparticles). Particle size and distribution indicated that the CPPS-pWnt3a nanoparticles at a CPPS:pWnt3a weight ratio of 40:1 might be a potential candidate for DNA plasmid transfection. A cytotoxicity assay demonstrated that the nanoparticles prepared at a CPPS:pWnt3a weight ratio of 40:1 were nontoxic to HUMSCs compared to those of Lipofectamine 2000 and polyethylenimine (25 kDa). These nanoparticles were further transfected to HUMSCs. Western blotting demonstrated that the nanoparticles (CPPS:pWnt3a weight ratio 40:1) had the greatest transfection efficiency in HUMSCs, which was significantly higher than that of Lipofectamine 2000; however, when the CPPS:pWnt3a weight ratio was increased to 80:1, the nanoparticle-treated group showed no obvious improvement in translation efficiency over Lipofectamine 2000. Therefore, CPPS, a novel cationic polysaccharide derived from P. yezoensis, could be developed into a safe, efficient, nonviral gene vector in a gene-delivery system.

  4. Fluorescent protein-mediated colour polymorphism in reef corals: multicopy genes extend the adaptation/acclimatization potential to variable light environments.

    PubMed

    Gittins, John R; D'Angelo, Cecilia; Oswald, Franz; Edwards, Richard J; Wiedenmann, Jörg

    2015-01-01

    The genomic framework that enables corals to adjust to unfavourable conditions is crucial for coral reef survival in a rapidly changing climate. We have explored the striking intraspecific variability in the expression of coral pigments from the green fluorescent protein (GFP) family to elucidate the genomic basis for the plasticity of stress responses among reef corals. We show that multicopy genes can greatly increase the dynamic range over which corals can modulate transcript levels in response to the light environment. Using the red fluorescent protein amilFP597 in the coral Acropora millepora as a model, we demonstrate that its expression increases with light intensity, but both the minimal and maximal gene transcript levels vary markedly among colour morphs. The pigment concentration in the tissue of different morphs is strongly correlated with the number of gene copies with a particular promoter type. These findings indicate that colour polymorphism in reef corals can be caused by the environmentally regulated expression of multicopy genes. High-level expression of amilFP597 is correlated with reduced photodamage of zooxanthellae under acute light stress, supporting a photoprotective function of this pigment. The cluster of light-regulated pigment genes can enable corals to invest either in expensive high-level pigmentation, offering benefits under light stress, or to rely on low tissue pigment concentrations and use the conserved resources for other purposes, which is preferable in less light-exposed environments. The genomic framework described here allows corals to pursue different strategies to succeed in habitats with highly variable light stress levels. In summary, our results suggest that the intraspecific plasticity of reef corals' stress responses is larger than previously thought.

  5. Gene and enhancer traps for gene discovery.

    PubMed

    Rojas-Pierce, Marcela; Springer, Patricia S

    2003-01-01

    Gene traps and enhancer traps provide a valuable tool for gene discovery. With this system, genes can be identified based solely on the expression pattern of an inserted reporter gene. The use of a reporter gene, such as beta-glucuoronidase (GUS), provides a very sensitive assay for the identification of tissue- and cell-type specific expression patterns. In this chapter, protocols for examining and documenting GUS reporter gene activity in individual lines are described. Methods for the amplification of sequences flanking transposant insertions and subsequent molecular and genetic characterization of individual insertions are provided.

  6. The involvement of Opaque 2 on beta-prolamin gene regulation in maize and Coix suggests a more general role for this transcriptional activator.

    PubMed

    Cord Neto, G; Yunes, J A; da Silva, M J; Vettore, A L; Arruda, P; Leite, A

    1995-03-01

    The maize opaque 2 (o2) mutation is known to have numerous pleiotropic effects. Some polypeptides have their expression depressed while others are enhanced. The best characterized effects of the o2 mutation are those exerted on endosperm genes encoding the storage protein class of the 22 kDa alpha-zeins and the ribosome inactivating protein b-32. The Opaque 2 (O2) locus encodes a basic domain-leucine zipper DNA-binding factor, O2, which transcriptionally regulates these genes. In the maize-related grass Coix lacryma-jobi, an O2-homologous protein regulates the 25 kDa alpha-coixin family. We show in this paper that O2 transcriptionally regulates the structurally and developmentally different class of the beta-prolamins. A new O2-binding box was identified in beta-prolamin genes from maize and Coix that, together with the boxes previously identified in other endosperm expressed genes, forms a curious collection of O2 cis elements. This may have regulatory implications on the role of O2 in the mechanism that controls coordinated gene expression in the developing endosperm. Considering that the O2 locus controls at least three distinct classes of genes in maize endosperm, we propose that the O2 protein may play a more general role in maize endosperm development than previously conceived.

  7. Gene doping: gene delivery for olympic victory.

    PubMed

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place.

  8. Functionalization of lignin through ATRP grafting of poly(2-dimethylaminoethyl methacrylate) for gene delivery.

    PubMed

    Liu, Xiaohong; Yin, Hui; Zhang, Zhongxing; Diao, Bishuo; Li, Jun

    2015-01-01

    The biomass kraft lignin was modified into lignin-based macroinitiators (LnMI) through esterification of the alcohol and phenol functional groups on lignin backbone with 2-bromo-isobutyric bromide under mild condition. Then a series of cationic amphiphilic lignin-based graft copolymers were synthesized by atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) starting from the lignin-based macroinitiators. These copolymers, denoted as LnPDMAEMA, had a hyperbranched structure with a hydrophobic backbone of lignin and multiple cationic hydrophilic arms of PDMAEMA. The LnPDMAEMA copolymers were characterized by (1)H NMR and elemental analysis (EA), and studied in terms of their DNA binding capability, formation of nanoparticles with plasmid DNA (pDNA), cytotoxicity, and gene transfection in cultured cells. It was found that all the copolymers could efficiently compact pDNA into nanoparticles with sizes ranging from 100 to 200 nm at N/P ratios of 5 or higher. The cytotoxicity of these copolymers depends greatly on the chain length of PDMAEMA arms, the longer the PAMAEMA chain the higher the cytotoxicity. Luciferase assay was used to study the in vitro gene transfection for the LnPDMAEMA copolymers in different cell lines. The gene transfection efficiency of these copolymers was dependent on the grafted PDMAEMA chain length and N/P ratio. Generally, the transfection efficiency decreased with the increase of PAMAEMA length at N/P ratio of 20 or higher. It is very interesting that one of the LnPDMAEMA copolymers with very short arm length (degree of average DMAEMA units=5.5) showed excellent in vitro transfection efficiency that was comparable or even higher than that of branched PEI (25K). These novel biomass-based LnPDMAEMA hyperbranched copolymers can be a promising nonviral gene vectors for future gene delivery application.

  9. Inhibition of protein translation by the DISC1-Boymaw fusion gene from a Scottish family with major psychiatric disorders

    PubMed Central

    Ji, Baohu; Higa, Kerin K.; Kim, Minjung; Zhou, Lynn; Young, Jared W.; Geyer, Mark A.; Zhou, Xianjin

    2014-01-01

    The t(1; 11) translocation appears to be the causal genetic lesion with 70% penetrance for schizophrenia, major depression and other psychiatric disorders in a Scottish family. Molecular studies identified the disruption of the disrupted-in-schizophrenia 1 (DISC1) gene by chromosome translocation at chromosome 1q42. Our previous studies, however, revealed that the translocation also disrupted another gene, Boymaw (also termed DISC1FP1), on chromosome 11. After translocation, two fusion genes [the DISC1-Boymaw (DB7) and the Boymaw-DISC1 (BD13)] are generated between the DISC1 and Boymaw genes. In the present study, we report that expression of the DB7 fusion gene inhibits both intracellular NADH oxidoreductase activities and protein translation. We generated humanized DISC1-Boymaw mice with gene targeting to examine the in vivo functions of the fusion genes. Consistent with the in vitro studies on the DB7 fusion gene, protein translation activity is decreased in the hippocampus and in cultured primary neurons from the brains of the humanized mice. Expression of Gad67, Nmdar1 and Psd95 proteins are also reduced. The humanized mice display prolonged and increased responses to the NMDA receptor antagonist, ketamine, on various mouse genetic backgrounds. Abnormal information processing of acoustic startle and depressive-like behaviors are also observed. In addition, the humanized mice display abnormal erythropoiesis, which was reported to associate with depression in humans. Expression of the DB7 fusion gene may reduce protein translation to impair brain functions and thereby contribute to the pathogenesis of major psychiatric disorders. PMID:24908665

  10. Autism and Genes

    ERIC Educational Resources Information Center

    National Institutes of Health, 2005

    2005-01-01

    This document defines and discusses autism and how genes play a role in the condition. Answers to the following questions are covered: (1) What are genes? (2) What is autism? (3) What causes autism? (4) Why study genes to learn about autism? (5) How do researchers look for the genes involved in autism? (screen the whole genome; conduct cytogenetic…

  11. Compare Gene Calls

    SciTech Connect

    Ecale Zhou, Carol L.

    2016-07-05

    Compare Gene Calls (CGC) is a Python code used for combining and comparing gene calls from any number of gene callers. A gene caller is a computer program that predicts the extends of open reading frames within genomes of biological organisms.

  12. Production of dioxins and furans for various solid fuels burnt in 25 kW automatic boiler

    NASA Astrophysics Data System (ADS)

    Hopan, František; Horák, Jiří; Krpec, Kamil; Kubesa, Petr; Dej, Milan; Laciok, Vendula

    2016-06-01

    There has been brown coal, black coal and maize straw in a pellet form burnt in an automatic boiler. Production of dibenzodioxins and dibenzofuranes, recomputated through toxicity equivalents, expressed as the emission factor relative to the fuel unit, has differentiated in a range of ca. three orders (0.05 up to 78.9 ng/kg) in dependence on a sort of the used fuel. The measured values have been compared with emission factors used for the emission inventory in the Czech Republic and Poland and with the emission limit applicable for waste incineration plants. The study has proven the influence of chlorine content in fuel on production of dioxins and furanes.

  13. /sup 3/He constant-volume gas thermometry: calculations for a temperature scale between 0. 8 and 25 K

    SciTech Connect

    Pavese, F.; Steur, P.P.M.

    1987-10-01

    A discussion is presented on the possibilities of a /sup 3/He gas thermometer for defining a temperature scale below 30 K, based on recent new measurements of the virial coefficient. The influence of all corrections of interest is given in comparison with /sup 4/He gas thermometry and with /sup 4/He and /sup 3/He vapor pressure thermometry. It is shown that a /sup 3/He gas thermometer can be operated down to temperatures < 1 K, with an estimated inaccuracy of less than +/- 0.5 mK, thereby obviating the explicit need of the /sup 3/He and /sup 4/He vapor pressure scales below 5K, and directly joining a possible scale based on the /sup 3/He melting curve.

  14. 77 FR 19525 - Specification for 15 kV and 25 kV Primary Underground Power Cable

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-02

    ... implications to require preparation of a Federalism Assessment. Regulatory Flexibility Act Certification It has... retardant or ethylene propylene rubber insulation, concentric neutral, and insulating outer jacket and... polyethylene (TR-XLPE) or ethylene propylene rubber (EPR), with concentrically wound copper neutral...

  15. Polyethylene glycol-grafted polyethylenimine used to enhance adenovirus gene delivery.

    PubMed

    Singarapu, Kumar; Pal, Ivy; Ramsey, Joshua D

    2013-07-01

    An improved adenoviral-based gene delivery vector was developed by complexing adenovirus (Ad) with a biocompatible, grafted copolymer PEG-g-PEI composed of polyethylene glycol (PEG) and polyethylenimine (PEI). Although an Ad-based gene vector is considered relatively safe, its native tropism, tendency to elicit an immune response, and susceptibility to inactivating antibodies makes the virus less than ideal. The goal of the current study was to determine whether Ad could be complexed with a PEG-g-PEI copolymer that would enable the virus to transduce cells lacking the Ad receptor, while avoiding the issues commonly associated with PEI. A copolymer library was synthesized using 2 kDa PEG and either linear or branched PEI (25 kDa) with a PEG to PEI grafting ratio of 10, 20, or 30. The results of the study indicate that PEG-g-PEI/Ad complexes are indeed able to transduce CAR-negative NIH 3T3 cells. The results also demonstrate that the PEG-g-PEI/Ad complexes are less toxic, less hemolytic, and more appropriately sized than PEI/Ad complexes.

  16. Cloning and Characterization of the Autoinducer Synthase Gene from Lipid-Degrading Bacterium Cedecea neteri

    PubMed Central

    Tan, Kian-Hin; How, Kah-Yan; Tan, Jia-Yi; Yin, Wai-Fong; Chan, Kok-Gan

    2017-01-01

    The process of intercellular communication among bacteria, termed quorum sensing (QS), is mediated by small diffusible molecules known as the autoinducers. QS allows the population to react to the change of cell density in unison, in processes such as biofilm formation, plasmid conjugation, virulence, motility and root nodulation. In Gram-negative proteobacteria, N-acyl homoserine lactone (AHL) is the common “language” to coordinate gene expression. This signaling molecule is usually synthesized by LuxI-type proteins. We have previously discovered that a rare bacterium, Cedecea neteri, exhibits AHL-type QS activity. With information generated from genome sequencing, we have identified the luxIR gene pair responsible for AHL-type QS and named it cneIR. In this study, we have cloned and expressed the 636 bp luxI homolog in an Escherichia coli host for further characterization. Our findings show that E. coli harboring cneI produced the same AHL profile as the wild type C. neteri, with the synthesis of AHL known as N-butyryl-homoserine lactone. This 25 kDa LuxI homolog shares high similarity with other AHL synthases from closely related species. This work is the first documentation of molecular cloning and characterization of luxI homolog from C. neteri. PMID:28197135

  17. Epilepsy-associated genes.

    PubMed

    Wang, Jie; Lin, Zhi-Jian; Liu, Liu; Xu, Hai-Qing; Shi, Yi-Wu; Yi, Yong-Hong; He, Na; Liao, Wei-Ping

    2017-01-01

    Development in genetic technology has led to the identification of an increasing number of genes associated with epilepsy. These discoveries will both provide the basis for including genetic tests in clinical practice and improve diagnosis and treatment of epilepsy. By searching through several databases (OMIM, HGMD, and EpilepsyGene) and recent publications on PubMed, we found 977 genes that are associated with epilepsy. We classified these genes into 4 categories according to the manifestation of epilepsy in phenotypes. We found 84 genes that are considered as epilepsy genes: genes that cause epilepsies or syndromes with epilepsy as the core symptom. 73 genes were listed as neurodevelopment-associated genes: genes associated with both brain-development malformations and epilepsy. Several genes (536) were epilepsy-related: genes associated with both physical or other systemic abnormalities and epilepsy or seizures. We found 284 additional genes putatively associated with epilepsy; this requires further verification. These integrated data will provide new insights useful for both including genetic tests in the clinical practice and evaluating the results of genetic tests. We also summarized the epilepsy-associated genes according to their function, with the goal to better characterize the association between genes and epilepsies and to further understand the mechanisms underlying epilepsy.

  18. Molecular Cloning and Characterization of Four Genes Encoding Ethylene Receptors Associated with Pineapple (Ananas comosus L.) Flowering.

    PubMed

    Li, Yun-He; Wu, Qing-Song; Huang, Xia; Liu, Sheng-Hui; Zhang, Hong-Na; Zhang, Zhi; Sun, Guang-Ming

    2016-01-01

    Exogenous ethylene, or ethephon, has been widely used to induce pineapple flowering, but the molecular mechanism behind ethephon induction is still unclear. In this study, we cloned four genes encoding ethylene receptors (designated AcERS1a, AcERS1b, AcETR2a, and AcETR2b). The 5' flanking sequences of these four genes were also cloned by self-formed adaptor PCR and SiteFinding-PCR, and a group of putative cis-acting elements was identified. Phylogenetic tree analysis indicated that AcERS1a, AcERS1b, AcETR2a, and AcETR2b belonged to the plant ERS1s and ETR2/EIN4-like groups. Quantitative real-time PCR showed that AcETR2a and AcETR2b (subfamily 2) were more sensitive to ethylene treatment compared with AcERS1a and AcERS1b (subfamily 1). The relative expression of AcERS1b, AcETR2a, and AcETR2b was significantly increased during the earlier period of pineapple inflorescence formation, especially at 1-9 days after ethylene treatment (DAET), whereas AcERS1a expression changed less than these three genes. In situ hybridization results showed that bract primordia (BP) and flower primordia (FP) appeared at 9 and 21 DAET, respectively, and flowers were formed at 37 DAET. AcERS1a, AcERS1b, AcETR2a, and AcETR2b were mainly expressed in the shoot apex at 1-4 DAET; thereafter, with the appearance of BP and FP, higher expression of these genes was found in these new structures. Finally, at 37 DAET, the expression of these genes was mainly focused in the flower but was also low in other structures. These findings indicate that these four ethylene receptor genes, especially AcERS1b, AcETR2a, and AcETR2b, play important roles during pineapple flowering induced by exogenous ethephon.

  19. Molecular Cloning and Characterization of Four Genes Encoding Ethylene Receptors Associated with Pineapple (Ananas comosus L.) Flowering

    PubMed Central

    Li, Yun-He; Wu, Qing-Song; Huang, Xia; Liu, Sheng-Hui; Zhang, Hong-Na; Zhang, Zhi; Sun, Guang-Ming

    2016-01-01

    Exogenous ethylene, or ethephon, has been widely used to induce pineapple flowering, but the molecular mechanism behind ethephon induction is still unclear. In this study, we cloned four genes encoding ethylene receptors (designated AcERS1a, AcERS1b, AcETR2a, and AcETR2b). The 5′ flanking sequences of these four genes were also cloned by self-formed adaptor PCR and SiteFinding-PCR, and a group of putative cis-acting elements was identified. Phylogenetic tree analysis indicated that AcERS1a, AcERS1b, AcETR2a, and AcETR2b belonged to the plant ERS1s and ETR2/EIN4-like groups. Quantitative real-time PCR showed that AcETR2a and AcETR2b (subfamily 2) were more sensitive to ethylene treatment compared with AcERS1a and AcERS1b (subfamily 1). The relative expression of AcERS1b, AcETR2a, and AcETR2b was significantly increased during the earlier period of pineapple inflorescence formation, especially at 1–9 days after ethylene treatment (DAET), whereas AcERS1a expression changed less than these three genes. In situ hybridization results showed that bract primordia (BP) and flower primordia (FP) appeared at 9 and 21 DAET, respectively, and flowers were formed at 37 DAET. AcERS1a, AcERS1b, AcETR2a, and AcETR2b were mainly expressed in the shoot apex at 1–4 DAET; thereafter, with the appearance of BP and FP, higher expression of these genes was found in these new structures. Finally, at 37 DAET, the expression of these genes was mainly focused in the flower but was also low in other structures. These findings indicate that these four ethylene receptor genes, especially AcERS1b, AcETR2a, and AcETR2b, play important roles during pineapple flowering induced by exogenous ethephon. PMID:27252725

  20. Recycling Gene Carrier with High Efficiency and Low Toxicity Mediated by L-Cystine-Bridged Bis(β-cyclodextrin)s

    NASA Astrophysics Data System (ADS)

    Zhang, Yu-Hui; Chen, Yong; Zhang, Ying-Ming; Yang, Yang; Chen, Jia-Tong; Liu, Yu

    2014-12-01

    Constructing safe and effective gene delivery carriers is becoming highly desirable for gene therapy. Herein, a series of supramolecular crosslinking system were prepared through host-guest binding of adamantyl-modified low molecular weight of polyethyleneimine with L-cystine-bridged bis(β-cyclodextrin)s and characterized by 1H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, flow cytometry and confocal fluorescence microscopy. The results showed that these nanometersized supramolecular crosslinking systems exhibited higher DNA transfection efficiencies and lower cytotoxicity than the commercial DNA carrier gold standard (25 kDa bPEI) for both normal cells and cancer cells, giving a very high DNA transfection efficiency up to 54% for 293T cells. Significantly, this type of supramolecular crosslinking system possesses a number of enzyme-responsive disulfide bonds, which can be cleaved by reductive enzyme to promote the DNA release but recovered by oxidative enzyme to make the carrier renewable. These results demonstrate that these supramolecular crosslinking systems can be used as promising gene carriers.

  1. Exploring associations between taste perception, oral anatomy and polymorphisms in the carbonic anhydrase (gustin) gene CA6

    PubMed Central

    Feeney, Emma L.; Hayes, John E.

    2014-01-01

    Recent reports suggest that polymorphisms in the carbonic anhydrase gene CA6 (also known as gustin) may explain additional variation in the bitterness of 6-n-propylthiouracil beyond that explained by variation in the bitter receptor gene TAS2R38. CA6 (gustin) has been implicated in taste bud function and salivary buffer capacity. In the present study we examined associations between polymorphisms in the CA6 gene with salt and bitter taste perception, and oral anatomy. 243 subjects (146 female) aged 18–45 rated the intensity of five concentrations of 6-n-propylthiouracil and NaCl on a generalized Labeled Magnitude Scale (gLMS) in duplicate and one concentration of potassium chloride (KCl). Using salivary DNA, we examined 12 SNPs within CA6 in relation to taste intensity and number of fungiform papillae. We observed no difference in bitter taste perception from 6-n-propylthiouracil (PROP) or from potassium chloride for any of the SNPs examined. Perceived saltiness of NaCl on the other hand was significantly associated with a number of CA6 polymorphisms, and particularly rs3737665. Nonetheless, FP density did not vary between alleles of rs3737665, nor with any of the other CA6 SNPs. Also, we fail to find any evidence that CA6 effects on taste perception are due to differences in fungiform papilla number. Additional work is needed to confirm whether variations within the CA6 gene may be responsible for differences in salt taste perception. PMID:24534176

  2. Gene regulation in cancer gene therapy strategies.

    PubMed

    Scanlon, Ian; Lehouritis, Panos; Niculescu-Duvaz, Ion; Marais, Richard; Springer, Caroline J

    2003-10-01

    Regulation of expression in gene therapy is considered to be a very desirable goal, preventing toxic effects and improving biological efficacy. A variety of systems have been reported in an ever widening range of applications, this paper describes these systems with specific reference to cancer gene therapy.

  3. Human Gene Therapy: Genes without Frontiers?

    ERIC Educational Resources Information Center

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  4. Human gene therapy.

    PubMed

    Sandhu, J S; Keating, A; Hozumi, N

    1997-01-01

    Human gene therapy and its application for the treatment of human genetic disorders, such as cystic fibrosis, cancer, and other diseases, are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors and non-viral vectors, have been developed for both ex vivo and in vivo gene transfer into cells. Vectors need to be developed that efficiently transfer genes to target cells, and promoter systems are required that regulate gene expression according to physiologic needs of the host cell. There are several safety and ethical issues related to manipulating the human genome that need to be resolved. Current gene therapy efforts focus on gene insertion into somatic cells only. Gene therapy has potential for the effective treatment of genetic disorders, and gene transfer techniques are being used for basic research, for example, in cancer, to examine the underlying mechanism of disease. There are still many technical obstacles to be overcome before human gene therapy can become a routine procedure. The current human genome project provides the sequences of a vast number of human genes, leading to the identification, characterization, and understanding of genes that are responsible for many human diseases.

  5. The Bradyrhizobium japonicum napEDABC genes encoding the periplasmic nitrate reductase are essential for nitrate respiration.

    PubMed

    Delgado, María J; Bonnard, Nathalie; Tresierra-Ayala, Alvaro; Bedmar, Eulogio J; Müller, Peter

    2003-12-01

    The napEDABC gene cluster that encodes the periplasmic nitrate reductase from Bradyrhizobium japonicum USDA110 has been isolated and characterized. napA encodes the catalytic subunit, and the napB and napC gene products are predicted to be a soluble dihaem c and a membrane-anchored tetrahaem c-type cytochrome, respectively. napE encodes a transmembrane protein of unknown function, and the napD gene product is a soluble protein which is assumed to play a role in the maturation of NapA. Western blots of the periplasmic fraction from wild-type cells grown anaerobically with nitrate revealed the presence of a protein band with a molecular size of about 90 kDa corresponding to NapA. A B. japonicum mutant carrying an insertion in the napA gene was unable to grow under nitrate-respiring conditions, lacked nitrate reductase activity, and did not show the 90 kDa protein band. Complementation of the mutant with a plasmid bearing the napEDABC genes restored both nitrate-dependent anaerobic growth of the cells and nitrate reductase activity. A membrane-bound and a periplasmic c-type cytochrome, with molecular masses of 25 kDa and 15 kDa, respectively, were not detected in the napA mutant strain incubated anaerobically with nitrate, which identifies those proteins as the NapC and the NapB components of the B. japonicum periplasmic nitrate reductase enzyme. These results suggest that the periplasmic nitrate reductase is the enzyme responsible for anaerobic growth of B. japonicum under nitrate-respiring conditions. The promoter region of the napEDABC genes has been characterized by primer extension. A major transcript initiates 66.5 bp downstream of the centre of a putative FNR-like binding site.

  6. Gene therapy for blindness.

    PubMed

    Sahel, José-Alain; Roska, Botond

    2013-07-08

    Sight-restoring therapy for the visually impaired and blind is a major unmet medical need. Ocular gene therapy is a rational choice for restoring vision or preventing the loss of vision because most blinding diseases originate in cellular components of the eye, a compartment that is optimally suited for the delivery of genes, and many of these diseases have a genetic origin or genetic component. In recent years we have witnessed major advances in the field of ocular gene therapy, and proof-of-concept studies are under way to evaluate the safety and efficacy of human gene therapies. Here we discuss the concepts and recent advances in gene therapy in the retina. Our review discusses traditional approaches such as gene replacement and neuroprotection and also new avenues such as optogenetic therapies. We conjecture that advances in gene therapy in the retina will pave the way for gene therapies in other parts of the brain.

  7. Scientists Spot 'Teetotaler' Gene

    MedlinePlus

    ... gov/news/fullstory_162265.html Scientists Spot 'Teetotaler' Gene Discovery might one day lead to drugs to ... HealthDay News) -- Scientists say they've identified a gene variant that dampens the desire to drink alcohol. ...

  8. Genes and Hearing Loss

    MedlinePlus

    ... gametes (reproductive cells). One gamete will carry the mutant form of the gene of interest, and the ... by having parents who are heterozygous carriers for mutant forms of the gene in question but are ...

  9. Myocardial gene therapy

    NASA Astrophysics Data System (ADS)

    Isner, Jeffrey M.

    2002-01-01

    Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.

  10. Reading and Generalist Genes

    ERIC Educational Resources Information Center

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  11. Chromosome 18 DNA markers and manic-depressive illness: evidence for a susceptibility gene.

    PubMed Central

    Berrettini, W H; Ferraro, T N; Goldin, L R; Weeks, D E; Detera-Wadleigh, S; Nurnberger, J I; Gershon, E S

    1994-01-01

    In the course of a systematic genomic survey, 22 manic-depressive (bipolar) families were examined for linkage to 11 chromosome 18 pericentromeric marker loci, under dominant and recessive models. Overall logarithm of odds score analysis for the pedigree series was not significant under either model, but several families yielded logarithm of odds scores consistent with linkage under dominant or recessive models. Affected sibling pair analysis of these data yielded evidence for linkage (P < 0.001) at D18S21. Affected pedigree member analysis also suggests linkage, with multilocus results for five loci giving P < 0.0001 and P = 0.0007 for weighting functions f(p) = 1 and 1/square root p, respectively, where p is the allele frequency. These results imply a susceptibility gene in the pericentromeric region of chromosome 18, with a complex mode of inheritance. Two plausible candidate genes, a corticotropin receptor and the alpha subunit of a GTP binding protein, have been localized to this region. PMID:8016089

  12. Dexamethasone-loaded reconstitutable charged polymeric (PLGA)n -b-bPEI micelles for enhanced nuclear delivery of gene therapeutics.

    PubMed

    Mishra, Deepa; Kang, Han Chang; Cho, Hana; Bae, You Han

    2014-06-01

    This study investigates the potential of dexamethasone (Dex) to enhance the nuclear accumulation and subsequent gene expression of plasmid DNA (pDNA) delivered using a charged polymeric micelle-based gene delivery system. (PLGA)n -b-bPEI25kDa block copolymers are synthesized and used to prepare Dex-loaded cationic micelles (DexCM). After preparing DexCM/pDNA complexes, bPEI1.8kDa is coated on the complexes using a Layer-by-Layer (LbL) technique to construct DexCM/pDNA/bPEI1.8kDa complexes (i.e., LbL-DexCM polyplexes) that are 100-180 nm in diameter and have a zeta potential of 30-40 mV. In MCF7 cells, LbL-DexCM polyplexes cause 3-13-fold higher transfection efficiencies compared to LbL-CM polyplexes and show negligible cytotoxicity. LbL-DexCM3 polyplexes induce much higher nuclear delivery of pDNA compared to LbL-CM3 polyplexes. These results suggest that Dex-loaded polyplexes could be used in gene and drug delivery applications to increase nuclear accumulation of therapeutic payloads, further leading to a decrease in the dose of the drug and gene necessary to achieve equivalent therapeutic effects.

  13. Isolation of the opdE gene that encodes for a new hydrolase of Enterobacter sp. capable of degrading organophosphorus pesticides.

    PubMed

    Chino-Flores, Concepción; Dantán-González, Edgar; Vázquez-Ramos, Alejandra; Tinoco-Valencia, Raunel; Díaz-Méndez, Rafael; Sánchez-Salinas, Enrique; Castrejón-Godínez, Maria Luisa; Ramos-Quintana, Fernando; Ortiz-Hernández, Maria Laura

    2012-06-01

    Microbial enzymes that can hydrolyze organophosphorus compounds have been isolated, identified and characterized from different microbial species in order to use them in biodegradation of organophosphorus compounds. We isolated a bacterial strain Cons002 from an agricultural soil bacterial consortium, which can hydrolyze methyl-parathion (MP) and other organophosphate pesticides. HPLC analysis showed that strain Cons002 is capable of degrading pesticides MP, parathion and phorate. Pulsed-field gel electrophoresis and 16S rRNA amplification were performed for strain characterization and identification, respectively, showing that the strain Cons002 is related to the genus Enterobacter sp. which has a single chromosome of 4.6 Mb and has no plasmids. Genomic library was constructed from DNA of Enterobacter sp. Cons002. A gene called opdE (Organophosphate Degradation from Enterobacter) consists of 753 bp and encodes a protein of 25 kDa, which was isolated using activity methods. This gene opdE had no similarity to any genes reported to degrade organophosphates. When kanamycin-resistance cassette was placed in the gene opdE, hydrolase activity was suppressed and Enterobacter sp. Cons002 had no growth with MP as a nutrients source.

  14. Gene hunting in autoinflammation

    PubMed Central

    2013-01-01

    Steady progress in our understanding of the genetic basis of autoinflammatory diseases has been made over the past 16 years. Since the discovery of the familial Mediterranean fever gene MEFV (also known as marenostrin) in 1997, 18 other genes responsible for monogenic autoinflammatory diseases have been identified to date. The discovery of these genes was made through the utilisation of many genetic mapping techniques, including next generation sequencing platforms. This review article clearly describes the gene hunting approaches, methods of data analysis and the technological platforms used, which has relevance to all those working within the field of gene discovery for Mendelian disorders. PMID:24070009

  15. Gene therapy review.

    PubMed

    Moss, Joseph Anthony

    2014-01-01

    The use of genes to treat disease, more commonly known as gene therapy, is a valid and promising tool to manage and treat diseases that conventional drug therapies cannot cure. Gene therapy holds the potential to control a wide range of diseases, including cystic fibrosis, heart disease, diabetes, cancer, and blood diseases. This review assesses the current status of gene therapy, highlighting therapeutic methodologies and applications, terminology, and imaging strategies. This article presents an overview of roadblocks associated with each therapeutic methodology, along with some of the scientific, social, and ethical issues associated with gene therapy.

  16. Regulated Gene Therapy.

    PubMed

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  17. Gene therapy in periodontics.

    PubMed

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-03-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

  18. Genes, dreams, and cancer.

    PubMed

    Sikora, K

    1994-05-07

    There have been tremendous advances in our understanding of cancer from the application of molecular biology over the past decade. The disease is caused by a series of defects in the genes that accelerate growth--oncogenes--and those that slow down cellular turnover--tumour suppressor genes. The proteins they encode provide a promising hunting ground in which to design and test new anticancer drugs. Several treatment strategies are now under clinical trial entailing direct gene transfer. These include the use of gene marking to detect minimal residual disease, the production of novel cancer vaccines by the insertion of genes which uncloak cancer cells so making them visible to the host's immune system, the isolation and coupling of cancer specific molecular switches upstream of drug activating genes, and the correction of aberrant oncogenes or tumour suppressor genes. The issues in these approaches are likely to have a profound impact on the management of cancer patients as we enter the next century.

  19. Conventional murine gene targeting.

    PubMed

    Zimmermann, Albert G; Sun, Yue

    2013-01-01

    Murine gene knockout models engineered over the last two decades have continued to demonstrate their potential as invaluable tools in understanding the role of gene function in the context of normal human development and disease. The more recent elucidation of the human and mouse genomes through sequencing has opened up the capability to elucidate the function of every human gene. State-of-the-art mouse model generation allows, through a multitude of experimental steps requiring careful standardization, gene function to be reliably and predictably ablated in a live model system. The application of these standardized methodologies to directly target gene function through murine gene knockout has to date provided comprehensive and verifiable genetic models that have contributed tremendously to our understanding of the cellular and molecular pathways underlying normal and disease states in humans. The ensuing chapter provides an overview of the latest steps and procedures required to ablate gene function in a murine model.

  20. Leading European Intergovernmental Research Organisations at FP6 Launch Conference

    NASA Astrophysics Data System (ADS)

    2002-11-01

    EIROforum at "European Research 2002" (Brussels, November 11-13, 2002) Go to the EIROforum website Last year, seven of Europe's leading intergovernmental research organisations set up a high-level co-ordination and collaboration group, known as EIROforum , cf. ESO PR 12/01. They include CERN (particle physics), EMBL (molecular biology), ESA (space activities), ESO (astronomy and astrophysics), ESRF (synchrotron radiation), ILL (neutron source) and EFDA (fusion). All of them have powerful research infrastructures and laboratories which are used by an extensive network of scientists. Together, they represent European spearheads in some of the most crucial basic and applied research fields. The EIROforum organisations will be highly visible at the upcoming EU-conference on "European Research 2002 - The European Research Area and the Framework Programme" , to be held on November 11-13, 2002, at the "Palais du Heysel" in Brussels (Belgium). This meeting will be attended by more than 8000 scientists and decision-makers from all over Europe and serves to launch the 6th EC Framework Programme (2002 - 2006), which will have an important impact on Europe's R&D landscape during the coming years. A joint 400 sq.m. exhibition , featuring the individual EIROforum organisations, their current programmes and many front-line achievements in their respective areas of activity, will be set up at Stand L in Hall 11 . It includes a central area, with a small cinema, displaying information about their current interactions via EIROforum. The stands will be manned throughout the conference by high-level representatives from the seven organisations. On Tuesday, November 12, 2002, 14:00 hrs, a Press Conference will take place at this exhibition stand, in the presence of the European Commissioner for Research, M. Phillippe Busquin, and most of the Directors General (or equivalent) of the EIROforum organisations. The main themes will be the increasingly intense interaction and co-operation between the European Commission and EIROforum, as well as the role of EIROforum and its member organisations within the European Research Area. Moreover, the official signing of the EIROforum Charter by the Directors General on this occasion will signify the formal establishment of EIROforum. Representatives of the EIROforum organisations will also participate in many of the numerous events that will take place during this large conference. Details will be found in the conference programme. The current EIROforum chairperson is Prof. Fotis C. Kafatos (EMBL) . The EIROforum website at http://www.eiroforum.org contains useful information about this unique collaboration. For more details, please contact the respective PR Departments of the organisations (addresses below).

  1. The Euratom Seventh Framework Programme FP7 (2007-2011)

    NASA Astrophysics Data System (ADS)

    Garbil, R.

    2010-10-01

    The objective of the Seventh Euratom Framework Program in the area of nuclear fission and radiation protection is to establish a sound scientific and technical basis to accelerate practical developments of nuclear energy related to resource efficiency, enhancing safety performance, cost-effectiveness and safer management of long-lived radioactive waste. Key cross-cutting topics such as the nuclear fuel cycle, actinide chemistry, risk analysis, safety assessment, even societal and governance issues are linked to the individual technical areas. Research need to explore new scientific and techno- logical opportunities and to respond in a flexible way to new policy needs that arise. The following activities are to be pursued. (a) Management of radioactive waste, research on partitioning and transmutation and/or other concepts aimed at reducing the amount and/or hazard of the waste for disposal; (b) Reactor systems research to underpin the con- tinued safe operation of all relevant types of existing reactor systems (including fuel cycle facilities), life-time extension, development of new advanced safety assessment methodologies and waste-management aspects of future reactor systems; (c) Radiation protection research in particular on the risks from low doses on medical uses and on the management of accidents; (d) Infrastructures and support given to the availability of, and cooperation between, research infrastructures necessary to maintain high standards of technical achievement, innovation and safety in the European nuclear sector and Research Area. (e) Human resources, mobility and training support to be provided for the retention and further development of scientific competence, human capacity through joint training activities in order to guarantee the availability of suitably qualified researchers, engineers and employees in the nuclear sector over the longer term.

  2. Foliar biofilms of Burkholderia pyrrocinia FP62 on geraniums

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Biofilm formation on foliar surfaces is commonly associated with plants in water-saturated environments (e.g. tropics or modified environments). On most leaf surfaces bacteria are thought to reside in aggregates with limited production of an exopolysaccharide (EPS) matrix. However, the biocontrol ag...

  3. Progress on FP13 Total Cross Section Measurements Capability

    SciTech Connect

    Ullmann, John Leonard; Couture, Aaron Joseph; Koehler, Paul E.; Mocko, Michal; Mosby, Shea Morgan; Wender, Stephen Arthur

    2016-09-26

    An accurate knowledge of the neutron capture cross section is important for many applications. Experimental measurements are important since theoretical calculations of capture have been notoriously difficult, with the ratio of measured to calculated cross sections often a factor of 2 or more in the 10 keV to 1 MeV region. However, a direct measurement of capture cannot be made on many interesting radioactive nuclides because of their short half-life or backgrounds caused by their nuclear decay. On the other hand, neutron transmission measurements of the total cross section are feasible for a wide range of radioactive nuclides since the detectors are far from the sample, and often are less sensitive to decay radiation. The parameters extracted from a total cross section measurement, which include the average resonance spacing, the neutron strength function, and the average total radiation width, (Γγ), provide tight constraints on the calculation of the capture cross section, and when applied produce much more accurate results. These measurements can be made using the intense epithermal neutron flux at the Lujan Center on relatively small quantities of target material. It was the purpose of this project to investigate and develop the capability to make these measurements. A great deal of progress was made towards establishing this capability during 2016, including setting up the flight path and obtaining preliminary results, but more work remains to be done.

  4. Peptide micelle-mediated delivery of tissue-specific suicide gene and combined therapy with avastin in a glioblastoma model.

    PubMed

    Oh, Binna; Han, Jaesik; Choi, Eunji; Tan, Xiaonan; Lee, Minhyung

    2015-04-01

    Bevacizumab (Avastin) is an angiogenesis inhibitor used as a treatment for various cancers. In this study, the combination therapy of Avastin and glioblastoma-specific thymidine kinase gene [pEpo-NI2-SV-herpes simplex virus thymidine kinase(HSVtk)] was evaluated in a glioblastoma animal model. The R7L10 peptide was used as a gene carrier of pEpo-NI2-SV-HSVtk. Gel retardation assays confirmed that R7L10 formed stable complexes with pEpo-NI2-SV-HSVtk. R7L10 protected DNA from nuclease digestion. R7L10 had lower transfection efficiency than polyethylenimine (PEI; 25 kDa). However, the in vitro and in vivo toxicity assays showed that R7L10 had lower cytotoxicity than PEI, suggesting that R7L10 is safer than PEI. For the combination therapy, Avastin was injected intravenously and the pEpo-NI2-SV-HSVtk/R7L10 complexes were injected intratumorally in the glioblastoma animal model. Tumor growth was most effectively inhibited by the combination therapy of Avastin and the gene. The immunostaining results confirmed that the HSVtk genes were expressed in the groups with the pEpo-NI2-SV-HSVtk/R7L10 complex. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed a higher level of apoptotic cells in the combination group than the pEpo-NI2-SV-HSVtk/R7L10 complex or Avastin group. In conclusion, the combination of Avastin and the glioblastoma-specific HSVtk gene has a higher antitumor effect than single therapy of Avastin or HSVtk after intratumoral administration in glioblastoma animal model.

  5. Primetime for Learning Genes.

    PubMed

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  6. Human HOX gene disorders.

    PubMed

    Quinonez, Shane C; Innis, Jeffrey W

    2014-01-01

    The Hox genes are an evolutionarily conserved family of genes, which encode a class of important transcription factors that function in numerous developmental processes. Following their initial discovery, a substantial amount of information has been gained regarding the roles Hox genes play in various physiologic and pathologic processes. These processes range from a central role in anterior-posterior patterning of the developing embryo to roles in oncogenesis that are yet to be fully elucidated. In vertebrates there are a total of 39 Hox genes divided into 4 separate clusters. Of these, mutations in 10 Hox genes have been found to cause human disorders with significant variation in their inheritance patterns, penetrance, expressivity and mechanism of pathogenesis. This review aims to describe the various phenotypes caused by germline mutation in these 10 Hox genes that cause a human phenotype, with specific emphasis paid to the genotypic and phenotypic differences between allelic disorders. As clinical whole exome and genome sequencing is increasingly utilized in the future, we predict that additional Hox gene mutations will likely be identified to cause distinct human phenotypes. As the known human phenotypes closely resemble gene-specific murine models, we also review the homozygous loss-of-function mouse phenotypes for the 29 Hox genes without a known human disease. This review will aid clinicians in identifying and caring for patients affected with a known Hox gene disorder and help recognize the potential for novel mutations in patients with phenotypes informed by mouse knockout studies.

  7. Primetime for Learning Genes

    PubMed Central

    Keifer, Joyce

    2017-01-01

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli. PMID:28208656

  8. Do Housekeeping Genes Exist?

    PubMed Central

    Sun, Bingyun

    2015-01-01

    The searching of human housekeeping (HK) genes has been a long quest since the emergence of transcriptomics, and is instrumental for us to understand the structure of genome and the fundamentals of biological processes. The resolved genes are frequently used in evolution studies and as normalization standards in quantitative gene-expression analysis. Within the past 20 years, more than a dozen HK-gene studies have been conducted, yet none of them sampled human tissues completely. We believe an integration of these results will help remove false positive genes owing to the inadequate sampling. Surprisingly, we only find one common gene across 15 examined HK-gene datasets comprising 187 different tissue and cell types. Our subsequent analyses suggest that it might not be appropriate to rigidly define HK genes as expressed in all tissue types that have diverse developmental, physiological, and pathological states. It might be beneficial to use more robustly identified HK functions for filtering criteria, in which the representing genes can be a subset of genome. These genes are not necessarily the same, and perhaps need not to be the same, everywhere in our body. PMID:25970694

  9. Efficient gene delivery to human umbilical cord mesenchymal stem cells by cationized Porphyra yezoensis polysaccharide nanoparticles

    PubMed Central

    Yu, Qingtong; Cao, Jin; Chen, Baoding; Deng, Wenwen; Cao, Xia; Chen, Jingjing; Wang, Yan; Wang, Shicheng; Yu, Jiangnan; Xu, Ximing; Gao, Xiangdong

    2015-01-01

    This study centered on an innovative application of Porphyra yezoensis polysaccharide (PPS) with cationic modification as a safe and efficient nonviral gene vector to deliver a plasmid encoding human Wnt3a (pWnt3a) into human umbilical cord mesenchymal stem cells (HUMSCs). After modification with branched low-molecular-weight (1,200 Da) polyethylenimine, the cationized PPS (CPPS) was combined with pWnt3a to form spherical nanoscale particles (CPPS-pWnt3a nanoparticles). Particle size and distribution indicated that the CPPS-pWnt3a nanoparticles at a CPPS:pWnt3a weight ratio of 40:1 might be a potential candidate for DNA plasmid transfection. A cytotoxicity assay demonstrated that the nanoparticles prepared at a CPPS:pWnt3a weight ratio of 40:1 were nontoxic to HUMSCs compared to those of Lipofectamine 2000 and polyethylenimine (25 kDa). These nanoparticles were further transfected to HUMSCs. Western blotting demonstrated that the nanoparticles (CPPS:pWnt3a weight ratio 40:1) had the greatest transfection efficiency in HUMSCs, which was significantly higher than that of Lipofectamine 2000; however, when the CPPS:pWnt3a weight ratio was increased to 80:1, the nanoparticle-treated group showed no obvious improvement in translation efficiency over Lipofectamine 2000. Therefore, CPPS, a novel cationic polysaccharide derived from P. yezoensis, could be developed into a safe, efficient, nonviral gene vector in a gene-delivery system. PMID:26604758

  10. Molecular characterization and genetic diversity of insecticidal crystal protein genes in native Bacillus thuringiensis isolates.

    PubMed

    Mahadeva Swamy, H M; Asokan, R; Mahmood, Riaz; Nagesha, S N

    2013-04-01

    The Western Ghats of Karnataka natural ecosystem are among the most diverse and is one of the eight hottest hotspots of biological diversity in the world, that runs along the western part of India through four states including Karnataka. Bacillus thuringiensis (Bt) strains were isolated from soils of Western Ghats of Karnataka and characterized by molecular and analytical methods as a result of which 28 new Bt-like isolates were identified. Bt strains were isolated from soil samples using sodium acetate selection method. The morphology of crystals was studied using light and phase contrast microscopy. Isolates were further characterized for insecticidal cry gene by PCR, composition of toxins in bacterial crystals by SDS-PAGE cloning, sequencing and evaluation of toxicity was done. As a result 28 new Bt-like isolates were identified. Majority of the isolates showed the presence of a 55 kDa protein bands on SDS-PAGE while the rest showed 130, 73, 34, and 25 kDa bands. PCR analysis revealed predominance of Coleopteran-active cry genes in these isolates. The variations in the nucleotide sequences, crystal morphology, and mass of crystal protein(s) purified from the Bt isolates revealed genetic and molecular diversity. Three strains containing Coleopteran-active cry genes showed higher activity against larvae Myllocerus undecimpustulatus undatus Marshall (Coleoptera: Curculionidae) than B. thuringiensis subsp. Morrisoni. Results indicated that Bt isolates could be utilized for bioinsecticide production, aiming to reduce the use of chemical insecticide which could be useful to use in integrated pest management to control agriculturally important pests for sustainable crop production.

  11. Identification of Aging-Associated Gene Expression Signatures That Precede Intestinal Tumorigenesis

    PubMed Central

    Okuchi, Yoshihisa; Imajo, Masamichi; Mizuno, Rei; Kamioka, Yuji; Miyoshi, Hiroyuki; Taketo, Makoto Mark; Nagayama, Satoshi; Sakai, Yoshiharu; Matsuda, Michiyuki

    2016-01-01

    Aging-associated alterations of cellular functions have been implicated in various disorders including cancers. Due to difficulties in identifying aging cells in living tissues, most studies have focused on aging-associated changes in whole tissues or certain cell pools. Thus, it remains unclear what kinds of alterations accumulate in each cell during aging. While analyzing several mouse lines expressing fluorescent proteins (FPs), we found that expression of FPs is gradually silenced in the intestinal epithelium during aging in units of single crypt composed of clonal stem cell progeny. The cells with low FP expression retained the wild-type Apc allele and the tissues composed of them did not exhibit any histological abnormality. Notably, the silencing of FPs was also observed in intestinal adenomas and the surrounding normal mucosae of Apc-mutant mice, and mediated by DNA methylation of the upstream promoter. Our genome-wide analysis then showed that the silencing of FPs reflects specific gene expression alterations during aging, and that these alterations occur in not only mouse adenomas but also human sporadic and hereditary (familial adenomatous polyposis) adenomas. Importantly, pharmacological inhibition of DNA methylation, which suppresses adenoma development in Apc-mutant mice, reverted the aging-associated silencing of FPs and gene expression alterations. These results identify aging-associated gene expression signatures that are heterogeneously induced by DNA methylation and precede intestinal tumorigenesis triggered by Apc inactivation, and suggest that pharmacological inhibition of the signature genes could be a novel strategy for the prevention and treatment of intestinal tumors. PMID:27589228

  12. Gene expression signature discriminates sporadic from post-radiotherapy-induced thyroid tumors

    PubMed Central

    Ory, Catherine; Ugolin, Nicolas; Levalois, Céline; Lacroix, Ludovic; Caillou, Bernard; Bidart, Jean-Michel; Schlumberger, Martin; Diallo, Ibrahima; de Vathaire, Florent; Hofman, Paul; Santini, José; Malfoy, Bernard; Chevillard, Sylvie

    2011-01-01

    Both external and internal exposure to ionizing radiation are strong risk factors for the development of thyroid tumors. Until now, the diagnosis of radiation-induced thyroid tumors has been deduced from a network of arguments taken together with the individual history of radiation exposure. Neither the histological features nor the genetic alterations observed in these tumors have been shown to be specific fingerprints of an exposure to radiation. The aim of our work is to define ionizing radiation-related molecular specificities in a series of secondary thyroid tumors developed in the radiation field of patients treated by radiotherapy. To identify molecular markers that could represent a radiation-induction signature, we compared 25K microarray transcriptome profiles of a learning set of 28 thyroid tumors, which comprised 14 follicular thyroid adenomas (FTA) and 14 papillary thyroid carcinomas (PTC), either sporadic or consecutive to external radiotherapy in childhood. We identified a signature composed of 322 genes which discriminates radiation-induced tumors (FTA and PTC) from their sporadic counterparts. The robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 29 tumors (16 FTA and 13 PTC). After the histology code break by the clinicians, 26/29 tumors were well classified regarding tumor etiology, 1 was undetermined, and 2 were misclassified. Our results help shed light on radiation-induced thyroid carcinogenesis, since specific molecular pathways are deregulated in radiation-induced tumors. PMID:21148326

  13. Cellular uptake pathways of lipid-modified cationic polymers in gene delivery to primary cells.

    PubMed

    Hsu, Charlie Y M; Uludağ, Hasan

    2012-11-01

    Hydrophobic modifications have emerged as a promising approach to improve the efficiency of non-viral gene delivery vectors (GDV). Functional GDVs from non-toxic polymers have been created with this approach but the mechanism(s) behind lipid-mediated enhancement in transfection remains to be clarified. Using a linoleic acid-substituted 2 kDa polyethylenimine (PEI2LA), we aimed to define the cellular uptake pathways and intracellular trafficking of plasmid DNA in normal human foreskin fibroblast cells. Several pharmacological compounds were applied to selectively inhibit uptake by clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis (CvME) and macropinocytosis. We found that PEI2LA complexes were taken up predominantly through CME, and to a lesser extent by CvME. In contrast, its precursor molecule, PEI2 complexes was internalized primarily by CvME and macropinocytosis. The commonly used 25 kDa PEI 25 complexes utilized all endocytic pathways, suggesting its efficiency is derived from a different set of transfection pathways than PEI2LA. We further applied several endosome disruptive agents and found that hypertonic media enhanced the transfection of PEI2LA by 6.5-fold. We infer that lipid substitution changes the normal uptake pathways significantly and transfection with hydrophobically modified GDVs may be further enhanced by incorporating endosome disruptive elements into vector design.

  14. Compromised virus-induced gene silencing in RDR6-deficient plants.

    PubMed

    Vaistij, Fabián E; Jones, Louise

    2009-03-01

    RNA silencing in plants serves as a potent antiviral defense mechanism through the action of small interfering RNAs (siRNAs), which direct RNA degradation. siRNAs can be derived directly from the viral genome or via the action of host-encoded RNA-dependent RNA polymerases (RDRs). Plant genomes encode multiple RDRs, and it has been demonstrated that plants defective for RDR6 hyperaccumulate several classes of virus. In this study, we compared the effectiveness of virus-induced gene silencing (VIGS) and RNA-directed DNA methylation (RdDM) in wild-type and RDR6-deficient Nicotiana benthamiana plants. For the potexvirus Potato virus X (PVX) and the potyvirus Plum pox virus (PPV), the efficiency of both VIGS and RdDM were compromised in RDR6-defective plants despite accumulating high levels of viral siRNAs similar to infection of wild-type plants. The reduced efficiency of VIGS and RdDM was unrelated to the size class of siRNA produced and, at least for PVX, was not dependent on the presence of the virus-encoded silencing suppressor protein, 25K. We suggest that primary siRNAs produced from PVX and PPV in the absence of RDR6 may not be good effectors of silencing and that RDR6 is required to produce secondary siRNAs that drive a more effective antiviral response.

  15. A Family of Bioreducible Poly(disulfide amine)s for Gene Delivery

    PubMed Central

    Ou, Mei; Xu, Rongzuo; Kim, Sun Hwa; Bull, David A.; Kim, Sung Wan

    2009-01-01

    A family of bioreducible poly(disulfide amine)s, which differ in the length of polymethylene spacer [–(CH2)n–] in the main chain and the side chain, has been synthesized. These bioreducible poly(disulfide amine)s exhibit local environment specific degradability and are associated with lower cytotoxicity than branched poly(ethylenimine) (bPEI, 25kDa). These cationic polymers also show higher buffering capacity and protonation degree than bPEI, facilitating the endosomal escape of carried genetic materials. The transfection efficiency of these agents is polymethylene length dependent. Poly(cystaminebisacrylamide-spermine) [poly(CBA-SP);], poly(cystaminebisacrylamide-bis(3-aminopropyl)-1,3-propanediamine) [poly(CBA-APPD);], and poly(cyxtaminebisacrylamide-bis(3-aminopropyl)-ethylenediamine) [ploy(CBA-APED);] with longer propylene [–(CH2)3–] side spacer, demonstrate higher transfection efficacy than the counterpart poly(cystaminebisacrylamide-bis(2-aminoethyl)-1,3-propanediamine) [poly(CBA-AEPD);] and poly(cystaminebisacrylamide-triethylenetetramine) [poly(CBA-TETA);], which have shorter ethylene [–(CH2)2–] side spacer. The poly(CBA-SP), poly(CBA-APPD), poly(CBA-APED) with the main chain spacer of –(CH2)4–, –(CH2)3–, –(CH2)2– demonstrate similar transfection efficiency, indicating the length of polymer main chain spacer has less influence on transfection efficiency. However, with the same short ethylene [–(CH2)2–] side spacer, poly(CBA-AEPD), with the longer main chain oligomethylene units [–(CH2)3–], showed relatively higher transfection efficiency than poly(CBA-TETA), having shorter main chain oligomethylene units [–(CH2)2–]. Of these polymeric carriers, poly(CBA-SP) demonstrated the highest transfection in the C2C12 cell line, while poly(CBA-APED) showed the highest transfection in the Hela cell line. All of these agents showed greater transfection activity than commercialized bPEI 25kDa. The poly(disulfide amine)s are promising

  16. Cholesterol-based cationic lipids for gene delivery: contribution of molecular structure factors to physico-chemical and biological properties.

    PubMed

    Sheng, Ruilong; Luo, Ting; Li, Hui; Sun, Jingjing; Wang, Zhao; Cao, Amin

    2014-04-01

    In this work, we prepared a series of cholesterol-based cationic (Cho-cat) lipids bearing cholesterol hydrophobe, natural amino acid headgroups (lysine/histidine) and linkage (carbonate ester/ether) bonds. In which, the natural amino acid headgroups made dominant contribution to their physico-chemical and biological properties. Among the lipids, the l-lysine headgroup bearing lipids (Cho-es/et-Lys) showed higher pDNA binding affinity and were able to form larger sized and higher surface charged lipoplexes than that of l-histidine headgroup bearing lipids (Cho-es/et-His), they also demonstrated higher transfection efficacy and higher membrane disruption capacities than that of their l-histidine headgroup bearing counterparts. However, compared to the contributions of the headgroups, the (carbonate ester/ether) linkage bonds showed much less affects. Besides, it could be noted that, Cho-es/et-Lys lipids exhibited very high luciferase gene transfection efficiency that almost reached the transfection level of "gold standard" bPEI-25k, made them potential transfection reagents for practical application. Moreover, the results facilitated the understanding for the structure-activity relationship of the cholesterol-based cationic lipids, and also paved a simple and efficient way for achieving high transfection efficiency by modification of suitable headgroups on lipid gene carriers.

  17. Synthesis, characterisation and preliminary investigation of the haemocompatibility of polyethyleneimine-grafted carboxymethyl chitosan for gene delivery.

    PubMed

    Liu, Xuan; Mo, Yunfei; Liu, Xiaoyu; Guo, Rui; Zhang, Yi; Xue, Wei; Zhang, Yuanming; Wang, Changyong; Ramakrishna, Seeram

    2016-05-01

    The development of safe and efficient gene carriers is the key to the clinical success of gene therapy. In the present study, carboxymethyl chitosan (CMCS) was prepared by chitosan (CS) alkalisation and carboxymethylation reactions. Then polyethyleneimine (PEI) was grafted to the backbone of CMCS by an amidation reaction. The CMCS-PEI copolymer showed strong complexation capability with DNA to form nanoparticles, and achieved lower cytotoxicity and higher transfection efficiency compared with PEI (25 kDa) towards 293T and 3T3 cells. Moreover, the haemocompatibility of the CMCS-PEI copolymer was investigated through the aggregation, morphology and lysis of human red blood cells (RBCs), along with the impact on the clotting function with activated partial thromboplastin time (APTT), prothrombin time (PT) and thromboelastographic (TEG) assays. The results demonstrated that the CMCS-PEI copolymer with a concentration lower than 0.05 mg/mL had little impact on the aggregation, morphology or lysis of RBCs, or on blood coagulation. Therefore, the copolymer may be a strong alternative candidate as an effective and safe non-viral vector.

  18. [Cloning of mMR-1 gene and expression in Pichia pastoris systems].

    PubMed

    Li, Tian-Bo; Hu, Yang; Wang, Yi-Guang; Xia, Huan-Zhang

    2005-01-01

    hMR-1 (Homo Myofibrillogenesis Regulator 1, AF417001) is a novel homo gene, which was firstly cloned in our laboratory. The former studies revealed that hMR-1 is a transmembrane protein which shows protein interaction with sarcomeric proteins like myomesin I, myosin regulatory light chain, alpha-enolase and some cell regulator proteins such as eukaryotic translation initiation factor3 subunit 5 (eIF3S5) and etc. In this work, we focused on cloning the homologous gene of hMR-1 from mouse C57BL/6J and exploring its expression using Pichia pastoris yeast system. Two pairs of primers were synthesized according to the hMR-1 gene homologous sequence on mouse genome chromosome 1. The mouse MR-1 gene (mMR-1) was cloned by PCR following the first round RT-PCR from mouse C57BL/6J spleen total RNA. Sequence analysis verified that mMR-1 gene and amino acids sequence showed 90.4% and 90.1% identity with hMR-1, respectively. The prediction of hydrophobic transmembrane structure of mMR-1 suggested it is also a transmembrane protein. The mMR-1 Pichia pastoris expression vector pPIC9-mMR-1 was constructed by fusion of the flanking mMR-1 ORF in the pPIC9 plasmid. After linearization of pPIC9-mMR-1 with Sal I, the 8.5kb DNA fragment was transformed into Pichia pastoris GS115 strain by electroporation. GS115/Mut+ pPIC9-mMR-1 transformants were selected on minimal methanol medium. Integration of mMR-1 gene into the yeast genome in the recombinants was verified by PCR from the transformants total DNA. The mMR-1 protein was expressed by induction under the concentration of 0.5 % methanol. The specific induced protein of 25 kD molecular mass in SDS-PAGE was confirmed to be the mMR-1 protein by Western blot rsing hMR-1 polyclonal antibody. The expression level of this recombinant mMR-1 protein was about 50 mg/L. The successful expression of mMR-1 in the Pichia pastoris GS115 will facilitate the further functional analysis of the novel gene MR-1 in animal model.

  19. Parkinson's disease: gene therapies.

    PubMed

    Coune, Philippe G; Schneider, Bernard L; Aebischer, Patrick

    2012-04-01

    With the recent development of effective gene delivery systems, gene therapy for the central nervous system is finding novel applications. Here, we review existing viral vectors and discuss gene therapy strategies that have been proposed for Parkinson's disease. To date, most of the clinical trials were based on viral vectors to deliver therapeutic transgenes to neurons within the basal ganglia. Initial trials used genes to relieve the major motor symptoms caused by nigrostriatal degeneration. Although these new genetic approaches still need to prove more effective than existing symptomatic treatments, there is a need for disease-modifying strategies. The investigation of the genetic factors implicated in Parkinson's disease is providing precious insights in disease pathology that, combined with innovative gene delivery systems, will hopefully offer novel opportunities for gene therapy interventions to slow down, or even halt disease progression.

  20. Green genes gleaned.

    PubMed

    Beale, Samuel I

    2005-07-01

    A recent paper by Ayumi Tanaka and colleagues identifying an Arabidopsis thaliana gene for 3,8-divinyl(proto)chlorophyllide 8-vinyl reductase brings a satisfying conclusion to the hunt for genes encoding enzymes for the steps in the chlorophyll biosynthetic pathway. Now, at least in angiosperm plants represented by Arabidopsis, genes for all 15 steps in the pathway from glutamyl-tRNA to chlorophylls a and b have been identified.

  1. Gene-Category Analysis.

    PubMed

    Bauer, Sebastian

    2017-01-01

    Gene-category analysis is one important knowledge integration approach in biomedical sciences that combines knowledge bases such as Gene Ontology with lists of genes or their products, which are often the result of high-throughput experiments, gained from either wet-lab or synthetic experiments. In this chapter, we will motivate this class of analyses and describe an often used variant that is based on Fisher's exact test. We show that this approach has some problems in the context of Gene Ontology of which users should be aware. We then describe some more recent algorithms that try to address some of the shortcomings of the standard approach.

  2. Antiangiogenic Eye Gene Therapy.

    PubMed

    Corydon, Thomas J

    2015-08-01

    The idea of treating disease in humans with genetic material was conceived over two decades ago and with that a promising journey involving development and efficacy studies in cells and animals of a large number of novel therapeutic reagents unfolded. In the footsteps of this process, successful gene therapy treatment of genetic conditions in humans has shown clear signs of efficacy. Notably, significant advancements using gene supplementation and silencing strategies have been made in the field of ocular gene therapy, thereby pinpointing ocular gene therapy as one of the compelling "actors" bringing gene therapy to the clinic. Most of all, this success has been facilitated because of (1) the fact that the eye is an effortlessly accessible, exceedingly compartmentalized, and immune-privileged organ offering a unique advantage as a gene therapy target, and (2) significant progress toward efficient, sustained transduction of cells within the retina having been achieved using nonintegrating vectors based on recombinant adeno-associated virus and nonintegrating lentivirus vectors. The results from in vivo experiments and trials suggest that treatment of inherited retinal dystrophies, ocular angiogenesis, and inflammation with gene therapy can be both safe and effective. Here, the progress of ocular gene therapy is examined with special emphasis on the potential use of RNAi- and protein-based antiangiogenic gene therapy to treat exudative age-related macular degeneration.

  3. History of gene therapy.

    PubMed

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality.

  4. Towards Consensus Gene Ages

    PubMed Central

    Liebeskind, Benjamin J.; McWhite, Claire D.; Marcotte, Edward M.

    2016-01-01

    Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene’s age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914

  5. Cell and gene therapy.

    PubMed

    Rao, Rajesh C; Zacks, David N

    2014-01-01

    Replacement or repair of a dysfunctional gene combined with promoting cell survival is a two-pronged approach that addresses an unmet need in the therapy of retinal degenerative diseases. In this chapter, we discuss various strategies toward achieving both goals: transplantation of wild-type cells to replace degenerating cells and to rescue gene function, sequential gene and cell therapy, and in vivo reprogramming of rods to cones. These approaches highlight cutting-edge advances in cell and gene therapy, and cellular lineage conversion in order to devise new therapies for various retinal degenerative diseases.

  6. A potyvirus-based gene vector allows producing active human S-COMT and animal GFP, but not human sorcin, in vector-infected plants.

    PubMed

    Kelloniemi, Jani; Mäkinen, Kristiina; Valkonen, Jari P T

    2006-05-01

    Potato virus A (PVA), a potyvirus with a (+)ssRNA genome translated to a large polyprotein, was engineered and used as a gene vector for expression of heterologous proteins in plants. Foreign genes including jellyfish GFP (Aequorea victoria) encoding the green fluorescent protein (GFP, 27 kDa) and the genes of human origin (Homo sapiens) encoding a soluble resistance-related calcium-binding protein (sorcin, 22 kDa) and the catechol-O-methyltransferase (S-COMT; 25 kDa) were cloned between the cistrons for the viral replicase and coat protein (CP). The inserts caused no adverse effects on viral infectivity and virulence, and the inserted sequences remained intact in progeny viruses in the systemically infected leaves. The heterologous proteins were released from the viral polyprotein following cleavage by the main viral proteinase, NIa, at engineered proteolytic processing sites flanking the insert. Active GFP, as indicated by green fluorescence, and S-COMT with high levels of enzymatic activity were produced. In contrast, no sorcin was detected despite the expected equimolar amounts of the foreign and viral proteins being expressed as a polyprotein. These data reveal inherent differences between heterologous proteins in their suitability for production in plants.

  7. Smart Genes, Stupid Science.

    ERIC Educational Resources Information Center

    Randerson, Sherman; Mahadeva, Madhu N.

    1983-01-01

    Because many people still believe that specific, identifiable genes dictate the level of human intelligence and that the number/quality of these genes can be evaluated, presents evidence from human genetics (related to nervous system development) to counter this view. Also disputes erroneous assumptions made in "heritability studies" of human…

  8. Genes, genome and Gestalt.

    PubMed

    Grisolia, Cesar Koppe

    2005-03-31

    According to Gestalt thinking, biological systems cannot be viewed as the sum of their elements, but as processes of the whole. To understand organisms we must start from the whole, observing how the various parts are related. In genetics, we must observe the genome over and above the sum of its genes. Either loss or addition of one gene in a genome can change the function of the organism. Genomes are organized in networks of genes, which need to be well integrated. In the case of genetically modified organisms (GMOs), for example, soybeans, rats, Anopheles mosquitoes, and pigs, the insertion of an exogenous gene into a receptive organism generally causes disturbance in the networks, resulting in the breakdown of gene interactions. In these cases, genetic modification increased the genetic load of the GMO and consequently decreased its adaptability (fitness). Therefore, it is hard to claim that the production of such organisms with an increased genetic load does not have ethical implications.

  9. [Gene therapy and ethics].

    PubMed

    Müller, H; Rehmann-Sutter, C

    1995-01-10

    Gene therapy represents a new strategy to treat human disorders. It was originally conceived as a cure for severe monogenetic disorders. Since its conception, the spectrum of possible application for gene therapy has been to include the treatment of acquired diseases, such as various forms of cancer and some viral infections, most notably human immune deficiency virus (HIV) and hepatitis B virus. Since somatic gene therapy does not cause substantially new ethical problems, it has gained broad approval. This is by no means the case with germ-line gene therapy. Practically all bodies who were evaluating the related ethical aspects wanted to ban its medical application on grounds of fundamental and pragmatic considerations. In this review, practical and ethical views concerning gene therapy are summarized which were presented at the "Junitagung 1994" of the Swiss Society for Biomedical Ethics in Basle.

  10. A novel murrel Channa striatus mitochondrial manganese superoxide dismutase: gene silencing, SOD activity, superoxide anion production and expression.

    PubMed

    Arockiaraj, Jesu; Palanisamy, Rajesh; Bhatt, Prasanth; Kumaresan, Venkatesh; Gnanam, Annie J; Pasupuleti, Mukesh; Kasi, Marimuthu

    2014-12-01

    We have reported the molecular characterization including gene silencing, superoxide activity, superoxide anion production, gene expression and molecular characterization of a mitochondrial manganese superoxide dismutase (mMnSOD) from striped murrel Channa striatus (named as CsmMnSOD). The CsmMnSOD polypeptide contains 225 amino acids with a molecular weight of 25 kDa and a theoretical isoelectric point of 8.3. In the N-terminal region, CsmMnSOD carries a mitochondrial targeting sequence and a superoxide dismutases (SOD) Fe domain (28-109), and in C-terminal region, it carries another SOD Fe domain (114-220). The CsmMnSOD protein sequence shared significant similarity with its homolog of MnSOD from rock bream Oplegnathus fasciatus (96%). The phylogenetic analysis showed that the CsmMnSOD fell in the clade of fish mMnSOD group. The monomeric structure of CsmMnSOD possesses 9 α-helices (52.4%), 3 β-sheets (8.8%) and 38.8% random coils. The highest gene expression was noticed in liver, and its expression was inducted with fungal (Aphanomyces invadans) and bacterial (Aeromonas hydrophila) infections. The gene silencing results show that the fish that received dsRNA exhibited significant (P < 0.05) changes in expression when compared to their non-injected and fish physiological saline-injected controls. The SOD activity shows that the activity increases with the spread of infection and decreases once the molecule controls the pathogen. The capacity of superoxide anion production was determined by calculating the granular blood cell count during infection in murrel. It shows that the infection influenced the superoxide radical production which plays a major role in killing the pathogens. Overall, this study indicated the defense potentiality of CsmMnSOD; however, further research is necessary to explore its capability at protein level.

  11. Regional localization of the CCAAT displacement protein gene (CUTL1) to 7q22 by analysis of somatic cell hybrids

    SciTech Connect

    Scherer, S.W.; Tsui, L.C. The Hospital for Sick Children, Toronto, Ontario ); Neufeld, E.J.; Lievens, P.M.J. Dana Farber Cancer Inst., Cambridge, MA Harvard Medical School, Cambridge, MA ); Orkin, S.H. Dana Farber Cancer Inst., Cambridge, MA Harvard Medical School, Cambridge, MA Howard Hughes Medical Inst., Cambridge, MA ); Kim, J. )

    1993-03-01

    CCAAT displacement protein (CDP) is a putative repressor of tissue-specific gene expression, implicated in regulation of expression of the human myeloid-specific gene, gp91-phox. The cDNA sequence of the human gene predicts a polypeptide of 1506 amino acids, with a homeodomain and three repeated motifs closely homologous to cut, a protein known to specify the cell fate of peripheral neurons and other tissues during embryonic development of Drosophila. Therefore, the human gene locus for CDP has been named CUTL1, for cut-like 1. Preliminary data revealed that CUTL1 mapped to human chromosome 7 (E.J.N., P.M.-J.L., and S.H.O., unpublished results). Since diseases with abnormalities of myeloid differentitation often have aberrations of chromosome 7, especially in patients previously exposed to mutagenic agents or radiation therapy, the cell-type specificity of CDP makes it an attractive candidate for involvement in these conditions. As a first step in addressing this question, we have examined the regional localization of CUTL1 using a panel of rodent-human somatic cell hybrids containing various portions of chromosome 7. The results of our hybridization analysis are summarized. The regional localization of CUTL1 to 7q22 was based primarily on the negative hybridization signal with the human/hamster hybrid 1EF2/3/K017 (7cen-q21) and the positive result with 1CF2/5/K016 (7cen-q22). Since no hybridization signal was detected in GM1059Rag5 (a human-mouse hybrid carrying a single human chromosome 7 with an interstitial deletion 7pter-q22:q32-qter) and 2068Rag22-2 (7qter-q22), the regional assignment of CUTL1 could be narrowed to the distal boundary of 7q22.

  12. 4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. AERIAL VIEW OF GENE WASH RESERVOIR AND GENE CAMP LOOKING SOUTHWEST. DAM AND SPILLWAY VISIBLE IN BOTTOM OF PHOTO. - Gene Wash Reservoir & Dam, 2 miles west of Parker Dam, Parker Dam, San Bernardino County, CA

  13. Coupling of a bifunctional peptide R13 to OTMCS-PEI copolymer as a gene vector increases transfection efficiency and tumor targeting

    PubMed Central

    Lv, Hui; Zhu, Qing; Liu, Kewu; Zhu, Manman; Zhao, Wenfang; Mao, Yuan; Liu, Kehai

    2014-01-01

    Background A degradable polyethylenimine (PEI) derivative coupled to a bifunctional peptide R13 was developed to solve the transfection efficiency versus cytotoxicity and tumor-targeting problems of PEI when used as a gene vector. Methods We crossed-linked low molecular weight PEI with N-octyl-N-quaternary chitosan (OTMCS) to synthesize a degradable PEI derivative (OTMCS-PEI), and then used a bifunctional peptide, RGDC-TAT (49–57) called R13 to modify OTMCS-PEI so as to prepare a new gene vector, OTMCS-PEI-R13. This new gene vector was characterized by various physicochemical methods. Its cytotoxicity and gene transfection efficiency were also determined both in vitro and in vivo. Results The vector showed controlled degradation and excellent buffering capacity. The particle size of the OTMCS-PEI-R13/DNA complexes was around 150–250 nm and the zeta potential ranged from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 23.5 U DNase I/μg DNA. Further, the polymer was resistant to dissociation induced by 50% fetal bovine serum and 400 μg/mL sodium heparin. Compared with PEI 25 kDa, the OTMCS-PEI-R13/DNA complexes showed higher transfection efficiency both in vitro and in vivo. Further, compared with OTMCS-PEI, distribution of OTMCS-PEI-R13 at tumor sites was markedly enhanced, indicating the tumor-targeting specificity of R13. Conclusion OTMCS-PEI-R13 could be a potential candidate as a safe and efficient gene delivery carrier for gene therapy. PMID:24648730

  14. Use of a new rat chondrosarcoma cell line to delineate a 119-base pair chondrocyte-specific enhancer element and to define active promoter segments in the mouse pro-alpha 1(II) collagen gene.

    PubMed

    Mukhopadhyay, K; Lefebvre, V; Zhou, G; Garofalo, S; Kimura, J H; de Crombrugghe, B

    1995-11-17

    We show that a new rat chondrosarcoma (RCS) cell line established in long-term culture from the Swarm tumor displayed a stable differentiated chondrocyte-like phenotype. Indeed, these cells produced the collagen types II, IX, and XI and alcian blue-stainable cartilage-specific proteoglycans, but no type I or type III collagen. To functionally characterize their chondrocytic nature, the cells were stably transfected with a type II collagen/beta geo chimeric gene which confers essentially perfect chondrocyte-specific expression in transgenic mice. RCS cells expressed both beta-galactosidase and G418 resistance, in comparison with similarly transfected 10T1/2 and NIH/3T3 fibroblasts which did not. These cells were then used to perform a systematic deletion analysis of the first intron of the mouse type II collagen gene (Col2a1) using transient expression experiments to determine which segments stimulated expression of a luciferase reporter gene in RCS cells but not in 10T1/2 fibroblasts. Cloning of two tandem copies of a 156-base pair (bp) intron 1 fragment (+2188 to +2343) in a construction containing a 314-bp Col2a1 promoter caused an almost 200-fold increase in promoter activity in RCS cells but no increase in 10T1/2 cells. DNase I footprint analysis over this 156-bp fragment revealed two adjacent protected regions, FP1 and FP2, located in the 3'-half of this segment, but no differences were seen with nuclear extracts of RCS cells and 10T1/2 fibroblasts. Deletion of FP2 to leave a 119-bp segment decreased enhancer activity by severalfold, but RCS cell specificity was maintained. Further deletions indicated that sequences both in the 5' part of the 119-bp fragment and in FP1 were needed simultaneously for RCS cell-specific enhancer activity. A series of deletions in the promoter region of the mouse Col2a1 gene progressively reduced activity when these promoters were tested by themselves in transient expression experiments. However, these promoter deletions were all

  15. Fecundity genes in sheep.

    PubMed

    Davis, G H

    2004-07-01

    Since 1980 there has been increasing interest in the identification and utilisation of major genes for prolificacy in sheep. Mutations that increase ovulation rate have been discovered in the BMPR-1B, BMP15 and GDF9 genes, and others are known to exist from the expressed inheritance patterns although the mutations have not yet been located. In the case of BMP15, four different mutations have been discovered but each produces the same phenotype. The modes of inheritance of the different prolificacy genes include autosomal dominant genes with additive effects on ovulation rate (BMPR-1B; Lacaune), autosomal over-dominant genes with infertility in homozygous females (GDF9), X-linked over-dominant genes with infertility in homozygous females (BMP15), and X-linked maternally imprinted genes (FecX2). The size of the effect of one copy of a mutation on ovulation rate ranges from an extra 0.4 ovulations per oestrus for the FecX2 mutation to an extra 1.5 ovulations per oestrus for the BMPR-1B mutation. DNA tests enable some of these mutations to be used in genetic improvement programmes based on marker assisted selection.

  16. Gene therapy for hemophilia.

    PubMed

    Chuah, M K; Evens, H; VandenDriessche, T

    2013-06-01

    Hemophilia A and B are X-linked monogenic disorders resulting from deficiencies of factor VIII and FIX, respectively. Purified clotting factor concentrates are currently intravenously administered to treat hemophilia, but this treatment is non-curative. Therefore, gene-based therapies for hemophilia have been developed to achieve sustained high levels of clotting factor expression to correct the clinical phenotype. Over the past two decades, different types of viral and non-viral gene delivery systems have been explored for hemophilia gene therapy research with a variety of target cells, particularly hepatocytes, hematopoietic stem cells, skeletal muscle cells, and endothelial cells. Lentiviral and adeno-associated virus (AAV)-based vectors are among the most promising vectors for hemophilia gene therapy. In preclinical hemophilia A and B animal models, the bleeding phenotype was corrected with these vectors. Some of these promising preclinical results prompted clinical translation to patients suffering from a severe hemophilic phenotype. These patients receiving gene therapy with AAV vectors showed long-term expression of therapeutic FIX levels, which is a major step forwards in this field. Nevertheless, the levels were insufficient to prevent trauma or injury-induced bleeding episodes. Another challenge that remains is the possible immune destruction of gene-modified cells by effector T cells, which are directed against the AAV vector antigens. It is therefore important to continuously improve the current gene therapy approaches to ultimately establish a real cure for hemophilia.

  17. Differentially Coexpressed Disease Gene Identification Based on Gene Coexpression Network.

    PubMed

    Jiang, Xue; Zhang, Han; Quan, Xiongwen

    2016-01-01

    Screening disease-related genes by analyzing gene expression data has become a popular theme. Traditional disease-related gene selection methods always focus on identifying differentially expressed gene between case samples and a control group. These traditional methods may not fully consider the changes of interactions between genes at different cell states and the dynamic processes of gene expression levels during the disease progression. However, in order to understand the mechanism of disease, it is important to explore the dynamic changes of interactions between genes in biological networks at different cell states. In this study, we designed a novel framework to identify disease-related genes and developed a differentially coexpressed disease-related gene identification method based on gene coexpression network (DCGN) to screen differentially coexpressed genes. We firstly constructed phase-specific gene coexpression network using time-series gene expression data and defined the conception of differential coexpression of genes in coexpression network. Then, we designed two metrics to measure the value of gene differential coexpression according to the change of local topological structures between different phase-specific networks. Finally, we conducted meta-analysis of gene differential coexpression based on the rank-product method. Experimental results demonstrated the feasibility and effectiveness of DCGN and the superior performance of DCGN over other popular disease-related gene selection methods through real-world gene expression data sets.

  18. Differentially Coexpressed Disease Gene Identification Based on Gene Coexpression Network

    PubMed Central

    Quan, Xiongwen

    2016-01-01

    Screening disease-related genes by analyzing gene expression data has become a popular theme. Traditional disease-related gene selection methods always focus on identifying differentially expressed gene between case samples and a control group. These traditional methods may not fully consider the changes of interactions between genes at different cell states and the dynamic processes of gene expression levels during the disease progression. However, in order to understand the mechanism of disease, it is important to explore the dynamic changes of interactions between genes in biological networks at different cell states. In this study, we designed a novel framework to identify disease-related genes and developed a differentially coexpressed disease-related gene identification method based on gene coexpression network (DCGN) to screen differentially coexpressed genes. We firstly constructed phase-specific gene coexpression network using time-series gene expression data and defined the conception of differential coexpression of genes in coexpression network. Then, we designed two metrics to measure the value of gene differential coexpression according to the change of local topological structures between different phase-specific networks. Finally, we conducted meta-analysis of gene differential coexpression based on the rank-product method. Experimental results demonstrated the feasibility and effectiveness of DCGN and the superior performance of DCGN over other popular disease-related gene selection methods through real-world gene expression data sets. PMID:28042568

  19. Association of SNAP-25 Gene Ddel and Mnll Polymorphisms with Adult Attention Deficit Hyperactivity Disorder

    PubMed Central

    Herken, Hasan; Erdal, Mehmet Emin; Ünal, Gonca Ayşe; Çakaloz, Burcu; Ay, Mustafa Ertan; Yücel, Erinç; Edgünlü, Tuba; Şengül, Cem

    2014-01-01

    Objective The synaptosomal-associated protein of 25 kDa (SNAP-25) gene is a presynaptic plasma membrane protein and an integral component of the vesicle docking and fusion machinery mediating secretion of neurotransmitters. Previously, several studies reported association between SNAP-25 and attention deficit hyperactivity disorder (ADHD). We investigated whether these SNAP-25 polymorphisms (MnlI T/G and DdelI T/C) were also associated with ADHD in the Turkish population. Methods Our study comprised unrelated 139 subjects who met DSM-IV criteria for ADHD and 73 controls and all were of Turkish origin. Genetic analyses were performed and patients were evaluated with Wender-Utah Rating Scale and Adult ADD/ADHD DSM IV-Based Diagnostic Screening and Rating Scale. Results SNAP-25 DdelI polymorphism was not associated with ADHD but there was a statistically significant difference between ADHD patients and controls for SNAP-25 MnlI polymorphism. For SNAP-25 MnlI polymorphism patients with G/G genotype of the SNAP-25 gene MnlI polymorphism had higher Wender-Utah scores and higher scores in the 1st and 3rd parts of adult ADD/ADHD Scale. Conclusion We detected a significant association of the MnlI polymorphism in our ADHD sample which was similar to previous findings. Our study also revealed that SNAP-25 MnlI polymorphism was also associated with symptom severity of ADHD. This study is also, the first report on the association of SNAP-25 with ADHD in the Turkish population. PMID:25395980

  20. Ultraviolet damage and nucleosome folding of the 5S ribosomal RNA gene.

    SciTech Connect

    Liu, X; Mann, David B.; Suquet, C; Springer, David L. ); Smerdon, Michael J.

    2000-01-25

    The Xenopus borealis somatic 5S ribosomal RNA gene was used as a model system to determine the mutual effects of nucleosome folding and formation of ultraviolet (UV) photoproducts (primarily cis-syn cyclobutane pyrimidine dimers, or CPDs) in chromatin. We analyzed the preferred rotational and translational settings of 5S rDNA on the histone octamer surface after induction of up to 0.8 CPD/nucleosome core (2.5 kJ/m(2) UV dose). DNase I and hydroxyl radical footprints indicate that UV damage at these levels does not affect the average rotational setting of the 5S rDNA molecules. Moreover, a combination of nuclease trimming and restriction enzyme digestion indicates the preferred translational positions of the histone octamer are not affected by this level of UV damage. We also did not observe differences in the UV damage patterns of irradiated 5S rDNA before or after nucleosome formation, indicating there is little difference in the inhibition of nucleosome folding by specific CPD sites in the 5S rRNA gene. Conversely, nucleosome folding significantly restricts CPD formation at all sites in the three helical turns of the nontranscribed strand located in the dyad axis region of the nucleosome, where DNA is bound exclusively by the histone H3-H4 tetramer. Finally, modulation of the CPD distribution in a 14 nt long pyrimidine tract correlates with its rotational setting on the histone surface, when the strong sequence bias for CPD formation in this tract is minimized by normalization. These results help establish the mutual roles of histone binding and UV photoproducts on their formation in chromatin.

  1. Structural and Functional Consequences of Poly(ethylene glycol) Inclusion on DNA Condensation For Gene Delivery

    PubMed Central

    Millili, Peter G.; Selekman, Joshua A.; Blocker, Kory M.; Johnson, David A.; Naik, Ulhas P.; Sullivan, Millicent O.

    2010-01-01

    Polycationic polymers have been used to condense therapeutic DNA into sub-micron particles, offering protection from shear-induced or enzymatic degradation. However, the spontaneous nature of this self-assembly process gives rise to the formation of multimolecular aggregates, resulting in significant polyplex heterogeneity. Additionally, cytotoxicity issues and serum instability have limited the in vivo efficacy of such systems. One way these issues can be addressed is through the inclusion of poly(ethylene glycol) (PEG). PEG has known steric effects that inhibit polyplex self-aggregation. A variety of PEGylated gene delivery formulations have been previously pursued in an effort to take advantage of this material’s benefits. Due to such interest, our aim was to further explore the consequences of PEG inclusion on the structure and activity of gene delivery vehicle formulations. We explored the complexation of plasmid DNA with varying ratios of a PEGylated tri-lysine peptide (PEG-K3) and 25 kDa polyethylenimine (PEI). Atomic force and scanning electron microscopy were utilized to assess the polyplex size and shape, and revealed that a critical threshold of PEG was necessary to promote the formation of homogeneous polyplexes. Flow cytometry and fluorescence microscopy analyses suggested that the presence of PEG inhibited transfection efficiency as a consequence of changes in intracellular trafficking, and promoted an increased reliance on energy-independent mechanisms of cellular uptake. These studies provide new information on the role of PEG in delivery vehicle design and lay the foundation for future work aimed at elucidating the details of the intracellular transport of PEGylated polyplexes. PMID:20232467

  2. Development of a successive targeting liposome with multi-ligand for efficient targeting gene delivery

    PubMed Central

    Ma, Kun; Shen, Haijun; Shen, Song; Xie, Men; Mao, Chuanbin; Qiu, Liyan; Jin, Yi

    2012-01-01

    Background A successful gene delivery system needs to breakthrough several barriers to allow efficient transgenic expression. In the present study, successive targeting liposomes (STL) were constructed by integrating various targeting groups into a nanoparticle to address this issue. Methods Polyethylenimine (PEI) 1800-triamcinolone acetonide (TA) with nuclear targeting capability was synthesized by a two-step reaction. Lactobionic acid was connected with cholesterol to obtain a compound of [(2-lactoylamido) ethylamino]formic acid cholesterol ester (CHEDLA) with hepatocyte-targeting capability. The liposome was modified with PEI 1800-TA and CHEDLA to prepare successive targeting liposome (STL). Its physicochemical properties and transfection efficiency were investigated both in vitro and in vivo. Results The diameter of STL was approximately 100 nm with 20 mV of potential. The confocal microscopy observation and potential assay verified that lipid bilayer of STL was decorated with PEI 1800-TA. Cytotoxicity of STL was significantly lower than that of PEI 1800-TA and PEI 25K. The transfection efficiency of 10% CHEDLA STL in HepG2 cells was the higher than of the latter two with serum. Its transfection efficiency was greatly reduced with excessive free galactose, indicating that STL was absorbed via galactose receptor-mediated endocytosis. The in vivo study in mice showed that 10% CHEDLA STL had better transgenic expression in liver than the other carriers. Conclusions STL with multi-ligand was able to overcome the various barriers to target nucleus and special cells and present distinctive transgenic expression. Therefore, it has a great potential for gene therapy as a nonviral carrier. PMID:21574214

  3. Genes and social behavior.

    PubMed

    Robinson, Gene E; Fernald, Russell D; Clayton, David F

    2008-11-07

    What genes and regulatory sequences contribute to the organization and functioning of neural circuits and molecular pathways in the brain that support social behavior? How does social experience interact with information in the genome to modulate brain activity? Here, we address these questions by highlighting progress that has been made in identifying and understanding two key "vectors of influence" that link genes, the brain, and social behavior: (i) Social information alters gene expression in the brain to influence behavior, and (ii) genetic variation influences brain function and social behavior. We also discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior.

  4. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

    PubMed Central

    Nagarkar-Jaiswal, Sonal; Lee, Pei-Tseng; Campbell, Megan E; Chen, Kuchuan; Anguiano-Zarate, Stephanie; Cantu Gutierrez, Manuel; Busby, Theodore; Lin, Wen-Wen; He, Yuchun; Schulze, Karen L; Booth, Benjamin W; Evans-Holm, Martha; Venken, Koen JT; Levis, Robert W; Spradling, Allan C; Hoskins, Roger A; Bellen, Hugo J

    2015-01-01

    Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstrate reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates. DOI: http://dx.doi.org/10.7554/eLife.05338.001 PMID:25824290

  5. "Bad genes" & criminal responsibility.

    PubMed

    González-Tapia, María Isabel; Obsuth, Ingrid

    2015-01-01

    The genetics of the accused is trying to break into the courts. To date several candidate genes have been put forward and their links to antisocial behavior have been examined and documented with some consistency. In this paper, we focus on the so called "warrior gene", or the low-activity allele of the MAOA gene, which has been most consistently related to human behavior and specifically to violence and antisocial behavior. In preparing this paper we had two objectives. First, to summarize and analyze the current scientific evidence, in order to gain an in depth understanding of the state of the issue and determine whether a dominant line of generally accepted scientific knowledge in this field can be asserted. Second, to derive conclusions and put forward recommendations related to the use of genetic information, specifically the presence of the low-activity genotype of the MAOA gene, in modulation of criminal responsibility in European and US courts.

  6. Genes underlying altruism.

    PubMed

    Thompson, Graham J; Hurd, Peter L; Crespi, Bernard J

    2013-01-01

    William D. Hamilton postulated the existence of 'genes underlying altruism', under the rubric of inclusive fitness theory, a half-century ago. Such genes are now poised for discovery. In this article, we develop a set of intuitive criteria for the recognition and analysis of genes for altruism and describe the first candidate genes affecting altruism from social insects and humans. We also provide evidence from a human population for genetically based trade-offs, underlain by oxytocin-system polymorphisms, between alleles for altruism and alleles for non-social cognition. Such trade-offs between self-oriented and altruistic behaviour may influence the evolution of phenotypic diversity across all social animals.

  7. Clock genes and sleep.

    PubMed

    Landgraf, Dominic; Shostak, Anton; Oster, Henrik

    2012-01-01

    In most species--from cyanobacteria to humans--endogenous clocks have evolved that drive 24-h rhythms of behavior and physiology. In mammals, these circadian rhythms are regulated by a hierarchical network of cellular oscillators controlled by a set of clock genes organized in a system of interlocked transcriptional feedback loops. One of the most prominent outputs of the circadian system is the synchronization of the sleep-wake cycle with external (day-) time. Clock genes also have a strong impact on many other biological functions, such as memory formation, energy metabolism, and immunity. Remarkably, large overlaps exist between clock gene and sleep (loss) mediated effects on these processes. This review summarizes sleep clock gene interactions for these three phenomena, highlighting potential mediators linking sleep and/or clock function to physiological output in an attempt to better understand the complexity of diurnal adaptation and its consequences for health and disease.

  8. GeneLab

    NASA Technical Reports Server (NTRS)

    Berrios, Daniel C.; Thompson, Terri G.

    2015-01-01

    NASA GeneLab is expected to capture and distribute omics data and experimental and process conditions most relevant to research community in their statistical and theoretical analysis of NASAs omics data.

  9. Evolutionary Fingerprinting of Genes

    PubMed Central

    Kosakovsky Pond, Sergei L.; Scheffler, Konrad; Gravenor, Michael B.; Poon, Art F.Y.; Frost, Simon D.W.

    2010-01-01

    Over time, natural selection molds every gene into a unique mosaic of sites evolving rapidly or resisting change—an “evolutionary fingerprint” of the gene. Aspects of this evolutionary fingerprint, such as the site-specific ratio of nonsynonymous to synonymous substitution rates (dN/dS), are commonly used to identify genetic features of potential biological interest; however, no framework exists for comparing evolutionary fingerprints between genes. We hypothesize that protein-coding genes with similar protein structure and/or function tend to have similar evolutionary fingerprints and that comparing evolutionary fingerprints can be useful for discovering similarities between genes in a way that is analogous to, but independent of, discovery of similarity via sequence-based comparison tools such as Blast. To test this hypothesis, we develop a novel model of coding sequence evolution that uses a general bivariate discrete parameterization of the evolutionary rates. We show that this approach provides a better fit to the data using a smaller number of parameters than existing models. Next, we use the model to represent evolutionary fingerprints as probability distributions and present a methodology for comparing these distributions in a way that is robust against variations in data set size and divergence. Finally, using sequences of three rapidly evolving RNA viruses (HIV-1, hepatitis C virus, and influenza A virus), we demonstrate that genes within the same functional group tend to have similar evolutionary fingerprints. Our framework provides a sound statistical foundation for efficient inference and comparison of evolutionary rate patterns in arbitrary collections of gene alignments, clustering homologous and nonhomologous genes, and investigation of biological and functional correlates of evolutionary rates. PMID:19864470

  10. Cystic fibrosis modifier genes.

    PubMed Central

    Davies, Jane; Alton, Eric; Griesenbach, Uta

    2005-01-01

    Since the recognition that CFTR genotype was not a good predictor of pulmonary disease severity in CF, several candidate modifier genes have been identified. It is unlikely that a single modifier gene will be found, but more probable that several haplotypes in combination may contribute, which in itself presents a major methodological challenge. The aims of such studies are to increase our understanding of disease pathogenesis, to aid prognosis and ultimately to lead to the development of novel treatments. PMID:16025767

  11. Evidence for homosexuality gene

    SciTech Connect

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  12. GeneClinics

    PubMed Central

    Tarczy-Hornoch, Peter; Shannon, Paul; Baskin, Patty; Espeseth, Miriam; Pagon, Roberta A.

    2000-01-01

    GeneClinics is an online genetic information resource consisting of descriptions of specific inherited disorders (“disease profiles”) as well as information on the role of genetic testing in the diagnosis, management, and genetic counseling of patients with these inherited conditions. GeneClinics is intended to promote the use of genetic services in medical care and personal decision making by providing health care practitioners and patients with information on genetic testing for specific inherited disorders. GeneClinics is implemented as an object-oriented database containing a combination of data and semistructured text that is rendered as HTML for publishing a given “disease profile” on the Web. Content is acquired from authors via templates, converted to an XML document reflecting the underlying database schema (with tagging of embedded data), and then loaded into the database and subjected to peer review. The initial implementation of a production system and the first phase of population of the GeneClinics database content are complete. Further expansion of the content to cover more disease, significant scaling up of rate of content creation, and evaluation redesign are under way. The ultimate goal is to have an entry in GeneClinics for each entry in the GeneTests directory of medical genetics laboratories—that is, for each disease for which clinical genetic testing is available. PMID:10833163

  13. Gene therapy for newborns.

    PubMed

    Kohn, D B; Parkman, R

    1997-07-01

    Application of gene therapy to treat genetic and infectious diseases may have several advantages if performed in newborns. Because of the minimal adverse effect of the underlying disease on cells of the newborn, the relatively small size of infants, and the large amount of future growth, gene therapy may be more successful in newborns than in older children or adults. The presence of umbilical cord blood from newborns provides a unique and susceptible target for the genetic modification of hematopoietic stem cells. In our first trial of gene therapy in newborns, we inserted a normal adenosine deaminase gene into umbilical cord blood cells of three neonates with a congenital immune deficiency. The trial demonstrated the successful transduction and engraftment of stem cells, which continue to contribute to leukocyte production more than 3 years later. A similar approach may be taken to insert genes that inhibit replication of HIV-1 into umbilical cord blood cells of HIV-1-infected neonates. Many other metabolic and infectious disorders could be treated by gene therapy during the neonatal period if prenatal diagnoses are made and the appropriate technical and regulatory requirements have been met.

  14. Gene indexing: characterization and analysis of NLM's GeneRIFs.

    PubMed

    Mitchell, Joyce A; Aronson, Alan R; Mork, James G; Folk, Lillian C; Humphrey, Susanne M; Ward, Janice M

    2003-01-01

    We present an initial analysis of the National Library of Medicine's (NLM) Gene Indexing initiative. Gene Indexing occurs at the time of indexing for all 4600 journals and over 500,000 articles added to PubMed/MEDLINE each year. Gene Indexing links articles about the basic biology of a gene or protein within eight model organisms to a specific record in the NLM's LocusLink database of gene products. The result is an entry called a Gene Reference Into Function (GeneRIF) within the LocusLink database. We analyzed the numbers of GeneRIFs produced in the first year of GeneRIF production. 27,645 GeneRIFs were produced, pertaining to 9126 loci over eight model organisms. 60% of these were associated with human genes and 27% with mouse genes. About 80% discuss genes with an established MeSH Heading or other MeSH term. We developed a prototype functional alerting system for researchers based on the GeneRIFs, and a strategy to find all of the literature related to genes. We conclude that the Gene Indexing initiative adds considerable value to the life sciences research community.

  15. Harnessing gene expression networks to prioritize candidate epileptic encephalopathy genes.

    PubMed

    Oliver, Karen L; Lukic, Vesna; Thorne, Natalie P; Berkovic, Samuel F; Scheffer, Ingrid E; Bahlo, Melanie

    2014-01-01

    We apply a novel gene expression network analysis to a cohort of 182 recently reported candidate Epileptic Encephalopathy genes to identify those most likely to be true Epileptic Encephalopathy genes. These candidate genes were identified as having single variants of likely pathogenic significance discovered in a large-scale massively parallel sequencing study. Candidate Epileptic Encephalopathy genes were prioritized according to their co-expression with 29 known Epileptic Encephalopathy genes. We utilized developing brain and adult brain gene expression data from the Allen Human Brain Atlas (AHBA) and compared this to data from Celsius: a large, heterogeneous gene expression data warehouse. We show replicable prioritization results using these three independent gene expression resources, two of which are brain-specific, with small sample size, and the third derived from a heterogeneous collection of tissues with large sample size. Of the nineteen genes that we predicted with the highest likelihood to be true Epileptic Encephalopathy genes, two (GNAO1 and GRIN2B) have recently been independently reported and confirmed. We compare our results to those produced by an established in silico prioritization approach called Endeavour, and finally present gene expression networks for the known and candidate Epileptic Encephalopathy genes. This highlights sub-networks of gene expression, particularly in the network derived from the adult AHBA gene expression dataset. These networks give clues to the likely biological interactions between Epileptic Encephalopathy genes, potentially highlighting underlying mechanisms and avenues for therapeutic targets.

  16. 5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. OVERHEAD VIEW OF GENE CAMP LOOKING SOUTH. GENE PUMP PLANT IS AT CENTER WITH ADMINISTRATIVE COMPLEX IN FOREGROUND AND RESIDENTIAL AREA BEYOND PLANT. - Gene Pump Plant, South of Gene Wash Reservoir, 2 miles west of Whitsett Pump Plant, Parker Dam, San Bernardino County, CA

  17. Classification of genes based on gene expression analysis

    SciTech Connect

    Angelova, M. Myers, C. Faith, J.

    2008-05-15

    Systems biology and bioinformatics are now major fields for productive research. DNA microarrays and other array technologies and genome sequencing have advanced to the point that it is now possible to monitor gene expression on a genomic scale. Gene expression analysis is discussed and some important clustering techniques are considered. The patterns identified in the data suggest similarities in the gene behavior, which provides useful information for the gene functionalities. We discuss measures for investigating the homogeneity of gene expression data in order to optimize the clustering process. We contribute to the knowledge of functional roles and regulation of E. coli genes by proposing a classification of these genes based on consistently correlated genes in expression data and similarities of gene expression patterns. A new visualization tool for targeted projection pursuit and dimensionality reduction of gene expression data is demonstrated.

  18. De novo Transcriptome Assembly of Phomopsis liquidambari Provides Insights into Genes Associated with Different Lifestyles in Rice (Oryza sativa L.).

    PubMed

    Zhou, Jun; Li, Xin; Chen, Yan; Dai, Chuan-Chao

    2017-01-01

    The mechanisms that trigger the switch from endophytic fungi to saprophytic fungi are largely unexplored. Broad host range Phomopsis liquidambari is established in endophytic and saprophytic systems with rice (Oryza sativa L.). Endophytic P. liquidambari promotes rice growth, increasing rice yield and improving the efficiency of nitrogen fertilizer. This species's saprophytic counterpart can decompose rice litterfall, promoting litter organic matter cycling and the release of nutrients and improving the soil microbial environment. Fluorescence microscopy, confocal laser scanning microscopy and quantitative PCR investigated the colonization dynamics and biomass of P. liquidambari in rice in vivo. P. liquidambari formed infection structures similar to phytopathogens with infected vascular tissues that systematically spread to acrial parts. However, different from pathogenic infection, P. liquidambari colonization exhibits space restriction and quantity restriction. Direct comparison of a fungal transcriptome under three different habitats provided a better understanding of lifestyle conversion during plant-fungi interactions. The isolated total RNA of Ck (pure culture), EP (endophytic culture) and FP (saprophytic culture) was subjected to Illumina transcriptome sequencing. To the best of our knowledge, this study is the first to investigate Phomopsis sp. using RNA-seq technology to obtain whole transcriptome information. A total of 27,401,258 raw reads were generated and 22,700 unigenes were annotated. Functional annotation indicated that carbohydrate metabolism and biosynthesis of secondary metabolites played important roles. There were 2522 differentially expressed genes (DEGs) between the saprophytic and endophytic lifestyles. Quantitative PCR analysis validated the DEGs of RNA-seq. Analysis of DEGs between saprophytic and endophytic lifestyles revealed that most genes from amino acids metabolism, carbohydrate metabolism, fatty acid biosynthesis, secondary

  19. De novo Transcriptome Assembly of Phomopsis liquidambari Provides Insights into Genes Associated with Different Lifestyles in Rice (Oryza sativa L.)

    PubMed Central

    Zhou, Jun; Li, Xin; Chen, Yan; Dai, Chuan-Chao

    2017-01-01

    The mechanisms that trigger the switch from endophytic fungi to saprophytic fungi are largely unexplored. Broad host range Phomopsis liquidambari is established in endophytic and saprophytic systems with rice (Oryza sativa L.). Endophytic P. liquidambari promotes rice growth, increasing rice yield and improving the efficiency of nitrogen fertilizer. This species's saprophytic counterpart can decompose rice litterfall, promoting litter organic matter cycling and the release of nutrients and improving the soil microbial environment. Fluorescence microscopy, confocal laser scanning microscopy and quantitative PCR investigated the colonization dynamics and biomass of P. liquidambari in rice in vivo. P. liquidambari formed infection structures similar to phytopathogens with infected vascular tissues that systematically spread to acrial parts. However, different from pathogenic infection, P. liquidambari colonization exhibits space restriction and quantity restriction. Direct comparison of a fungal transcriptome under three different habitats provided a better understanding of lifestyle conversion during plant-fungi interactions. The isolated total RNA of Ck (pure culture), EP (endophytic culture) and FP (saprophytic culture) was subjected to Illumina transcriptome sequencing. To the best of our knowledge, this study is the first to investigate Phomopsis sp. using RNA-seq technology to obtain whole transcriptome information. A total of 27,401,258 raw reads were generated and 22,700 unigenes were annotated. Functional annotation indicated that carbohydrate metabolism and biosynthesis of secondary metabolites played important roles. There were 2522 differentially expressed genes (DEGs) between the saprophytic and endophytic lifestyles. Quantitative PCR analysis validated the DEGs of RNA-seq. Analysis of DEGs between saprophytic and endophytic lifestyles revealed that most genes from amino acids metabolism, carbohydrate metabolism, fatty acid biosynthesis, secondary

  20. GeneCards Version 3: the human gene integrator.

    PubMed

    Safran, Marilyn; Dalah, Irina; Alexander, Justin; Rosen, Naomi; Iny Stein, Tsippi; Shmoish, Michael; Nativ, Noam; Bahir, Iris; Doniger, Tirza; Krug, Hagit; Sirota-Madi, Alexandra; Olender, Tsviya; Golan, Yaron; Stelzer, Gil; Harel, Arye; Lancet, Doron

    2010-08-05

    GeneCards (www.genecards.org) is a comprehensive, authoritative compendium of annotative information about human genes, widely used for nearly 15 years. Its gene-centric content is automatically mined and integrated from over 80 digital sources, resulting in a web-based deep-linked card for each of >73,000 human gene entries, encompassing the following categories: protein coding, pseudogene, RNA gene, genetic locus, cluster and uncategorized. We now introduce GeneCards Version 3, featuring a speedy and sophisticated search engine and a revamped, technologically enabling infrastructure, catering to the expanding needs of biomedical researchers. A key focus is on gene-set analyses, which leverage GeneCards' unique wealth of combinatorial annotations. These include the GeneALaCart batch query facility, which tabulates user-selected annotations for multiple genes and GeneDecks, which identifies similar genes with shared annotations, and finds set-shared annotations by descriptor enrichment analysis. Such set-centric features address a host of applications, including microarray data analysis, cross-database annotation mapping and gene-disorder associations for drug targeting. We highlight the new Version 3 database architecture, its multi-faceted search engine, and its semi-automated quality assurance system. Data enhancements include an expanded visualization of gene expression patterns in normal and cancer tissues, an integrated alternative splicing pattern display, and augmented multi-source SNPs and pathways sections. GeneCards now provides direct links to gene-related research reagents such as antibodies, recombinant proteins, DNA clones and inhibitory RNAs and features gene-related drugs and compounds lists. We also portray the GeneCards Inferred Functionality Score annotation landscape tool for scoring a gene's functional information status. Finally, we delineate examples of applications and collaborations that have benefited from the GeneCards suite. Database

  1. Plasmid-encapsulated polyethylene glycol-grafted polyethylenimine nanoparticles for gene delivery into rat mesenchymal stem cells

    PubMed Central

    Chen, Xiao-Ai; Zhang, Li-Jun; He, Zhi-Jie; Wang, Wei-Wei; Xu, Bo; Zhong, Qian; Shuai, Xin-Tao; Yang, Li-Qun; Deng, Yu-Bin

    2011-01-01

    Background: Mesenchymal stem cell transplantation is a promising method in regenerative medicine. Gene-modified mesenchymal stem cells possess superior characteristics of specific tissue differentiation, resistance to apoptosis, and directional migration. Viral vectors have the disadvantages of potential immunogenicity, carcinogenicity, and complicated synthetic procedures. Polyethylene glycol-grafted polyethylenimine (PEG-PEI) holds promise in gene delivery because of easy preparation and potentially targeting modification. Methods: A PEG8k-PEI25k graft copolymer was synthesized. Agarose gel retardation assay and dynamic light scattering were used to determine the properties of the nanoparticles. MTT reduction, wound and healing, and differentiation assays were used to test the cytobiological characteristics of rat mesenchymal stem cells, fluorescence microscopy and flow cytometry were used to determine transfection efficiency, and atomic force microscopy was used to evaluate the interaction between PEG-PEI/plasmid nanoparticles and mesenchymal stem cells. Results: After incubation with the copolymer, the bionomics of mesenchymal stem cells showed no significant change. The mesenchymal stem cells still maintained high viability, resettled the wound area, and differentiated into adipocytes and osteoblasts. The PEG-PEI completely packed plasmid and condensed plasmid into stable nanoparticles of 100–150 nm diameter. After optimizing the N/P ratio, the PEG-PEI/plasmid microcapsules delivered plasmid into mesenchymal stem cells and obtained an optimum transfection efficiency of 15%–21%, which was higher than for cationic liposomes. Conclusion: These data indicate that PEG-PEI is a valid gene delivery agent and has better transfection efficiency than cationic liposomes in mesenchymal stem cells. PMID:21589652

  2. Sulfated galactans from Gracilaria fisheri bind to shrimp haemocyte membrane proteins and stimulate the expression of immune genes.

    PubMed

    Rudtanatip, Tawut; Withyachumnarnkul, Boonsirm; Wongprasert, Kanokpan

    2015-11-01

    Previous studies demonstrated that sulfated galactans (SG) from Gracilaria fisheri (G. fisheri) exhibit immunostimulant activity in shrimp. The present study was conducted to test the hypothesis that SG stimulates signaling molecules of the immune response of shrimp by binding to receptors on the host cell membrane. Accordingly, we evaluated the ability of SG to bind to shrimp haemocytes and showed that SG bound to the shrimp haemocyte membrane (SHM), potentially to specific receptors. Furthermore, this binding was associated with an activation of immune response genes of shrimp. Data from confocal laser scanning micrographs revealed that FITC-labeled SG bound to haemocytes. Far western blot analysis demonstrated that SHM peptides, with molecular sizes of 13, 14, 15, 17, and 25 kDa, were associated with SG. Peptide sequence analysis of the isolated bands using LC-MS/MS and NCBI blast search revealed the identity of the 13, 14, and 17 kDa peptides as lipopolysaccharide and β-1,3-glucan binding protein (LGBP). SG induced the expression of immune related genes and downstream signaling mediators of LGBP including IMD, IKKs, NF-κB, antimicrobial peptides (crustin and PEN-4), the antiviral immunity (dicer), and proPO system (proPO-I and proPO-II). A LGBP neutralizing assay with anti-LGBP antibody indicated a decrease in SG-induced expression of LGBP downstream signaling mediators and the immune related genes. In conclusion, this study demonstrated that the SG-stimulated immune activity in haemocytes is mediated, in part, through the LGBP, and IMD-NF-κB pathway.

  3. Biochemical characterisation of the proteins encoded by the DiGeorge critical region 6 (DGCR6) genes.

    PubMed

    Pfuhl, Thorsten; Dürr, Matthias; Spurk, Andreas; Schwalbert, Björn; Nord, Ruth; Mysliwietz, Josef; Kremmer, Elisabeth; Grässer, Friedrich A

    2005-06-01

    The DiGeorge critical region 6 (DGCR6) gene exists in two highly homologous copies (DGCR6 and DGCR6L) on chromosome 22q11 and is deleted in patients with velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). The DGCR6 mRNA levels are increased in metastatic mammary tumour cells and regulate the expression of neighbouring genes at the 22q11 region. Newly developed monoclonal antibodies detected predominantly nuclear phosphoproteins of approximately 25 kDa, with low expression levels in the cytoplasm. Both proteins have half-lives of about 2.5 h. Exogenously expressed DGCR6 and DGCR6L migrated with slightly different mobility in SDS-gels in accordance with two immunoreactive bands observed for the endogenous proteins. DGCR6 is found at low levels in primary human fibroblasts or peripheral blood mononuclear cells, while tumour cells, B-cells transformed by EBV as well as activated normal human T cells, contain elevated levels of the proteins. The proteins are differentially expressed in mammalian tissues, with high protein levels in heart, liver and skeletal muscle. These observations are important as some patients with DGCR6 syndrome exhibit a T-cell deficiency and/or cardiac malformations. As the DGCR6 protein(s) influence gene expression in trans, we analysed the influence of DGCR6/DGCR6L on the Epstein-Barr virus-encoded oncoproteins EBNA2 and EBNA3c in the activation of the viral LMP1 promoter, as well as LMP1-mediated activation of NFkB, but found no effect in either setting.

  4. Complexation of bioreducible cationic polymers with gold nanoparticles for improving stability in serum and application on nonviral gene delivery.

    PubMed

    Chuang, Chun-Chiao; Chang, Chien-Wen

    2015-04-15

    Widespread applications of conventional polymeric gene carriers are greatly hampered by their inefficient transfection performance under serum-containing environment. Aiming to overcome this limitation, we propose a bioreducible polyethylenimine-gold nanocomplex system (SSPEI-Au NC), which can be prepared by a simple layer-by-layer (LBL) assembly procedure. SSPEI-Au NC contains sequentially deposited layers of bioreducible polyethylenimine (SSPEI) and poly(γ-glutamic acid) (γ-PGA) for efficient binding and delivery of plasmid DNA (pDNA). SSPEI-Au NC was characterized for various physicochemical properties, including: UV-vis spectra, TEM imaging, hydrodynamic size, and pDNA binding ability. The SSPEI-Au NC were efficiently uptaken by mammalian cells as observed using dark-field microscopy. Comparing to nondegradable PEI25k, the bioreducible SSPEI-Au NC exhibited superior transfection capability under serum-containing condition while causing lower cytotoxicity on mammalian cell lines. The effect of serum on SSPEI-Au NC dispersity was studied using UV-vis spectrometry and the results suggest that serum-assisted colloidal stability of SSPEI-Au NC contributed to its serum-resistant transfection.

  5. Neighboring Genes Show Correlated Evolution in Gene Expression.

    PubMed

    Ghanbarian, Avazeh T; Hurst, Laurence D

    2015-07-01

    When considering the evolution of a gene's expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (<100 kb) but extends much further. Sex-specific expression change is also genomically clustered. As genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking.

  6. Hox genes and evolution.

    PubMed

    Hrycaj, Steven M; Wellik, Deneen M

    2016-01-01

    Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan.

  7. Selenoprotein Gene Nomenclature.

    PubMed

    Gladyshev, Vadim N; Arnér, Elias S; Berry, Marla J; Brigelius-Flohé, Regina; Bruford, Elspeth A; Burk, Raymond F; Carlson, Bradley A; Castellano, Sergi; Chavatte, Laurent; Conrad, Marcus; Copeland, Paul R; Diamond, Alan M; Driscoll, Donna M; Ferreiro, Ana; Flohé, Leopold; Green, Fiona R; Guigó, Roderic; Handy, Diane E; Hatfield, Dolph L; Hesketh, John; Hoffmann, Peter R; Holmgren, Arne; Hondal, Robert J; Howard, Michael T; Huang, Kaixun; Kim, Hwa-Young; Kim, Ick Young; Köhrle, Josef; Krol, Alain; Kryukov, Gregory V; Lee, Byeong Jae; Lee, Byung Cheon; Lei, Xin Gen; Liu, Qiong; Lescure, Alain; Lobanov, Alexei V; Loscalzo, Joseph; Maiorino, Matilde; Mariotti, Marco; Sandeep Prabhu, K; Rayman, Margaret P; Rozovsky, Sharon; Salinas, Gustavo; Schmidt, Edward E; Schomburg, Lutz; Schweizer, Ulrich; Simonović, Miljan; Sunde, Roger A; Tsuji, Petra A; Tweedie, Susan; Ursini, Fulvio; Whanger, Philip D; Zhang, Yan

    2016-11-11

    The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15-kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV), and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing, and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates.

  8. Engineered Gene Circuits

    NASA Astrophysics Data System (ADS)

    Hasty, Jeff

    2003-03-01

    Uncovering the structure and function of gene regulatory networks has become one of the central challenges of the post-genomic era. Theoretical models of protein-DNA feedback loops and gene regulatory networks have long been proposed, and recently, certain qualitative features of such models have been experimentally corroborated. This talk will focus on model and experimental results that demonstrate how a naturally occurring gene network can be used as a ``parts list'' for synthetic network design. The model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics, and the utility of such a formulation will be demonstrated through the consideration of specific design criteria for several novel genetic devices. Fluctuations originating from small molecule-number effects will be discussed in the context of model predictions, and the experimental validation of these stochastic effects underscores the importance of internal noise in gene expression. Potential biotech applications will be highlighted within the framework of cellular control schemes. Specifically, the coupling of an oscillating cellular process to a synthetic oscillator will be considered, and the resulting model behavior will be analyzed in the context of synchronization. The underlying methodology highlights the utility of engineering-based methods in the design of synthetic gene regulatory networks.

  9. Hox genes and evolution

    PubMed Central

    Hrycaj, Steven M.; Wellik, Deneen M.

    2016-01-01

    Hox proteins are a deeply conserved group of transcription factors originally defined for their critical roles in governing segmental identity along the antero-posterior (AP) axis in Drosophila. Over the last 30 years, numerous data generated in evolutionarily diverse taxa have clearly shown that changes in the expression patterns of these genes are closely associated with the regionalization of the AP axis, suggesting that Hox genes have played a critical role in the evolution of novel body plans within Bilateria. Despite this deep functional conservation and the importance of these genes in AP patterning, key questions remain regarding many aspects of Hox biology. In this commentary, we highlight recent reports that have provided novel insight into the origins of the mammalian Hox cluster, the role of Hox genes in the generation of a limbless body plan, and a novel putative mechanism in which Hox genes may encode specificity along the AP axis. Although the data discussed here offer a fresh perspective, it is clear that there is still much to learn about Hox biology and the roles it has played in the evolution of the Bilaterian body plan. PMID:27239281

  10. Different types of degradable vectors from low-molecular-weight polycation-functionalized poly(aspartic acid) for efficient gene delivery.

    PubMed

    Dou, X B; Hu, Y; Zhao, N N; Xu, F J

    2014-03-01

    Poly(aspartic acid) (PAsp) has been employed as the potential backbone for the preparation of efficient gene carriers, due to its low cytotoxicity, good biodegradability and excellent biocompatibility. In this work, the degradable linear or star-shaped PBLA was first prepared via ring-opining polymerization of β-benzyl-L-aspartate N-carboxy anhydride (BLA-NCA) initiated by ethylenediamine (ED) or ED-functionalized cyclodextrin cores. Then, PBLA was functionalized via aminolysis reaction with low-molecular-weight poly(2-(dimethylamino)ethyl methacrylate) with one terminal primary amine group (PDMAEMA-NH2), followed by addition of excess ED or ethanolamine (EA) to complete the aminolysis process. The obtained different types of cationic PAsp-based vectors including linear or star PAsp-PDM-NH2 and PAsp-PDM-OH exhibited good condensation capability and degradability, benefiting gene delivery process. In comparison with gold standard polyethylenimine (PEI, ∼ 25 kDa), the cationic PAsp-based vectors, particularly star-shaped ones, exhibited much better transfection performances.

  11. Hyperbranched-dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

    NASA Astrophysics Data System (ADS)

    Alavi, Seyyed Jamal; Gholami, Leila; Askarian, Saeedeh; Darroudi, Majid; Massoudi, Abdolhossein; Rezaee, Mehdi; Kazemi Oskuee, Reza

    2017-02-01

    The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate-PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI-PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI-PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)-dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

  12. Sandwich-type Au-PEI/DNA/PEI-Dexa nanocomplex for nucleus-targeted gene delivery in vitro and in vivo.

    PubMed

    Chen, Zhenzhen; Zhang, Lifen; He, Yuling; Li, Yanfeng

    2014-08-27

    Many synthetic Au-based cationic nanoparticles (AuNPs) for nonviral gene delivery show high efficiency in vitro, but their excessive charge density, harsh reducing conditions, and nontarget delivery prevent their application in vivo. Herein, we constructed a sandwich-type layered polyethylenimine (PEI)-coated gold nanocomposite outerlaid with a nucleus-targeted Dexamethasone (Dexa), namely, Au-PEI/DNA/PEI-Dexa nanocomplex, for DNA delivery system using a low molecular weight PEI as a mild reducing agent. The nucleus-targeting Au-PEI/DNA/PEI-Dexa nanocomplex with low positive charge and low cytotoxicity condensed DNA and protected from enzymatic degradation. In vitro transfection studies demonstrated that Au-PEI/DNA/PEI-Dexa nanocomplex exhibited much more efficient nucleus transfection than Au-PEI/DNA/PEI without nucleus-targeted residues and commercially available PEI 25 kDa due to the Dexa targeting of the nucleus. Furthermore, the nanocomplex markedly transfected pTRAIL (TRAIL = tumor-necrosis-factor-related apoptosis-inducing ligand) to tumors in vivo and subsequently inhibited the tumor growth with minimal side effects. These findings suggest that nucleus-targeting Au-PEI/DNA/PEI-Dexa ternary complexes have promising potential in gene delivery.

  13. D-ribulose-5-phosphate 3-epimerase: Cloning and heterologous expression of the spinach gene, and purification and characterization of the recombinant enzyme

    SciTech Connect

    Chen, Y.R.; Hartman, F.C.; Lu, T.Y.S.; Larimer, F.W.

    1998-09-01

    The authors have achieved, to their knowledge, the first high-level heterologous expression of the gene encoding D-ribulose-5-phosphate 3-epimerase from any source, thereby permitting isolation and characterization of the epimerase as found in photosynthetic organisms. The extremely labile recombinant spinach (Spinacia oleracea L.) enzyme was stabilized by DL-{alpha}-glycerophosphate or ethanol and destabilized by D-ribulose-5-phosphate or 2-mercaptoethanol. Despite this lability, the unprecedentedly high specific activity of the purified material indicates that the structural integrity of the enzyme is maintained throughout isolation. Ethylenediaminetetraacetate and divalent metal cations did not affect epimerase activity, thereby excluding a requirement for the latter in catalysis. As deduced from the sequence of the cloned spinach gene and the electrophoretic mobility under denaturing conditions of the purified recombinant enzyme, its 25-kD subunit size was about the same as that of the corresponding epimerases of yeast and mammals. However, in contrast to these other species, the recombinant spinach enzyme was octameric rather than dimeric, as assessed by gel filtration and polyacrylamide gel electrophoresis under nondenaturing conditions. Western-blot analyses with antibodies to the purified recombinant enzyme confirmed that the epimerase extracted from spinach leaves is also octameric.

  14. Gene therapy prospects--intranasal delivery of therapeutic genes.

    PubMed

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  15. FunGene: the functional gene pipeline and repository

    PubMed Central

    Fish, Jordan A.; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C. Titus; Tiedje, James M.; Cole, James R.

    2013-01-01

    Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes. PMID:24101916

  16. Gene Therapy for Skin Diseases

    PubMed Central

    Gorell, Emily; Nguyen, Ngon; Lane, Alfred; Siprashvili, Zurab

    2014-01-01

    The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene therapy widely available clinically. PMID:24692191

  17. Characterizing gene family evolution

    PubMed Central

    Liberles, David A.

    2008-01-01

    Gene families are widely used in comparative genomics, molecular evolution, and in systematics. However, they are constructed in different manners, their data analyzed and interpreted differently, with different underlying assumptions, leading to sometimes divergent conclusions. In systematics, concepts like monophyly and the dichotomy between homoplasy and homology have been central to the analysis of phylogenies. We critique the traditional use of such concepts as applied to gene families and give examples of incorrect inferences they may lead to. Operational definitions that have emerged within functional genomics are contrasted with the common formal definitions derived from systematics. Lastly, we question the utility of layers of homology and the meaning of homology at the character state level in the context of sequence evolution. From this, we move forward to present an idealized strategy for characterizing gene family evolution for both systematic and functional purposes, including recent methodological improvements. PMID:19461954

  18. Alphaviruses in Gene Therapy

    PubMed Central

    Lundstrom, Kenneth

    2015-01-01

    Alphavirus vectors present an attractive approach for gene therapy applications due to the rapid and simple recombinant virus particle production and their broad range of mammalian host cell transduction. Mainly three types of alphavirus vectors, namely naked RNA, recombinant particles and DNA/RNA layered vectors, have been subjected to preclinical studies with the goal of achieving prophylactic or therapeutic efficacy, particularly in oncology. In this context, immunization with alphavirus vectors has provided protection against challenges with tumor cells. Moreover, alphavirus intratumoral and systemic delivery has demonstrated substantial tumor regression and significant prolonged survival rates in various animal tumor models. Recent discoveries of the strong association of RNA interference and disease have accelerated gene therapy based approaches, where alphavirus-based gene delivery can play an important role. PMID:25961488

  19. Virus induced gene silencing of Arabidopsis gene homologues in wheat identify genes conferring improved drought tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In a non-model staple crop like wheat, functional validation of potential drought stress responsive genes identified in Arabidopsis could provide gene targets for wheat breeding. Virus induced gene silencing (VIGS) of genes of interest can overcome the inherent problems of polyploidy and limited tra...

  20. GeneTIER: prioritization of candidate disease genes using tissue-specific gene expression profiles

    PubMed Central

    Antanaviciute, Agne; Daly, Catherine; Crinnion, Laura A.; Markham, Alexander F.; Watson, Christopher M.; Bonthron, David T.; Carr, Ian M.

    2015-01-01

    Motivation: In attempts to determine the genetic causes of human disease, researchers are often faced with a large number of candidate genes. Linkage studies can point to a genomic region containing hundreds of genes, while the high-throughput sequencing approach will often identify a great number of non-synonymous genetic variants. Since systematic experimental verification of each such candidate gene is not feasible, a method is needed to decide which genes are worth investigating further. Computational gene prioritization presents itself as a solution to this problem, systematically analyzing and sorting each gene from the most to least likely to be the disease-causing gene, in a fraction of the time it would take a researcher to perform such queries manually. Results: Here, we present Gene TIssue Expression Ranker (GeneTIER), a new web-based application for candidate gene prioritization. GeneTIER replaces knowledge-based inference traditionally used in candidate disease gene prioritization applications with experimental data from tissue-specific gene expression datasets and thus largely overcomes the bias toward the better characterized genes/diseases that commonly afflict other methods. We show that our approach is capable of accurate candidate gene prioritization and illustrate its strengths and weaknesses using case study examples. Availability and Implementation: Freely available on the web at http://dna.leeds.ac.uk/GeneTIER/. Contact: umaan@leeds.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25861967

  1. Genes and functions controlled by floral organ identity genes.

    PubMed

    Sablowski, Robert

    2010-02-01

    Floral organ identity genes specify the identity of floral organs in a manner analogous to the specification of body segments by Hox genes in animals. Different combinations of organ identity genes co-ordinate the expression of genes required for the development of each type of floral organ, from organ initiation until final differentiation. Here, I review what is known about the genes and functions subordinate to the organ identity genes. The sets of target genes change as organ development progresses and ultimately organ identity genes modify the expression of thousands of genes with a multitude of predicted functions, particularly in reproductive organs. However, genes involved in transcriptional control and hormone functions feature prominently among the early and direct targets. Functional analysis showed that control of organ-specific tissues and structures can be delegated to specialised intermediate regulators, but organ identity genes also fine-tune genes with general roles in shoot organ development, consistent with the notion that organ identity genes modify a core leaf-like developmental program. Future challenges include obtaining data with cellular resolution, predictive modelling of the regulatory network, and quantitative analysis of how organ identity genes and their targets control cell behaviour and ultimately organ shape.

  2. Gene Therapy and Children (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Gene Therapy and Children KidsHealth > For Parents > Gene Therapy and ... by a "bad" gene. continue Two Types of Gene Therapy The two forms of gene therapy are: Somatic ...

  3. The gene tree delusion.

    PubMed

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  4. Genes and Vocal Learning

    PubMed Central

    White, Stephanie A.

    2009-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in primates, rodents and birds suggests that FoxP2 and other language-related genes are interactors in the neuromolecular networks that underlie subsystems of language, such symbolic understanding, vocal learning and theory of mind. The whole picture will only come together through comparative and integrative study into how the human language singularity evolved. PMID:19913899

  5. Gene network biological validity based on gene-gene interaction relevance.

    PubMed

    Gómez-Vela, Francisco; Díaz-Díaz, Norberto

    2014-01-01

    In recent years, gene networks have become one of the most useful tools for modeling biological processes. Many inference gene network algorithms have been developed as techniques for extracting knowledge from gene expression data. Ensuring the reliability of the inferred gene relationships is a crucial task in any study in order to prove that the algorithms used are precise. Usually, this validation process can be carried out using prior biological knowledge. The metabolic pathways stored in KEGG are one of the most widely used knowledgeable sources for analyzing relationships between genes. This paper introduces a new methodology, GeneNetVal, to assess the biological validity of gene networks based on the relevance of the gene-gene interactions stored in KEGG metabolic pathways. Hence, a complete KEGG pathway conversion into a gene association network and a new matching distance based on gene-gene interaction relevance are proposed. The performance of GeneNetVal was established with three different experiments. Firstly, our proposal is tested in a comparative ROC analysis. Secondly, a randomness study is presented to show the behavior of GeneNetVal when the noise is increased in the input network. Finally, the ability of GeneNetVal to detect biological functionality of the network is shown.

  6. Gene therapy in pancreatic cancer.

    PubMed

    Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

    2014-10-07

    Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC.

  7. Lateral gene transfer, rearrangement, reconciliation

    PubMed Central

    2013-01-01

    Background Models of ancestral gene order reconstruction have progressively integrated different evolutionary patterns and processes such as unequal gene content, gene duplications, and implicitly sequence evolution via reconciled gene trees. These models have so far ignored lateral gene transfer, even though in unicellular organisms it can have an important confounding effect, and can be a rich source of information on the function of genes through the detection of transfers of clusters of genes. Result We report an algorithm together with its implementation, DeCoLT, that reconstructs ancestral genome organization based on reconciled gene trees which summarize information on sequence evolution, gene origination, duplication, loss, and lateral transfer. DeCoLT optimizes in polynomial time on the number of rearrangements, computed as the number of gains and breakages of adjacencies between pairs of genes. We apply DeCoLT to 1099 gene families from 36 cyanobacteria genomes. Conclusion DeCoLT is able to reconstruct adjacencies in 35 ancestral bacterial genomes with a thousand gene families in a few hours, and detects clusters of co-transferred genes. DeCoLT may also be used with any relationship between genes instead of adjacencies, to reconstruct ancestral interactions, functions or complexes. Availability http://pbil.univ-lyon1.fr/software/DeCoLT/ PMID:24564205

  8. Genes and Vocal Learning

    ERIC Educational Resources Information Center

    White, Stephanie A.

    2010-01-01

    Could a mutation in a single gene be the evolutionary lynchpin supporting the development of human language? A rare mutation in the molecule known as FOXP2 discovered in a human family seemed to suggest so, and its sequence phylogeny reinforced a Chomskian view that language emerged wholesale in humans. Spurred by this discovery, research in…

  9. Gene stacking by recombinases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Efficient methods of stacking genes into plant genomes are needed to expedite transfer of multigenic traits into diverse crops grown in a variety of environments. Over two decades of research has identified several site-specific recombinases that carry out efficient cis and trans recombination betw...

  10. Genes in mammalian reproduction

    SciTech Connect

    Gwatkin, R.B.L.

    1996-11-01

    This is an informative book which deals mainly with genomic imprinting, the role of steroid hormones in development, the expression of a variety of genes during development and the link to hereditary diseases. It is an up-to-date review in a field that is quickly changing and provides valuable basic information and current research trends.

  11. Inferring Horizontal Gene Transfer

    PubMed Central

    Lassalle, Florent; Dessimoz, Christophe

    2015-01-01

    Horizontal or Lateral Gene Transfer (HGT or LGT) is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages [1]. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric") methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic") approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events. PMID:26020646

  12. Naming genes beyond Caenorhabditis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The nomenclature of genes in Caenorhabditis elegans is based on long-standing, successful guidelines established in the late 1970s. Over time these guidelines have matured into a comprehensive, systematic nomenclature that is easy to apply, descriptive and therefore highly informative. Recently, a f...

  13. Gene-Environment Interdependence

    ERIC Educational Resources Information Center

    Rutter, Michael

    2007-01-01

    Behavioural genetics was initially concerned with partitioning population variance into that due to genetics and that due to environmental influences. The implication was that the two were separate and it was assumed that gene-environment interactions were usually of so little importance that they could safely be ignored. Theoretical…

  14. Proinflammatory cytokine and cytokine receptor gene expression kinetics following challenge with Flavobacterium psychrophilum in resistant and susceptible lines of rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flavobacterium psychrophilum (Fp) is the causative agent of bacterial cold water disease (BCWD) which causes appreciable economic losses in rainbow trout aquaculture. We previously reported development of a genetic line, designated ARS-Fp-R that exhibits higher survival relative to a susceptible lin...

  15. Entrez Gene: gene-centered information at NCBI.

    PubMed

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2007-01-01

    Entrez Gene (www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene) is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is provided via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programing utilities (E-Utilities), and for bulk transfer by ftp.

  16. Entrez Gene: gene-centered information at NCBI.

    PubMed

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2011-01-01

    Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP.

  17. Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents.

    PubMed

    Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation.

  18. Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents

    PubMed Central

    Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    2015-01-01

    A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation. PMID:26225356

  19. Autographa californica nuclear polyhedrosis virus: subcellular localization and protein trafficking of BV/ODV-E26 to intranuclear membranes and viral envelopes.

    PubMed

    Beniya, H; Braunagel, S C; Summers, M D

    1998-01-05

    The Autographa californica nuclear polyhedrosis virus da26 gene codes for an envelope protein of both budded virus (BV) and occlusion derived virus (ODV). Western blot and temporal analysis of infected cell extracts detected a protein of 26 kDa by 4 h postinfection (p.i.). The amount of protein increased by 16 h p.i. and remained at high levels throughout infection. By 36 h p.i. several additional immunoreactive proteins were detected which migrated at approximately 18 kDa and remained through 96 h p.i. Western blot analysis of purified virus envelope and nucleocapsid preparations revealed that both the 26- and 18-kDa proteins are structural proteins of the envelope of BV and ODV. Immunoelectron microscopy performed at a time when only the 26-kDa species of the protein was present confirmed that the protein located to ODV envelope. The protein was named BV/ODV-E26 to designate incorporation into viral progeny, envelope location, and apparent molecular weight. Studies designed to follow localization of BV/ODV-E26 demonstrated that early in infection, the protein was incorporated into cytoplasmic vesicles and by 16 h p.i., BV/ODV-E26 was detected in the nucleus associated with virus-induced intranuclear microvesicles and ODV envelope. Coimmunoprecipitation and yeast two-hybrid assays showed that BV/ODV-E26 and FP25K were capable of interacting with each other to form a complex and coimmunoprecipitation assays indicated that cellular actin was a third component of this complex. Together, these data suggest that FP25K and cellular actin may participate in the regulation, or movement through the cell, of baculovirus proteins and/or virus nucleocapsids.

  20. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    PubMed

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  1. Immunotherapy and gene therapy.

    PubMed

    Simpson, Elizabeth

    2004-02-01

    The Immunotherapy and Gene Therapy meeting of the Academy of Medical Sciences reviewed the state-of-the-art and translational prospects for therapeutic interventions aimed at killing tumor cells, correcting genetic defects and developing vaccines for chronic infections. Crucial basic science concepts and information about dendritic cells, the structure and function of T-cell receptors, and manipulation of the immune response by cytokine antagonists and peptides were presented. This information underpins vaccine design and delivery, as well as attempts to immunomodulate autoimmune disease. Results from studies using anticancer DNA vaccines, which include appropriate signals for both the innate and adaptive immune response, were presented in several talks. The vaccines incorporated helper epitopes and cancer target epitopes such as immunoglobulin idiotypes (for lymphomas and myelomas), melanoma-associated antigens (for melanoma and other solid tumors) and minor histocompatibility antigens (for leukemia). The results of using vaccines employing similar principles and designed to reduce viral load in HIV/AIDS patients were also presented. The introduction of suicide genes incorporating the bacterial enzyme nitroreductase gene (ntr) targeted at tumor cells prior to administration of the prodrug CB-1954, converted by ntr into a toxic alkylating agent, was discussed against the background of clinical trials and improved suicide gene design. The introduction into hematopoietic stem cells of missing genes for the common gamma-chain, deficiency of which causes severe combined immunodeficiency (SCID), used similar retroviral transduction. The outcome of treating six SCID patients in the UK, and ten in France was successful immune reconstitution in the majority of patients, but in two of the French cases a complication of lymphoproliferative disease due to insertional mutagenesis was observed. The adoptive transfer of T-cells specific for minor histocompatibility antigens (for

  2. Simple generation of albino C57BL/6J mice with G291T mutation in the tyrosinase gene by the CRISPR/Cas9 system.

    PubMed

    Mizuno, Seiya; Dinh, Tra Thi Huong; Kato, Kanako; Mizuno-Iijima, Saori; Tanimoto, Yoko; Daitoku, Yoko; Hoshino, Yoshikazu; Ikawa, Masahito; Takahashi, Satoru; Sugiyama, Fumihiro; Yagami, Ken-ichi

    2014-08-01

    Single nucleotide mutations (SNMs) are associated with a variety of human diseases. The CRISPR/Cas9 genome-editing system is expected to be useful as a genetic modification method for production of SNM-induced mice. To investigate whether SNM-induced mice can be generated by zygote microinjection of CRISPR/Cas9 vector and single-stranded DNA (ssDNA) donor, we attempted to produce albino C57BL/6J mice carrying the Tyr gene SNM (G291T) from pigmented C57BL/6J zygotes. We first designed and constructed a CRISPR/Cas9 expression vector for the Tyr gene (px330-Tyr-M). DNA cleavage activity of px330-Tyr-M at the target site of the Tyr gene was confirmed by the EGxxFP system. We also designed an ssDNA donor for homology-directed repair (HDR)-mediated gene modification. The px330-Tyr-M vector and ssDNA donor were co-microinjected into the pronuclei of 224 one-cell-stage embryos derived from C57BL/6J mice. We obtained 60 neonates, 28 of which showed the ocular albinism and absence of coat pigmentation. Genomic sequencing analysis of the albino mice revealed that the target of SNM, G291T in the Tyr gene, occurred in 11 mice and one founder was homozygously mutated. The remaining albino founders without Tyr G291T mutation also possessed biallelic deletion and insertion mutants adjacent to the target site in the Tyr locus. Simple production of albino C57BL/6J mice was provided by C57BL/6J zygote microinjection with px330-Tyr-M DNA vector and mutant ssDNA (G291T in Tyr) donor. A combination of CRISPR/Cas9 vector and optional mutant ssDNA could be expected to efficiently produce novel SNM-induced mouse models for investigating human diseases.

  3. Effectiveness of circulating tumor DNA for detection of KRAS gene mutations in colorectal cancer patients: a meta-analysis

    PubMed Central

    Hao, Yi-Xin; Fu, Qiang; Guo, Yan-Yan; Ye, Ming; Zhao, Hui-Xia; Wang, Qi; Peng, Xiu-Mei; Li, Qiu-Wen; Wang, Ru-Liang; Xiao, Wen-Hua

    2017-01-01

    Circulating tumor DNA (ctDNA) can be identified in the peripheral blood of patients and harbors the genomic alterations found in tumor tissues, which provides a noninvasive approach for detection of gene mutations. We conducted this meta-analysis to investigate whether ctDNA can be used for monitoring KRAS gene mutations in colorectal cancer (CRC) patients. Medline, Embase, Cochrane Library and Web of Science were searched for the included eligible studies in English, and data were extracted for statistical analysis according to the numbers of true-positive (TP), true-negative (TN), false-positive (FP) and false-negative (FN) cases. Sensitivity, specificity and diagnostic odds ratio (DOR) were calculated, and the area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. After independent searching and reviewing, 21 studies involving 1,812 cancer patients were analyzed. The overall sensitivity, specificity and DOR were 0.67 (95% confidence interval [CI] =0.55–0.78), 0.96 (95% CI =0.93–0.98) and 53.95 (95% CI =26.24–110.92), respectively. The AUROC was 0.95 (95% CI =0.92–0.96), which indicated the high diagnostic accuracy of ctDNA. After stratified analysis, we found the higher diagnostic accuracy in subgroup of patients detected in blood sample of plasma. The ctDNA may be an ideal source for detection of KRAS gene mutations in CRC patients with high specificity and diagnostic value. PMID:28243130

  4. Multiple Genes in a Single Host: Cost-Effective Production of Bacterial Laccase (cotA), Pectate Lyase (pel), and Endoxylanase (xyl) by Simultaneous Expression and Cloning in Single Vector in E. coli

    PubMed Central

    Kumar, Sandeep; Jain, Kavish Kumar; Bhardwaj, Kailash N.; Chakraborty, Subhojit; Kuhad, Ramesh Chander

    2015-01-01

    This study attempted to reduce the enzyme production cost for exploiting lignocellulosic materials by expression of multiple genes in a single host. Genes for bacterial laccase (CotA), pectate lyase (Pel) and endoxylanase (Xyl), which hold significance in lignocellulose degradation, were cloned in pETDuet-1 vector containing two independent cloning sites (MCS). CotA and xyl genes were cloned in MCS1 and MCS 2, respectively. Pel gene was cloned by inserting complete cassette (T7 promoter, ribosome binding site, pel gene, His tag and complete gene ORF) preceded by cotA open reading frame in the MCS1. IPTG induction of CPXpDuet-1 construct in E. coli BL21(DE3) resulted in expression of all three heterologous proteins of ~65 kDa (CotA), ~45 kDa (Pel) and ~25 kDa (Xyl), confirmed by SDS-PAGE and western blotting. Significant portions of the enzymes were also found in culture supernatant (~16, ~720 and ~370 IU/ml activities of CotA, Pel and Xyl, respectively). Culture media optimization resulted in 2, 3 and 7 fold increased secretion of recombinant CotA, Pel and Xyl, respectively. Bioreactor level optimization of the recombinant cocktail expression resulted in production of 19 g/L dry cell biomass at OD600nm 74 from 1 L induced culture after 15 h of cultivation, from which 9, 627 and 1090 IU/ml secretory enzyme activities of CotA, Xyl and Pel were obtained, respectively. The cocktail was also found to increase the saccharification of orange peel in comparison to the xylanase alone. Thus, simultaneous expression as well as extra cellular secretion of these enzymes as cocktail can reduce the enzyme production cost which increases their applicability specially for exploiting lignocellulosic materials for their conversion to value added products like alcohol and animal feed. PMID:26642207

  5. Gene Testing for Hereditary Ataxia

    MedlinePlus

    ... have a family history of ataxia, but diagnostic tests for known ataxia genes cannot explain the ataxia in their family. In recent years, scientists have developed technologies to sequence thousands of genes at the same ...

  6. Chapter 15: Disease Gene Prioritization

    PubMed Central

    Bromberg, Yana

    2013-01-01

    Disease-causing aberrations in the normal function of a gene define that gene as a disease gene. Proving a causal link between a gene and a disease experimentally is expensive and time-consuming. Comprehensive prioritization of candidate genes prior to experimental testing drastically reduces the associated costs. Computational gene prioritization is based on various pieces of correlative evidence that associate each gene with the given disease and suggest possible causal links. A fair amount of this evidence comes from high-throughput experimentation. Thus, well-developed methods are necessary to reliably deal with the quantity of information at hand. Existing gene prioritization techniques already significantly improve the outcomes of targeted experimental studies. Faster and more reliable techniques that account for novel data types are necessary for the development of new diagnostics, treatments, and cure for many diseases. PMID:23633938

  7. SOX genes: architects of development.

    PubMed

    Prior, H M; Walter, M A

    1996-07-01

    Development in higher organisms involves complex genetic regulation at the molecular level. The emerging picture of development control includes several families of master regulatory genes which can affect the expression of down-stream target genes in developmental cascade pathways. One new family of such development regulators is the SOX gene family. The SOX genes are named for a shared motif called the SRY box a region homologous to the DNA-binding domain of SRY, the mammalian sex determining gene. Like SRY, SOX genes play important roles in chordate development. At least a dozen human SOX genes have been identified and partially characterized (Tables 1 and 2). Mutations in SOX9 have recently been linked to campomelic dysplasia and autosomal sex reversal, and other SOX genes may also be associated with human disease.

  8. Brains, Genes