Production of transplutonium elements in the high flux isotope reactor (HFIR)

International Nuclear Information System (INIS)

Bigelow, J.E.; Corbett, B.L.; King, L.J.; McGuire, S.C.; Sims, T.M.

1980-01-01

The techniques described have been demonstrated to be adequate to predict the contents of transplutonium element production targets which have been irradiated in the HFIR. The deviations, at least for isotopes of mass 253 or less, are generally within the usual analytical uncertainties, or else are for isiotopes which are of little overall import to the program. Work is especially needed to get a better picture of the production of 250 Cm, 254 Es, 255 Es, and ultimately 257 Fm, since researchers are frequently stating their interest in obtaining larger quantities of these rare and difficult-to-produce nuclides

Calculation of RABBIT and Simulator Worth in the HFIR Hydraulic Tube and Comparison with Measured Values

Energy Technology Data Exchange (ETDEWEB)

Slater, CO

2005-09-08

To aid in the determinations of reactivity worths for target materials in a proposed High Flux Isotope Reactor (HFIR) target configuration containing two additional hydraulic tubes, the worths of cadmium rabbits within the current hydraulic tube were calculated using a reference model of the HFIR and the MCNP5 computer code. The worths were compared to measured worths for both static and ejection experiments. After accounting for uncertainties in the calculations and the measurements, excellent agreement between the two was obtained. Computational and measurement limitations indicate that accurate estimation of worth is only possible when the worth exceeds 10 cents. Results indicate that MCNP5 and the reactor model can be used to predict reactivity worths of various samples when the expected perturbations are greater than 10 cents. The level of agreement between calculation and experiment indicates that the accuracy of such predictions would be dependent solely on the quality of the nuclear data for the materials to be irradiated. Transients that are approximated by ''piecewise static'' computational models should likewise have an accuracy that is dependent solely on the quality of the nuclear data.

A summary of the artificial intelligence applications at the HFIR

International Nuclear Information System (INIS)

Wehe, D.K.; Clapp, N.E.; Clark, F.H.; Mullens, J.A.; Otaduy, P.J.

1986-01-01

The AI group within the Instrumental and Controls Division at the Oak Ridge National Laboratory is developing expertise in AI techniques, and applying it to various projects. One such project involves the High Flux Isotope Reactor (HFIR). This paper summarizes the progress which has been made in the first year of this three-year project. While the HFIR is as a research reactor, it shares many of the characteristics of a full-scale, commercial PWR. It has a pressurized primary system (including a component similar to a pressurizer), with multiple primary and secondary coolant legs. In essence, it possesses many of the complexities found in commercial plants. The principle differences are its small, loosely coupled, annular core which produces 100 MWt, the concentric, cylindrical control elements which are located external to the core, and the beryllium reflectors which are external to the control elements. Much like a commercial plant, operational emphasis is placed on maximizing fuel utilization and plant, availability, while minimizing safety risks, radiation exposure, and production of low-level wastes. Thus, the HFIR is a realistic platform for developing and testing real-time expert systems for the nuclear industry

Calculations for HFIR [High Flux Isotope Reactor] fuel plate non- bonding and fuel segregation uncertainty factors

International Nuclear Information System (INIS)

Kirkpatrick, J.R.

1990-10-01

The effects of non-bonds and of fuel segregation on the package factors of the heat flux in the High Flux Isotope Reactor (HFIR) are examined. The effects of the two defects are examined both separately and together. It is concluded that the peaking factors that are used in the present HFIR thermal analysis code are conservative and thus no changes in the peaking factors are necessary to continue to ensure that HFIR is safe. A study was made of the effect of the non-bond spot diameter on the peaking factor. The conclusion is that the spot can have diameter more than three times the maximum value allowed by the specifications before the peaking factor is greater than the maximum value specified in the present HFIR thermal analysis code. 6 refs., 7 figs., 8 tabs

Reevaluation of HFIR source term: Supplement 2

International Nuclear Information System (INIS)

Thomas, W.E.

1986-11-01

The HFIR source term has been reevaluated to assess the impact of the increase in core lifetime from 15 to 24 days. Calculations were made to determine the nuclide activities of the iodines, noble gases, and other fission products. The results show that there is no significant change in off-site dose due to the increased fuel cycle for the release scenario postulated in ORNL-3573

Safety analysis report for packaging: the ORNL HFIR spent-fuel-element shipping cask

International Nuclear Information System (INIS)

Evans, J.H.; Chipley, K.K.; Eversole, R.E.; Just, R.A.; Llewellyn, G.H.

1977-11-01

The Oak Ridge National Laboratory High Flux Isotope Reactor (HFIR) spent-fuel-element shipping cask is used to transport HFIR, Oak Ridge Research Reactor (ORR), and other reactor fuel elements. The cask was analytically evaluated to determine its compliance with the applicable regulations governing containers in which radioactive materials are transported. Computational procedures and tests were used to determine behavior of the cask relative to the general standards for the hypothetical accident conditions. The results of the evaluation show that the cask is in compliance with the applicable regulations

Performance of HTGR fertile particles irradiated in HFIR capsule HT-32

International Nuclear Information System (INIS)

Long, E.L. Jr.; Robbins, J.M.; Tiegs, T.N.; Kania, M.J.

1980-04-01

The HT-32 experiment was an uninstrumented capsule irradiated for four cycles in the target position of the High-Flux Isotope Reactor (HFIR). The experiment was designed to: provide supplemental simulated fuel rods for thermal transport and expansion measurements; test fertile kernels with Al 2 O 3 and SiO 2 additives for improved fission product retention; study the stability and permeability of low-temperature isotropic (LTI) pyrocarbon coatings; test Biso- and Triso-coatings derived in a large (0.24-m-dia) coating furnace with a frit distributor; investigate the performance of particles with an outer layer of SiC both as loose particles and as resin-bonded fuel rods; and evaluate high-density alumina as a potential high-temperature thermometry sheathing material

HFIR Fuel Casting Support

Energy Technology Data Exchange (ETDEWEB)

Imhoff, Seth D. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Gibbs, Paul Jacob [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Solis, Eunice Martinez [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2017-09-28

Process exploration for fuel production for the High Flux Isotope Reactor (HFIR) using cast LEU-10wt.%Mo as an initial processing step has just begun. This project represents the first trials concerned with casting design and quality. The studies carried out over the course of this year and information contained in this report address the initial mold development to be used as a starting point for future operations. In broad terms, the final billet design is that of a solid rolling blank with an irregular octagonal cross section. The work covered here is a comprehensive view of the initial attempts to produce a sound casting. This report covers the efforts to simulate, predict, cast, inspect, and revise the initial mold design.

Evaluation of HFIR vessel surveillance data and hydro-test conditions

International Nuclear Information System (INIS)

Cheverton, R.D.; Nanstad, R.K.

1994-01-01

Surveillance specimens for the High Flux Isotope Reactor (HFIR) pressure vessel were removed and tested during 1993, after the vessel had accumulated 701,469 MWd of operation. The data agree well with HFIR surveillance data obtained in previous years. In conjunction with this effort, the vessel hydro-test conditions were reevaluated and found to be more than adequate. In view of this result, and because there are economic incentives for reducing the frequency of hydro testing, an analysis was performed to determine the minimum permissible frequency. The value obtained is substantially less than that presently specified. It was also determined that a somewhat lower cooling-tower-basin temperature is acceptable (improves operational flexibility). In 1986, after ∼20 years of reactor operation, it was discovered that the vessel embrittlement rate was substantially greater than expected. Possible reasons for the accelerated rate are reviewed in this report

Safety analysis report for packaging: the ORNL HFIR unirradiated fuel element shipping container

International Nuclear Information System (INIS)

Evans, J.H.; Boulet, J.A.M.; Eversole, R.E.

1977-11-01

The ORNL HFIR unirradiated fuel element shipping container was designed and fabricated at the Oak Ridge National Laboratory for the transport of HFIR unirradiated fuel elements. The container was evaluated analytically and experimentally to determine its compliance with the applicable regulations governing containers in which radioactive and fissile materials are transported, and the evaluation is the subject of this report. Computational and test procedures were used to determine the structural integrity and thermal behavior of the cask relative to the general standards for normal conditions of transport and the standards for the hypothetical accident conditions. The results of the evaluation demonstrate that the container is in compliance with the applicable regulations

3D COMSOL Simulations for Thermal Deflection of HFIR Fuel Plate in the "Cheverton-Kelley" Experiments

Energy Technology Data Exchange (ETDEWEB)

Jain, Prashant K [ORNL; Freels, James D [ORNL; Cook, David Howard [ORNL

2012-08-01

Three dimensional simulation capabilities are currently being developed at Oak Ridge National Laboratory using COMSOL Multiphysics, a finite element modeling software, to investigate thermal expansion of High Flux Isotope Reactor (HFIR) s low enriched uranium fuel plates. To validate simulations, 3D models have also been developed for the experimental setup used by Cheverton and Kelley in 1968 to investigate the buckling and thermal deflections of HFIR s highly enriched uranium fuel plates. Results for several simulations are presented in this report, and comparisons with the experimental data are provided when data are available. A close agreement between the simulation results and experimental findings demonstrates that the COMSOL simulations are able to capture the thermal expansion physics accurately and that COMSOL could be deployed as a predictive tool for more advanced computations at realistic HFIR conditions to study temperature-induced fuel plate deflection behavior.

Management of safety and risk at the HFIR [High-Flux Isotope Reactor

International Nuclear Information System (INIS)

Glovier, H.A.

1990-01-01

This paper discusses the management of safety and risk at the High-Flux Isotope Reactor (HFIR), a category A research reactor at Oak Ridge National Laboratory (ORNL). The HFIR went critical in 1966 and operated at its designed 100 MW for 20 yr until it was shut down on November 14, 1986. It operated at a >90% availability and without significant event during this period. The result was a complacent management program lacking rigor. This complacency came to an end with the Chernobyl accident, which led to the appointment of an internal committee to assess the safety of ORNL reactor operations. This committee found that HFIR pressure vessel material specimens removed several years earlier had not been analyzed. This issue led to a general review of management practices that were found lacking in quality assurance, safety documentation, training process, and emergency planning, among others. Management accountability was lacking, as shown by design basis and safety analyses that were not up to data and by the fact that reactor operators whose requalification examinations had not been graded were allowed to continue operating the reactor over a long period of time. Between shutdown in 1986 and restart in April 1989, significant management changes and initiatives were made in the area of risk and safety management of ORNL reactors. These are presented briefly in this paper

Cadmium verification measurements of HFIR shroud assembly 22

International Nuclear Information System (INIS)

Chapman, J.A.; Schultz, F.J.

1994-04-01

This report discusses radiation-based nondestructive examination methods which have been used to successfully verify the presence of cadmium in High Flux Isotope Reactor (HFIR) spent-fuel shroud assembly number 22 (SA22). These measurements show, in part, that SA22 is certified to meet the criticality safety specifications for a proposed reconfiguration of the HFIR spent-fuel storage array. Measurement of the unique 558.6-keV gamma-ray from neutron radiative capture on cadmium provided conclusive evidence for the presence of cadmium in the outer shroud of the assembly. Cadmium verification in the center post and outer shroud was performed by measuring the degree of neutron transmission in SA22 relative to two calibration shroud assemblies. Each measurement was performed at a single location on the center post and outer shroud. These measurements do not provide information on the spatial distribution or uniformity of cadmium within an assembly. Separate measurements using analog and digital radiography were performed to (a) globally map the continuity of cadmium internal mass, and (b) locally determine the thickness of cadmium. Radiography results will be reported elsewhere. The measurements reported here should not be used to infer the thickness of cadmium in either the center post or outer shroud of an assembly

Extraction of 152Gd from HFIR control plates

International Nuclear Information System (INIS)

Kohring, M.W.

1986-01-01

The primary method of 153 Gd production at the Oak Ridge National Lab. (ORNL) research reactors since 1980 has been the irradiation of a natural europium oxide powder (Eu 2 O 3 ) followed by the chemical extraction of the gadolinium fraction. The specific activity of the resulting source is 45 to 50 Ci/g with a radiochemical purity of > 99.99%. A potential alternative method involves the extraction of gadolinium from the europium-bearing region of highly radioactive, spent control plates used in the High Flux Isotope Reactor (HFIR), followed by neutron irradiation. This alternative to the traditional process is attractive in that chemical separation of the europium and gadolinium occurs before the 153 Gd production irradiation, thus reducing process and decay losses and, most significantly, the gadolinium is highly enriched in the parent isotope, 152 Gd. Investigation into the usefulness of the gadolinium isotopes contained in spent HFIR control plates began in the late 1960s. However, separation of the gadolinium from the europium to the purity levels required for a marketable specific activity could not be attained. Due to the recent increase in 153 Gd demand and separation process improvements, research into this valuable source of parent material was resurrected

Modernization of the High Flux Isotope Reactor (HFIR) to Provide a Cold Neutron Source and Experimentation Facility

International Nuclear Information System (INIS)

Rothrock, Benjamin G.; Farrar, Mike B.

2009-01-01

In June 1961, construction was started on the High Flux Isotope Reactor (HFIR) facility inside the Oak Ridge National Laboratory (ORNL), at the recommendation of the U.S. Atomic Energy Commission (AEC) Division of Research. Construction was completed in early 1965 with criticality achieved on August 25, 19651. From the first full power operating cycle beginning in September 1966, the HFIR has achieved an outstanding record of service to the scientific community. In early 1995, the ORNL deputy director formed a group to examine the need for upgrades to the HFIR following the cancellation of the Advanced Neutron Source Project by DOE. This group indicated that there was an immediate need for the installation of a cold neutron source facility in the HFIR to produce cold neutrons for neutron scattering research uses. Cold neutrons have long wavelengths in the range of 4-12 angstroms. Cold neutrons are ideal for research applications with long length-scale molecular structures such as polymers, nanophase materials, and biological samples. These materials require large scale examination (and therefore require a longer wavelength neutron). These materials represent particular areas of science are at the forefront of current research initiatives that have a potentially significant impact on the materials we use in our everyday lives and our knowledge of biology and medicine. This paper discusses the installation of a cold neutron source at HFIR with respect to the project as a modernization of the facility. The paper focuses on why the project was required, the scope of the cold source project with specific emphasis on the design, and project management information.

Heat transfer calculations for the High Flux Isotope Reactor (HFIR). Technical specifications: bases for safety limits and limiting safety system settings

International Nuclear Information System (INIS)

Sims, T.M.; Swanks, J.H.

1977-09-01

Heat transfer analyses, in support of the preparation of the HFIR technical specifications, were made to establish the bases for the safety limits and limiting safety system settings applicable to the HFIR. The results of these analyses, along with the detailed bases, are presented

Preliminary Assessment of the Impact on Reactor Vessel dpa Rates Due to Installation of a Proposed Low Enriched Uranium (LEU) Core in the High Flux Isotope Reactor (HFIR)

Energy Technology Data Exchange (ETDEWEB)

Daily, Charles R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2015-10-01

An assessment of the impact on the High Flux Isotope Reactor (HFIR) reactor vessel (RV) displacements-per-atom (dpa) rates due to operations with the proposed low enriched uranium (LEU) core described by Ilas and Primm has been performed and is presented herein. The analyses documented herein support the conclusion that conversion of HFIR to low-enriched uranium (LEU) core operations using the LEU core design of Ilas and Primm will have no negative impact on HFIR RV dpa rates. Since its inception, HFIR has been operated with highly enriched uranium (HEU) cores. As part of an effort sponsored by the National Nuclear Security Administration (NNSA), conversion to LEU cores is being considered for future HFIR operations. The HFIR LEU configurations analyzed are consistent with the LEU core models used by Ilas and Primm and the HEU balance-of-plant models used by Risner and Blakeman in the latest analyses performed to support the HFIR materials surveillance program. The Risner and Blakeman analyses, as well as the studies documented herein, are the first to apply the hybrid transport methods available in the Automated Variance reduction Generator (ADVANTG) code to HFIR RV dpa rate calculations. These calculations have been performed on the Oak Ridge National Laboratory (ORNL) Institutional Cluster (OIC) with version 1.60 of the Monte Carlo N-Particle 5 (MCNP5) computer code.

Microstructural development of PCAs irradiated in HFIR at 300 to 4000C

International Nuclear Information System (INIS)

Tanaka, M.P.; Maziasz, P.J.; Hishinuma, A.; Hamada, S.

1986-01-01

Microstructural developments were determined on solution-annealed (SA) and cold-worked (CW) JPCA and US PCAs irradiated in the High Flux Isotope Reactor (HFIR) at 300 and 400 0 C. Irradiation produced damage levels of about 10 and 34 dpa and helium concentrations of around 580 and 2500 at. ppM, respectively. High concentrations of fine bubbles and MC precipitates, as well as Frank faulted loops, were observed in both SA and CW PCAs. Mutual stability of the MC particles and associated fine bubbles contributed to the extension of the transient regime of swelling to higher fluence. The irradiation responses of JPCA and US-PCA were similar in the HFIR, despite minor compositional differences (P,B) between the two materials. Useful fusion applications of SA-PCA as well as CW-PCA in the 300 0 C temperature range are suggested from these data

Preliminary Evaluation of Alternate Designs for HFIR Low-Enriched Uranium Fuel

Energy Technology Data Exchange (ETDEWEB)

Renfro, David [ORNL; Chandler, David [ORNL; Cook, David [ORNL; Ilas, Germina [ORNL; Jain, Prashant [ORNL; Valentine, Jennifer [ORNL

2014-10-30

Engineering design studies of the feasibility of conversion of the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) to low-enriched uranium (LEU) fuel are ongoing at Oak Ridge National Laboratory (ORNL) as part of an effort sponsored by the U.S. Department of Energy’s Global Threat Reduction Initiative (GTRI)/Reduced Enrichment for Research and Test Reactors (RERTR) program. The fuel type selected by the program for the conversion of the five high-power research reactors in the U.S. that still use HEU fuel is a new U-Mo monolithic fuel. Studies by ORNL have previously indicated that HFIR can be successfully converted using the new fuel provided (1) the reactor power can be increased from 85 MW to 100 MW and (2) the fuel can be fabricated to a specific reference design. Fabrication techniques for the new fuel are under development by the program but are still immature, especially for the “complex” aspects of the HFIR fuel design. In FY 2012, the program underwent a major shift in focus to emphasize developing and qualifying processes for the fabrication of reliable and affordable LEU fuel. In support of this new focus and in an effort to ensure that the HFIR fuel design is as suitable for reliable fabrication as possible, ORNL undertook the present study to propose and evaluate several alternative design features. These features include (1) eliminating the fuel zone axial contouring in the previous reference design by substituting a permanent neutron absorber in the lower unfueled region of all of the fuel plates, (2) relocating the burnable neutron absorber from the fuel plates of the inner fuel element to the side plates of the inner fuel element (the fuel plates of the outer fuel element do not contain a burnable absorber), (3) relocating the fuel zone inside the fuel plate to be centered on the centerline of the depth of the plate, and (4) reshaping the radial contour of the relocated fuel zone to be symmetric about this centerline. The

Preliminary Evaluation of Alternate Designs for HFIR Low-Enriched Uranium Fuel

Energy Technology Data Exchange (ETDEWEB)

Renfro, David G [ORNL; Chandler, David [ORNL; Cook, David Howard [ORNL; Ilas, Germina [ORNL; Jain, Prashant K [ORNL; Valentine, Jennifer R [ORNL

2014-11-01

Engineering design studies of the feasibility of conversion of the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) to low-enriched uranium (LEU) fuel are ongoing at Oak Ridge National Laboratory (ORNL) as part of an effort sponsored by the U.S. Department of Energy s Global Threat Reduction Initiative (GTRI)/Reduced Enrichment for Research and Test Reactors (RERTR) program. The fuel type selected by the program for the conversion of the five high-power research reactors in the U.S. that still use HEU fuel is a new U-Mo monolithic fuel. Studies by ORNL have previously indicated that HFIR can be successfully converted using the new fuel provided (1) the reactor power can be increased from 85 MW to 100 MW and (2) the fuel can be fabricated to a specific reference design. Fabrication techniques for the new fuel are under development by the program but are still immature, especially for the complex aspects of the HFIR fuel design. In FY 2012, the program underwent a major shift in focus to emphasize developing and qualifying processes for the fabrication of reliable and affordable LEU fuel. In support of this new focus and in an effort to ensure that the HFIR fuel design is as suitable for reliable fabrication as possible, ORNL undertook the present study to propose and evaluate several alternative design features. These features include (1) eliminating the fuel zone axial contouring in the previous reference design by substituting a permanent neutron absorber in the lower unfueled region of all of the fuel plates, (2) relocating the burnable neutron absorber from the fuel plates of the inner fuel element to the side plates of the inner fuel element (the fuel plates of the outer fuel element do not contain a burnable absorber), (3) relocating the fuel zone inside the fuel plate to be centered on the centerline of the depth of the plate, and (4) reshaping the radial contour of the relocated fuel zone to be symmetric about this centerline. The present

Assessment of helium effects on swelling by reirradiation in FFTF of Path A alloys previously irradiated in HFIR

International Nuclear Information System (INIS)

Maziasz, P.J.; Garner, F.A.; Brager, H.R.

1985-01-01

Specimens of the Path A Prime Candidate Alloys and of N-lot SS 316 were irradiated in HFIR at 400 to 600 0 C to fluences producing approximately 10 to 44 dpa and 500 to 3600 at. ppm He, in both the solution annealed and 20 to 25% cold-worked conditions. The cavity swelling and total microstructural evolution of most samples were observed via transmission electron microscopy on identical disks irradiated side by side in HFIR, and immersion densities were also measured prior to insertion into FFTF/MOTA (Materials Open Test Assembly of the Fast Flux Test Facility). These disks are being irradiated in the FFTF/MOTA (cycles 5 and 6), side by side with disks of the same materials which were not previously irradiated in HFIR. These specimens have been divided into two subsets for discharges after 30 and 60 dpa. 4 references, 1 table

Project Plan Remote Target Fabrication Refurbishment Project

International Nuclear Information System (INIS)

Bell, Gary L.; Taylor, Robin D.

2009-01-01

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

External event Probabilistic Risk Assessment for the High Flux Isotope Reactor (HFIR)

International Nuclear Information System (INIS)

Flanagan, G.F.; Johnson, D.H.; Buttemer, D.; Perla, H.F.; Chien, S.H.

1989-01-01

The High Flux Isotope Reactor (HFIR) is a high performance isotope production and research reactor which has been in operation at Oak Ridge National Laboratory (ORNL) since 1965. In late 1986 the reactor was shut down as a result of discovery of unexpected neutron embrittlement of the reactor vessel. In January of 1988 a level 1 Probabilistic Risk Assessment (PRA) (excluding external events) was published as part of the response to the many reviews that followed the shutdown and for use by ORNL to prioritize action items intended to upgrade the safety of the reactor. A conservative estimate of the core damage frequency initiated by internal events for HFIR was 3.11 x 10 -4 . In June 1989 a draft external events initiated PRA was published. The dominant contributions from external events came from seismic, wind, and fires. The overall external event contribution to core damage frequency is about 50% of the internal event initiated contribution and is dominated by seismic events

The Monbusho/US shielded HFIR irradiation experiment: HFIR-MFE-RB-11J and 12J (P3-3)

Energy Technology Data Exchange (ETDEWEB)

Grossbeck, M.L.; Lenox, K.E.; Janney, M.A. [Oak Ridge National Lab., TN (United States)] [and others

1997-08-01

This experiment is a joint project between the Japanese Monbushu, the Japan Atomic Energy Research Institute, and the U.S. Fusion Energy Sciences Program. It is the first of a series of experiments using europium oxide as a thermal neutron shield to minimize transmutations in vanadium alloys and ferritic/martensitic steels. The europium oxide shields were developed using ceramic processing techniques culminating in cold pressing and sintering. This experiment, which is a prototype for future fast neutron experiments in the HFIR, contains approximately 3200 specimens of 18 different types. The experiment began operating at 300 and 500{degrees}C in February 1997 and is projected to attain its goal fluence of {approximately} 5 dpa in February 1998.

Microstructure of HFIR-irradiated 12-Cr 1 MoVW ferritic steel

International Nuclear Information System (INIS)

Vitek, J.M.; Klueh, R.L.

1983-01-01

As part of the fusion materials development program in the United States, a 12 Cr-1 MoVW ferritic steel was irradiated in the High Flux Isotope Reactor (HFIR) to a damage level of 36 dpa at 300, 400, 500, and 600 0 C. During irradiation in HFIR, a transmutation reaction of nickel results in the production of helium, to a level of 99 at. ppM in the present experiment. The microstructures were evaluated after irradiation and the results are presented. Cavities were found at all temperatures. Small cavities (3 to 9 nm) were observed after irradiation at 300, 500 and 600 0 C. At 500 and 600 0 C, the cavities were found preferentially at dislocations, lath boundaries, and prior austenite grain boundaries. After irradiation at 400 0 C, larger cavities (4 to 30 nm) were observed homogeneously distributed throughout the tempered martensite structure. The maximum swelling was 0.07% after irradiation at 400 0 C. Comparision of the results with other studies in which helium was not present at such high levels indicated helium enhances the swelling of 12 Cr-1 MoVW

Reirradiation in FFTF of swelling-resistant Path A alloys previously irradiated in HFIR

International Nuclear Information System (INIS)

Maziasz, P.J.

1985-01-01

Disks of Path A Prime Candidate Alloys (in several pretreatment conditions) and several heats of cold-worked (CW) type 316 and D9 type austenitic stainless steels have been irradiated in HFIR at 300, 500, and 600 0 C to fluences producing about 10 to 44 dpa and 450 to 3600 at. ppm He. These samples are being reirradiated in the Materials Open Test Assembly (MOTA) in FFTF at 500 and 600 0 C, together (side by side) with previously unirradiated disks of exactly the same materials, to greater than 100 dpa. These samples many of which have either very fine helium cluster or helium bubble distributions after HFIR irradiation, are intended to test the possibility and magnitude of a helium-induced extension of the initial low-swelling transient regime relative to the void swelling behavior normally found during FFTF irradiation. Further, these samples will reveal the microstructural stability or evolution differences that correlate with such helium effects. 17 references, 4 tables

Comparison of Calculated and Measured Neutron Fluence in Fuel/Cladding Irradiation Experiments in HFIR

International Nuclear Information System (INIS)

Ellis, Ronald James

2011-01-01

A recently-designed thermal neutron irradiation facility has been used for a first series of irradiations of PWR fuel pellets in the high flux isotope reactor (HFIR) at Oak Ridge National Laboratory. Since June 2010, irradiations of PWR fuel pellets made of UN or UO 2 , clad in SiC, have been ongoing in the outer small VXF sites in the beryllium reflector region of the HFIR, as seen in Fig. 1. HFIR is a versatile, 85 MW isotope production and test reactor with the capability and facilities for performing a wide variety of irradiation experiments. HFIR is a beryllium-reflected, light-water-cooled and -moderated, flux-trap type reactor that uses highly enriched (in 235 U) uranium (HEU) as the fuel. The reactor core consists of a series of concentric annular regions, each about 2 ft (0.61 m) high. A 5-in. (12.70-cm)-diam hole, referred to as the flux trap, forms the center of the core. The fuel region is composed of two concentric fuel elements made up of many involute-shaped fuel plates: an inner element that contains 171 fuel plates, and an outer element that contains 369 fuel plates. The fuel plates are curved in the shape of an involute, which provides constant coolant channel width between plates. The fuel (U 3 O 8 -Al cermet) is nonuniformly distributed along the arc of the involute to minimize the radial peak-to-average power density ratio. A burnable poison (B 4 C) is included in the inner fuel element primarily to reduce the negative reactivity requirements of the reactor control plates. A typical HEU core loading in HFIR is 9.4 kg of 235 U and 2.8 g of 10 B. The thermal neutron flux in the flux trap region can exceed 2.5 x 10 15 n/cm 2 · s while the fast flux in this region exceeds 1 x 10 15 n/cm 2 · s. The inner and outer fuel elements are in turn surrounded by a concentric ring of beryllium reflector approximately 1 ft (0.30 m) thick. The beryllium reflector consists of three regions: the removable reflector, the semi-permanent reflector, and the

In-situ measurement of the electrical conductivity of aluminum oxide in HFIR

Energy Technology Data Exchange (ETDEWEB)

Zinkle, S.J.; White, D.P.; Snead, L.L. [Oak Ridge National Lab., TN (United States)] [and others

1996-10-01

A collaborative DOE/Monbusho irradiation experiment has been completed which measured the in-situ electrical resistivity of 12 different grades of aluminum oxide during HFIR neutron irradiation at 450{degrees}C. No evidence for bulk RIED was observed following irradiation to a maximum dose of 3 dpa with an applied dc electric field of 200 V/mm.

Fatigue performance of HFIR-irradiated Nimonic PE-16 at 4300C

International Nuclear Information System (INIS)

Grossbeck, M.L.; Liu, K.C.

1983-01-01

Nimonic PE-16 was irradiated in the HFIR to 6 to 9 dpa and 560 to 1000 at. ppM He at 430 0 C. Postirradiation fatigue tests revealed a reduction in fatigue life by about a factor of 10 at 430 0 C. In contrast to AISI type 316 stainless steel, no endurance limit was observed. All irradiated specimens exhibited some intergranular fracture with an increasing tendency toward cleavage-like intragranular fracture for low strain ranges

Fracture analysis of HFIR beam tube caused by radiation embrittlement

International Nuclear Information System (INIS)

Chang, S.J.

1994-01-01

With an attempt to estimate the neutron beam tube embrittlement condition for the Oak Ridge High Flux Isotope Reactor (HFIR), fracture mechanics calculations are carried out in this paper. The analysis provides some numerical result on how the tube has been structurally weakened. In this calculation, a lateral impact force is assumed. Numerical result is obtained on how much the critical crack size should be reduced if the beam tube has been subjected to an extended period of irradiation. It is also calculated that buckling strength of the tube is increased, not decreased, with irradiation

Evaluation of HFIR [High Flux Isotope Reactor] pressure-vessel integrity considering radiation embrittlement

International Nuclear Information System (INIS)

Cheverton, R.D.; Merkle, J.G.; Nanstad, R.K.

1988-04-01

The High Flux Isotope Reactor (HFIR) pressure vessel has been in service for 20 years, and during this time, radiation damage was monitored with a vessel-material surveillance program. In mid-November 1986, data from this program indicated that the radiation-induced reduction in fracture toughness was greater than expected. As a result, a reevaluation of vessel integrity was undertaken. Updated methods of fracture-mechanics analysis were applied, and an accelerated irradiations program was conducted using the Oak Ridge Research Reactor. Results of these efforts indicate that (1) the vessel life can be extended 10 years if the reactor power level is reduced 15% and if the vessel is subjected to a hydrostatic proof test each year; (2) during the 10-year life extension, significant radiation damage will be limited to a rather small area around the beam tubes; and (3) the greater-than-expected damage rate is the result of the very low neutron flux in the HFIR vessel relative to that in samples of material irradiated in materials-testing reactors (a factor of ∼10 4 less), that is, a rate effect

Fuel loading and homogeneity analysis of HFIR design fuel plates loaded with uranium silicide fuel

International Nuclear Information System (INIS)

Blumenfeld, P.E.

1995-08-01

Twelve nuclear reactor fuel plates were analyzed for fuel loading and fuel loading homogeneity by measuring the attenuation of a collimated X-ray beam as it passed through the plates. The plates were identical to those used by the High Flux Isotope Reactor (HFIR) but were loaded with uranium silicide rather than with HFIR's uranium oxide fuel. Systematic deviations from nominal fuel loading were observed as higher loading near the center of the plates and underloading near the radial edges. These deviations were within those allowed by HFIR specifications. The report begins with a brief background on the thermal-hydraulic uncertainty analysis for the Advanced Neutron Source (ANS) Reactor that motivated a statistical description of fuel loading and homogeneity. The body of the report addresses the homogeneity measurement techniques employed, the numerical correction required to account for a difference in fuel types, and the statistical analysis of the resulting data. This statistical analysis pertains to local variation in fuel loading, as well as to ''hot segment'' analysis of narrow axial regions along the plate and ''hot streak'' analysis, the cumulative effect of hot segment loading variation. The data for all twelve plates were compiled and divided into 20 regions for analysis, with each region represented by a mean and a standard deviation to report percent deviation from nominal fuel loading. The central regions of the plates showed mean values of about +3% deviation, while the edge regions showed mean values of about -7% deviation. The data within these regions roughly approximated random samplings from normal distributions, although the chi-square (χ 2 ) test for goodness of fit to normal distributions was not satisfied

Design of a creep experiment for SiC/SiC composites in HFIR

Energy Technology Data Exchange (ETDEWEB)

Hecht, S.L.; Hamilton, M.L.; Jones, R.H. [and others

1997-08-01

A new specimen was designed for performing in-reactor creep tests on composite materials, specifically on SiC/SiC composites. The design was tailored for irradiation at 800{degrees}C in a HFIR RB position. The specimen comprises a composite cylinder loaded by a pressurized internal bladder that is made of Nb1Zr. The experiment was designed for approximately a one year irradiation.

Design of a creep experiment for SiC/SiC composites in HFIR

International Nuclear Information System (INIS)

Hecht, S.L.; Hamilton, M.L.; Jones, R.H.

1997-01-01

A new specimen was designed for performing in-reactor creep tests on composite materials, specifically on SiC/SiC composites. The design was tailored for irradiation at 800 degrees C in a HFIR RB position. The specimen comprises a composite cylinder loaded by a pressurized internal bladder that is made of Nb1Zr. The experiment was designed for approximately a one year irradiation

Void formation and helium effects in 9Cr-1MoVNb and 12Cr-1MoVW steels irradiated in HFIR and FFTF at 400/degree/C

International Nuclear Information System (INIS)

Maziasz, P.J.; Klueh, R.L.

1988-01-01

Martensitic/ferritic 9Cr-1MoVNb and 12Cr-1MoVW steels doped with up to 2 wt% Ni have up to 450 appm He after HFIR irradiation to /approximately/38 dpa, but only 5 appm He after 47 dpa in FFTF. No fine He bubbles and few or no larger voids were observable in any of these steels after FFTF irradiation at 407/degree/C. By contrast, many voids were found in the undoped steels (30-90 appm He) irradiated in HFIR at 400/degree/C, while voids plus many more fine He bubbles were found in the Ni-doped steels (400-450 appm He). Irradiation in both reactors at /approximately/400/degree/C produced significant changes in the as-tempered lath/subgrain boundary, dislocation, and precipitation structures that were sensitive to alloy composition, including doping with Ni. However, for each specific alloy the irradiation-produced changes were exactly the same comparing samples irradiated in FFTF and HFIR, particularly the Ni-doped steels. Therefore, the increased void formation appears solely due to the increased helium generation found in HFIR. While the levels of void swelling are relatively low after 37-39 dpa in HFIR (0.1-0.4%), details of the microstructural evolution suggest that void nucleation is still progressing, and swelling could increase with dose. The effect of helium on void swelling remains a valid concern for fusion application that requires higher dose experiments. 15 refs., 14 figs., 8 tabs

Fabrication procedures for HFIR control plates

Energy Technology Data Exchange (ETDEWEB)

Bowden, G.A.; Hicks, G.R.; Knight, R.W.

1984-10-01

The HFIR control system uses Alclad cylindrically shaped components, which have regions containing 31 vol % Eu/sub 2/O/sub 3/ and 38 vol % Ta, respectively. Exacting control of the water passage between these components and adjacent reactor parts is mandatory, and precise dimensional control of the finished products is required. This report describes the procedures developed for manufacturing outer control plates and inner control cylinders. Results are cited which demonstrate that circular-shaped outer control plates can be produced with less than 0.025-in. variation from the specified 9.300-in. radius in any region of the plate. Other results show that, by the exercise of careful control, inner control, inner control plates can be welded into cylindrical geometry with diametrical variations held to less than +- 0.010 in. of the intended 17.846-in. average diam. The cylinders can then be explosively sized, while under compression, with diametric variations of less than 0.005 in. while controlling roundness variations to less than 0.030 in. from the specified 17.842-in. finished diam.

Fabrication procedures for HFIR control plates

International Nuclear Information System (INIS)

Bowden, G.A.; Hicks, G.R.; Knight, R.W.

1984-10-01

The HFIR control system uses Alclad cylindrically shaped components, which have regions containing 31 vol % Eu 2 O 3 and 38 vol % Ta, respectively. Exacting control of the water passage between these components and adjacent reactor parts is mandatory, and precise dimensional control of the finished products is required. This report describes the procedures developed for manufacturing outer control plates and inner control cylinders. Results are cited which demonstrate that circular-shaped outer control plates can be produced with less than 0.025-in. variation from the specified 9.300-in. radius in any region of the plate. Other results show that, by the exercise of careful control, inner control, inner control plates can be welded into cylindrical geometry with diametrical variations held to less than +- 0.010 in. of the intended 17.846-in. average diam. The cylinders can then be explosively sized, while under compression, with diametric variations of less than 0.005 in. while controlling roundness variations to less than 0.030 in. from the specified 17.842-in. finished diam

Ductility and microstructure of precipitation-strengthened alloys irradiated in HFIR

International Nuclear Information System (INIS)

Yang, W.J.S.; Hamilton, M.L.

1983-08-01

Six γ' and γ'/γ'' strengthened Ni-base alloys have shown near-zero ductility after irradiation at 300 to 600 0 C in HFIR to a peak exposure of 9 dpa. Microstructural examination of the irradiated specimens showed that the loss of ductility in these alloys arises from the simultaneous existence of a strong matrix and weak grain boundaries. The strong matrix is attributed to the irradiation-induced γ' and γ'/γ'' precipitates, the faulted loops and a high density of fine helium bubbles. The weak grain boundaries are attributed to the formation of an unfavorable precipitate, such as eta-plates, recrystallized grains, a thin layer of γ' and helium bubbles

Evaluation of fatigue properties of HFIR-irradiated nimonic PE-16 at 4300C

International Nuclear Information System (INIS)

Grossbeck, M.L.; Liu, K.C.

1984-01-01

Nimonic PE-16 was irradiated in the HFIR to 6 to 9 dpa and 560 to 1000 at. ppM He at 430 0 C. Postirradiation fatigue tests revealed a reduction in fatigue life by about a factor of 10 at 430 0 C. In contrast with AISI type 316 stainless steel, no endurance limit was observed. All irradiated specimens exhibited some intergranular fracture with an increasing tendency toward cleavage like intragranular fracture for low strain ranges

Justification for an Increase in Authorized Operating Power at HFIR

International Nuclear Information System (INIS)

Primm, Trent; Ilas, Germina

2011-01-01

Using verified and validated reactor physics methods coupled to a currently accepted thermal hydraulic analysis methodology, onset of incipient boiling power agrees well with the currently-accepted safety basis value. The MCNP-based methodology is acceptable for scoping studies of LEU fuel conversion. A balance-of-plant assessment would have to be conducted to determine if the power up-rate to 100 MW could be supported for LEU fuel. While analyses performed 45 years ago have been shown to be in agreement with today s methods, there is an advantage to the current methodology in that people working at HFIR today can explain/justify/defend the safety analyses rather than relying solely on documentation.

Safety and environmental requirements and design targets for TIBER-II

International Nuclear Information System (INIS)

Piet, S.J.

1987-09-01

A consistent set of safety and environmental requirements and design targets was proposed and adopted for the TIBER-II (Tokamak Ignition/Burn Experimental Reactor) design effort. TIBER-II is the most recent US version of a fusion experimental test reactor (ETR). These safety and environmental design targets were one contribution of the Fusion Safety Program in the TIBER-II design effort. The other contribution, safety analyses, is documented in the TIBER-II design report. The TIBER-II approach, described here, concentrated on logical development of, first, a complete and consistent set of safety and environmental requirements that are likely appropriate for an ETR, and, second, an initial set of design targets to guide TIBER-II. Because of limited time in the TIBER-II design effort, the iterative process only included one iteration - one set of targets and one design. Future ETR design efforts should therefore build on these design targets and the associated safety analyses. 29 refs., 5 figs., 3 tabs

RTNS-II [Rotating Target Neutron Source II] operational summary

International Nuclear Information System (INIS)

Heikkinen, D.W.

1988-09-01

The Rotating Target Neutron Source II facility (RTNS-II) operated for over nine years. Its purpose was to provide high intensities of 14 MeV neutrons for materials studies in the fusion energy program. For the period from 1982-1987, the facility was supported by both the US (Department of Energy) and Japan (Ministry of Education, Culture, and Science). RTNS-II contains two accelerator-based neutron sources which use the T(d,n) 4 He reaction. In this paper, we will summarize the operational history of RTNS-II. Typical operating parameters are given. In addition, a brief description of the experimental program is presented. The current status and future options for the facility are discussed. 7 refs., 5 tabs

Achieving increased spent fuel storage capacity at the High Flux Isotope Reactor (HFIR)

International Nuclear Information System (INIS)

Cook, D.H.; Chang, S.J.; Dabs, R.D.; Freels, J.D.; Morgan, K.A.; Rothrock, R.B.; Griess, J.C.

1994-01-01

The HFIR facility was originally designed to store approximately 25 spent cores, sufficient to allow for operational contingencies and for cooling prior to off-site shipment for reprocessing. The original capacity has now been increased to 60 positions, of which 53 are currently filled (September 1994). Additional spent cores are produced at a rate of about 10 or 11 per year. Continued HFIR operation, therefore, depends on a significant near-term expansion of the pool storage capacity, as well as on a future capability of reprocessing or other storage alternatives once the practical capacity of the pool is reached. To store the much larger inventory of spent fuel that may remain on-site under various future scenarios, the pool capacity is being increased in a phased manner through installation of a new multi-tier spent fuel rack design for higher density storage. A total of 143 positions was used for this paper as the maximum practical pool capacity without impacting operations; however, greater ultimate capacities were addressed in the supporting analyses and approval documents. This paper addresses issues related to the pool storage expansion including (1) seismic effects on the three-tier storage arrays, (2) thermal performance of the new arrays, (3) spent fuel cladding corrosion concerns related to the longer period of pool storage, and (4) impacts of increased spent fuel inventory on the pool water quality, water treatment systems, and LLLW volume

Simulated Irradiation of Samples in HFIR for use as Possible Test Materials in the MPEX (Material Plasma Exposure Experiment) Facility

Energy Technology Data Exchange (ETDEWEB)

Ellis, Ronald James [ORNL; Rapp, Juergen [ORNL

2014-01-01

The importance of Plasma Material Interaction (PMI) is a major concern in fusion reactor design and analysis. The Material-Plasma Exposure eXperiment (MPEX) facility will explore PMI under fusion reactor plasma conditions. Samples with accumulated displacements per atom (DPA) damage produced by irradiations in the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL) will be studied in the MPEX facility. The project presented in this paper involved performing assessments of the induced radioactivity and resulting radiation fields of a variety of potential fusion reactor materials. The scientific code packages MCNP and SCALE were used to simulate irradiation of the samples in HFIR; generation and depletion of nuclides in the material and the subsequent composition, activity levels, gamma radiation fields, and resultant dose rates as a function of cooling time. These state-of-the-art simulation methods were used in addressing the challenge of the MPEX project to minimize the radioactive inventory in the preparation of the samples for inclusion in the MPEX facility.

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN TUNGSTEN SUBJECTED TO NEUTRON FLUX WITH PKA SPECTRUM CORRESPONDING TO THE HFIR

Energy Technology Data Exchange (ETDEWEB)

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.; Roche, Kenneth J.; Kurtz, Richard J.; Wirth, Brian D.

2015-12-31

The objective of this work is to study the damage accumulation in pure tungsten (W) subjected to neutron bombardment with a primary knock-on atom (PKA) spectrum corresponding to the High Flux Isotope Reactor (HFIR), using the object kinetic Monte Carlo (OKMC) method.

Tritium-target performance at RTNS-II

International Nuclear Information System (INIS)

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

1982-01-01

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

Tensile properties of vanadium alloys irradiated at 200{degrees}C in the HFIR

Energy Technology Data Exchange (ETDEWEB)

Chung, H.M.; Nowicki, L.; Smith, D.L. [Argonne National Lab., IL (United States)

1997-08-01

Vanadium alloys were irradiated in a helium environment to {approx}10 dpa at {approx}200{degrees}C in the High Flux Isotope Reactor (HFIR). This report presents results of postirradiation tests of tensile properties of laboratory heats of V-(1-18)Ti, V-4Cr-4Ti, V-8Cr-6Ti, V-9Cr-5Ti, V-3Ti-1Si, and V-3Ti-0.1C alloys. Because of significant loss of work-hardening capability, all alloys except V-18Ti exhibited a very low uniform plastic strain <1%. For V-Ti. The mechanism of the loss of work-hardening capability in the other alloys is not understood.

Analysis of dpa Rates in the HFIR Reactor Vessel using a Hybrid Monte Carlo/Deterministic Method*

Directory of Open Access Journals (Sweden)

Risner J.M.

2016-01-01

Full Text Available The Oak Ridge High Flux Isotope Reactor (HFIR, which began full-power operation in 1966, provides one of the highest steady-state neutron flux levels of any research reactor in the world. An ongoing vessel integrity analysis program to assess radiation-induced embrittlement of the HFIR reactor vessel requires the calculation of neutron and gamma displacements per atom (dpa, particularly at locations near the beam tube nozzles, where radiation streaming effects are most pronounced. In this study we apply the Forward-Weighted Consistent Adjoint Driven Importance Sampling (FW-CADIS technique in the ADVANTG code to develop variance reduction parameters for use in the MCNP radiation transport code. We initially evaluated dpa rates for dosimetry capsule locations, regions in the vicinity of the HB-2 beamline, and the vessel beltline region. We then extended the study to provide dpa rate maps using three-dimensional cylindrical mesh tallies that extend from approximately 12 in. below to approximately 12 in. above the height of the core. The mesh tally structures contain over 15,000 mesh cells, providing a detailed spatial map of neutron and photon dpa rates at all locations of interest. Relative errors in the mesh tally cells are typically less than 1%.

High Flux Isotopes Reactor (HFIR) Cooling Towers Demolition Waste Management

Energy Technology Data Exchange (ETDEWEB)

Pudelek, R. E.; Gilbert, W. C.

2002-02-26

This paper describes the results of a joint initiative between Oak Ridge National Laboratory, operated by UT-Battelle, and Bechtel Jacobs Company, LLC (BJC) to characterize, package, transport, treat, and dispose of demolition waste from the High Flux Isotope Reactor (HFIR), Cooling Tower. The demolition and removal of waste from the site was the first critical step in the planned HFIR beryllium reflector replacement outage scheduled. The outage was scheduled to last a maximum of six months. Demolition and removal of the waste was critical because a new tower was to be constructed over the old concrete water basin. A detailed sampling and analysis plan was developed to characterize the hazardous and radiological constituents of the components of the Cooling Tower. Analyses were performed for Resource Conservation and Recovery Act (RCRA) heavy metals and semi-volatile constituents as defined by 40 CFR 261 and radiological parameters including gross alpha, gross beta, gross gamma, alpha-emitting isotopes and beta-emitting isotopes. Analysis of metals and semi-volatile constituents indicated no exceedances of regulatory limits. Analysis of radionuclides identified uranium and thorium and associated daughters. In addition 60Co, 99Tc, 226Rm, and 228Rm were identified. Most of the tower materials were determined to be low level radioactive waste. A small quantity was determined not to be radioactive, or could be decontaminated. The tower was dismantled October 2000 to January 2001 using a detailed step-by-step process to aid waste segregation and container loading. The volume of waste as packaged for treatment was approximately 1982 cubic meters (70,000 cubic feet). This volume was comprised of plastic ({approx}47%), wood ({approx}38%) and asbestos transite ({approx}14%). The remaining {approx}1% consisted of the fire protection piping (contaminated with lead-based paint) and incidental metal from conduit, nails and braces/supports, and sludge from the basin. The waste

Recovery and purification of nickel-63 from HFIR-irradiated targets

International Nuclear Information System (INIS)

Williams, D.F.; O'Kelley, G.D.; Knauer, J.B.; Porter, C.E.; Wiggins, J.T.

1993-06-01

The production of large quantities of high-specific-activity 63 Ni (>10 Ci/g) requires both a highly enriched 62 Ni target and a long irradiation period at high neutron flux. Trace impurities in the nickel and associated target materials are also activated and account for a significant fraction of the discharged activity and essentially all of the gamma activity. While most of these undesirable activation products can be removed as chloride complexes during anion exchange, chromium, present at 51 Cr, and scandium, present as 46 Sc, are exceptions and require additional processing to achieve the desired purity. Optimized flowsheets are discussed based upon the current development and production experience

Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

International Nuclear Information System (INIS)

Bucholz, J.A.

2000-01-01

The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory is in the midst of a massive upgrade program to enhance experimental facilities. The reactor presently has four horizontal experimental beam tubes, all of which will be replaced or redesigned. The HB-2 beam tube will be enlarged to support more guide tubes, while the HB-4 beam tube will soon include a cold neutron source

Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

Energy Technology Data Exchange (ETDEWEB)

Bucholz, J.A.

2000-07-01

The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory is in the midst of a massive upgrade program to enhance experimental facilities. The reactor presently has four horizontal experimental beam tubes, all of which will be replaced or redesigned. The HB-2 beam tube will be enlarged to support more guide tubes, while the HB-4 beam tube will soon include a cold neutron source.

Electroforming copper targets for RTNS-II

International Nuclear Information System (INIS)

Kelley, W.K.; Dini, J.W.; Logan, C.M.

1981-01-01

Copper targets used in RTNS II, which is the world's most intense 14-MeV neutron source, contain water cooling channels for temperature control. There are two methods for fabricating these targets: (1) diffusion bonding a copper panel containing photoetched channels to another copper panel, and (2) an electroforming technique which involves filling the photoetched channels with wax, plating thick copper to seal over the channels and then removing the wax. Development of this latter process and results obtained with it are described

Irradiation performance of HTGR fuel in HFIR experiment HRB-13

International Nuclear Information System (INIS)

Tiegs, T.N.

1982-03-01

Irradiation capsule HRB-13 tested High-Temperature Gas-Cooled Reactor (HTGR) fuel under accelerated conditions in the High Flux Isotope Reactor (HFIR) at ORNL. The ORNL part of the capsule was designed to provide definitive results on how variously misshapen kernels affect the irradiation performance of weak-acid-resin (WAR)-derived fissile fuel particles. Two batches of WAR fissile fuel particles were Triso-coated and shape-separated into four different fractions according to their deviation from spericity, which ranged from 9.6 to 29.7%. The fissile particles were irradiated for 7721 h. Heavy-metal burnups ranged from 80 to 82.5% FIMA (fraction of initial heavy-metal atoms). Fast neutron fluences (>0.18 MeV) ranged from 4.9 x 10 25 neutrons/m 2 to 8.5 x 10 25 neutrons/m 2 . Postirradiation examination showed that the two batches of fissile particles contained chlorine, presumably introduced during deposition of the SiC coating

Improved swelling resistance for PCA austenitic stainless steel under HFIR irradiation through microstructural control

International Nuclear Information System (INIS)

Maziasz, P.J.; Braski, D.N.

1983-01-01

Six microstructural variants of Prime Candidate Alloy (PCA) were evaluated for swelling resistance during HFIR irradiation, together with several heats of type 316 stainless steel (316). Swelling was negligible in all the steels at 300 0 C after approx. 44 dpa. At 500 to 600 0 C 25%-cold-worked PCA showed better void swelling resistance than type 316 at approx. 44 dpa. There was less swelling variability among alloys at 400 0 C, but again 25%-cold-worked PCA was the best. Microstructurally, swelling resistance correlated with development of fine, stable bubbles whereas high swelling was due to coarser distributions of bubbles becoming unstable and converting to voids (bias-driven cavities)

Neutron scattering for studies of soft matter at SNS and HFIR

International Nuclear Information System (INIS)

Smith, Gregory S.

2013-01-01

In this talk, we will present an overview of the scientific program of the Structure and Dynamics of Soft Matter Group, in the Biology and Soft Matter Division of the Neutron Sciences Directorate. From the broader area of soft materials research, the group members have chosen four main areas of scientific focus including: Confinement and Low-Dimensional Systems, Structure and Dynamics of Colloids, Nanoparticle-Polymer Composites, Transport in Membranes, and New Neutron Techniques for soft matter science. We will present several examples of neutron scattering experimental studies in each of these areas highlighting the experimental and theoretical (or modeling) capabilities of the group at both HFIR and SNS. Example topics to be discussed include SANS, reflectometry, and/or quasielastic studies of membranes on patterned interfaces, dynamics and structure of soft colloidal materials (including both polymeric dendrimers and biomimetic materials), gas confinement in mesoporous structures, transport in polyelectrolyte thin films, and development of spin-echo SANS concepts. (author)

Saturation behavior of irradiation hardening in F82H irradiated in the HFIR

Energy Technology Data Exchange (ETDEWEB)

Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Shiba, K.; Tanigawa, H.; Ando, M. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Klueh, R.L. [Oak Ridge National Laboratory, TN (United States); Stoller, R. [ORNL - Oak Ridge National Laboratory, Materials Science and Technology Div., Oak Ridge, AK TN (United States)

2007-07-01

Full text of publication follows: Post irradiation tensile tests on reduced activation ferritic/martensitic steel, F82H have been conducted over the past two decades using Japan Materials Testing Reactor (JMTR) of JAEA, and Fast Flux Testing Facility (FFTF) of PNNL and High Flux Isotope Reactor (HFIR) of ORNL, USA, under Japan/US collaboration programs. According to these results, F82H does not demonstrate irradiation hardening above 673 K up to 60 dpa. The current study has been concentrated on hardening behavior at temperature around 573 K. A series of low temperature irradiation experiment has been conducted at the HFIR under the international collaborative research between JAEA/US-DOE. In this collaboration, the irradiation condition is precisely controlled by the well matured capsule designing and instrumentation. This paper summarizes recent results of the irradiation experiments focused on F82H and its modified steels compared with the irradiation properties database on F82H. Post irradiation tensile tests have been conducted on the F82H and its modified steels irradiated at 573 K and the dose level was up to 25 dpa. According to these results, irradiation hardening of F82H is saturated by 9 dpa and the as-irradiated 0.2 % proof stress is less than 1 GPa at ambient temperature. The deterioration of total elongation was also saturated by 9 dpa irradiation. The ductility of some modified steels which showed larger total elongation than that of F82H before irradiation become the same level as that of standard F82H steel after irradiation, even though its magnitude of irradiation hardening is smaller than that of F82H. This suggests that the more ductile steel demonstrates the more ductility loss at this temperature, regardless to the hardening level. The difference in ductility loss behavior between various tensile specimens will be discussed as the ductility could depend on the specimen dimension. (authors)

Summary of the U.S. specimen matrix for the HFIR 13J varying temperature irradiation capsule

International Nuclear Information System (INIS)

Zinkle, S.J.

1998-01-01

The US specimen matrix for the collaborative DOE/Monbusho HFIR 13J varying temperature irradiation capsule contains two ceramics and 29 different metals, including vanadium alloys, ferritic/martensitic steels, pure iron, austenitic stainless steels, nickel alloys, and copper alloys. This experiment is designed to provide fundamental information on the effects of brief low-temperature excursions on the tensile properties and microstructural evolution of a wide range of materials irradiated at nominal temperatures of 350 and 500 C to a dose of ∼5 dpa. A total of 340 miniature sheet tensile specimens and 274 TEM disks are included in the US-supplied matrix for the irradiation capsule

An alternative bactericidal mechanism of action for lantibiotic peptides that target lipid II

NARCIS (Netherlands)

Hasper, Hester E.; Kramer, Naomi E.; Smith, James L.; Hillman, J. D.; Zachariah, Cherian; Kuipers, Oscar P.; de Kruijff, Ben; Breukink, Eefjan

2006-01-01

Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II - targeted lantibiotics are too short to be

Fabrication and operation of HFIR-MFE RB* spectrally tailored irradiation capsules

International Nuclear Information System (INIS)

Longest, A.W.; Pawel, J.E.; Heatherly, D.W.; Sitterson, R.G.; Wallace, R.L.

1993-01-01

Fabrication and operation of four HFIR-MFE RB * capsules (60, 200, 330, and 400 degrees C) to accommodate MFE specimens previously irradiated in spectrally tailored experiments in the ORR are proceeding satisfactorily. With the exception of the 60 degrees C capsule, where the test specimens were in direct contact with the reactor cooling water, specimen temperatures (monitored by 21 thermocouples) are controlled by varying the thermal conductance of a thin gap region between the specimen holder outer sleeve and containment tube. Irradiation of the 60 and 330 degrees C capsules, which started on July 17, 1990, was completed on November 14, 1992, after 24 cycles of irradiation to an incremental damage level of approximately 10.9 displacements per atom (dpa). Assembly of the follow-up 200 and 400 degrees C capsules was completed in November 1992, and their planned 20-cycle irradiation to approximately 9.1 incremental dpa was started on November 21, 1992. As of February 11, 1993, the 200 and 400 degrees C capsules had successfully completed three cycles of irradiation to approximately 1.4 incremental dpa

Correlation of mechanical property changes in neutron-irradiated pressure vessel steels on the basis of spectral effects

International Nuclear Information System (INIS)

Heinisch, H.L.

1991-01-01

Comparisons are made of tensile data on specimens of A212B and A302B pressure vessel steels irradiated at low temperatures (40-90degC) and to low doses (<0.1 dpa) with 14 MeV D-T fusion neutrons in the Rotating Target Neutron Source (RTNS-II), with fission reactor neutrons in the Omega West Reactor (OWR) and the Oak Ridge Research Reactor (ORR), and with the highly thermal spectrum at the pressure vessel surveillance positions of the High Flux Isotope Reactor (HFIR). For each neutron spectrum, damage cross sections are determined for several defect production functions derived from atomistic computer simulations of collision cascades. Displacements per atom (dpa) and the numbers of freely migrating defects are tested as damage correlation parameters for the tensile data. The data from RTNS-II, OWR and ORR correlate fairly well when compared on the basis of dpa, but the data from HFIR show only about one sixth as many dpa are needed to produce the same radiation-induced yield stress changes as in the other neutron spectra. In the HFIR surveillance position a significant fraction of the displacements is produced by recoils resulting from thermal neutron captures. Having energies of about 400 eV, these recoils are much more efficient per unit energy at producing freely migrating defects than the high energy recoils responsible for most of the displacements in the other neutron spectra considered. A significantly better correlation of data from HFIR with those from the other spectra is achieved when the property changes are compared on the basis of the production of freely migrating self-interstitial defects. (orig./MM)

TALE-PvuII fusion proteins--novel tools for gene targeting.

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

Fracture fragility of HFIR vessel caused by random crack size or random toughness

International Nuclear Information System (INIS)

Chang, Shih-Jung; Proctor, L.D.

1993-01-01

This report discuses the probability of fracture (fracture fragility) versus a range of applied hoop stresses along the HFIR vessel which is obtained as an estimate of its fracture capacity. Both the crack size and the fracture toughness are assumed to be random variables that follow given distribution functions. Possible hoop stress is based on the numerical solution of the vessel response by applying a point pressure-pulse it the center of the fluid volume within the vessel. Both the fluid-structure interaction and radiation embrittlement are taken into consideration. Elastic fracture mechanics is used throughout the analysis. The probability of vessel fracture for a single crack caused by either a variable crack depth or a variable toughness is first derived. Then the probability of fracture with multiple number of cracks is obtained. The probability of fracture is further extended to include different levels of confidence and variability. It, therefore, enables one to estimate the high confidence and low probability capacity accident load

Charpy impact test results of ferritic alloys from the HFIR[High Flux Isotope Reactor]-MFE-RB2 test

International Nuclear Information System (INIS)

Hu, W.L.; Gelles, D.S.

1987-03-01

Miniature Charpy specimens of HT-9 in base metal, weld metal and heat affected zone (HAZ) metal conditions, and 9Cr-1Mo in base metal and weld metal conditions have been tested following irradiation in HFIR-MFE-RB2 at 55 0 C to ≅10 dpa. All specimen conditions have degraded properties (both DBTT and USE) in comparison with specimens irradiated to lower dose. 9Cr-Mo degraded more than HT-9 and weld metal performed worse than base metal which performed worse than HAZ material. Property degradation was approximately linear as a function of dose, indicating that degradation response had not saturated by 10 dpa

TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

Science.gov (United States)

Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

2013-01-01

Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

Enhanced radiation response in radioresistant MCF-7 cells by targeting peroxiredoxin II

Directory of Open Access Journals (Sweden)

Diaz AJG

2013-10-01

Full Text Available Anthony Joseph Gomez Diaz,1 Daniel Tamae,2 Yun Yen,3 JianJian Li,4 Tieli Wang1 1Department of Chemistry and Biochemistry, California State University at Dominguez Hills, Carson, CA, 2Center of Excellence in Environmental Toxicology, Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 3Department of Clinical and Molecular Pharmacology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA, 4Department of Radiation Oncology, University of California Davis, Sacramento, CA, USA Abstract: In our previous study, we identified that a protein target, peroxiredoxin II (PrxII, is overexpressed in radioresistant MCF+FIR3 breast-cancer cells and found that its expression and function is associated with breast-cancer radiation sensitivity or resistance. Small interference RNA (siRNA targeting PrxII gene expression was able to sensitize MCF+FIR3 radioresistant breast-cancer cells to ionizing radiation. The major focus of this work was to investigate how the radiation response of MCF+FIR3 radioresistant cells was affected by the siRNA that inhibits PrxII gene expression. Our results, presented here, show that silencing PrxII gene expression increased cellular toxicity by altering cellular thiol status, inhibiting Ca2+ efflux from the cells, and perturbing the intracellular Ca2+ homeostasis. By combining radiotherapy and siRNA technology, we hope to develop new therapeutic strategies that may have potential to enhance the efficacy of chemotherapeutic agents due to this technology's property of targeting to specific cancer-related genes. Keywords: siRNA, PrxII, radiation resistance, Ca2+, MCF+FIR3

Features of target cell lysis by class I and class II MHC restricted cytolytic T lymphocytes

International Nuclear Information System (INIS)

Maimone, M.M.; Morrison, L.A.; Braciale, V.L.; Braciale, T.J.

1986-01-01

The lytic activity of influenza virus-specific muvine cytolytic T lymphocyte (CTL) clones that are restricted by either H-2K/D (class I) or H-2I (class II) major histocompatibility (MHC) locus products was compared on an influenza virus-infected target cell expressing both K/D and I locus products. With the use of two in vitro measurements of cytotoxicity, conventional 51 Cr release, and detergent-releasable radiolabeled DNA (as a measure of nuclear disintegration in the early post-lethal hit period), the authors found no difference between class I and class II MHC-restricted CTL in the kinetics of target cell destruction. In addition, class II MHC-restricted antiviral CTL failed to show any lysis of radiolabeled bystander cells. Killing of labeled specific targets by these class II MHC-restricted CTL was also efficiently inhibited by unlabeled specific competitor cells in a cold target inhibition assay. In sum, these data suggest that class I and class II MHC-restricted CTL mediate target cell destruction by an essentially similar direct mechanism

Baseball II-T, a new target plasma startup experiment

International Nuclear Information System (INIS)

Chargin, A.; Denhoy, B.; Frank, A.; Thomas, S.

1975-01-01

A brief description is given of modifications and additions to the existing Baseball II experiment. These changes will make it possible to study target plasma buildup in a steady-state magnetic field. This experiment, now called Baseball II-T + will use a pellet generator to deliver ammonia pellets into the center of the magnetic mirror field where they will be heated with a 300-J, 50-ns, CO 2 laser. The plasma created by this method will have a density of approximately 10 13 cm -3 and a temperature of about 1 keV. This target plasma will be used for neutral beam injection startup studies with a 50-A, 20-keV neutral beam. Later, the beam power will be increased to study buildup. With ion injection energies of up to 50 keV, it may be possible to achieve etatau as high as 10 12 cm -3 s. The new components necessary to achieve these goals are described

Microstructural design of PCA austenitic stainless steel for improved resistance to helium embrittlement under HFIR irradiation

International Nuclear Information System (INIS)

Maziasz, P.J.; Braski, D.N.

1983-01-01

Several variants of Prime Candidate Alloy (PCA) with different preirradiation thermal-mechanical treatments were irradiated in HFIR and were evaluated for embrittlement resistance via disk-bend tensile testing. Comparison tests were made on two heats of 20%-cold-worked type 316 stainless steel. None of the alloys were brittle after irradiation at 300 to 400 0 C to approx. 44 dpa and helium levels of 3000 to approx.3600 at. ppm. However, all were quite brittle after similar exposure at 600 0 C. Embrittlement varied with alloy and pretreatment for irradiation to 44 dpa at 500 0 C and to 22 dpa at 600 0 C. Better relative embrittlement resistance among PCA variants was found in alloys which contained prior grain boundary MC carbide particles that remained stable under irradiation

Tensile properties and bend ductility of (Fe,Ni)3V long-range-ordered alloys after irradiation in HFIR

International Nuclear Information System (INIS)

Braski, D.N.

1984-01-01

The objective of this work was to determine the effect of neutron irradiation on the tensile properties and bend ductility of (Fe,Ni) 3 V long-range-ordered (LRO) alloys. Several (Fe,Ni) 3 V LRO alloys were irradiated in HFIR-CTR-42 and -43 at 400 to 600 0 C, to approximately 10 dpa and approximately 1000 at. ppm He. Additions of cerium or carbon and the use of cold-worked microstructures did not improve the embrittlement resistance of the LRO alloys. The LRO-37-5RS alloy, with a microstructure produced by rapid solidification, exhibited the highest ductilities, and further study of the RS microstructure is warranted. The correlation between bend ductility and tensile ductility was poor

Department of Energy's High Flux Isotope Reactor (HFIR), October 20--24, 1980: A special report prepared for the Nuclear Facilities Personnel Qualification and Training Committee: An independent on-site safety review

International Nuclear Information System (INIS)

1981-02-01

The intent of this on-site safety review was to make a broad management assessment of HFIR operations, rather than conduct a detailed in-depth audit. The result of the review should only be considered as having identified trends or indications. The Team's observations and recommendations are based upon licensed reactor facility practices used to meet industry standards. For the most part, these standards form the basis for many of the comments in this report. The Team believes that a uniform minimum standard of performance should be achieved in the operation of DOE reactors. In order to assure that this is accomplished, clear standards are necessary. Consistent with the provisions of past AEC and ERDA policy, the Team has used the standards of the commercial nuclear power industry. It is recognized that this approach is conservative in that the HFIR reactor has a significantly greater degree of inherent safety (low temperature, low pressure, low power) than a licensed reactor

The SNS/HFIR Web Portal System How Can it Help Me?

International Nuclear Information System (INIS)

Miller, Stephen D.; Geist, Al; Herwig, Kenneth W.; Peterson, Peter F.; Reuter, Michael A.; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I.; Kohl, James Arthur; Vazhkudai, Sudharshan S.; Cobb, John W.; Lynch, Vickie E.; Chen, Meili; Trater, James R.

2010-01-01

In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a live cataloging system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members access to their

The precipitation response of 20%-cold-worked type 316 stainless steel to simulated fusion irradiation

International Nuclear Information System (INIS)

Maziasz, P.J.

1979-01-01

The precipitation response of 20%-cold-worked type 316 stainless steel has been examined after irradiation in HFIR at 380-600 0 C, after irradiation in EBR-II at 500 0 C, and after thermal aging at 600 to 750 0 C. Eta phase forms during exposure to all environments. It constitutes a major portion of the precipitation response, and is rich in Ni, Si and Mo relative to M 23 C 6 after thermal aging. It is not normally reported in 20%-cold-worked type 316 stainless steel. The eta, M 23 C 6 , Laves, sigma, and chi precipitate phases appear at similar temperatures after HFIR, EBR-II, or thermal exposure. There are, however, some differences in relative amounts, size, and distribution of phases among the various environments. Eta phase is the only carbide-type phase observed after irradiation in HFIR from 380-550 0 C. The large cavities associated with it at 380 0 C contribute significantly to swelling. Re-solution of fine M 23 C 6 , eta, and Laves particles and re-precipitation of massive particles of sigma, M 23 C 6 and chi are observed after recrystallization in HFIR. (orig.)

2D Thermal Hydraulic Analysis and Benchmark in Support of HFIR LEU Conversion using COMSOL

Energy Technology Data Exchange (ETDEWEB)

Freels, James D [ORNL; Bodey, Isaac T [ORNL; Lowe, Kirk T [ORNL; Arimilli, Rao V [ORNL

2010-09-01

The research documented herein was funded by a research contract between the Research Reactors Division (RRD) of Oak Ridge National Laboratory (ORNL) and the University of Tennessee, Knoxville (UTK) Mechanical, Aerospace and Biomedical Engineering Department (MABE). The research was governed by a statement of work (SOW) which clearly defines nine specific tasks. This report is outlined to follow and document the results of each of these nine specific tasks. The primary goal of this phase of the research is to demonstrate, through verification and validation methods, that COMSOL is a viable simulation tool for thermal-hydraulic modeling of the High Flux Isotope Reactor (HFIR) core. A secondary goal of this two-dimensional phase of the research is to establish methodology and data base libraries that are also needed in the full three-dimensional COMSOL simulation to follow. COMSOL version 3.5a was used for all of the models presented throughout this report.

Comparison of the effects of long-term thermal aging and HFIR irradiation on the microstructural evolution of 9Cr-1MoVNb steel

International Nuclear Information System (INIS)

Maziasz, P.J.; Klueh, R.L.

1990-01-01

Both thermal aging at 482--704 degree C for up to 25,000h and HFIR irradiation at 300--600 degree C for up to 39 dpa produce substantial changes in the as-tempered microstructure of 9Cr-1MoVNb martensitic/ferritic steel. However, the changes in the dislocation/subgrain boundary and the precipitate structures caused by thermal aging or neutron irradiation are quite different in nature. During thermal aging, the as-tempered lath/subgrain boundary and carbide precipitate structures remain stable below 650 degree C, but coarsen and recover somewhat at 650--704 degree C. The formation of abundant intergranular Laves phase, intra-lath dislocation networks, and fine dispersions of VC needles are thermal aging effects that are superimposed upon the as-tempered microstructure at 482--593 degree C. HFIR irradiation produces dense dispersions of very small ''black'' dislocations loops at 300 degree C and produces helium bubbles and voids at 400 degree C At 300--500 degree C, there is considerable recovery of the as-tempered lath/subgrain boundary structure and microstructural/microcompositional instability of the as-tempered carbide precipitates during irradiation. By contrast, the as-tempered microstructure remains essentially unchanged during irradiation at 600 degree C. Comparison of thermally aged with irradiation material suggests that the instabilities of the as-tempered lath/subgrain boundary and precipitate structures at lower irradiation temperatures are radiation-induced effects, whereas the absence of both Laves phase and fine VC needles during irradiation is a radiation-retarded thermal effect

Swelling and microstructural development in path A PCA and type 316 stainless steel irradiated in HFIR to about 22 dpa

International Nuclear Information System (INIS)

Maziasz, P.J.; Braski, D.N.

1983-01-01

Irradiation of several microstructural variants of PCA and 20%-cold-worked N-lot type 316 stainess steel (CW 316) in HFIR to about 10 dpa produced no visible cavities at 300 0 C, bubbles at 400 0 C, and varying distributions of bubbles and voids at 500 and 600 0 C. The PCA-B1 swells the most and CW 316 (N-lot) the least at 600 0 C. Irradiations have been extended to about 22 dpa. The PCA-Al swells 0.06%/dpa at 600 0 C but at a much lower rate at 500 0 C. The PCA-A3 shows the lowest swelling at 600 0 C, about the half the swelling rate of type 316 stainless steel

Effects of HFIR irradiation at 550C on the microstructure and toughness of HT-9 and 9Cr-1Mo

International Nuclear Information System (INIS)

Gelles, D.S.; Hu, W.L.; Huang, F.H.; Johnson, G.D.

1984-01-01

Results are reported for base metal and weld metal specimens of HT-9 and Modified 9Cr-1Mo following irradiation in HFIR at 55 0 C to 5 dpa. The DBTT shifts in irradiated base metal specimens were 30 0 C for HT-9 and 90 0 C for 9Cr-1Mo with further shifts of 20 0 C for weld metal. Concurrently, strength as measured by hardness increased 15 percent for HT-9 and 25 percent for 9Cr-1Mo. The hardness increases can be attributed in part to defect clusters 1.5 to 3.0 nm in diameter at densities approaching 10 17 cm -3 and also to lower rates of cavity nucleation ahead of the propagating crack

Stress analysis of the HFIR HB-2 and HB-3 beam tube nozzles

International Nuclear Information System (INIS)

Williams, P.T.

1998-08-01

The results of three-dimensional linear elastic stress analyses of the HFIR HB-2 and HB-3 nozzles are presented in this report. Finite element models were developed using the PATRAN pre-processing code and translated into ABAQUS input file format. A scoping analysis using simple geometries with internal pressure loading was carried out to assess the capabilities of the ABAQUS/Standard code to calculate maximum principal stress distributions within cylinders with and without holes. These scoping calculations were also used to provide estimates for the variation in tangential stress around the rim of a nozzle using the superposition of published closed-form solutions for the stress around a hole in an infinite flat plate under uniaxial tension. From the results of the detailed finite element models, peak stress concentration factors (based on the maximum principal stresses in tension) were calculated to be 3.0 for the HB-2 nozzle and 2.8 for the HB-3 nozzle. Submodels for each nozzle were built to calculate the maximum principal stress distribution in the weldment region around the nozzle, where displacement boundary conditions for the submodels were automatically calculated by ABAQUS using the results of the global nozzle models. Maximum principal stresses are plotted and tabulated for eight positions around each nozzle and nozzle weldment

Simulations on Nickel target preparation and separation of Ni(II)-Cu(II) matrix for production of radioisotope "6"4Cu

International Nuclear Information System (INIS)

Sunarhadijoso Soenarjo; Wira Y Rahman; Sriyono; Triyanto

2011-01-01

The simulations on Nickel target preparation and separation of Ni(II)-Cu(II) matrix has been carried out as a preliminary study for production of medical radioisotope Cu-64 based on nuclear reaction of "6"4Ni (p,n) "6"4Cu. The nickel target preparation was performed by means of electroplating method using acidic solution of nickel chloride - boric acid mixture and basic solution of nickel sulphate - nickel chloride mixture on a silver - surfaced-target holder. The simulated solution of Ni(II) - Cu(II) matrix was considered as the solution of post-proton-irradiated nickel target containing both irradiated nickel and radioactive copper, but in the presented work the proton irradiation of nickel target was omitted, while the radioactive copper was originally obtained from neutron irradiation of CuO target. The separation of radioactive copper from the nickel target matrix was based on anion exchange column chromatography in which the radiocopper was conditioned to form anion complex CuCl_4"2"- and retained on the column while the nickel was kept in the form of Ni"2"+ cation and eluted off from the column. The retained radioactive copper was then eluted out the column in the condition of dilute HCl changing back the copper anion complex into Cu"2"+ cation. It was found that the electroplating result from the acidic solution was more satisfied than that from the basic solution. By conditioning the matrix solution at HCl 6 M, the radioactive copper was found in the forms of Cu"2"+ and CuCl_4"2"- while the nickel was totally in the form of Ni"2"+. In the condition of HCl 9 M, the radioactive copper was mostly in the form of CuCl_4"2"- while the nickel was found as both Ni"2"+ and NiCl_4"2"-. The best condition of separation was in HCl 8 M in which the radioactive copper was mostly in the form of CuCl_4"2"- while the nickel was mostly in the form of Ni"2"+. The retained CuCl_4"2"- was then changed back into Cu_2_+ cation form and eluted out the column by using HCl 0.05 M

Thermal-hydraulic simulation of natural convection decay heat removal in the High Flux Isotope Reactor (HFIR) using RELAP5 and TEMPEST: Part 2, Interpretation and validation of results

International Nuclear Information System (INIS)

Ruggles, A.E.; Morris, D.G.

1989-01-01

The RELAP5/MOD2 code was used to predict the thermal-hydraulic behavior of the HFIR core during decay heat removal through boiling natural circulation. The low system pressure and low mass flux values associated with boiling natural circulation are far from conditions for which RELAP5 is well exercised. Therefore, some simple hand calculations are used herein to establish the physics of the results. The interpretation and validation effort is divided between the time average flow conditions and the time varying flow conditions. The time average flow conditions are evaluated using a lumped parameter model and heat balance. The Martinelli-Nelson correlations are used to model the two-phase pressure drop and void fraction vs flow quality relationship within the core region. Systems of parallel channels are susceptible to both density wave oscillations and pressure drop oscillations. Periodic variations in the mass flux and exit flow quality of individual core channels are predicted by RELAP5. These oscillations are consistent with those observed experimentally and are of the density wave type. The impact of the time varying flow properties on local wall superheat is bounded herein. The conditions necessary for Ledinegg flow excursions are identified. These conditions do not fall within the envelope of decay heat levels relevant to HFIR in boiling natural circulation. 14 refs., 5 figs., 1 tab

Transuranium Processing Plant semiannual report of production, status, and plans for period ending June 30, 1975

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1976-03-01

During the period January 1, 1975, through June 30, 1975, the following amounts of transuranium elements were recovered from 22 irradiated HFIR targets: 2g 243 Am, 59 g 244 Cm, 51 mg 249 Bk, 465 mg 252 Cf, 2.5 mg 253 Es, and 1.4 pg 257 Fm. In addition, 45 mg of high-purity 248 Cm was operated from 252 Cf which had been recovered and purified during earlier periods, and 56 mg of a lower-quality 248 Cm was separated from californium purification rework solutions. Five HFIR targets, each containing approximately 9 g of actinides (predominantly curium), were fabricated. A new long-term projection showed that 252 Cf production in the TRU-HFIR complex could increase to as much as 2.5 g/year. During the next 18 months, we expect to recover totals of 46 mg of 249 Bk, 520 mg of 252 Cf, 2.0 mg of 253 Es (in a mixture of isotopes), 220 μg of high-purity 253 Es, and 1.6 pg of 257 Fm. We also expect to obtain 125 mg of high-purity 248 Cm from purified californium now in storage. There are no plans to process any of the remaining SRP Pu-Al tubes or to irradiate any plutonium targets in the HFIR; thus, we do not expect to recover any 244 Pu. Two neutron sources were fabricated, bringing the total fabricated to 77. Two sources that had been used previously in various projects were returned to the TRU inventory and are available for reassignment. In special projects, we (1) produced about 1 mg of 250 Cf by irradiation of 249 Bk in HFIR rabbits, and (2) processed some irradiated 248 Cm samples and obtained yield and isotopic composition data for use in determining the capture cross section of 249 Cm in the HFIR. The values that are currently being used for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated in the Appendix

Adipokines: Potential Therapeutic Targets for Vascular Dysfunction in Type II Diabetes Mellitus and Obesity

Directory of Open Access Journals (Sweden)

Mostafa Wanees Ahmed El husseny

2017-01-01

Full Text Available Adipokines are bioactive molecules that regulate several physiological functions such as energy balance, insulin sensitization, appetite regulation, inflammatory response, and vascular homeostasis. They include proinflammatory cytokines such as adipocyte fatty acid binding protein (A-FABP and anti-inflammatory cytokines such as adiponectin, as well as vasodilator and vasoconstrictor molecules. In obesity and type II diabetes mellitus (DM, insulin resistance causes impairment of the endocrine function of the perivascular adipose tissue, an imbalance in the secretion of vasoconstrictor and vasodilator molecules, and an increased production of reactive oxygen species. Recent studies have shown that targeting plasma levels of adipokines or the expression of their receptors can increase insulin sensitivity, improve vascular function, and reduce the risk of cardiovascular morbidity and mortality. Several reviews have discussed the potential of adipokines as therapeutic targets for type II DM and obesity; however, this review is the first to focus on their therapeutic potential for vascular dysfunction in type II DM and obesity.

Swelling and swelling resistance possibilities of austenitic stainless steels in fusion reactors

International Nuclear Information System (INIS)

Maziasz, P.J.

1983-01-01

Fusion reactor helium generation rates in stainless steels are intermediate to those found in EBR-II and HFIR, and swelling in fusion reactors may differ from the fission swelling behavior. Advanced titanium-modified austenitic stainless steels exhibit much better void swelling resistance than AISI 316 under EBR-II (up to approx. 120 dpa) and HFIR (up to approx. 44 dpa) irradiations. The stability of fine titanium carbide (MC) precipitates plays an important role in void swelling resistance for the cold-worked titanium-modified steels irradiated in EBR-II. Futhermore, increased helium generation in these steels can (a) suppress void conversion, (b) suppress radiation-induced solute segregation (RIS), and (c) stabilize fine MC particles, if sufficient bubble nucleation occurs early in the irradation. The combined effects of helium-enhanced MC stability and helium-suppressed RIS suggest better void swelling resistance in these steels for fusion service than under EBR-II irradiation

Spallation Neutron Source Second Target Station Integrated Systems Update

Energy Technology Data Exchange (ETDEWEB)

Ankner, John Francis [ORNL; An, Ke [ORNL; Blokland, Willem [ORNL; Charlton, Timothy R. [ORNL; Coates, Leighton [ORNL; Dayton, Michael J. [ORNL; Dean, Robert A. [ORNL; Dominguez-Ontiveros, Elvis E. [ORNL; Ehlers, Georg [ORNL; Gallmeier, Franz X. [ORNL; Graves, Van B. [ORNL; Heller, William T. [ORNL; Holmes, Jeffrey A. [ORNL; Huq, Ashfia [ORNL; Lumsden, Mark D. [ORNL; McHargue, William M. [ORNL; McManamy, Thomas J. [ORNL; Plum, Michael A. [ORNL; Rajic, Slobodan [ORNL; Remec, Igor [ORNL; Robertson, Lee [ORNL; Sala, Gabriele [ORNL; Stoica, Alexandru Dan [ORNL; Trotter, Steven M. [ORNL; Winn, Barry L. [ORNL; Abudureyimu, Reheman [ORNL; Rennich, Mark J. [ORNL; Herwig, Kenneth W. [ORNL

2017-04-01

The Spallation Neutron Source (SNS) was designed from the beginning to accommodate both an accelerator upgrade to increase the proton power and a second target station (STS). Four workshops were organized in 2013 and 2014 to identify key science areas and challenges where neutrons will play a vital role [1-4]. Participants concluded that the addition of STS to the existing ORNL neutron sources was needed to complement the strengths of High Flux Isotope Reactor (HFIR) and the SNS first target station (FTS). To address the capability gaps identified in the workshops, a study was undertaken to identify instrument concepts that could provide the required new science capabilities. The study outlined 22 instrument concepts and presented an initial science case for STS [5]. These instrument concepts formed the basis of a planning suite of instruments whose requirements determined an initial site layout and moderator selection. An STS Technical Design Report (TDR) documented the STS concept based on those choices [6]. Since issue of the TDR, the STS concept has significantly matured as described in this document.

On RELAP5-simulated High Flux Isotope Reactor reactivity transients: Code change and application

International Nuclear Information System (INIS)

Freels, J.D.

1993-01-01

This paper presents a new and innovative application for the RELAP5 code (hereafter referred to as ''the code''). The code has been used to simulate several transients associated with the (presently) draft version of the High-Flux Isotope Reactor (HFIR) updated safety analysis report (SAR). This paper investigates those thermal-hydraulic transients induced by nuclear reactivity changes. A major goal of the work was to use an existing RELAP5 HFIR model for consistency with other thermal-hydraulic transient analyses of the SAR. To achieve this goal, it was necessary to incorporate a new self-contained point kinetics solver into the code because of a deficiency in the point-kinetics reactivity model of the Mod 2.5 version of the code. The model was benchmarked against previously analyzed (known) transients. Given this new code, four event categories defined by the HFIR probabilistic risk assessment (PRA) were analyzed: (in ascending order of severity) a cold-loop pump start; run-away shim-regulating control cylinder and safety plate withdrawal; control cylinder ejection; and generation of an optimum void in the target region. All transients are discussed. Results of the bounding incredible event transient, the target region optimum void, are shown. Future plans for RELAP5 HFIR applications and recommendations for code improvements are also discussed

Microstructural evolution of HFIR-irradiated low activation F82H and F82H-10B steels

International Nuclear Information System (INIS)

Wakai, E.; Shiba, K.; Sawai, T.; Hashimoto, N.; Robertson, J.P.; Klueh, R.L.

1998-01-01

Microstructures of reduced-activation F82H (8Cr-2W-0.2V-0.04Ta) and the F82H steels doped with 10 B, irradiated at 250 and 300 C to 3 and 57 dpa in the High Flux Isotope Reactor (HFIR), were examined by TEM. In the F82H irradiated at 250 C to 3 dpa, dislocation loops, small unidentified defect clusters with a high number density, and a few MC precipitates were observed in the matrix. The defect microstructure after 300 C irradiation to 57 dpa is dominated by the loops, and the number density of loops was lower than that of the F82H- 10 B steel. Cavities were observed in the F82H- 10 B steels, but the swelling value is insignificant. Small particles of M 6 C formed on the M 23 C 6 carbides that were present in both steels before the irradiation at 300 C to 57 dpa. A low number density of MC precipitate particles formed in the matrix during irradiation at 300 C to 57 dpa

Hardness distribution and tensile properties in an electron-beam-welded F82H irradiated in HFIR

International Nuclear Information System (INIS)

Hashimoto, N.; Oka, H.; Muroga, T.; Kimura, A.; Sokolov, M.A.; Yamamoto, T.

2014-01-01

F82H-IEA and its EB-weld joint were irradiated at 573 and 773 K up to 9.6 dpa in the HFIR and the irradiation effect on its mechanical properties and microstructure were investigated. A hardness profile across the weld joint before irradiation showed the hardness in transformed region (TR) was high and especially that in the edge of TR was the highest (high hardness region: HHR) compared to base metal. This hardness distribution corresponds to grain size distribution. After irradiation, hardening in HHR was small compared to other region in the sample. In tensile test, the amount of hardening in yield strength and ultimate tensile strength of F82H EB-weld joint was almost similar to that of F82H-1EA but the fracture position of EB-weld joint was at the boundary of TR and BM. Therefore, the TR/BM boundary is the structural weak point in F82H EB-weld joint after irradiation. As the plastic instability was observed, the dislocation channeling deformation can be expected though the dislocation channel was not observed in this study. (author)

The High Flux Isotope Reactor (HFIR) cold source project at ORNL

International Nuclear Information System (INIS)

Selby, D.L.; Lucas, A.T.; Chang, S.J.; Freels, J.D. . E-mail-yb2@ornl.gov

1998-01-01

Following the decision to cancel the Advanced Neutron Source (ANS) Project at Oak Ridge National Laboratory (ORNL), it was determined that a hydrogen cold source should be retrofitted into an existing beam tube of the High Flux Isotope Reactor (HFIR) at ORNL. The preliminary design of this system has been completed and an 'approval in principle' of the design has been obtained from the internal ORNL safety review committees and the U.S. Department of Energy (DOE) safety review committee. The cold source concept is basically a closed loop forced flow supercritical hydrogen system. The supercritical approach was chosen because of its enhanced stability in the proposed high heat flux regions. Neutron and gamma physics of the moderator have been analyzed using the 3D Monte Carlo code MCNP 1 A D structural analysis model of the moderator vessel, vacuum tube, and beam tube was completed to evaluate stress loadings and to examine the impact of hydrogen detonations in the beam tube. A detailed ATHENA 2 system model of the hydrogen system has been developed to simulate loop performance under normal and off-normal transient conditions. Semi-prototypic hydrogen loop tests of the system have been performed at the Arnold Engineering Design Center (AEDC) located in Tullahoma, Tennessee to verify the design and benchmark the analytical system model. A 3.5 kW refrigerator system has been ordered and is expected to be delivered to ORNL by the end of this calendar year. Our present schedule shows the assembling of the cold source loop on site during the fall of 1999 for final testing before insertion of the moderator plug assembly into the reactor beam tube during the end of the year 2000. (author)

Transuranium Processing Plant semiannual report of production, status, and plans for period ending June 30, 1975

Energy Technology Data Exchange (ETDEWEB)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1976-03-01

During the period January 1, 1975, through June 30, 1975, the following amounts of transuranium elements were recovered from 22 irradiated HFIR targets: 2g /sup 243/Am, 59 g /sup 244/Cm, 51 mg /sup 249/Bk, 465 mg /sup 252/Cf, 2.5 mg /sup 253/Es, and 1.4 pg /sup 257/Fm. In addition, 45 mg of high-purity /sup 248/Cm was operated from /sup 252/Cf which had been recovered and purified during earlier periods, and 56 mg of a lower-quality /sup 248/Cm was separated from californium purification rework solutions. Five HFIR targets, each containing approximately 9 g of actinides (predominantly curium), were fabricated. A new long-term projection showed that /sup 252/Cf production in the TRU-HFIR complex could increase to as much as 2.5 g/year. During the next 18 months, we expect to recover totals of 46 mg of /sup 249/Bk, 520 mg of /sup 252/Cf, 2.0 mg of /sup 253/Es (in a mixture of isotopes), 220 ..mu..g of high-purity /sup 253/Es, and 1.6 pg of /sup 257/Fm. We also expect to obtain 125 mg of high-purity /sup 248/Cm from purified californium now in storage. There are no plans to process any of the remaining SRP Pu-Al tubes or to irradiate any plutonium targets in the HFIR; thus, we do not expect to recover any /sup 244/Pu. No changes were made in the chemical processing flowsheets normally used at TRU. Two neutron sources were fabricated, bringing the total fabricated to 77. In special projects, we (1) produced about 1 mg of /sup 250/Cf by irradiation of /sup 249/Bk in HFIR rabbits, and (2) processed some irradiated /sup 248/Cm samples and obtained yield and isotopic composition data for use in determining the capture cross section of /sup 249/Cm in the HFIR. The values that are currently being used for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated in the Appendix.

A liquid hydrogen target for the calibration of the MEG and MEG II liquid xenon calorimeter

Energy Technology Data Exchange (ETDEWEB)

Signorelli, G., E-mail: giovanni.signorelli@pi.infn.it [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Baldini, A.M. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Bemporad, C.; Cei, F.; Nicolò, D. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Università di Pisa, Dipartimento di Fisica, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Galli, L.; Gallucci, G.; Grassi, M. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Papa, A. [Paul Scherrer Institut, 5232 Villigen (Switzerland); Sergiampietri, F. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Venturini, M. [INFN Sezione di Pisa, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa (Italy)

2016-07-11

We designed, built and operated a liquid hydrogen target for the calibration of the liquid xenon calorimeter of the MEG experiment. The target was used throughout the entire data taking period, from 2008 to 2013 and it is being refurbished and partly re-designed to be integrated and used in the MEG-II experiment.

Possible Therapeutic Application of Targeting Type II Natural Killer T Cell-Mediated Suppression of Tumor Immunity

Science.gov (United States)

Kato, Shingo; Berzofsky, Jay A.; Terabe, Masaki

2018-01-01

Natural killer T (NKT) cells are a unique T cell subset that exhibits characteristics from both the innate immune cells and T cells. There are at least two subsets of NKT cells, type I and type II. These two subsets of NKT cells have opposite functions in antitumor immunity. Type I NKT cells usually enhance and type II NKT cells suppress antitumor immunity. In addition, these two subsets of NKT cells cross-regulate each other. In this review, we mainly focus on immunosuppressive NKT cells, type II NKT cells. After summarizing their definition, experimental tools to study them, and subsets of them, we will discuss possible therapeutic applications of type II NKT cell pathway targeted therapies. PMID:29520281

Small interfering RNA targeted to stem-loop II of the 5' untranslated region effectively inhibits expression of six HCV genotypes

Directory of Open Access Journals (Sweden)

Dash Srikanta

2006-11-01

Full Text Available Abstract Background The antiviral action of interferon alpha targets the 5' untranslated region (UTR used by hepatitis C virus (HCV to translate protein by an internal ribosome entry site (IRES mechanism. Although this sequence is highly conserved among different clinical strains, approximately half of chronically infected hepatitis C patients do not respond to interferon therapy. Therefore, development of small interfering RNA (siRNA targeted to the 5'UTR to inhibit IRES mediated translation may represent an alternative approach that could circumvent the problem of interferon resistance. Results Four different plasmid constructs were prepared for intracellular delivery of siRNAs targeting the stem loop II-III of HCV 5' UTR. The effect of siRNA production on IRES mediated translation was investigated using chimeric clones between the gene for green fluorescence protein (GFP and IRES sequences of six different HCV genotypes. The siRNA targeted to stem loop II effectively mediated degradation of HCV IRES mRNA and inhibited GFP expression in the case of six different HCV genotypes, where as siRNAs targeted to stem loop III did not. Furthermore, intracytoplasmic expression of siRNA into transfected Huh-7 cells efficiently degraded HCV genomic RNA and inhibited core protein expression from infectious full-length infectious clones HCV 1a and HCV 1b strains. Conclusion These in vitro studies suggest that siRNA targeted to stem-loop II is highly effective inhibiting IRES mediated translation of the major genotypes of HCV. Stem-loop II siRNA may be a good target for developing an intracellular immunization strategy based antiviral therapy to inhibit hepatitis C virus strains that are not inhibited by interferon.

Neutron and Gamma Fluxes and dpa Rates for HFIR Vessel Beltline Region (Present and Upgrade Designs)

Energy Technology Data Exchange (ETDEWEB)

Blakeman, E.D.

2001-01-11

The Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR) is currently undergoing an upgrading program, a part of which is to increase the diameters of two of the four radiation beam tubes (HB-2 and HB-4). This change will cause increased neutron and gamma radiation dose rates at and near locations where the tubes penetrate the vessel wall. Consequently, the rate of radiation damage to the reactor vessel wall at those locations will also increase. This report summarizes calculations of the neutron and gamma flux (particles/cm{sup 2}/s) and the dpa rate (displacements/atom/s) in iron at critical locations in the vessel wall. The calculated dpa rate values have been recently incorporated into statistical damage evaluation codes used in the assessment of radiation induced embrittlement. Calculations were performed using models based on the discrete ordinates methodology and utilizing ORNL two-dimensional and three-dimensional discrete ordinates codes. Models for present and proposed beam tube designs are shown and their results are compared. Results show that for HB-2, the dpa rate in the vessel wall where the tube penetrates the vessel will be increased by {approximately}10 by the proposed enlargement. For HB-4, a smaller increase of {approximately}2.6 is calculated.

Analysis of in-situ electrical conductivity data from the HFIR TRIST-ER1 experiment

International Nuclear Information System (INIS)

Zinkle, S.J.; Snead, L.L.; Shikama, T.

1997-01-01

The current vs. applied voltage data generated from the HFIR TRIST-ER1 experiment have been analyzed to determine the electrical conductivity of the 15 aluminum oxide specimens and the MgO-insulated electrical cables as a function of irradiation dose. With the exception of the 0.05%Cr-doped sapphire (ruby) specimen, the electrical conductivity of the alumina specimens remained at the expected radiation induced conductivity (RIC) level of -6 S/m during full-power reactor irradiation (10-16 kGy/s) at 450-500 degrees C up to a maximum dose of ∼3 dpa. The ruby specimen showed a rapid initial increase in conductivity to ∼2 x 10 -4 S/m after ∼0.1 dpa, followed by a gradual decrease to -6 S/m after 2 dpa. Nonohmic electrical behavior was observed in all of the specimens, and was attributed to preferential attraction of ionized electrons in the capsule gas to the unshielded low-side bare electrical leads emanating from the subcapsules. The electrical conductivity was determined from the slope of the specimen current vs. voltage curve at negative voltages, where the gas ionization effect was minimized. Dielectric breakdown tests performed on unirradiated mineral-insulated coaxial cables identical to those used in the high voltage coaxial cables during the 3-month irradiation is attributable to thermal dielectric breakdown in the glass seals at the end of the cables, as opposed to a radiation-induced electrical degradation (RIED) effect

Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting

Science.gov (United States)

Piazza, Carol Lyn; Smith, Dorie

2018-01-01

Group II introns are mobile ribozymes that are rare in bacterial genomes, often cohabiting with various mobile elements, and seldom interrupting housekeeping genes. What accounts for this distribution has not been well understood. Here, we demonstrate that Ll.LtrB, the group II intron residing in a relaxase gene on a conjugative plasmid from Lactococcus lactis, inhibits its host gene expression and restrains the naturally cohabiting mobile element from conjugative horizontal transfer. We show that reduction in gene expression is mainly at the mRNA level, and results from the interaction between exon-binding sequences (EBSs) in the intron and intron-binding sequences (IBSs) in the mRNA. The spliced intron targets the relaxase mRNA and reopens ligated exons, causing major mRNA loss. Taken together, this study provides an explanation for the distribution and paucity of group II introns in bacteria, and suggests a potential force for those introns to evolve into spliceosomal introns. PMID:29905149

Transuranium processing plant semiannual report of production, status, and plans for period ending December 31, 1974

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1975-07-01

During the period July 1, 1974, through December 31, 1974, the following amounts of transuranium elements were recovered from 11 irradiated HFIR targets: 1.5 g 243 Am, 45 g 244 Cm, 24 mg 249 Bk, 252 mg 252 Cf, 1.25 mg 253 Es, and 0.5 pg 257 Fm. In addition, 34 mg of high-purity 248 Cm was separated from 252 Cf which had been recovered and purified during earlier periods. Nine HFIR targets, each containing 8 to 9 g of actinides (predominantly curium), were fabricated. Some of the chemical processing steps used for processing HFIR targets were added, deleted, or rearranged in order to reduce processing time and increase product yields. One cubicle equipment rack was replaced and the out-of-cell piping and equipment associated with the remotely operated valves in the TRU cubicles was revised. One neutron source was fabricated. Three sources that had been used previously in various projects and returned to TRU were reloaned. A special project was begun to recover 126 Sn from TRU process solutions. The values currently in use for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated in the Appendix. (U.S.)

SVMRFE based approach for prediction of most discriminatory gene target for type II diabetes

Directory of Open Access Journals (Sweden)

Atul Kumar

2017-06-01

Full Text Available Type II diabetes is a chronic condition that affects the way our body metabolizes sugar. The body's important source of fuel is now becoming a chronic disease all over the world. It is now very necessary to identify the new potential targets for the drugs which not only control the disease but also can treat it. Support vector machines are the classifier which has a potential to make a classification of the discriminatory genes and non-discriminatory genes. SVMRFE a modification of SVM ranks the genes based on their discriminatory power and eliminate the genes which are not involved in causing the disease. A gene regulatory network has been formed with the top ranked coding genes to identify their role in causing diabetes. To further validate the results pathway study was performed to identify the involvement of the coding genes in type II diabetes. The genes obtained from this study showed a significant involvement in causing the disease, which may be used as a potential drug target.

Analysis of in-situ electrical conductivity data from the HFIR TRIST-ER1 experiment

Energy Technology Data Exchange (ETDEWEB)

Zinkle, S.J.; Snead, L.L. [Oak Ridge National Lab., TN (United States); Shikama, T. [Tohoku Univ. (Japan)] [and others

1997-08-01

The current vs. applied voltage data generated from the HFIR TRIST-ER1 experiment have been analyzed to determine the electrical conductivity of the 15 aluminum oxide specimens and the MgO-insulated electrical cables as a function of irradiation dose. With the exception of the 0.05%Cr-doped sapphire (ruby) specimen, the electrical conductivity of the alumina specimens remained at the expected radiation induced conductivity (RIC) level of <10{sup -6} S/m during full-power reactor irradiation (10-16 kGy/s) at 450-500{degrees}C up to a maximum dose of {approximately}3 dpa. The ruby specimen showed a rapid initial increase in conductivity to {approximately}2 x 10{sup -4} S/m after {approximately}0.1 dpa, followed by a gradual decrease to <1 x 10{sup -6} S/m after 2 dpa. Nonohmic electrical behavior was observed in all of the specimens, and was attributed to preferential attraction of ionized electrons in the capsule gas to the unshielded low-side bare electrical leads emanating from the subcapsules. The electrical conductivity was determined from the slope of the specimen current vs. voltage curve at negative voltages, where the gas ionization effect was minimized. Dielectric breakdown tests performed on unirradiated mineral-insulated coaxial cables identical to those used in the high voltage coaxial cables during the 3-month irradiation is attributable to thermal dielectric breakdown in the glass seals at the end of the cables, as opposed to a radiation-induced electrical degradation (RIED) effect.

U-target irradiation at FRM II aiming the production of Mo-99 - A feasibility study

International Nuclear Information System (INIS)

Gerstenberg, H.; Mueller, C.; Neuhaus, I.; Roehrmoser, A.

2010-01-01

Following the shortage in radioisotope availability the Technische Unversitaet Muenchen and the Belgian Institut National des Radioelements conducted a common study on the suitability of the FRM II reactor for the generation of Mo-99 as a fission product. A suitable irradiation channel was determined and neutronic calculations resulted in sufficiently high neutron flux densities to make FRM II a promising candidate for Mo-99 production. In addition the feasibility study provides thermohydraulic calculations as input for the design and integration of the additional cooling circuit into the existing heat removal systems of FRM II. The required in-house processes for a regular uranium target irradiation programme have been defined and necessary upgrades identified. Finally the required investment cost was estimated and a possible time schedule was given. (author)

Non-surgical breast-conservation treatment (KORTUC-BCT) using a new image-guided, enzyme-targeted, and breast cancer stem cell targeted radiosensitization treatment (KORTUC II) for patients with stage I or II breast cancer

International Nuclear Information System (INIS)

Ogawa, Yasuhiro; Kubota, Kei; Tadokoro, Michiko

2012-01-01

injected into breast tumor tissue twice a week under ultrasound guidance, just prior to each administration of radiation therapy, and we confirmed an even distribution of micro-bubbles of oxygen throughout the target tumor. The injection was started at the 6th fraction of radiation therapy. This injection protocol effectively preserves oxygen concentration in the tumor tissue for more than 24 h following intra-tumoral injection (Tokuhiro S, et al: Oncol Letters 1:1025-1028, 2010). Concerning radiation therapy, hypofraction radiotherapy was given using tangential fields approach and Field-in-field method; energy level was 4MV and the total radiation therapy dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added 3 times just following the 14th, 15th and 16th administrations of 4 MV X-ray irradiation. From a needle biopsy specimen, hormonal status (estrogen and progesterone receptors), HER-2 antigen, and CD44 receptor were examined by immunohistochemistry. Treatment was well tolerated with a minimum of adverse effects in all 39 patients. A total of 36 patients achieved clinically complete response on dynamic MRI study, and the study has not been performed yet for another 3. All of the patients did not show any complications (with the exception of mild dermatitis of Grade I for 24 and Grade II for 15), and cosmetic results were excellent/good for 35 patients. 15 patients under 75 y with stage II breast cancer underwent induction chemotherapy (EC and/or Taxan) prior to the KORTUC II treatment, and 36 patients with estrogen receptor-positive tumors also undertook hormonal therapy following KORTUC II. The mean follow-up period at the end of September 2011 was 30.1 months, at which time all 39 patients were alive without any distant metastases. Only 1 patient had local recurrence, which was discovered at 34 months follow-up. Non-surgical BCT (KORTUC-BCT) can be performed with KORTUC II. KORTUC II has 3 major characteristics: it is image-guided by

PLANS FOR WARM DENSE MATTER EXPERIMENTS AND IFE TARGET EXPERIMENTS ON NDCX-II

International Nuclear Information System (INIS)

Waldron, W.L.; Barnard, J.J.; Bieniosek, F.M.; Friedman, A.; Henestroza, E.; Leitner, M.; Logan, B.G.; Ni, P.A.; Roy, P.K.; Seidl, P.A.; Sharp, W.M.

2008-01-01

The Heavy Ion Fusion Science Virtual National Laboratory (HIFS-VNL) is currently developing design concepts for NDCX-II, the second phase of the Neutralized Drift Compression Experiment, which will use ion beams to explore Warm Dense Matter (WDM) and Inertial Fusion Energy (IFE) target hydrodynamics. The ion induction accelerator will consist of a new short pulse injector and induction cells from the decommissioned Advanced Test Accelerator (ATA) at Lawrence Livermore National Laboratory (LLNL). To fit within an existing building and to meet the energy and temporal requirements of various target experiments, an aggressive beam compression and acceleration schedule is planned. WDM physics and ion-driven direct drive hydrodynamics will initially be explored with 30 nC of lithium ions in experiments involving ion deposition, ablation, acceleration and stability of planar targets. Other ion sources which may deliver higher charge per bunch will be explored. A test stand has been built at Lawrence Berkeley National Laboratory (LBNL) to test refurbished ATA induction cells and pulsed power hardware for voltage holding and ability to produce various compression and acceleration waveforms. Another test stand is being used to develop and characterize lithium-doped aluminosilicate ion sources. The first experiments will include heating metallic targets to 10,000 K and hydrodynamics studies with cryogenic hydrogen targets

Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

Science.gov (United States)

Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

2011-08-01

Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

A design concept of target-moderator-reflector assemblies for KENS-II

International Nuclear Information System (INIS)

Watanabe, N.

1991-01-01

A design concept of KENS-II target-moderator-reflector assemblies is described. One of the assemblies is dedicated to the cold neutron source, and the other, to the thermal and epithermal neutron source. A flux-trap type moderator-configuration was adopted with a vertical proton-beam injection scheme. All moderators for the cold neutron source are coupled liquid hydrogen moderators with premoderators. A new scheme of proton beam delivery is proposed. The new system can provide several times higher total performance than a reference system based on a traditional single assembly with all decoupled moderators in a wing geometry and with a horizontal proton-beam injection scheme. (author)

The microRNA-132/212 family fine-tunes multiple targets in Angiotensin II signalling in cardiac fibroblasts

DEFF Research Database (Denmark)

Eskildsen, Tilde V; Schneider, Mikael; Sandberg, Maria B

2015-01-01

INTRODUCTION: MicroRNAs (miRNAs) are emerging as key regulators of cardiovascular development and disease; however, the cardiac miRNA target molecules are not well understood. We and others have described the Angiotensin II (AngII)-induced miR-132/212 family as novel regulators of cardiovascular...... in silico and in vitro experiments to identify miR-132/212 molecular targets in primary rat cardiac fibroblasts. RESULTS: MiR-132/212 overexpression increased fibroblast cell size and mRNA arrays detected several hundred genes that were differentially expressed, including a wide panel of receptors...... pathways that fine-tuned by miR-132/212, suggesting a role for this miRNA family as master signalling switches in cardiac fibroblasts. Our data underscore the potential for miRNA tools to manipulate a large array of molecules and thereby control biological function....

Mu2e-II Injection from PIP-II

Energy Technology Data Exchange (ETDEWEB)

Neuffer, David [Fermilab

2018-04-26

We discuss injection of 800 MeV proton beam from PIP-II into the production target for Mu2e-II, assuming a targeting and μ production scenario similar to mu2e. The incoming beam trajectory must be modified from the mu2e parameters to match the focusing fields. Adding a vertical deflection at injection enables the injected beam to reach the target. Other differences from the mu2e system must be considered, including changes in the target structure, the radiation shielding and beam dump/absorber. H- beam should be stripped to p+. Other variations are discussed.

The SNS/HFIR Web Portal System - How Can it Help Me?

Energy Technology Data Exchange (ETDEWEB)

Miller, Stephen D; Geist, Al; Herwig, Kenneth W; Peterson, Peter F; Reuter, Michael A; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I; Kohl, James A; Vazhkudai, Sudharshan S; Cobb, John W; Lynch, Vickie E; Chen Meili; Trater, James R; Smith, Bradford C; Swain, Tom; Huang Jian [University of Tennessee, Knoxville, TN (United States); Mikkelson, Ruth; Mikkelson, Dennis, E-mail: millersd@ornl.gov

2010-11-01

In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops - the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a 'live cataloging' system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members

The SNS/HFIR Web Portal System - How Can it Help Me?

International Nuclear Information System (INIS)

Miller, Stephen D; Geist, Al; Herwig, Kenneth W; Peterson, Peter F; Reuter, Michael A; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I; Kohl, James A; Vazhkudai, Sudharshan S; Cobb, John W; Lynch, Vickie E; Chen Meili; Trater, James R; Smith, Bradford C; Swain, Tom; Huang Jian; Mikkelson, Ruth; Mikkelson, Dennis

2010-01-01

In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops - the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a 'live cataloging' system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members access to

The SNS/HFIR Web Portal System - How Can it Help Me?

Science.gov (United States)

Miller, Stephen D.; Geist, Al; Herwig, Kenneth W.; Peterson, Peter F.; Reuter, Michael A.; Ren, Shelly; Bilheux, Jean-Christophe; Campbell, Stuart I.; Kohl, James A.; Vazhkudai, Sudharshan S.; Cobb, John W.; Lynch, Vickie E.; Chen, Meili; Trater, James R.; Smith, Bradford C.; (William Swain, Tom; Huang, Jian; Mikkelson, Ruth; Mikkelson, Dennis; een, Mar K. L. Gr

2010-11-01

In a busy world, continuing with the status-quo, to do things the way we are already familiar, often seems to be the most efficient way to conduct our work. We look for the value-add to decide if investing in a new method is worth the effort. How shall we evaluate if we have reached this tipping point for change? For contemporary researchers, understanding the properties of the data is a good starting point. The new generation of neutron scattering instruments being built are higher resolution and produce one or more orders of magnitude larger data than the previous generation of instruments. For instance, we have grown out of being able to perform some important tasks with our laptops - the data are too big and the computations would simply take too long. These large datasets can be problematic as facility users now begin to grapple with many of the same issues faced by more established computing communities. These issues include data access, management, and movement, data format standards, distributed computing, and collaboration among others. The Neutron Science Portal has been architected, designed, and implemented to provide users with an easy-to-use interface for managing and processing data, while also keeping an eye on meeting modern cybersecurity requirements imposed on institutions. The cost of entry for users has been lowered by utilizing a web interface providing access to backend portal resources. Users can browse or search for data which they are allowed to see, data reduction applications can be run without having to load the software, sample activation calculations can be performed for SNS and HFIR beamlines, McStas simulations can be run on TeraGrid and ORNL computers, and advanced analysis applications such as those being produced by the DANSE project can be run. Behind the scenes is a "live cataloging" system which automatically catalogs and archives experiment data via the data management system, and provides proposal team members access to

Simulated Target Preparation and Separation of Cd (II) - In (III) Matrices Using 8-Hydroxyquinoline Reagent for Producing Indium - III Radioisotope

International Nuclear Information System (INIS)

Sunarhadijoso Soenarjo; Swasono R Tamat; Lukiyawati; Lintang Maharani

2002-01-01

The potency of production and application of 111 In in Indonesia is not supported yet by capability in required processing technology. The presented paper is a preliminary study on processing technology of 111 In production from 112 Cd target covering simulated target preparation and separation of Cd(II)-In(III) matrices. The target preparation was performed by means of electroplating of CdSO 4 solution prepared from reaction of CdO and sulphuric acid. The separation of Cd(II)-In(III) matrices was proceeded by means of solvent extraction in the presence of 8-hydroxyquinoline as In(III)-complexing agent. The Cd-electroplating deposit was satisfactorily found by using 40-60 mA currents with an electroplating time of 5-7 hours. Simulated matrix solution containing mixture of Cd(II) and In(III) was extracted into chloroform with the presence of 8-hydroxyquinoline. The chloroform phase being assumed to contain In(III)-8-hydroxyquinoline complex was then re-extracted with 1 M HCl or saline solution. Each extraction fraction was spectrophotometrically identified in the region of 200-400 nm. From the resulting absorption spectra, it can be shown that the In(III) species is selectively separated from the Cd(II)-matrix. The use of saline in the re-extraction process is better then 1 M HCl solution due to solubility of 8-hydroxyquinoline in HCl. (author)

Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis.

Science.gov (United States)

Enyeart, Peter J; Mohr, Georg; Ellington, Andrew D; Lambowitz, Alan M

2014-01-13

Mobile group II introns are bacterial retrotransposons that combine the activities of an autocatalytic intron RNA (a ribozyme) and an intron-encoded reverse transcriptase to insert site-specifically into DNA. They recognize DNA target sites largely by base pairing of sequences within the intron RNA and achieve high DNA target specificity by using the ribozyme active site to couple correct base pairing to RNA-catalyzed intron integration. Algorithms have been developed to program the DNA target site specificity of several mobile group II introns, allowing them to be made into 'targetrons.' Targetrons function for gene targeting in a wide variety of bacteria and typically integrate at efficiencies high enough to be screened easily by colony PCR, without the need for selectable markers. Targetrons have found wide application in microbiological research, enabling gene targeting and genetic engineering of bacteria that had been intractable to other methods. Recently, a thermostable targetron has been developed for use in bacterial thermophiles, and new methods have been developed for using targetrons to position recombinase recognition sites, enabling large-scale genome-editing operations, such as deletions, inversions, insertions, and 'cut-and-pastes' (that is, translocation of large DNA segments), in a wide range of bacteria at high efficiency. Using targetrons in eukaryotes presents challenges due to the difficulties of nuclear localization and sub-optimal magnesium concentrations, although supplementation with magnesium can increase integration efficiency, and directed evolution is being employed to overcome these barriers. Finally, spurred by new methods for expressing group II intron reverse transcriptases that yield large amounts of highly active protein, thermostable group II intron reverse transcriptases from bacterial thermophiles are being used as research tools for a variety of applications, including qRT-PCR and next-generation RNA sequencing (RNA-seq). The

Molecular mechanisms and signaling pathways of angiotensin II-induced muscle wasting: potential therapeutic targets for cardiac cachexia

Science.gov (United States)

Yoshida, Tadashi; Tabony, A. Michael; Galvez, Sarah; Mitch, William E.; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

2013-01-01

Cachexia is a serious complication of many chronic diseases, such as congestive heart failure (CHF) and chronic kidney disease (CKD). Many factors are involved in the development of cachexia, and there is increasing evidence that angiotensin II (Ang II), the main effector molecule of the renin-angiotensin system (RAS), plays an important role in this process. Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. In rodent models, an increase in systemic Ang II leads to weight loss through increased protein breakdown, reduced protein synthesis in skeletal muscle and decreased appetite. Ang II activates the ubiquitin-proteasome system via generation of reactive oxygen species and via inhibition of the insulin-like growth factor-1 signaling pathway. Furthermore, Ang II inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance. Ang II also increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A, glucocorticoids and myostatin, which regulate muscle protein synthesis and degradation. Ang II acts on hypothalamic neurons to regulate orexigenic/anorexigenic neuropeptides, such as neuropeptide-Y, orexin and corticotropin-releasing hormone, leading to reduced appetite. Also, Ang II may regulate skeletal muscle regenerative processes. Several clinical studies have indicated that blockade of Ang II signaling via ACE inhibitors or Ang II type 1 receptor blockers prevents weight loss and improves muscle strength. Thus the RAS is a promising target for the treatment of muscle atrophy in patients with CHF and CKD. PMID:23769949

Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity.

Science.gov (United States)

Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

2016-01-01

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II -/- ) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II -/- mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II -/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II -/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

Directory of Open Access Journals (Sweden)

Ji Huang

2016-11-01

Full Text Available Obesity is associated with development and progression of chronic kidney disease (CKD. Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I and arginase-II (Arg-II in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS, leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT C57BL/6 mice and mice deficient in Arg-II gene (Arg-II-/- were fed with either a normal chow (NC or a high-fat-diet (HFD for 14 weeks (starting at the age of 7 weeks to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal ROS levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II-/- mice. Moreover, mesangial expansion as analysed by Periodic Acid Schiff (PAS staining and renal expression of vascular adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II-/- mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II-/- mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

Science.gov (United States)

Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

2016-02-05

Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity.

Dissolution flowsheet for high flux isotope reactor fuel

Energy Technology Data Exchange (ETDEWEB)

Foster, T. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-09-27

As part of the Spent Nuclear Fuel (SNF) processing campaign, H-Canyon is planning to begin dissolving High Flux Isotope Reactor (HFIR) fuel in late FY17 or early FY18. Each HFIR fuel core contains inner and outer fuel elements which were fabricated from uranium oxide (U₃O₈) dispersed in a continuous Al phase using traditional powder metallurgy techniques. Fuels fabricated in this manner, like other SNF’s processed in H-Canyon, dissolve by the same general mechanisms with similar gas generation rates and the production of H₂. The HFIR fuel cores will be dissolved and the recovered U will be down-blended into low-enriched U. HFIR fuel was previously processed in H-Canyon using a unique insert in both the 6.1D and 6.4D dissolvers. Multiple cores will be charged to the same dissolver solution maximizing the concentration of dissolved Al. The objective of this study was to identify flowsheet conditions through literature review and laboratory experimentation to safely and efficiently dissolve the HFIR fuel in H-Canyon. Laboratory-scale experiments were performed to evaluate the dissolution of HFIR fuel using both Al 1100 and Al 6061 T6 alloy coupons. The Al 1100 alloy was considered a representative surrogate which provided an upper bound on the generation of flammable (i.e., H₂) gas during the dissolution process. The dissolution of the Al 6061 T6 alloy proceeded at a slower rate than the Al 1100 alloy and was used to verify that the target Al concentration in solution could be achieved for the selected Hg concentration. Mass spectrometry and Raman spectroscopy were used to provide continuous monitoring of the concentration of H₂ and other permanent gases in the dissolution offgas allowing the development of H₂ generation rate profiles. The H₂ generation rates were subsequently used to evaluate if a full HFIR core could be dissolved in an H-Canyon dissolver without exceeding 60% of the

Target-plasma production by laser irradiation of a pellet in the Baseball II-T experiment

International Nuclear Information System (INIS)

Damm, C.C.; Foote, J.H.; Futch, A.H.; Goodman, R.K.; Hornady, R.S.; Osher, J.E.; Porter, G.D.

1977-01-01

One way to generate a plasma target that can be used in conjunction with an injected neutral beam to initiate a high-energy plasma in a steady-state, magnetic-mirror field is by the laser irradiation of a solid pellet located within the confinement region. In the Lawrence Livermore Laboratory Baseball II-T experiment, a CO 2 laser was used to provide a two-sided irradiation of an ammonia pellet; the maximum laser intensity on the pellet was approximately 4 x 10 12 W/cm 2 . The 150-μm-dia pellets were guided to the laser focal spot in the Baseball II-T magnetic field using steering voltages controlled by a microcomputer-based system. Diagnostics showed complete ionization of the pellet, average ion energies in the keV range, synchronized triggering of the laser and the neutral beam, and rapid expansion of the plasma to a diameter that was a good match to the diameter of the neutral beam. Predictions obtained from the LASNEX code compared well with measured results. Although the laser-pellet approach was proven usable as a target-plasma startup system, it would be much more complicated and expensive than the method in which streaming plasma is used to trap the neutal beams

Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

Czech Academy of Sciences Publication Activity Database

Yan, B.; Stantic, M.; Zobalová, Renata; Bezawork-Geleta, A.; Stapelberg, M.; Stursa, J.; Prokopová, Kateřina; Dong, L.; Neužil, Jiří

2015-01-01

Roč. 15, č. 401 (2015) ISSN 1471-2407 R&D Projects: GA MZd NT14078; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Tumour-initiating cells * Mitochondrially targeted vitamin E succinate * Complex II Subject RIV: FD - Oncology ; Hematology Impact factor: 3.265, year: 2015

GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

Science.gov (United States)

Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

2017-06-13

Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

Multi-unit inertial fusion plants based on HYLIFE-II, with shared heavy-ion RIA driver and target factory, producing electricity and hydrogen fuel

Energy Technology Data Exchange (ETDEWEB)

Logan, G.; Moir, R. [Lawrence Livermore National Lab., CA (United States); Hoffman, M. [Univ. of California, Davis, CA (United States)

1994-05-05

Following is a modification of the IFEFUEL systems code, called IFEFUEL2, to treat specifically the HYLIFE-II target chamber concept. The same improved Recirculating Induction Accelerator (RIA) energy scaling model developed recently by Bieri is used in this survey of the economics of multi-unit IFE plants producing both electricity and hydrogen fuel. Reference cases will assume conventional HI-indirect target gains for a 2 mm spot, and improved HYLIFE-II BoP models as per Hoffman. Credits for improved plant availability and lower operating costs due to HYLIFE-II`s 30-yr target chamber lifetime are included, as well as unit cost reductions suggested by Delene to credit greater {open_quotes}learning curve{close_quotes} benefits for the duplicated portions of a multi-unit plant. To illustrate the potential impact of more advanced assumptions, additional {open_quotes}advanced{close_quotes} cases will consider the possible benefits of an MHD + Steam BoP, where direct MHD conversion of plasma from baseball-size LiH target blanket shells is assumed to be possible in a new (as yet undesigned) liquid Flibe-walled target chamber, together and separately, with advanced, higher-gain heavy-ion targets with Fast Ignitors. These runs may help decide the course of a possible future {open_quotes}HYLIFE-III{close_quotes} IFE study. Beam switchyard and final focusing system costs per target chamber are assumed to be consistent with single-sided illumination, for either {open_quotes}conventional{close_quotes} or {open_quotes}advanced{close_quotes} indirect target gain assumptions. Target costs are scaled according to the model by Woodworth. In all cases, the driver energy and rep rate for each chosen number of target chambers and total plant output will be optimized to minimize the cost of electricity (CoE) and the associated cost of hydrogen (CoH), using a relationship between CoE and CoH to be presented in the next section.

Radiation embrittlement of PWR vessel supports

International Nuclear Information System (INIS)

Cheverton, R.D.; Robinson, G.C.; Pennell, W.E.; Nanstad, R.K.

1989-01-01

Several studies pertaining to radiation damage of PWR vessel supports were conducted between 1978 and 1987. During this period, apparently there was no reason to believe that low-temperature (<100 degree C) MTR embrittlement data were not appropriate for evaluating embrittlement of PWR vessel supports. However, late in 1986, data from the High Flux Isotope Reactor (HFIR) vessel surveillance program indicated that the embrittlement rates of the several HFIR vessel materials (A212-B, A350-LF3, A105-II) were substantially greater than anticipated on the basis of MTR data. Further evaluation of the HFIR data suggested that a fluence-rate effect was responsible for the apparent discrepancy, and shortly thereafter it became apparent that this rate effect was applicable to the evaluation of LWR vessel supports. As a result, the Nuclear Regulatory Commission (NRC) requested that the Oak Ridge National Laboratory (ORNL) evaluate the impact of the apparent embrittlement rate effect on the integrity of light-water-reactor (LWR) vessel supports. The purpose of the study was to provide an indication of whether the integrity of reactor vessel supports is likely to be challenged by radiation-induced embrittlement. The scope of the evaluation included correlation of the HFIR data for application to the evaluation of LWR vessel supports; a survey and cursory evaluation of all US LWR vessel support designs, selection of two plants for specific-plant evaluation, and a specific-plant evaluation of both plants to determine critical flaw sizes for their vessel supports. 19 refs., 8 figs., 2 tabs

Calibration of NRSF2 Instrument at HFIR

International Nuclear Information System (INIS)

Tang, Fei; Hubbard, Camden R.

2006-01-01

the sample table, 2θ 0 offset, and response of the position sensitive detector; (2) Counting statistics - if the peak profile count is too low, then the peak position derived from fitting a profile and background will have larger error. Therefore, adequate counting statistics and well-defined peaks are always good for precise peak position determination; and (3) Sample - Large grain size materials make it difficult to get enough diffracting grains, contributing to the different profile. With a low number the peak becomes 'spot' and results in inaccuracy in peak position. Texture in the sample can change the effective elastic constants and also affect the peak intensity. Phase and composition inhomogeneity can make it difficult to determine an accurate stress-free d 0 for strain calculation. A partially buried gauge volume due to proximity to the sample surface or buried interface can also shift the peak position. The calibration method presented in this report will address the first two categories of difficulties listed above. The FWHM can be minimized for each sample d-spacing by adjusting the horizontal bending of the monochromator crystal. For the monochromator, the optimum FWHM lies between 70 and 110 degree. This range is selected in order to maintain an approximately equiaxed gauge volume and avoid significant increases in peak breadth for the detectors above and below the horizontal plane. To adequately calibrate the position sensitive detectors, 2θ 0 , and wavelength, a set of high purity reference powders were selected. Since the selected reference powders have define grain size is, the measurement errors from sample grain size and texture can be excluded, although there may still be micro-strain in the powders, which can broaden the reference peak. In this report, the calibration procedure for the NRSF2 instrument will be presented and calibration results for five monochromator settings from HFIR cycle 403 will be presented. The monochromator settings

Solar photocatalytic removal of Cu(II), Ni(II), Zn(II) and Pb(II): Speciation modeling of metal-citric acid complexes

International Nuclear Information System (INIS)

Kabra, Kavita; Chaudhary, Rubina; Sawhney, R.L.

2008-01-01

The present study is targeted on solar photocatalytic removal of metal ions from wastewater. Photoreductive deposition and dark adsorption of metal ions Cu(II), Ni(II), Pb(II) and Zn(II), using solar energy irradiated TiO 2 , has been investigated. Citric acid has been used as a hole scavenger. Modeling of metal species has been performed and speciation is used as a tool for discussing the photodeposition trends. Ninety-seven percent reductive deposition was obtained for copper. The deposition values of other metals were significantly low [nickel (36.4%), zinc (22.2%) and lead (41.4%)], indicating that the photocatalytic treatment process, using solar energy, was more suitable for wastewater containing Cu(II) ions. In absence of citric acid, the decreasing order deposition was Cu(II) > Ni(II) > Pb(II) > Zn(II), which proves the theoretical thermodynamic predictions about the metals

Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

Science.gov (United States)

Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

2017-08-01

Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Chitosan encapsulation of essential oil "cocktails" with well-defined binary Zn(II)-Schiff base species targeting antibacterial medicinal nanotechnology.

Science.gov (United States)

Halevas, Eleftherios; Nday, Christiane M; Chatzigeorgiou, Evanthia; Varsamis, Vasileios; Eleftheriadou, Despoina; Jackson, Graham E; Litsardakis, Georgios; Lazari, Diamanto; Ypsilantis, Konstantinos; Salifoglou, Athanasios

2017-11-01

The advent of biodegradable nanomaterials with enhanced antibacterial activity stands as a challenge to the global research community. In an attempt to pursue the development of novel antibacterial medicinal nanotechnology, we herein a) synthesized ionic-gelated chitosan nanoparticles, b) compared and evaluated the antibacterial activity of essential oils extracted from nine different herbs (Greek origin) and their combinations with a well-defined antibacterial Zn(II)-Schiff base compound, and c) encapsulated the most effective hybrid combination of Zn(II)-essential oils inside the chitosan matrix, thereby targeting well-formulated nanoparticles of distinct biological impact. The empty and loaded chitosan nanoparticles were physicochemically characterized by FT-IR, Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), with the entrapment and drug release studies being conducted through UV-Visible and atomic absorption techniques. The antimicrobial properties of the novel hybrid materials were demonstrated against Gram positive (S. aureus, B. subtilis, and B. cereus) and Gram negative (E. coli and X. campestris) bacteria using modified agar diffusion methods. The collective physicochemical profile of the hybrid Zn(II)-essential oil cocktails, formulated so as to achieve optimal activity when loaded to chitosan nanoparticles, signifies the importance of design in the development of efficient nanomedicinal pharmaceuticals a) based on both natural products and biogenic metal ionic cofactors, and b) targeting bacterial infections and drug resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a swelling equation for 20%-CW 316 in a fusion device

International Nuclear Information System (INIS)

1980-01-01

The difficulties involved in the development of swelling correlations for AISI 316 in fusion environments are discussed. A set of void and bubble-swelling correlations has been developed which incorporates the limited available data from EBR-II and HFIR irradiations. It appears that at high fluences helium may play a minor role in the determination of total swelling over a considerable temperature range

Preliminary Multiphysics Analyses of HFIR LEU Fuel Conversion using COMSOL

Energy Technology Data Exchange (ETDEWEB)

Freels, James D [ORNL; Bodey, Isaac T [ORNL; Arimilli, Rao V [ORNL; Curtis, Franklin G [ORNL; Ekici, Kivanc [ORNL; Jain, Prashant K [ORNL

2011-06-01

4 of this report. The HFIR LEU conversion project has also obtained the services of Dr. Prashant K. Jain of the Reactor & Nuclear Systems Division (RNSD) of ORNL. Prashant has quickly adapted to the COMSOL tools and has been focusing on thermal-structure interaction (TSI) issues and development of alternative 3D model approaches that could yield faster-running solutions. Prashant is the primary contributor to Section 5 of the report. And finally, while incorporating findings from all members of the COMSOL team (i.e., the team) and contributing as the senior COMSOL leader and advocate, Dr. James D. Freels has focused on the 3D model development, cluster deployment, and has contributed primarily to Section 3 and overall integration of this report. The team has migrated to the current release of COMSOL at version 4.1 for all the work described in this report, except where stated otherwise. Just as in the performance of the research, each of the respective sections has been originally authored by the respective authors. Therefore, the reader will observe a contrast in writing style throughout this document.

Microstructural evolution of austenitic stainless steels irradiated to 17 dpa in spectrally tailored experiment of the ORR and HFIR at 400{degrees}C

Energy Technology Data Exchange (ETDEWEB)

Wakai, E.; Hashimoto, N.; Gibson, L.T. [Oak Ridge National Lab., TN (United States)] [and others

1997-08-01

The microstructural evolution of austenitic JPCA aged and solution annealed JPCA, 316R, C, K, and HP steels irradiated at 400{degrees}C in spectrally tailored experiments of the ORR and HFIR has been investigated. The helium generation rates were about 12-16 appm He/dpa on the average up to 17.3 dpa. The number densities and average diameters of dislocation loops in the steels have ranges of 3.3 x 10{sup 21} m{sup -3} and 15.2-26.3 nm, respectively, except for HP steel for which they are 1.1 x 10{sup 23} m{sup -3} and 8.0 nm. Precipitates are formed in all steels except for HP steel, and the number densities and average diameters have ranges of 5.2 x 10{sup 20} - 7.7 x 10{sup 21} m{sup -3} and 3.4- 19.3 nm, respectively. In the 216R, C, and K steels, the precipitates are also formed at grain boundaries, and the mean sizes of these are about 110, 50, and 50 nm, respectively. The number densities of cavities are about 1 x 10{sup 22} m{sup -3} in all the steels. The swelling is low in the steels which form the precipitates.

Revised ANL-reported tensile data for unirradiated and irradiated (FFTF, HFIR) V-Ti and V-Cr-Ti alloys

International Nuclear Information System (INIS)

Billone, M.C.

1998-01-01

The tensile data for all unirradiated and irradiated vanadium alloys samples tested at Argonne National Laboratory (ANL) have been critically reviewed and, when necessary, revised. The review and revision are based on reanalyzing the original load-displacement strip chart recordings by a methodology consistent with current ASTM standards. For unirradiated alloys (162 samples), the revised values differ from the previous values as follows: -11±19 MPa (-4±6%) for yield strength (YS), -3±15 MPa (-1±3%) for ultimate tensile strength (UTS), -5±2% strain for uniform elongation (UE), and -4±2% strain for total elongation (TE). Of these changes, the decrease in -1±6 MPa (0±1%) for UTS, -5±2% for UE, and -4±2% for TE. Of these changes, the decrease in UE values for alloys irradiated and tested at 400--435 C is the most significant. This decrease results from the proper subtraction of nongauge-length deformation from measured crosshead deformation. In previous analysis of the tensile curves, the nongauge-length deformation was not correctly determined and subtracted from the crosshead displacement. The previously reported and revised tensile values for unirradiated alloys (20--700 C) are tabulated in Appendix A. The revised tensile values for the FFTF-irradiated (400--600 C) and HFIR-irradiated (400 C) alloys are tabulated in Appendix B, along with the neutron damage and helium levels. Appendix C compares the revised values to the previously reported values for irradiated alloys. Appendix D contains previous and revised values for the tensile properties of unirradiated V-5Cr-5Ti (BL-63) alloy exposed to oxygen

Methylation of WNT target genes AXIN2 and DKK1 as robust biomarkers for recurrence prediction in stage II colon cancer

NARCIS (Netherlands)

Kandimalla, R.; Linnekamp, J. F.; van Hooff, S.; Castells, A.; Llor, X.; Andreu, M.; Jover, R.; Goel, A.; Medema, J. P.

2017-01-01

Stage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2

Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.

Science.gov (United States)

Minus, Matthew B; Liu, Wei; Vohidov, Farrukh; Kasembeli, Moses M; Long, Xin; Krueger, Michael J; Stevens, Alexandra; Kolosov, Mikhail I; Tweardy, David J; Sison, Edward Allan R; Redell, Michele S; Ball, Zachary T

2015-10-26

Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Transuranium processing plant semiannual report of production, status, and plans for period ending December 31, 1977

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1978-08-01

Transuranium elements were obtained from 13 irradiated HFIR targets. One batch of high-purity 248 Cm (approximately 75 mg) was separated from 252 Cf. Eighteen shipments were made from TRU during the period. Seven HFIR targets, each containing 8 to 9 g of curium, were fabricated. A new scrubber system was installed in the dissolver off-gas (DOG) stream to remove the bulk of the 131 I and to reduce the amount sorbed in the Hopcalite--charcoal system. During TRU target Campaign 53, the DOG stream was scrubbed with hyperazeotropic nitric acid (the IODOX process). Both the equipment and the process performed satisfactorily. Three neutron sources were fabricated during this report period, bringing the total fabricated to date to 100. Six sources were returned to TRU and are available for reassignment. Special projects included the production of several grams of ultrahigh-purity 243 Am and the development of a method for purification of the ZnBr 2 solution from a shielding window. The values currently being used for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated

Receptor-targeted metalloradiopharmaceuticals. Final technical report

International Nuclear Information System (INIS)

Green, Mark A.

2000-01-01

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

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

Science.gov (United States)

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

2010-05-28

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

TargetSpy: a supervised machine learning approach for microRNA target prediction

Directory of Open Access Journals (Sweden)

Langenberger David

2010-05-01

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

The DOS 1 neutron dosimetry experiment at the HB-4-A key 7 surveillance site on the HFIR pressure vessel

International Nuclear Information System (INIS)

Farrell, K.; Kam, F.B.; Baldwin, C.A.

1994-01-01

A comprehensive neutron dosimetry experiment was made at one of the prime surveillance sites at the High Flux Isotope Reactor (HFIR) pressure vessel to aid radiation embrittlement studies of the vessel and to benchmark neutron transport calculations. The thermal neutron flux at the key 7, position 5 site was found, from measurements of radioactivation of four cobalt wires and four silver wires, to be 2.4 x 10 12 n·m -2 ·s -1 . The thermal flux derived from two helium accumulation monitors was 2.3 x 10 12 n·m -2 · -1 . The thermal flux estimated by neutron transport calculations was 3.7 x 10 12 n·m -2 s -1 . The fast flux, >1 MeV, determined from two nickel activation wires, was 1.5 x 10 12 n·m -2 ·s -1 , in keeping with values obtained earlier from stainless steel surveillance monitors and with a computed value of 1.2 x 10 13 n·m -2 · -1 . The fast fluxes given by two reaction-product-type monitors, neptunium-237 and beryllium, were 2.6 x 10 13 n·m -2 ·s -1 and 2.2 x 10 13 n·m -2 s -1 , respectively. Follow-up experiments indicate that these latter high values of fast flux are reproducible but are false; they are due to the creation of greater levels of reaction products by photonuclear events induced by an exceptionally high ratio of gamma flux to fast neutron flux at the vessel

RTNS-II: present status

International Nuclear Information System (INIS)

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

1980-10-01

The present status of the RTNS-II facility is described and typical operating parameters are given. A brief discussion is given of the methods used in production of the TiT 2 targets as well as their performance and tritium handling at RTNS-II. The various types of non-interactive beam diagnostics presently in use at the neutron sources are outlined. The on-line computer system which provides a time history of an irradiation and records target performance is described. Examples are listed of several representative experimental programs which have been carried out thus far at RTNS-II. These include both active and passive experiments. Finally, several of the major improvements to the facility made since the beginning of the experimental program are given

High Flux Isotope Reactor system RELAP5 input model

International Nuclear Information System (INIS)

Morris, D.G.; Wendel, M.W.

1993-01-01

A thermal-hydraulic computational model of the High Flux Isotope Reactor (HFIR) has been developed using the RELAP5 program. The purpose of the model is to provide a state-of-the art thermal-hydraulic simulation tool for analyzing selected hypothetical accident scenarios for a revised HFIR Safety Analysis Report (SAR). The model includes (1) a detailed representation of the reactor core and other vessel components, (2) three heat exchanger/pump cells, (3) pressurizing pumps and letdown valves, and (4) secondary coolant system (with less detail than the primary system). Data from HFIR operation, component tests, tests in facility mockups and the HFIR, HFIR specific experiments, and other pertinent experiments performed independent of HFIR were used to construct the model and validate it to the extent permitted by the data. The detailed version of the model has been used to simulate loss-of-coolant accidents (LOCAs), while the abbreviated version has been developed for the operational transients that allow use of a less detailed nodalization. Analysis of station blackout with core long-term decay heat removal via natural convection has been performed using the core and vessel portions of the detailed model

Low Temperature Irradiation Embrittlement of Reactor Pressure Vessel Steels

Energy Technology Data Exchange (ETDEWEB)

Wang, Jy-An John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2015-08-01

The embrittlement trend curve development project for HFIR reactor pressure vessel (RPV) steels was carried out with three major tasks. Which are (1) data collection to match that used in HFIR steel embrittlement trend published in 1994 Journal Nuclear Material by Remec et. al, (2) new embrittlement data of A212B steel that are not included in earlier HFIR RPV trend curve, and (3) the adjustment of nil-ductility-transition temperature (NDTT) shift data with the consideration of the irradiation temperature effect. An updated HFIR RPV steel embrittlement trend curve was developed, as described below. NDTT( C) = 23.85 log(x) + 203.3 log (x) + 434.7, with 2- uncertainty of 34.6 C, where parameter x is referred to total dpa. The developed update HFIR RPV embrittlement trend curve has higher embrittlement rate compared to that of the trend curve developed in 1994.

Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

Science.gov (United States)

Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

2017-01-01

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

Novel GABA receptor pesticide targets.

Science.gov (United States)

Casida, John E; Durkin, Kathleen A

2015-06-01

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

Targeting radioimmunotherapy of hepatocellular carcinoma with iodine (131I) metuximab injection: Clinical Phase I/II trials

International Nuclear Information System (INIS)

Chen Zhinan; Mi Li; Xu Jing

2006-01-01

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine ( 131 I) metuximab injection (Licartin), a novel 131 I-labeled HAb18G/CD147-specific monoclonal antibody F(ab') 2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56-63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p 131 I) metuximab injection is safe and active for HCC patients

Fission-fusion correlations for swelling and microstructure in stainless steels: effect of the helium-to-displacement-per-atom ratio

International Nuclear Information System (INIS)

Odette, G.R.; Maziaz, P.J.; Spitznagel, J.A.

1981-01-01

The initial irradiated structural materials data base for fusion applications will be developed in fission reactors. Hence, this data may need to be adjusted using physically-based procedures to represent behavior in fusion environments, viz. - fission-fusion correlations. Such correlation should reflect a sound mechanistic understanding, and be verified in facilities which most closely simulate fusion conditions. In this paper we review the effects of only one of a number of potentially significant damage variables, the helium to displacement per atom ratio, on microstructural evolution in austenitic stainless steels. Dual-ion and helium preinjection data are analyzed to provide mechanistic guidance; these results appear to be qualitatively consistent with a more detailed comparison made between fast (EBR-II) and mixed (HFIR) spectrum neutron data for a single heat of 20% cold-worked 316 stainless steel. These two fission environments bound fusion (He/dpa ratios. A model calibrated to the fission reactor data is used to extrapolate to fusion conditions. Both the theory and broad empirical observation suggest that helium to dpa ratios have both a qualitative and quantitative influence on microstructural evolution; and that the very high and low ratios found in HFIR and EBR-II may not result in behavior which brackets intermediate fusion conditions

Lessons learned form high-flux isotope reactor restart efforts

International Nuclear Information System (INIS)

Dahl, T.L.

1989-01-01

When the high-flux isotope reactor's (HFIR's) pressure vessel irradiation surveillance specimens were examined in December 1986, unexpected embrittlement was found. The resulting investigation disclosed widespread deficiencies in quality assurance and management practices. On March 24, 1987, the US Department of Energy (DOE) mandated a shutdown of all five Oak Ridge National Laboratory (ORNL) research reactors. Since the beginning of 1987, 18 different formal review groups have evaluated the management and operations of the HFIR. The root cause of the identified deficiencies in the HFIR program was defined as a lack of rigor in management practices and complacency built on twenty years of trouble-free operation. A number of lessons can be learned from the HFIR experience. Particular insight can be gained by comparing the HFIR organization prior to the shutdown with the organization that exists today. Key elements in such a comparison include staffing, funding, discipline, and formality in operations, maintenance, and management

Targeting mitochondria by Zn(II)N-alkylpyridylporphyrins: the impact of compound sub-mitochondrial partition on cell respiration and overall photodynamic efficacy.

Science.gov (United States)

Odeh, Ahmad M; Craik, James D; Ezzeddine, Rima; Tovmasyan, Artak; Batinic-Haberle, Ines; Benov, Ludmil T

2014-01-01

Mitochondria play a key role in aerobic ATP production and redox control. They harness crucial metabolic pathways and control cell death mechanisms, properties that make these organelles essential for survival of most eukaryotic cells. Cancer cells have altered cell death pathways and typically show a shift towards anaerobic glycolysis for energy production, factors which point to mitochondria as potential culprits in cancer development. Targeting mitochondria is an attractive approach to tumor control, but design of pharmaceutical agents based on rational approaches is still not well established. The aim of this study was to investigate which structural features of specially designed Zn(II)N-alkylpyridylporphyrins would direct them to mitochondria and to particular mitochondrial targets. Since Zn(II)N-alkylpyridylporphyrins can act as highly efficient photosensitizers, their localization can be confirmed by photodamage to particular mitochondrial components. Using cultured LS174T adenocarcinoma cells, we found that subcellular distribution of Zn-porphyrins is directed by the nature of the substituents attached to the meso pyridyl nitrogens at the porphyrin ring. Increasing the length of the aliphatic chain from one carbon (methyl) to six carbons (hexyl) increased mitochondrial uptake of the compounds. Such modifications also affected sub-mitochondrial distribution of the Zn-porphyrins. The amphiphilic hexyl derivative (ZnTnHex-2-PyP) localized in the vicinity of cytochrome c oxidase complex, causing its inactivation during illumination. Photoinactivation of critical cellular targets explains the superior efficiency of the hexyl derivative in causing mitochondrial photodamage, and suppressing cellular respiration and survival. Design of potent photosensitizers and redox-active scavengers of free radicals should take into consideration not only selective organelle uptake and localization, but also selective targeting of critical macromolecular structures.

Transuranium Processing Plant semiannual report of production, status, and plans for period ending December 31, 1975

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1976-10-01

Between July 1, 1975, and December 31, 1975, maintenance was conducted at TRU for a period of three months, 295 g of curium oxide (enough for approximately 26 HFIR targets) were prepared, 100 mg of high-purity 248 Cm, were separated from 252 Cf that had been purified during earlier periods, 11 HFIR targets were fabricated, and 28 product shipments were made. No changes were made in the chemical processing flowsheets normally used at TRU during this report period. However, three equipment racks were replaced (with two new racks) during this time. In Cubicle 6, the equipment replaced was that used to decontaminate the transplutonium elements from rare earth fission products and to separate curium from the heavier elements by means of the LiCl-based anion-exchange process. In Cubicle 5, the equipment used to separate the transcurium elements by high-pressure ion exchange and to purify berkelium by batch solvent extraction was replaced. Two neutron sources were fabricated, bringing the total fabricated to 79. One source that had been used in a completed project was returned to the TRU inventory and is available for reissue. Three sources, for which no further use was foreseen, were processed to isolate and recover the ingrown 248 Cm and the residual 252 Cf. Eight pellets, each containing 100 μg of high-purity 248 Cm were prepared for irradiation in HFIR to study the production of 250 Cm. The values currently being used for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated

Comparing the Suitability of Autodock, Gold and Glide for the Docking and Predicting the Possible Targets of Ru(II-Based Complexes as Anticancer Agents

Directory of Open Access Journals (Sweden)

Adebayo A. Adeniyi

2013-03-01

Full Text Available In cancer chemotherapy, metal-based complexes have been recognized as the most promising means of inhibiting cancer growth due to the successful application of cis-platin and its derivatives above many of the existing organic anticancer agents. The limitations in their rational design can be traced to the complexity of the mechanism of their operations, lack of proper knowledge of their targets and lack of force fields in docking packages to appropriately define the metal centre of the organometallic complexes. In this paper, some of the promising anticancer complexes of Ru(II such as the rapta-based complexes formulated as [Ru(η6-p-cymeneL2(pta] and those with unusual ligands are considered. CatB and kinases which have been experimentally confirmed as possible targets of the complexes are also predicted by the three methods as one of the most targeted receptors while TopII and HDAC7 are predicted by two and one of the methods as best targets. The interesting features of the binding of the complexes show that some of the complexes preferentially target specific macromolecules than the others, which is an indication of their specificity and possibility of their therapeutic combination without severe side effects that may come from competition for the same target. Also, introduction of unusual ligands is found to significantly improve the activities of most of the complexes studied. Strong correlations are observed for the predicted binding sites and the orientation of the complexes within the binding site by the three methods of docking. However there are disparities in the ranking of the complexes by the three method of docking, especially that of Glide.

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

Science.gov (United States)

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

2018-02-01

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

Dissolution Flowsheet for High Flux Isotope Reactor Fuel

Energy Technology Data Exchange (ETDEWEB)

Daniel, W. E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Rudisill, T. S. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); O' Rourke, P. E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Karay, N. S [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-09-27

As part of the Spent Nuclear Fuel (SNF) processing campaign, H-Canyon is planning to begin dissolving High Flux Isotope Reactor (HFIR) fuel in late FY17 or early FY18. Each HFIR fuel core contains inner and outer fuel elements which were fabricated from uranium oxide (U₃O₈) dispersed in a continuous Al phase using traditional powder metallurgy techniques. Fuels fabricated in this manner, like other SNF’s processed in H-Canyon, dissolve by the same general mechanisms with similar gas generation rates and the production of H₂. The HFIR fuel cores will be dissolved and the recovered U will be down-blended into low-enriched U. HFIR fuel was previously processed in H-Canyon using a unique insert in both the 6.1D and 6.4D dissolvers. Multiple cores will be charged to the same dissolver solution maximizing the concentration of dissolved Al. The objective of this study was to identify flowsheet conditions through literature review and laboratory experimentation to safely and efficiently dissolve the HFIR fuel in H-Canyon. Laboratory-scale experiments were performed to evaluate the dissolution of HFIR fuel using both Al 1100 and Al 6061 T6 alloy coupons. The Al 1100 alloy was considered a representative surrogate which provided an upper bound on the generation of flammable (i.e., H₂) gas during the dissolution process. The dissolution of the Al 6061 T6 alloy proceeded at a slower rate than the Al 1100 alloy, and was used to verify that the target Al concentration in solution could be achieved for the selected Hg concentration. Mass spectrometry and Raman spectroscopy were used to provide continuous monitoring of the concentration of H₂ and other permanent gases in the dissolution offgas, allowing the development of H₂ generation rate profiles. The H₂ generation rates were subsequently used to evaluate if a full HFIR core could be dissolved in an H-Canyon dissolver without exceeding 60% of the

Single photon emission computed tomographic studies (SPECT) of hepatic arterial perfusion scintigraphy (HAPS) in patients with colorectal liver metastases: improved tumour targetting by microspheres with angiotensin II.

Science.gov (United States)

Goldberg, J A; Bradnam, M S; Kerr, D J; McKillop, J H; Bessent, R G; McArdle, C S; Willmott, N; George, W D

1987-12-01

As intra-arterial chemotherapy for liver metastases of colorectal origin becomes accepted, methods of further improving drug delivery to the tumour have been devised. Degradable microspheres have been shown to reduce regional blood flow by transient arteriolar capillary block, thereby improving uptake of a co-administered drug, when injected into the hepatic artery. In our study of five patients, we combined hepatic arterial perfusion scintigraphy (HAPS) and SPECT to assess the localization of approximately 1 X 10(5) labelled microspheres of human serum albumin (99Tcm MSA) in tumour. In addition, in three patients, we assessed the effect of an intra-arterial infusion of the vasoactive agent angiotension II during HAPS. Results were interpreted by comparing transaxial slices with corresponding slices of a tin colloid liver-spleen scan. Two of five patients showed good localization of 99Tcm MSA in tumour without an angiotensin II infusion. Of the three patients receiving angiotensin II, all showed good tumour targetting with the vasoconstrictor compared with only one of these three before its use. Thus, hepatic arterial infusion of angiotensin II greatly improves microsphere localization in tumour in some patients with colorectal liver metastases. This technique may be useful in the assessment of tumour targetting before and during locoregional therapy.

Some neutronic calculations for KENS-II

International Nuclear Information System (INIS)

Kiyanagi, Y.; Arai, M.; Watanabe, N.

1989-01-01

Proton energies of the intense spallation neutron sources currently in operation or designed are in the range Ep ≤ 1.1 GeV. Optimization studies of the target station have so far been performed for these proton energies. The KENS-II project has been included in the Japanese Hadron Facility Project where the proton accelerator, a so-called First Ring is shared with Meson Arena for nuclear physics and μSR experiments. The possible highest proton energy for this accelerator is 2 GeV, which is the highest among the world's spallation neutron sources. The authors, therefore, performed some neutronic calculations with 2 GeV protons in order to have a good knowledge of the neutronic characteristics and the optimal parameters of the target station for KENS-II. The fraction of slow neutron intensity versus the proton energy becomes 0.8 for 2 GeV compared to that for 0.8 GeV, and this is higher than 0.67 calculated for source neutrons. The uranium target has a higher neutron productivity, 1.5 times that of the tungsten target, even for 2 GeV protons. The target radius and the moderator axial position have definite optimal values for 2 GeV protons in spite of the broader distribution of the source neutrons in target, and these are essentially similar to the results for 0.8 GeV protons. The broad distribution with a little increase in the maximum luminosity of source neutrons for 2 GeV protons could make it easier to remove the heat load from the target than the case for the same beam-power with lower energy and higher proton current. Therefore, they could conclude that the 2 GeV protons for KENS-II do not have significant difficulties in producing slow neutrons, and that non-fissile material has higher advantages to produce neutrons for higher proton energies. Detailed neutronic calculations are now under way to design a neutron target station for KENS-II. 5 refs., 10 figs

Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class II Collagenase for Successful Human Islet Isolation.

Science.gov (United States)

Balamurugan, Appakalai N; Green, Michael L; Breite, Andrew G; Loganathan, Gopalakrishnan; Wilhelm, Joshua J; Tweed, Benjamin; Vargova, Lenka; Lockridge, Amber; Kuriti, Manikya; Hughes, Michael G; Williams, Stuart K; Hering, Bernhard J; Dwulet, Francis E; McCarthy, Robert C

2016-01-01

Isolation following a good manufacturing practice-compliant, human islet product requires development of a robust islet isolation procedure where effective limits of key reagents are known. The enzymes used for islet isolation are critical but little is known about the doses of class I and class II collagenase required for successful islet isolation. We used a factorial approach to evaluate the effect of high and low target activities of recombinant class I (rC1) and class II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme formulations with divergent C1:C2 collagenase mass ratios were assessed, each supplemented with the same dose of neutral protease. Both split pancreas and whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g pancreas was compared with historical enzymes (n = 42). Varying the Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and consequently the C1:C2 mass ratio, had no significant effect on tissue digestion. Digestions using higher doses of Wunsch and CDA resulted in comparable islet yields to those obtained with 60% and 50% of those activities, respectively. Factorial analysis revealed no significant main effect of Wunsch activity or CDA for any parameter measured. Aggregate results from 4 different collagenase formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the body/tail of the pancreas (n = 12) when compared with those from the same segment using a standard natural collagenase/protease mixture (n = 6). Additionally, islet yields greater than 5000 islet equivalents/g pancreas were also obtained in whole human pancreas. A broader C1:C2 ratio can be used for human islet isolation than has been used in the past. Recombinant collagenase is an effective replacement for the natural enzyme and we have determined that high islet yield can be obtained even with low doses of rC1:rC2, which is beneficial for the survival of islets.

Type B investigation of the iridium contamination event at the High Flux Isotope Reactor on September 7, 1993

International Nuclear Information System (INIS)

1994-03-01

On the title date, at ORNL, area radiation alarms sounded during a routine transfer of a shielding cask (containing 60 Ci 192 Ir) from the HFIR pool side to a transport truck. Small amounts of Ir were released from the cask onto the reactor bay floor. The floor was cleaned, and the cask was shipped to a hot cell at Building 3047 on Oct. 3, 1993. The event was caused by rupture of one of the Ir target rods after it was loaded into the cask for normal transport operations; the rupture was the result of steam generation in the target rod soon after it was placed in the cask (water had entered the target rod through a tiny defect in a weld while it was in the reactor under pressure). While the target rods were in the reactor and reactor pool, there was sufficient cooling to prevent steam generation; when the target rod was loaded into the dry transport cask, the temperature increased enough to result in boiling of the trapped water and produced high enough pressure to result in rupture. The escaping steam ejected some of the Ir pellets. The event was reported as Occurrence Report Number ORO--MMES-X10HFIR-1993-0030, dated Sept. 8, 1993. Analysis indicated that the following conditions were probable causes: less than adequate welding procedures, practices, or techniques, material controls, or inspection methods, or combination thereof, could have led to weld defects, affecting the integrity of target rod IR-75; less than adequate secondary containment in the cask allowed Ir pellets to escape

Mitochondria are the primary target in the induction of apoptosis by chiral ruthenium(II) polypyridyl complexes in cancer cells.

Science.gov (United States)

Wang, Jin-Quan; Zhang, Ping-Yu; Qian, Chen; Hou, Xiao-Juan; Ji, Liang-Nian; Chao, Hui

2014-03-01

A series of novel chiral ruthenium(II) polypyridyl complexes (Δ-Ru1, Λ-Ru1, Δ-Ru2, Λ-Ru2, Δ-Ru3, Λ-Ru3) were synthesized and evaluated to determine their antiproliferative activities. Colocalization, inductively coupled plasma mass spectrometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay studies showed that these ruthenium(II) complexes accumulated preferentially in the mitochondria and exhibited cytotoxicity against various cancer cells in vitro. The complex Δ-Ru1 is of particular interest because it was found to have half-maximal inhibitory concentrations comparable to those of cisplatin and better activity than cisplatin against a cisplatin-resistant cell line, A549-CP/R. Δ-Ru1 induced alterations in the mitochondrial membrane potential and triggered intrinsic mitochondria-mediated apoptosis in HeLa cells, which involved the regulation of Bcl-2 family members and the activation of caspases. Taken together, these data suggest that Δ-Ru1 may be a novel mitochondria-targeting anticancer agent.

Structured cylindrical targets

International Nuclear Information System (INIS)

Arnold, R.

1986-01-01

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

Structured cylindrical targets

International Nuclear Information System (INIS)

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

1986-01-01

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

Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo

Science.gov (United States)

Thanh LE, Thao N.; Gill, Anthony J.; Bulanadi, Jerikho C.; Patel, Mili; Waddington, Lynne J.; Rye, Kerry-Anne; Moghaddam, Minoo J.; Smith, Ross C.

2016-01-01

Background Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo. Methods Cryo transmission electron microscopy (TEM) examined ApoA-II’s influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type-1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively. Results ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold. Conclusion Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities. PMID:27002321

Technical specifications for the Oak Ridge Critical Experiments Facility

International Nuclear Information System (INIS)

Stinnett, R.M.

1986-01-01

These Technical Specifications for the Oak Ridge Critical Experiments Facility (CEF) delineate limiting conditions of operation for the facility. The CEF is used primarily for testing the High Flux Isotope Reactor (HFIR) fuel assemblies. Specifically, the Criticality Testing Unit, Liquid (CTUL), located in the CEF, is used for the HFIR fuel assembly test. The test is performed to satisfy the surveillance requirements of the HFIR Technical Specifications. The test is used to determine the water-submerged shutdown margin for each fuel assembly. 11 refs

Low-Enriched Uranium Fuel Design with Two-Dimensional Grading for the High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Ilas, Germina [ORNL; Primm, Trent [ORNL

2011-05-01

An engineering design study of the conversion of the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) to low-enriched uranium (LEU) fuel is ongoing at Oak Ridge National Laboratory. The computational models developed during fiscal year 2010 to search for an LEU fuel design that would meet the requirements for the conversion and the results obtained with these models are documented and discussed in this report. Estimates of relevant reactor performance parameters for the LEU fuel core are presented and compared with the corresponding data for the currently operating HEU fuel core. The results obtained indicate that the LEU fuel design would maintain the current performance of the HFIR with respect to the neutron flux to the central target region, reflector, and beam tube locations under the assumption that the operating power for the reactor fueled with LEU can be increased from the current value of 85 MW to 100 MW.

The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.

Science.gov (United States)

Fox, Melanie J; Gao, Hongyu; Smith-Kinnaman, Whitney R; Liu, Yunlong; Mosley, Amber L

2015-01-01

The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs) and unstable transcripts. Known targets of the nuclear exosome include short (Polymerase II (RNAPII) localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote transcription termination in addition to 3' end RNA processing and/or degradation at specific targets.

Mitochondrially targeted vitamin E succinate efficiently kills breast tumour-initiating cells in a complex II-dependent manner

International Nuclear Information System (INIS)

Yan, Bing; Stantic, Marina; Zobalova, Renata; Bezawork-Geleta, Ayenachew; Stapelberg, Michael; Stursa, Jan; Prokopova, Katerina; Dong, Lanfeng; Neuzil, Jiri

2015-01-01

Accumulating evidence suggests that breast cancer involves tumour-initiating cells (TICs), which play a role in initiation, metastasis, therapeutic resistance and relapse of the disease. Emerging drugs that target TICs are becoming a focus of contemporary research. Mitocans, a group of compounds that induce apoptosis of cancer cells by destabilising their mitochondria, are showing their potential in killing TICs. In this project, we investigated mitochondrially targeted vitamin E succinate (MitoVES), a recently developed mitocan, for its in vitro and in vivo efficacy against TICs. The mammosphere model of breast TICs was established by culturing murine NeuTL and human MCF7 cells as spheres. This model was verified by stem cell marker expression, tumour initiation capacity and chemotherapeutic resistance. Cell susceptibility to MitoVES was assessed and the cell death pathway investigated. In vivo efficacy was studied by grafting NeuTL TICs to form syngeneic tumours. Mammospheres derived from NeuTL and MCF7 breast cancer cells were enriched in the level of stemness, and the sphere cells featured altered mitochondrial function. Sphere cultures were resistant to several established anti-cancer agents while they were susceptible to MitoVES. Killing of mammospheres was suppressed when the mitochondrial complex II, the molecular target of MitoVES, was knocked down. Importantly, MitoVES inhibited progression of syngeneic HER2 high tumours derived from breast TICs by inducing apoptosis in tumour cells. These results demonstrate that using mammospheres, a plausible model for studying TICs, drugs that target mitochondria efficiently kill breast tumour-initiating cells. The online version of this article (doi:10.1186/s12885-015-1394-7) contains supplementary material, which is available to authorized users

International cooperation at RTNS-II

International Nuclear Information System (INIS)

Logan, C.M.

1984-02-01

The Rotating Target Neutron Source-II (RTNS-II) facility at LLNL is a unique materials-test facility. It provides the most intense source of 14-MeV neutrons in the world. Dedicated operation in support of the fusion-materials-research community began in early 1979. Three years later, the Japanese Ministry of Education, Science, and Culture (Monbusho) and the US Department of Energy agreed to jointly support the RTNS-II operation and to share in the use of the facility

Impact of radiation embrittlement on integrity of pressure vessel supports for two PWR plants

Energy Technology Data Exchange (ETDEWEB)

Cheverton, R.D.; Pennell, W.E.; Robinson, G.C.; Nanstad, R.K.

1989-01-01

Recent data from the HFIR vessel surveillance program indicate a substantial radiation embrittlement rate effect at low irradiation temperatures (/approximately/120/degree/F) for A212-B, A350-LF3, A105-II, and corresponding welds. PWR vessel supports are fabricated of similar materials and are subjected to the same low temperatures and fast neutron fluxes (10/sup 8/ to 10/sup 9/ neutrons/cm/sup 2//center dot/s, E > 1.0 MeV) as those in the HFIR vessel. Thus, the embrittlement rate of these structures may be greater than previously anticipated. A study sponsored by the NRC is under way at ORNL to determine the impact of the rate effect on PWR vessel-support life expectancy. The scope includes the interpretation and application of the HFIR data, a survey of all light-water-reactor vessel support designs, and a structural and fracture-mechanics analysis of the supports for two specific PWR plants of particular interest with regard to a potential for support failure as a result of propagation of flaws. Calculations performed thus far indicate best-estimate critical flaw sizes, corresponding to 32 EFPY, of /approximately/0.2 in. for one plant and /approximately/0.4 in. for the other. These flaw sizes are small enough to be of concern. However, it appears that low-cycle fatigue is not a viable mechanism for creation of flaws of this size, and thus, presumably, such flaws would have to exist at the time of fabrication. 59 refs., 128 figs., 49 tabs.

MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

Directory of Open Access Journals (Sweden)

A. V. Zaborovskiy

2017-01-01

Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor.

Science.gov (United States)

Hombach, Andreas; Köhler, Heike; Rappl, Gunter; Abken, Hinrich

2006-10-15

Immune elimination of tumor cells requires the close cooperation between CD8+ CTL and CD4+ Th cells. We circumvent MHC class II-restriction of CD4+ T cells by expression of a recombinant immunoreceptor with an Ab-derived binding domain redirecting specificity. Human CD4+ T cells grafted with an immunoreceptor specific for carcinoembryonic Ag (CEA) are activated to proliferate and secrete cytokines upon binding to CEA+ target cells. Notably, redirected CD4+ T cells mediate cytolysis of CEA+ tumor cells with high efficiencies. Lysis by redirected CD4+ T cells is independent of death receptor signaling via TNF-alpha or Fas, but mediated by perforin and granzyme because cytolysis is inhibited by blocking the release of cytotoxic granules, but not by blocking of Fas ligand or TNF-alpha. CD4+ T cells redirected by Ab-derived immunoreceptors in a MHC class II-independent fashion substantially extend the power of an adoptive, Ag-triggered immunotherapy not only by CD4+ T cell help, but also by cytolytic effector functions. Because cytolysis is predominantly mediated via granzyme/perforin, target cells that are resistant to death receptor signaling become sensitive to a cytolytic attack by engineered CD4+ T cells.

Studies on the separation of {sup 89}Sr(II) from irradiated yttria target using 4, 4{sup '}(5{sup '}) di-tert-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) by solvent extraction technique

Energy Technology Data Exchange (ETDEWEB)

Saha, Debasish; Vithya, Jayagopal; Kumar, Ramalingam; Venkata Subramani, Canchipuram Ramamoorthy; Vasudeva Rao, Polur Ranga [Indira Gandhi Centre for Atomic Research (IGCAR), Kalpakkam (India). Chemistry Group

2016-07-01

The radioisotope {sup 89}Sr as {sup 89}SrCl{sub 2} is medically useful for bone pain palliation and is produced in fast reactors using the {sup 89}Y(n, p){sup 89}Sr reaction. A procedure for isolation of the radionuclide {sup 89}Sr by chemical processing of the irradiated Y{sub 2}O{sub 3} target has been standardised and trial runs have been carried out at the Fast Breeder Test Reactor (FBTR), Kalpakkam. The chemical processing of the irradiated Y{sub 2}O{sub 3} target involves (i) the removal of target Y(III) by TBP extraction and (ii) further purification of the separated {sup 89}Sr fraction by cationic exchange chromatography. However a selective isolation of {sup 89}Sr by the Sr-specific crown ether makes the above chemical processing faster and relatively simple. This work presents a study on the selective removal of Sr from the irradiated target dissolver solution using the Sr-specific crown ether 4,4{sup '}(5{sup '}) di-tert-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) in octanol medium. The separation behaviour of the other impurities such as Ce(IV), Y(III), Tb(III), Eu(III), Zn(II), Mn(II) and Rb(I) present along with Sr(II) in the irradiated sample was also investigated. The method of separation by using the crown ether DtBuCH18C6 is proved to be a potential tool for the purification of {sup 89}Sr(II) source produced from yttria target in fast reactors.

DARHT-II Downstream Transport Beamline

International Nuclear Information System (INIS)

Westenskow, G A; Bertolini, L R; Duffy, P T; Paul, A C

2001-01-01

This paper describes the mechanical design of the downstream beam transport line for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT II) Facility. The DARHT-II project is a collaboration between LANL, LBNL and LLNL. DARHT II is a 18.4-MeV, 2000-Amperes, 2-(micro)sec linear induction accelerator designed to generate short bursts of x-rays for the purpose of radiographing dense objects. The downstream beam transport line is approximately 22-meter long region extending from the end of the accelerator to the bremsstrahlung target. Within this proposed transport line there are 12 conventional solenoid, quadrupole and dipole magnets; as well as several specialty magnets, which transport and focus the beam to the target and to the beam dumps. There are two high power beam dumps, which are designed to absorb 80-kJ per pulse during accelerator start-up and operation. Aspects of the mechanical design of these elements are presented

Differential detection of type II methanotrophic bacteria in acidic peatlands using newly developed 16S rRNA-targeted fluorescent oligonucleotide probes.

Science.gov (United States)

Dedysh, Svetlana N; Dunfield, Peter F; Derakshani, Manigee; Stubner, Stephan; Heyer, Jürgen; Liesack, Werner

2003-04-01

Abstract Based on an extensive 16S rRNA sequence database for type II methanotrophic bacteria, a set of 16S rRNA-targeted oligonucleotide probes was developed for differential detection of specific phylogenetic groups of these bacteria by fluorescence in situ hybridisation (FISH). This set of oligonucleotides included a genus-specific probe for Methylocystis (Mcyst-1432) and three species-specific probes for Methylosinus sporium (Msins-647), Methylosinus trichosporium (Msint-1268) and the recently described acidophilic methanotroph Methylocapsa acidiphila (Mcaps-1032). These novel probes were applied to further characterise the type II methanotroph community that was detected in an acidic Sphagnum peat from West Siberia in a previous study (Dedysh et al. (2001) Appl. Environ. Microbiol. 67, 4850-4857). The largest detectable population of indigenous methanotrophs simultaneously hybridised with a group-specific probe targeting all currently known Methylosinus/Methylocystis spp. (M-450), with a genus-specific probe for Methylocystis spp. (Mcyst-1432), and with an additional probe (Mcyst-1261) that had been designed to target a defined phylogenetic subgroup of Methylocystis spp. The same subgroup of Methylocystis was also detected in acidic peat sampled from Sphagnum-dominated wetland in northern Germany. The population size of this peat-inhabiting Methylocystis subgroup was 2.0+/-0.1x10(6) cells g(-1) (wet weight) of peat from Siberia and 5.5+/-0.5x10(6) cells g(-1) of peat from northern Germany. This represented 60 and 95%, respectively, of the total number of methanotroph cells detected by FISH in these two wetland sites. Other major methanotroph populations were M. acidiphila and Methylocella palustris. Type I methanotrophs accounted for not more than 1% of total methanotroph cells. Neither M. trichosporium nor M. sporium were detected in acidic Sphagnum peat.

Photoreactions of ruthenium(II) and osmium(II) complexes with deoxyribonucleic acid (DNA).

Science.gov (United States)

Moucheron, C; Kirsch-De Mesmaeker, A; Kelly, J M

1997-09-01

The design of Ru(II) and Os(II) complexes which are photoreactive with deoxyribonucleic acid (DNA) represents one of the main targets for the development of novel molecular tools for the study of DNA and, in the future, for the production of new, metal-based, anti-tumor drugs. In this review, we explain how it is possible to make a complex photoreactive with nucleobases and nucleic acids. According to the photophysical behaviour of the Ru(II) compounds, two types of photochemistry are expected: (1) photosubstitution of a ligand by a nucleobase and another monodentate ligand, which takes place from the triplet, metal-centred (3MC) state; this state is populated thermally from the lowest lying triplet metal to ligand charge transfer (3MLCT) state; (2) photoreaction from the 3MLCT state, corresponding to photoredox processes with DNA bases. The two photoreactivities are in competition. By modulating appropriately the redox properties of the 3MLCT state, an electron transfer process from the base to the excited complex takes place, and is directly correlated with DNA cleavage or the formation of an adduct of the complex to DNA. In this adduct, guanine is linked by N2 to the alpha-position of a non-chelating nitrogen of the polyazaaromatic ligand without destruction of the complex. Different strategies are explained which increase the affinity of the complexes for DNA and direct the complex photoreactivity to sites of special DNA topology or targeted sequences of bases. Moreover, the replacement of the Ru(II) ion by the Os(II) ion in the photoreactive complexes leads to an increased specificity of photoreaction. Indeed, only one type of photoreactivity (from the 3MLCT state) is present for the Os(II) complexes because the 3MC state is too high in energy to be populated at room temperature.

Advanced Multiphysics Thermal-Hydraulics Models for the High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Jain, Prashant K [ORNL; Freels, James D [ORNL

2015-01-01

Engineering design studies to determine the feasibility of converting the High Flux Isotope Reactor (HFIR) from using highly enriched uranium (HEU) to low-enriched uranium (LEU) fuel are ongoing at Oak Ridge National Laboratory (ORNL). This work is part of an effort sponsored by the US Department of Energy (DOE) Reactor Conversion Program. HFIR is a very high flux pressurized light-water-cooled and moderated flux-trap type research reactor. HFIR s current missions are to support neutron scattering experiments, isotope production, and materials irradiation, including neutron activation analysis. Advanced three-dimensional multiphysics models of HFIR fuel were developed in COMSOL software for safety basis (worst case) operating conditions. Several types of physics including multilayer heat conduction, conjugate heat transfer, turbulent flows (RANS model) and structural mechanics were combined and solved for HFIR s inner and outer fuel elements. Alternate design features of the new LEU fuel were evaluated using these multiphysics models. This work led to a new, preliminary reference LEU design that combines a permanent absorber in the lower unfueled region of all of the fuel plates, a burnable absorber in the inner element side plates, and a relocated and reshaped (but still radially contoured) fuel zone. Preliminary results of estimated thermal safety margins are presented. Fuel design studies and model enhancement continue.

Transuranium Processing Plant semiannual report of production, status, and plans for period ending December 31, 1976

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1977-10-01

During the period July 1, 1976, through December 31, 1976, transuranium elements were obtained from 11 irradiated HFIR targets; products recovered are 0.3 g 243 Am, 16.6 g 244 Cm, 23 g 249 Bk, 211 g 252 Cf, 1.15 mg 253 Es, and 0.4 pg 247 Fm. Two batches of high-purity 248 Cm were purified chemically for shipment, and another batch containing about 62 mg of 248 Cm was separated from 252 Cf. Thirty shipments were made from TRU during the period; recipients and the amounts of nuclides are listed in tabular form. Nine HFIR targets, each containing 8 to 9 g of curium, were fabricated. The sequence of chemical processing steps used to purify the californium product was changed; this change yielded a shorter recovery time for high-purity 253 Es, which enabled a 50% increase in the amount obtained. Eight neutron sources were fabricated during this report period, bringing the total fabricated to date to 92. Three sources that had previously been returned to TRU were reassigned; two others are also available for reassignment. The values currently being used for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated in the Appendix

Awareness, Preference, Utilization, and Messaging Research for the Spallation Neutron Source and High Flux Isotope Reactor

International Nuclear Information System (INIS)

Bryant, Rebecca; Kszos, Lynn A.

2011-01-01

Oak Ridge National Laboratory (ORNL) offers the scientific community unique access to two types of world-class neutron sources at a single site - the Spallation Neutron Source (SNS) and the High Flux Isotope Reactor (HFIR). The 85-MW HFIR provides one of the highest steady-state neutron fluxes of any research reactor in the world, and the SNS is one of the world's most intense pulsed neutron beams. Management of these two resources is the responsibility of the Neutron Sciences Directorate (NScD). NScD commissioned this survey research to develop baseline information regarding awareness of and perceptions about neutron science. Specific areas of investigative interest include the following: (1) awareness levels among those in the scientific community about the two neutron sources that ORNL offers; (2) the level of understanding members of various scientific communities have regarding benefits that neutron scattering techniques offer; and (3) any perceptions that negatively impact utilization of the facilities. NScD leadership identified users of two light sources in North America - the Advanced Photon Source (APS) at Argonne National Laboratory and the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory - as key publics. Given the type of research in which these scientists engage, they would quite likely benefit from including the neutron techniques available at SNS and HFIR among their scientific investigation tools. The objective of the survey of users of APS, NSLS, SNS, and HFIR was to explore awareness of and perceptions regarding SNS and HFIR among those in selected scientific communities. Perceptions of SNS and FHIR will provide a foundation for strategic communication plan development and for developing key educational messages. The survey was conducted in two phases. The first phase included qualitative methods of (1) key stakeholder meetings; (2) online interviews with user administrators of APS and NSLS; and (3) one-on-one interviews

Awareness, Preference, Utilization, and Messaging Research for the Spallation Neutron Source and High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Bryant, Rebecca [Bryant Research, LLC; Kszos, Lynn A [ORNL

2011-03-01

Oak Ridge National Laboratory (ORNL) offers the scientific community unique access to two types of world-class neutron sources at a single site - the Spallation Neutron Source (SNS) and the High Flux Isotope Reactor (HFIR). The 85-MW HFIR provides one of the highest steady-state neutron fluxes of any research reactor in the world, and the SNS is one of the world's most intense pulsed neutron beams. Management of these two resources is the responsibility of the Neutron Sciences Directorate (NScD). NScD commissioned this survey research to develop baseline information regarding awareness of and perceptions about neutron science. Specific areas of investigative interest include the following: (1) awareness levels among those in the scientific community about the two neutron sources that ORNL offers; (2) the level of understanding members of various scientific communities have regarding benefits that neutron scattering techniques offer; and (3) any perceptions that negatively impact utilization of the facilities. NScD leadership identified users of two light sources in North America - the Advanced Photon Source (APS) at Argonne National Laboratory and the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory - as key publics. Given the type of research in which these scientists engage, they would quite likely benefit from including the neutron techniques available at SNS and HFIR among their scientific investigation tools. The objective of the survey of users of APS, NSLS, SNS, and HFIR was to explore awareness of and perceptions regarding SNS and HFIR among those in selected scientific communities. Perceptions of SNS and FHIR will provide a foundation for strategic communication plan development and for developing key educational messages. The survey was conducted in two phases. The first phase included qualitative methods of (1) key stakeholder meetings; (2) online interviews with user administrators of APS and NSLS; and (3) one

Computational design of binding proteins to EGFR domain II.

Directory of Open Access Journals (Sweden)

Yoon Sup Choi

Full Text Available We developed a process to produce novel interactions between two previously unrelated proteins. This process selects protein scaffolds and designs protein interfaces that bind to a surface patch of interest on a target protein. Scaffolds with shapes complementary to the target surface patch were screened using an exhaustive computational search of the human proteome and optimized by directed evolution using phage display. This method was applied to successfully design scaffolds that bind to epidermal growth factor receptor (EGFR domain II, the interface of EGFR dimerization, with high reactivity toward the target surface patch of EGFR domain II. One potential application of these tailor-made protein interactions is the development of therapeutic agents against specific protein targets.

Dynamic response of the high flux isotope reactor structure caused by nearby heavy load drop

International Nuclear Information System (INIS)

Chang, Shih-Jung.

1995-01-01

A heavy load of 50,000 lb is assumed to drop from 10 ft above the bottom of the High Flux Isotope Reactor (HFIR) pool at the loading station. The consequences of the dynamic impact to the bottom slab of the pool and to the nearby HFIR reactor vessel are analyzed by applying the ABAQUS computer code The results show that both the BM vessel structure and its supporting legs are subjected to elastic disturbances only and, therefore, will not be damaged. The bottom slab of the pool, however, will be damaged to about half of the slab thickness. The velocity response spectrum at the concrete floor next to the HFIR vessel as a result of the vibration caused by the impact is obtained. It is concluded, that the damage caused by heavy load drop at the loading station is controlled by the slab damage and the nearby HFIR vessel and the supporting legs will not be damaged

Zodiac II: Debris Disk Science from a Balloon

Science.gov (United States)

Bryden, Geoffrey; Traub, Wesley; Roberts, Lewis C., Jr.; Bruno, Robin; Unwin, Stephen; Backovsky, Stan; Brugarolas, Paul; Chakrabarti, Supriya; Chen, Pin; Hillenbrand, Lynne;

Target station design for a 1 MW pulsed spallation neutron source

International Nuclear Information System (INIS)

Russell, G.J.; Baker, G.D.; Brewton, R.J.

1993-01-01

Target stations are vital components of the 1 MW, next generation spallation neutron source proposed for LANSCE. By and large, target stations design determines the overall performance of the facility. Many traditional concepts will probably have to be rethought, and many new concepts will have to be put forward to meet the 1 MW challenge. This article gives a brief overview of the proposed neutron spallation source from the target station viewpoint, as well as the general philosophy adopted for the design of the LANSCE-II target stations. Some of the saliant concepts and features envisioned for LANSCE-II are briefly described

MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

Energy Technology Data Exchange (ETDEWEB)

Hua, Wei [Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Yang, An-Gang [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Zhang, Rui, E-mail: ruizhang@fmmu.edu.cn [State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 710032 Xi' an (China); Fan, Jing, E-mail: jingfan@fmmu.edu.cn [Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Bian, Ka, E-mail: kakamax85@hotmail.com [State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, 710032 Xi' an (China); Department of Otolaryngology, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

2015-08-07

The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells.

MicroRNA-139 suppresses proliferation in luminal type breast cancer cells by targeting Topoisomerase II alpha

International Nuclear Information System (INIS)

Hua, Wei; Sa, Ke-Di; Zhang, Xiang; Jia, Lin-Tao; Zhao, Jing; Yang, An-Gang; Zhang, Rui; Fan, Jing; Bian, Ka

2015-01-01

The classification of molecular subtypes of breast cancer improves the prognostic accuracy and therapeutic benefits in clinic. However, because of the complexity of breast cancer, more biomarkers and functional molecules need to be explored. Here, analyzing the data in a huge cohort of breast cancer patients, we found that Topoisomerase II alpha (TOP2a), an important target of chemotherapy is a biomarker for prognosis in luminal type breast cancer patients, but not in basal like or HER2 positive breast cancer patients. We identified that miR-139, a previous reported anti-metastatic microRNA targets 3’-untranslated region (3′UTR) of TOP2a mRNA. Further more, we revealed that the forced expression of miR-139 reduces the TOP2a expression at both mRNA and protein levels. And our functional experiments showed that the ectopic expression of miR-139 remarkably inhibits proliferation in luminal type breast cancer cells, while exogenous TOP2a expression could rescue inhibition of cell proliferation mediated by miR-139. Collectively, our present study demonstrates the miR-139-TOP2a regulatory axis is important for proliferation in luminal type breast cancer cells. This functional link may help us to further understand the specificity of subtypes of breast cancer and optimize the strategy of cancer treatment. - Highlights: • High levels of TOP2a expression are closely associated with poor prognosis in luminal type breast cancer patients. • TOP2a is a novel target of miR-139. • Overexpression of miR-139 inhibits proliferation in luminal type breast cancer cells. • TOP2a is essential for miR-139-induced growth arrest in luminal type breast cancer cells

The adsorption of Tl(I), Au(III), Cu(II) and the separation of 199Tl from alpha bombardment of gold target with PDB-18C6

International Nuclear Information System (INIS)

Zhou Dehai; Zhou Jimeng

1989-01-01

The adsorptive behavior of polymer of methyl aldehyde of dibenzo-18-crown-6 (PDB-18C6) in hydrochloric acid medium is studied and it is shown that the adsorption of T1(I), Au(III), and Cu(II) depends on the particle size of the crown ether resins, hydrochloric acid concentration and amount of the crown ether resins used. The difference in the adsorption behavior of different particle sizes of crown ether resins may be used for separating Tl(I), Au(III), and Cu(II) ions. The best eluant of Tl(I) and Au(III) is 0.4 mol/l perchloric acid and 2-ethoxy-ethanol. The recovery for Tl(I) is 82-98.8%. The gold target is bombarded in a 1.2 m cyclotron with 25-27 MeV α-particle with a cumulative beam intensities of 27μA·h, and 199 Tl is separated from the gold target with PDB-18C6. γ-spectrometry has shown that the Tl obtained is 199 Tl of high purity containing only about 0.50% 200 Tl

An integrated Drosophila model system reveals unique properties for F14512, a novel polyamine-containing anticancer drug that targets topoisomerase II.

Directory of Open Access Journals (Sweden)

Sonia Chelouah

Full Text Available F14512 is a novel anti-tumor molecule based on an epipodophyllotoxin core coupled to a cancer-cell vectoring spermine moiety. This polyamine linkage is assumed to ensure the preferential uptake of F14512 by cancer cells, strong interaction with DNA and potent inhibition of topoisomerase II (Topo II. The antitumor activity of F14512 in human tumor models is significantly higher than that of other epipodophyllotoxins in spite of a lower induction of DNA breakage. Hence, the demonstrated superiority of F14512 over other Topo II poisons might not result solely from its preferential uptake by cancer cells, but could also be due to unique effects on Topo II interactions with DNA. To further dissect the mechanism of action of F14512, we used Drosophila melanogaster mutants whose genetic background leads to an easily scored phenotype that is sensitive to changes in Topo II activity and/or localization. F14512 has antiproliferative properties in Drosophila cells and stabilizes ternary Topo II/DNA cleavable complexes at unique sites located in moderately repeated sequences, suggesting that the drug specifically targets a select and limited subset of genomic sequences. Feeding F14512 to developing mutant Drosophila larvae led to the recovery of flies expressing a striking phenotype, "Eye wide shut," where one eye is replaced by a first thoracic segment. Other recovered F14512-induced gain- and loss-of-function phenotypes similarly correspond to precise genetic dysfunctions. These complex in vivo results obtained in a whole developing organism can be reconciled with known genetic anomalies and constitute a remarkable instance of specific alterations of gene expression by ingestion of a drug. "Drosophila-based anticancer pharmacology" hence reveals unique properties for F14512, demonstrating the usefulness of an assay system that provides a low-cost, rapid and effective complement to mammalian models and permits the elucidation of fundamental mechanisms of

Irradiation of Wrought FeCrAl Tubes in the High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Linton, Kory D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Petrie, Christian M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-09-01

The Advanced Fuels Campaign within the Nuclear Technology Research and Development program of the Department of Energy Office of Nuclear Energy is seeking to improve the accident tolerance of light water reactors. Alumina-forming ferritic alloys (e.g., FeCrAl) are one of the leading candidate materials for fuel cladding to replace traditional zirconium alloys because of the superior oxidation resistance of FeCrAl. However, there are still some unresolved questions regarding irradiation effects on the microstructure and mechanical properties of FeCrAl at end-of-life dose levels. In particular, there are concerns related to irradiation-induced embrittlement of FeCrAl alloys due to secondary phase formation. To address this issue, Oak Ridge National Laboratory has developed a new experimental design to irradiate shortened cladding tube specimens with representative 17×17 array pressurized water reactor diameter and thickness in the High Flux Isotope Reactor (HFIR) under relevant temperatures (300–350°C). Post-irradiation examination will include studies of dimensional change, microstructural changes, and mechanical performance. This report briefly summarizes the capsule design concept and the irradiation test matrix for six rabbit capsules. Each rabbit contains two FeCrAl alloy tube specimens. The specimens include Generation I and Generation II FeCrAl alloys with varying processing conditions, Cr concentrations, and minor alloying elements. The rabbits were successfully assembled, welded, evaluated, and delivered to the HFIR along with a complete quality assurance fabrication package. Pictures of the rabbit assembly process and detailed dimensional inspection of select specimens are included in this report. The rabbits were inserted into HFIR starting in cycle 472 (May 2017).

Progress in light ion beam fusion research on PBFA II

International Nuclear Information System (INIS)

Cook, D.L.; Allshouse, G.O.; Bailey, J.

1986-01-01

PBFA II is a 100 TW pulsed power accelerator constructed at Sandia National Laboratories for use in the Light Ion Fusion Program. The objective of PBFA II is to accelerate and focus upon an inertial confinement fusion (ICF) target a lithium beam with sufficient energy, power, and power density to perform ignition scaling experiments. The technologies used in PBFA II include: (1) primary energy storage and compression with 6 MV, low-inductance Marx generators, (2) pulse forming in water-insulated, water-dielectric lines with self-closing water switches, (4) voltage addition in vacuum using self-magnetically-insulated biconic transmission lines, (5) inductive energy storage and pulse compression using a fast-opening plasma erosion switch, (6) beam formation using a magnetically-insulated ion diode, and (7) space-charge and current-neutralized beam propagation to the target in a gas-filled cell. The first multimodule shot was on December 11, 1985. The plans for PBFA II include development and demonstration of the pulse-shaping techniques which are necessary for high-gain target compressions. Following a modification of the accelerator which will probably include an ''extraction'' ion diode, a 4- to 5-meter plasma channel for beam bunching during propagation, and a target chamber located beneath the accelerator, temporally-shaped ion beam pulses will be available for pulse-shaped target experiments. (author)

Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

Directory of Open Access Journals (Sweden)

Rachael E Hawtin

2010-04-01

Full Text Available Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research.Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more potent.As a first-in-class anticancer

A novel approach to aluminium determination in biological tissues using a pair of pneumatic tube irradiation facilities

Energy Technology Data Exchange (ETDEWEB)

Dalsem, D.J. van [Kentucky Univ., Lexington, KY (United States). Dept. of Chemistry; [Oak Ridge National Lab., TN (United States); Robinson, L [Oak Ridge National Lab., TN (United States); Ehmann, W D [Kentucky Univ., Lexington, KY (United States). Dept. of Chemistry

1995-04-01

A novel method for the determination of trace aluminium (Al) in the presence of high levels of phosphorus (P) has been developed at the Oak Ridge National Laboratory High Flux Isotope Reactor (HFIR). Using successive irradiations in HFIR`s two pneumatic tube facilities (PT-1, PT-2) to measure the difference between the two apparent Al concentrations, the true Al concentration in the sample can be calculated without the need for an independent determination of P. Results are presented for brain samples from various regions, some that are strongly affected by Alzheimer`s disease (AD) and for NIST SMR 1577b, Bovine Liver. (author) 21 refs.; 3 tabs.

LipidII : Just Another Brick in the Wall?

NARCIS (Netherlands)

Scheffers, Dirk-Jan; Tol, Menno B

2015-01-01

Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s)

Effects of helium content of microstructural development in Type 316 stainless steel under neutron irradiation

International Nuclear Information System (INIS)

Maziasz, P.J.

1985-11-01

This work investigated the sensitivity of microstructural evolution, particularly precipitate development, to increased helium content during thermal aging and during neutron irradiation. Helium (110 at. ppM) was cold preinjected into solution annealed (SA) DO-heat type 316 stainess steel (316) via cyclotron irradiation. These specimens were then exposed side by side with uninjected samples. Continuous helium generation was increased considerably relative to EBR-II irradiation by irradiation in HFIR. Data were obtained from quantitative analytical electron microscopy (AEM) in thin foils and on extraction replicas. 480 refs., 86 figs., 19 tabs

Effects of helium content of microstructural development in Type 316 stainless steel under neutron irradiation

Energy Technology Data Exchange (ETDEWEB)

Maziasz, P.J.

1985-11-01

This work investigated the sensitivity of microstructural evolution, particularly precipitate development, to increased helium content during thermal aging and during neutron irradiation. Helium (110 at. ppM) was cold preinjected into solution annealed (SA) DO-heat type 316 stainess steel (316) via cyclotron irradiation. These specimens were then exposed side by side with uninjected samples. Continuous helium generation was increased considerably relative to EBR-II irradiation by irradiation in HFIR. Data were obtained from quantitative analytical electron microscopy (AEM) in thin foils and on extraction replicas. 480 refs., 86 figs., 19 tabs.

A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

Science.gov (United States)

Zhang, Zhenqin; Zhu, Zhenzhu; Luo, Cheng; Zhu, Chengcheng; Zhang, Changli; Guo, Zijian; Wang, Xiaoyong

2018-03-19

Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH 3 ) 2 Cl]NO 3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

Development of a general learning algorithm with applications in nuclear reactor systems

Energy Technology Data Exchange (ETDEWEB)

Brittain, C.R.; Otaduy, P.J.; Perez, R.B.

1989-12-01

The objective of this study was development of a generalized learning algorithm that can learn to predict a particular feature of a process by observation of a set of representative input examples. The algorithm uses pattern matching and statistical analysis techniques to find a functional relationship between descriptive attributes of the input examples and the feature to be predicted. The algorithm was tested by applying it to a set of examples consisting of performance descriptions for 277 fuel cycles of Oak Ridge National Laboratory's High Flux Isotope Reactor (HFIR). The program learned to predict the critical rod position for the HFIR from core configuration data prior to reactor startup. The functional relationship bases its predictions on initial core reactivity, the number of certain targets placed in the center of the reactor, and the total exposure of the control plates. Twelve characteristic fuel cycle clusters were identified. Nine fuel cycles were diagnosed as having noisy data, and one could not be predicted by the functional relationship. 13 refs., 6 figs.

Development of a general learning algorithm with applications in nuclear reactor systems

International Nuclear Information System (INIS)

Brittain, C.R.; Otaduy, P.J.; Perez, R.B.

1989-12-01

The objective of this study was development of a generalized learning algorithm that can learn to predict a particular feature of a process by observation of a set of representative input examples. The algorithm uses pattern matching and statistical analysis techniques to find a functional relationship between descriptive attributes of the input examples and the feature to be predicted. The algorithm was tested by applying it to a set of examples consisting of performance descriptions for 277 fuel cycles of Oak Ridge National Laboratory's High Flux Isotope Reactor (HFIR). The program learned to predict the critical rod position for the HFIR from core configuration data prior to reactor startup. The functional relationship bases its predictions on initial core reactivity, the number of certain targets placed in the center of the reactor, and the total exposure of the control plates. Twelve characteristic fuel cycle clusters were identified. Nine fuel cycles were diagnosed as having noisy data, and one could not be predicted by the functional relationship. 13 refs., 6 figs

Advanced Fuel/Cladding Testing Capabilities in the ORNL High Flux Isotope Reactor

International Nuclear Information System (INIS)

Ott, Larry J.; Ellis, Ronald James; McDuffee, Joel Lee; Spellman, Donald J.; Bevard, Bruce Balkcom

2009-01-01

The ability to test advanced fuels and cladding materials under reactor operating conditions in the United States is limited. The Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR) and the newly expanded post-irradiation examination (PIE) capability at the ORNL Irradiated Fuels Examination Laboratory provide unique support for this type of advanced fuel/cladding development effort. The wide breadth of ORNL's fuels and materials research divisions provides all the necessary fuel development capabilities in one location. At ORNL, facilities are available from test fuel fabrication, to irradiation in HFIR under either thermal or fast reactor conditions, to a complete suite of PIEs, and to final product disposal. There are very few locations in the world where this full range of capabilities exists. New testing capabilities at HFIR have been developed that allow testing of advanced nuclear fuels and cladding materials under prototypic operating conditions (i.e., for both fast-spectrum conditions and light-water-reactor conditions). This paper will describe the HFIR testing capabilities, the new advanced fuel/cladding testing facilities, and the initial cooperative irradiation experiment that begins this year.

Low-Enriched Uranium Fuel Conversion Activities for the High Flux Isotope Reactor, Annual Report for FY 2011

Energy Technology Data Exchange (ETDEWEB)

Renfro, David G [ORNL; Cook, David Howard [ORNL; Freels, James D [ORNL; Griffin, Frederick P [ORNL; Ilas, Germina [ORNL; Sease, John D [ORNL; Chandler, David [ORNL

2012-03-01

This report describes progress made during FY11 in ORNL activities to support converting the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) fuel to low-enriched uranium (LEU) fuel. Conversion from HEU to LEU will require a change in fuel form from uranium oxide to a uranium-molybdenum (UMo) alloy. With both radial and axial contouring of the fuel foil and an increase in reactor power to 100 MW, calculations indicate that the HFIR can be operated with LEU fuel with no degradation in performance to users from the current levels achieved with HEU fuel. Studies are continuing to demonstrate that the fuel thermal safety margins can be preserved following conversion. Studies are also continuing to update other aspects of the reactor steady state operation and accident response for the effects of fuel conversion. Technical input has been provided to Oregon State University in support of their hydraulic testing program. The HFIR conversion schedule was revised and provided to the GTRI program. In addition to HFIR conversion activities, technical support was provided directly to the Fuel Fabrication Capability program manager.

Low-Enriched Uranium Fuel Conversion Activities for the High Flux Isotope Reactor, Annual Report for FY 2011

International Nuclear Information System (INIS)

Renfro, David G.; Cook, David Howard; Freels, James D.; Griffin, Frederick P.; Ilas, Germina; Sease, John D.; Chandler, David

2012-01-01

This report describes progress made during FY11 in ORNL activities to support converting the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) fuel to low-enriched uranium (LEU) fuel. Conversion from HEU to LEU will require a change in fuel form from uranium oxide to a uranium-molybdenum (UMo) alloy. With both radial and axial contouring of the fuel foil and an increase in reactor power to 100 MW, calculations indicate that the HFIR can be operated with LEU fuel with no degradation in performance to users from the current levels achieved with HEU fuel. Studies are continuing to demonstrate that the fuel thermal safety margins can be preserved following conversion. Studies are also continuing to update other aspects of the reactor steady state operation and accident response for the effects of fuel conversion. Technical input has been provided to Oregon State University in support of their hydraulic testing program. The HFIR conversion schedule was revised and provided to the GTRI program. In addition to HFIR conversion activities, technical support was provided directly to the Fuel Fabrication Capability program manager.

Proton and neutron polarized targets for nucleon-nucleon experiments at SATURNE II

International Nuclear Information System (INIS)

Ball, J.; Combet, M.; Sans, J.L.; Benda, B.; Chaumette, P.; Deregel, J.; Durand, G.; Dzyubak, A.P.; Gaudron, C.; Lehar, F.; Janout, Z.; Khachaturov, B.A.

1996-01-01

A SATURNE polarized target has been used for nucleon-nucleon elastic scattering and transmission experiments for 15 years. The polarized proton target is a 70 cm 3 cartridge loaded with Pentanol-2. For polarized neutron target, two cartridges loaded with 6 LiD and 6 LiH are set in the refrigerator and can be quickly inserted in the beam. First experiments using 6 Li products in quasielastic pp or pn analyzing power measurements are compared with the same observables measured in a free nucleon-nucleon scattering using polarized proton targets. Angular distribution as a function of a kinematically conjugate angle and coplanarity in nucleon-nucleon scattering is shown for different targets. (author)

TP Atlas: integration and dissemination of advances in Targeted Proteins Research Program (TPRP)-structural biology project phase II in Japan.

Science.gov (United States)

Iwayanagi, Takao; Miyamoto, Sei; Konno, Takeshi; Mizutani, Hisashi; Hirai, Tomohiro; Shigemoto, Yasumasa; Gojobori, Takashi; Sugawara, Hideaki

2012-09-01

The Targeted Proteins Research Program (TPRP) promoted by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan is the phase II of structural biology project (2007-2011) following the Protein 3000 Project (2002-2006) in Japan. While the phase I Protein 3000 Project put partial emphasis on the construction and maintenance of pipelines for structural analyses, the TPRP is dedicated to revealing the structures and functions of the targeted proteins that have great importance in both basic research and industrial applications. To pursue this objective, 35 Targeted Proteins (TP) Projects selected in the three areas of fundamental biology, medicine and pharmacology, and food and environment are tightly collaborated with 10 Advanced Technology (AT) Projects in the four fields of protein production, structural analyses, chemical library and screening, and information platform. Here, the outlines and achievements of the 35 TP Projects are summarized in the system named TP Atlas. Progress in the diversified areas is described in the modules of Graphical Summary, General Summary, Tabular Summary, and Structure Gallery of the TP Atlas in the standard and unified format. Advances in TP Projects owing to novel technologies stemmed from AT Projects and collaborative research among TP Projects are illustrated as a hallmark of the Program. The TP Atlas can be accessed at http://net.genes.nig.ac.jp/tpatlas/index_e.html .

The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

International Nuclear Information System (INIS)

Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

2006-01-01

The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17α-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERα-selective agonist), diarylpropionitrile (DPN, an ERβ-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERα-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERβ-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

Science.gov (United States)

Katayama, Seiichi; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

2006-12-15

The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17alpha-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ERalpha-selective agonist), diarylpropionitrile (DPN, an ERbeta-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ERalpha-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ERbeta-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

Production of multicharged radioactive ion beams for spiral: studies and realization of the first target-ion source system

International Nuclear Information System (INIS)

Maunoury, L.

1998-01-01

In the framework of the SPIRAL project, which concerns the production and the acceleration of a multicharged radioactive ions beam, the following part has been studied: production and ionization of the radioactive ions beam. A first target-source (nanogan II), devoted exclusively to the production of multicharged radioactive ions gas type beams, has been studied and tested. The diffusion efficiency has been deduced from the diffusion equations (Fick laws). This efficiency is governed by the following parameters: the temperature, the grains size of the target, the Arrhenius parameters and the radioactive period. Another study concerning the production targets is presented. It deals with the temperature distribution allowing an utilization of more than one month at a temperature of 2400 K. Another development (SPIRAL II) is devoted to the production of high neutron content radioactive atoms created by the uranium fission, from fast neutrons. The neutrons beam is produced by the ''stripping break-up'' of a deutons beam in a converter. (A.L.B.)

Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage.

Science.gov (United States)

Barker, Catherine R; McNamara, Anne V; Rackstraw, Stephen A; Nelson, David E; White, Mike R; Watson, Alastair J M; Jenkins, John R

2006-01-01

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.

Benefits and Sustainability of a Learning Collaborative for Implementation of Treat to Target in Rheumatoid Arthritis: Results of the TRACTION Trial Phase II.

Science.gov (United States)

Solomon, Daniel H; Lu, Bing; Yu, Zhi; Corrigan, Cassandra; Harrold, Leslie R; Smolen, Josef S; Fraenkel, Liana; Katz, Jeffrey N; Losina, Elena

2018-01-05

We conducted a two-phase randomized controlled trial of a Learning Collaborative (LC) to facilitate implementation of treat to target (TTT) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of TTT in Phase I. Herein, we report on a second 9 months (Phase II) where we examined maintenance of response in Phase I and predictors of greater improvement in TTT adherence. We recruited 11 rheumatology sites and randomized them to either receive the LC during Phase I or to a wait-list control group that received the LC intervention during Phase II. The outcome was change in TTT implementation score (0 to 100, 100 is best) from pre- to post-intervention. TTT implementation score is defined as a percent of components documented in visit notes. Analyses examined: 1) the extent that the Phase I intervention teams sustained improvement in TTT; and, 2) predictors of TTT improvement. The analysis included 636 RA patients. At baseline, mean TTT implementation score was 11% in Phase I intervention sites and 13% in Phase II sites. After the intervention, TTT implementation score improved to 57% in the Phase I intervention sites and to 58% in the Phase II sites. Intervention sites from Phase I sustained the improvement during the Phase II (52%). Predictors of greater TTT improvement included only having rheumatologist providers at the site, academic affiliation of the site, fewer providers per site, and the rheumatologist provider being a trainee. Improvement in TTT remained relatively stable over a post-intervention period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Mitochondrial complex II, a novel target for anti-cancer agents

Czech Academy of Sciences Publication Activity Database

Klučková, Katarína; Bezawork-Geleta, A.; Rohlena, Jakub; Dong, L.; Neužil, Jiří

2013-01-01

Roč. 1827, č. 5 (2013), s. 552-564 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GAP301/10/1937; GA ČR GAP301/12/1851 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrion * Complex II * Anti-cancer agent Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.829, year: 2013

48 CFR 16.403-2 - Fixed-price incentive (successive targets) contracts.

Science.gov (United States)

2010-10-01

... target cost plus the firm target profit as a guide. (ii) If negotiation of a firm fixed price is... pricing information is not sufficient to permit the negotiation of a realistic firm target cost and profit...; and (2) Cost or pricing information adequate for establishing a reasonable firm target cost is...

Angiotensin II up-regulates PAX2 oncogene expression and activity in prostate cancer via the angiotensin II type I receptor.

Science.gov (United States)

Bose, Sudeep K; Gibson, Willietta; Giri, Shailendra; Nath, Narender; Donald, Carlton D

2009-09-01

Paired homeobox 2 gene (PAX2) is a transcriptional regulator, aberrantly expressed in prostate cancer cells and its down-regulation promotes cell death in these cells. The molecular mechanisms of tumor progression by PAX2 over-expression are still unclear. However, it has been reported that angiotensin-II (A-II) induces cell growth in prostate cancer via A-II type 1 receptor (AT1R) and is mediated by the phosphorylation of mitogen activated protein kinase (MAPK) as well as signal transducer and activator of transcription 3 (STAT3). Here we have demonstrated that A-II up-regulates PAX2 expression in prostate epithelial cells and prostate cancer cell lines resulting in increased cell growth. Furthermore, AT1R receptor antagonist losartan was shown to inhibit A-II induced PAX2 expression in prostate cancer. Moreover, analysis using pharmacological inhibitors against MEK1/2, ERK1/2, JAK-II, and phospho-STAT3 demonstrated that AT1R-mediated stimulatory effect of A-II on PAX2 expression was regulated in part by the phosphorylation of ERK1/2, JAK II, and STAT3 pathways. In addition, we have showed that down-regulation of PAX2 by an AT1R antagonist as well as JAK-II and STAT3 inhibitors suppress prostate cancer cell growth. Collectively, these findings show for the first time that the renin-angiotensin system (RAS) may promote prostate tumorigenesis via up-regulation of PAX2 expression. Therefore, PAX2 may be a novel therapeutic target for the treatment of carcinomas such as prostate cancer via the down-regulation of its expression by targeting the AT1R signaling pathways.

Cholesterol target value attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: Results from the Dyslipidemia International Study II.

Science.gov (United States)

Gitt, Anselm K; Lautsch, Dominik; Ferrières, Jean; De Ferrari, Gaetano M; Vyas, Ami; Baxter, Carl A; Bash, Lori D; Ashton, Veronica; Horack, Martin; Almahmeed, Wael; Chiang, Fu-Tien; Poh, Kian Keong; Brudi, Philippe; Ambegaonkar, Baishali

2017-11-01

Low-density lipoprotein cholesterol (LDL-C) is a major contributor to cardiovascular disease. In the Dyslipidemia International Study II (DYSIS II), we determined LDL-C target value attainment, use of lipid-lowering therapy (LLT), and cardiovascular outcomes in patients with stable coronary heart disease (CHD) and those suffering from an acute coronary syndrome (ACS). DYSIS II included patients from 18 countries. Patients with either stable CHD or an ACS were enrolled if they were ≥18 years old and had a full lipid profile available. Data were collected at a physician visit (CHD cohort) or at hospital admission and 120 days later (ACS cohort). A total of 10,661 patients were enrolled, 6794 with stable CHD and 3867 with an ACS. Mean LDL-C levels were low at 88 mg/dl and 108 mg/dl for the CHD and ACS cohorts respectively, with only 29.4% and 18.9% displaying a level below 70 mg/dl. LLT was utilized by 93.8% of the CHD cohort, with a mean daily statin dosage of 25 ± 18 mg. The proportion of the ACS cohort treated with LLT rose from 65.2% at admission to 95.6% at follow-up. LLT-treated patients, who were female, obese, or current smokers, were less likely to achieve an LDL-C level of <70 mg/dl, while those with type 2 diabetes, chronic kidney disease, or those taking a higher statin dosage were more likely. Few of these very high-risk patients achieved the LDL-C target, indicating huge potential for improving cardiovascular outcome by use of more intensive LLT. Copyright © 2017. Published by Elsevier B.V.

CRISPRTarget: bioinformatic prediction and analysis of crRNA targets

NARCIS (Netherlands)

Biswas, A.; Gagnon, J.N.; Brouns, S.J.J.; Fineran, P.C.; Brown, C.M.

2013-01-01

The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are

The Gpn3 Q279* cancer-associated mutant inhibits Gpn1 nuclear export and is deficient in RNA polymerase II nuclear targeting.

Science.gov (United States)

Barbosa-Camacho, Angel A; Méndez-Hernández, Lucía E; Lara-Chacón, Bárbara; Peña-Gómez, Sonia G; Romero, Violeta; González-González, Rogelio; Guerra-Moreno, José A; Robledo-Rivera, Angélica Y; Sánchez-Olea, Roberto; Calera, Mónica R

2017-11-01

Gpn3 is required for RNA polymerase II (RNAPII) nuclear targeting. Here, we investigated the effect of a cancer-associated Q279* nonsense mutation in Gpn3 cellular function. Employing RNAi, we replaced endogenous Gpn3 by wt or Q279* RNAi-resistant Gpn3R in epithelial model cells. RNAPII nuclear accumulation and transcriptional activity were markedly decreased in cells expressing only Gpn3R Q279*. Wild-type Gpn3R localized to the cytoplasm but a fraction of Gpn3R Q279* entered the cell nucleus and inhibited Gpn1-EYFP nuclear export. This property and the transcriptional deficit in Gpn3R Q279*-expressing cells required a PDZ-binding motif generated by the Q279* mutation. We conclude that an acquired PDZ-binding motif in Gpn3 Q279* caused Gpn3 nuclear entry, and inhibited Gpn1 nuclear export and Gpn3-mediated RNAPII nuclear targeting. © 2017 Federation of European Biochemical Societies.

Treatment outcomes regarding the addition of targeted agents in the therapeutic portfolio for stage II-III rectal cancer undergoing neoadjuvant chemoradiation.

Science.gov (United States)

Liang, Jin-Tung; Chen, Tzu-Chun; Huang, John; Jeng, Yung-Ming; Cheng, Jason Chia-Hsien

2017-11-24

To evaluate the impact of targeted agents in stage II-III rectal cancer undergoing neoadjuvant concurrent chemoradiation therapy (CCRT). A retrospective study was performed in 124 consecutive patients with clinically T 3 N 0-2 M 0 -staged rectal cancer incorporating targeted agents in CCRT. Pathologic complete response was detected in 34.2% (n=26) of bevacizumab+FOLFOX-treated patients (n=76), which was significantly higher (p=0.019, post-hoc statistical power =35.87%) than that (n=10, 20.8%) of the cetuximab+FOLFOX-treated patients (n=48). Patients receiving cetuximab+FOLFOX therapy tended to develop severe liver toxicity (91.7%, n=44 versus 17.1%, n=13, panalysis within bevacizumab+FOLFOX-treated patients with either wild-type (n=36) or mutant (n=40) K-ras status indicated K-ras status did not significantly influence the treatment outcomes. The addition of bevacizumab instead of cetuximab to FOLFOX in the neoadjuvant settings for T 3 N 0-2 M 0 -staged rectal cancer could induce a promising rate of pathologic complete response and lesser hepatotoxicity.

42 CFR 457.310 - Targeted low-income child.

Science.gov (United States)

2010-10-01

... family income at or below 200 percent of the Federal poverty line for a family of the size involved; (ii... 42 Public Health 4 2010-10-01 2010-10-01 false Targeted low-income child. 457.310 Section 457.310... Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

Enhanced membrane pore formation through high-affinity targeted antimicrobial peptides.

Directory of Open Access Journals (Sweden)

Christopher J Arnusch

Full Text Available Many cationic antimicrobial peptides (AMPs target the unique lipid composition of the prokaryotic cell membrane. However, the micromolar activities common for these peptides are considered weak in comparison to nisin, which follows a targeted, pore-forming mode of action. Here we show that AMPs can be modified with a high-affinity targeting module, which enables membrane permeabilization at low concentration. Magainin 2 and a truncated peptide analog were conjugated to vancomycin using click chemistry, and could be directed towards specific membrane embedded receptors both in model membrane systems and whole cells. Compared with untargeted vesicles, a gain in permeabilization efficacy of two orders of magnitude was reached with large unilamellar vesicles that included lipid II, the target of vancomycin. The truncated vancomycin-peptide conjugate showed an increased activity against vancomycin resistant Enterococci, whereas the full-length conjugate was more active against a targeted eukaryotic cell model: lipid II containing erythrocytes. This study highlights that AMPs can be made more selective and more potent against biological membranes that contain structures that can be targeted.

SU-E-J-88: Margin Reduction of Level II/III Planning Target Volume for Image-Guided Simultaneous Integrated Boost Head-And-Neck Treatment

International Nuclear Information System (INIS)

Can, S; Neylon, J; Qi, S; Santhanam, A; Low, D

2014-01-01

Purpose: To investigate the feasibility of improved normal tissue sparing for head-and-neck (H'N) image-guided radiotherapy (IGRT) by employing tighter CTV-to-PTV margins for target level II/III though a GPU-based deformable image registration and dose accumulation framework. Methods: Ten H'N simultaneous integrated boost cases treated on TomoTherapy were retrospectively analyzed. Weekly kVCT scans in addition to daily MVCT scans were acquired for each patient. Reduced margin plans were generated with 0- mm margin for level II and III PTV (while 3-5 mm margin for PTV1) and compared with the standard margin plan using 3-5mm margin to all CTV1-3 (reference plan). An in-house developed GPU-based 3D image deformation tool was used to register and deform the weekly KVCTs with the planning CT and determine the delivered mean/minimum/maximum dose, dose volume histograms (DVHs), etc. Results: Compared with the reference plans, the averaged cord maximum, the right and left parotid doses reduced by 22.7 %, 16.5 %, and 9 % respectively in the reduced margin plans. The V95 for PTV2 and PTV3 were found within 2 and 5% between the reference and tighter margin plans. For the reduced margin plans, the averaged cumulative mean doses were consistent with the planned dose for PTV1, PTV2 and PTV3 within 1.5%, 1.7% and 1.4%. Similar dose variations of the delivered dose were seen for the reference and tighter margin plans. The delivered maximum and mean doses for the cord were 3.55 % and 2.37% higher than the planned doses; a 5 % higher cumulative mean dose for the parotids was also observed for the delivered dose than the planned doses in both plans. Conclusion: By imposing tighter CTV-to-PTV margins for level II and III targets for H'N irradiation, acceptable cumulative doses were achievable when coupled with weekly kVCT guidance while improving normal structure sparing

Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage

OpenAIRE

Barker, Catherine R.; McNamara, Anne V.; Rackstraw, Stephen A.; Nelson, David E.; White, Mike R.; Watson, Alastair J. M.; Jenkins, John R.

2006-01-01

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the inc...

The TRUPACT-II Matrix Depleton Program

International Nuclear Information System (INIS)

Connolly, M.J.; Djordjevic, S.M.; Loehr, C.A.; Smith, M.C.; Banjac, V.; Lyon, W.F.

1995-01-01

Contact-handled transuranic (CH-TRU) wastes will be shipped and disposed at the Waste Isolation Pilot Plant (WIPP) repository in the Transuranic Package Transporter-II (TRUPACT-II) shipping package. A primary transportation requirement for the TRUPACT-II is that the concentration of potentially flammable gases (i.e., hydrogen and methane) must not exceed 5 percent by volume in the package or the payload during a 60-day shipping period. Decomposition of waste materials by radiation, or radiolysis, is the predominant mechanism of gas generation during transport. The gas generation potential of a target waste material is characterized by a G-value, which is the number of molecules of gas generated per 100 eV of ionizing radiation absorbed by the target material. To demonstrate compliance with the flammable gas concentration requirement, theoretical worst-case calculations were performed to establish allowable wattage (decay heat) limits for waste containers. The calculations were based on the G-value for the waste material with the highest potential for flammable gas generation. The calculations also made no allowances for decreases of the G-value over time due to matrix depletion phenomena that have been observed by many experimenters. Matrix depletion occurs over time when an alpha-generating source particle alters the target material (by evaporation, reaction, or decomposition) into a material of lower gas generating potential. The net effect of these alterations is represented by the ''effective G-value.''

Impact induced response spectrum for the safety evaluation of the high flux isotope reactor

International Nuclear Information System (INIS)

Chang, S.J.

1997-01-01

The dynamic impact to the nearby HFIR reactor vessel caused by heavy load drop is analyzed. The impact calculation is carried out by applying the ABAQUS computer code. An impact-induced response spectrum is constructed in order to evaluate whether the HFIR vessel and the shutdown mechanism may be disabled. For the frequency range less than 10 Hz, the maximum spectral velocity of impact is approximately equal to that of the HFIR seismic design-basis spectrum. For the frequency range greater than 10 Hz, the impact-induced response spectrum is shown to cause no effect to the control rod and the shutdown mechanism. An earlier seismic safety assessment for the HFIR control and shutdown mechanism was made by EQE. Based on EQE modal solution that is combined with the impact-induced spectrum, it is concluded that the impact will not cause any damage to the shutdown mechanism, even while the reactor is in operation. The present method suggests a general approach for evaluating the impact induced damage to the reactor by applying the existing finite element modal solution that has been carried out for the seismic evaluation of the reactor

Destruction of Ion-Exchange Resin In Waste From the HFIR, T1 and T2 Tanks Using Fenton's Reagent

International Nuclear Information System (INIS)

Taylor, P.A.

2002-01-01

The use of Fenton's reagent (hydrogen peroxide and a ferrous iron catalyst) has been tested as a method for destroying ion-exchange resin in radioactive waste from three underground storage tanks at the Oak Ridge National Laboratory. The resin in these wastes must be destroyed before they can be transferred to the Melton Valley Storage Tanks (MVSTs) prior to solidification and disposal at the Waste Isolation Pilot Plant. The reaction with ion-exchange resin requires a dilute acidic solution (pH = 3 to 5) and moderate temperatures (T = 60 to 100 C). Laboratory-scale tests of the process have been successfully completed using both simulants and actual waste samples. The ion-exchange resin is oxidized to carbon dioxide and inorganic salts. The reaction rate is quite slow for temperatures below 70 C but increases almost linearly as the temperature of the slurry increases from 70 to 90 C. Pilot-scale tests have demonstrated the process using larger samples of actual waste slurries. A sample from the High Flux Isotope Reactor (HFIR) tank, containing 500 mL of settled solids (resin and inorganic sludge) in a total volume of 1800 mL, was successfully treated to meet MVST waste acceptance requirements in 9 h of processing time, using 1650 mL of 50 wt% hydrogen peroxide. A composite sample from the T1 and T2 tanks, which contained 1000 mL of settled solids in a total volume of 2000 mL required 8 h of treatment, using 1540 mL of 50 wt% peroxide, to meet waste acceptance requirements. Hydrogen peroxide reaction rates were 0.71 to 0.74 g H 2 O 2 /L/min, with very low (<2000 mg/L) concentrations of peroxide in the slurry. The reaction produces mostly carbon dioxide gas during the early part of the treatment, when organic carbon concentrations in the slurry are high, and then produces increasing amounts of oxygen as the organic carbon concentration drops. Small amounts (<3 vol%) of carbon monoxide are also generated. The off-gas from the pilot-scale tests, which was 81 vol

Stress calculations for RTNS-iI 50-cm targets

International Nuclear Information System (INIS)

Schumacher, B.J.; House, P.A.

1981-04-01

Structural calculations made during design of a 50-cm target for the Rotating Target Neutron Source (RTNS-II) are detailed. The limited ability of the current 23-cm diameter target to dissipate the additional beam power required for a yield increase from 2 x 10 13 to 4 x 10 13 neutrons/second has resulted in the need for a larger target. The stresses of several design configurations for a 50-cm target were calculated. The stress contours that would occur in several different target designs with and without various types of structural reinforcement that reduce stress and deflection are presented

Precipitation response of austenitic stainless steel to simulated fusion irradiation

International Nuclear Information System (INIS)

Maziasz, P.J.

1978-01-01

The precipitation response of annealed type 316 stainless steel irradiated in HFIR is studied and compared to previously observed thermal aging and fast reactor irradiation responses. Irradiation in HFIR simultaneously produces high levels of helium and displacement damage and partially simulates a fusion environment. Samples have been irradiated at temperatures from 550 to 680 0 C to fluences producing up to 3300 appm He and 47 dpa

The PIP-II Conceptual Design Report

Energy Technology Data Exchange (ETDEWEB)

Ball, M. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Burov, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Chase, B. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Chakravarty, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Chen, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Dixon, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Edelen, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Grassellino, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Johnson, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Holmes, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Kazakov, S. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Klebaner, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Kourbanis, I. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Leveling, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Melnychuk, O. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Neuffer, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Nicol, T. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Ostiguy, J. -F. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasquinelli, R. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Passarelli, D. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Ristori, L. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pellico, W. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Patrick, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Prost, L. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Rakhno, I. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Saini, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Schappert, W. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Shemyakin, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Steimel, J. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Scarpine, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Vivoli, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Warner, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Yakovlev, V. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Ostroumov, P. [Argonne National Lab. (ANL), Argonne, IL (United States); Conway, Z. [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-03-01

The Proton Improvement Plan-II (PIP-II) encompasses a set of upgrades and improvements to the Fermilab accelerator complex aimed at supporting a world-leading neutrino program over the next several decades. PIP-II is an integral part of the strategic plan for U.S. High Energy Physics as described in the Particle Physics Project Prioritization Panel (P5) report of May 2014 and formalized through the Mission Need Statement approved in November 2015. As an immediate goal, PIP-II is focused on upgrades to the Fermilab accelerator complex capable of providing proton beam power in excess of 1 MW on target at the initiation of the Long Baseline Neutrino Facility/Deep Underground Neutrino Experiment (LBNF/DUNE) program, currently anticipated for the mid- 2020s. PIP-II is a part of a longer-term goal of establishing a high-intensity proton facility that is unique within the world, ultimately leading to multi-MW capabilities at Fermilab....

Embrittlement of the Shippingport reactor shield tank

International Nuclear Information System (INIS)

Chopra, O.K.; Shack, W.J.

1989-01-01

Surveillance specimens from the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory showed an unexpectedly high degree of embrittlement relative to the data obtained on similar materials in Materials Testing Reactors (MTRs). The results suggest a possible negative flux effect and raise the issue of embrittlement of the pressure vessel support structures of commercial light water reactors. To help resolve this issues, a program was initiated to characterize the irradiation embrittlement of the neutron shield tank (NST) from the decommissioned Shippingport reactor. The Shippingport NST operated at 55 degree C (130 degree F) and was fabricated from A212 Grade B steel, similar to the vessel material in HFIR. The inner wall of the NST was exposed to a total maximum fluence of ∼ 6 x 10 17 n/cm 2 (E > 1 MeV) over a life of 9.25 effective full power years. This corresponds to a fast flux of 2.1 x 10 9 n/cm 2 x s and is comparable to the conditions for the HFIR surveillance specimens. The results indicate that irradiation increases the 15 ft x lb Charpy transition temperature (CTT) by ∼25 degree C (45 degree F) and decreases the upper shelf energy. The shift in CTT is not as severe as that observed in the HFIR surveillance specimens and is consistent with that expected from the MTR data base. However, the actual value of CTT is high, and the toughness at service temperature is low, even when compared with the HFIR data. The increase in yield stress is ∼50 MPa, which is comparable to the HFIR data. The results also indicate a lower impact strength and higher transition temperature for the TL orientation than that for the LT orientation. Some effects of the location across the thickness of the wall are also observed for the LT specimens; CTT is slightly greater for the specimens from the inner region of the wall

Report of the ANS Project Feasibility Workshop for a High Flux Isotope Reactor-Center for Neutron Research Facility

International Nuclear Information System (INIS)

Peretz, F.J.; Booth, R.S.

1995-07-01

The Advanced Neutron Source (ANS) Conceptual Design Report (CDR) and its subsequent updates provided definitive design, cost, and schedule estimates for the entire ANS Project. A recent update to this estimate of the total project cost for this facility was $2.9 billion, as specified in the FY 1996 Congressional data sheet, reflecting a line-item start in FY 1995. In December 1994, ANS management decided to prepare a significantly lower-cost option for a research facility based on ANS which could be considered during FY 1997 budget deliberations if DOE or Congressional planners wished. A cost reduction for ANS of about $1 billion was desired for this new option. It was decided that such a cost reduction could be achieved only by a significant reduction in the ANS research scope and by maximum, cost-effective use of existing High Flux Isotope Reactor (HFIR) and ORNL facilities to minimize the need for new buildings. However, two central missions of the ANS -- neutron scattering research and isotope production-were to be retained. The title selected for this new option was High Flux Isotope Reactor-Center for Neutron Research (HFIR-CNR) because of the project's maximum use of existing HFIR facilities and retention of selected, central ANS missions. Assuming this shared-facility requirement would necessitate construction work near HFIR, it was specified that HFIR-CNR construction should not disrupt normal operation of HFIR. Additional objectives of the study were that it be highly credible and that any material that might be needed for US Department of Energy (DOE) and Congressional deliberations be produced quickly using minimum project resources. This requirement made it necessary to rely heavily on the ANS design, cost, and schedule baselines. A workshop methodology was selected because assessment of each cost and/or scope-reduction idea required nearly continuous communication among project personnel to ensure that all ramifications of propsed changes

Bi-Spectral Method for Radar Target Recognition

National Research Council Canada - National Science Library

Yeo, Jiunn W

2006-01-01

.... Since World War II, the Identification of Friend or Foe (IFF) systems installed in radar systems have served as the primary cooperative target identification techniques based on the "question and answer" interrogation loop of unidentified aircraft...

Investigation of non-corrin cobalt(II)-containing sites in protein structures of the Protein Data Bank.

Science.gov (United States)

Abriata, Luciano Andres

2013-04-01

Protein X-ray structures with non-corrin cobalt(II)-containing sites, either natural or substituting another native ion, were downloaded from the Protein Data Bank and explored to (i) describe which amino acids are involved in their first ligand shells and (ii) analyze cobalt(II)-donor bond lengths in comparison with previously reported target distances, CSD data and EXAFS data. The set of amino acids involved in Co(II) binding is similar to that observed for catalytic Zn(II) sites, i.e. with a large fraction of carboxylate O atoms from aspartate and glutamate and aromatic N atoms from histidine. The computed Co(II)-donor bond lengths were found to depend strongly on structure resolution, an artifact previously detected for other metal-donor distances. Small corrections are suggested for the target bond lengths to the aromatic N atoms of histidines and the O atoms of water and hydroxide. The available target distance for cysteine (Scys) is confirmed; those for backbone O and other donors remain uncertain and should be handled with caution in refinement and modeling protocols. Finally, a relationship between both Co(II)-O bond lengths in bidentate carboxylates is quantified.

2010 Neutron Review: ORNL Neutron Sciences Progress Report

International Nuclear Information System (INIS)

Bardoel, Agatha A.; Counce, Deborah Melinda; Ekkebus, Allen E.; Horak, Charlie M.; Nagler, Stephen E.; Kszos, Lynn A.

2011-01-01

During 2010, the Neutron Sciences Directorate focused on producing world-class science, while supporting the needs of the scientific community. As the instrument, sample environment, and data analysis tools at High Flux Isotope Reactor (HFIR ) and Spallation Neutron Source (SNS) have grown over the last year, so has promising neutron scattering research. This was an exciting year in science, technology, and operations. Some topics discussed are: (1) HFIR and SNS Experiments Take Gordon Battelle Awards for Scientific Discovery - Battelle Memorial Institute presented the inaugural Gordon Battelle Prizes for scientific discovery and technology impact in 2010. Battelle awards the prizes to recognize the most significant advancements at national laboratories that it manages or co-manages. (2) Discovery of Element 117 - As part of an international team of scientists from Russia and the United States, HFIR staff played a pivotal role in the discovery by generating the berkelium used to produce the new element. A total of six atoms of ''ununseptium'' were detected in a two-year campaign employing HFIR and the Radiochemical Engineering Development Center at Oak Ridge National Laboratory (ORNL) and the heavy-ion accelerator capabilities at the Joint Institute for Nuclear Research in Dubna, Russia. The discovery of the new element expands the understanding of the properties of nuclei at extreme numbers of protons and neutrons. The production of a new element and observation of 11 new heaviest isotopes demonstrate the increased stability of super-heavy elements with increasing neutron numbers and provide the strongest evidence to date for the existence of an island of enhanced stability for super-heavy elements. (3) Studies of Iron-Based High-Temperature Superconductors - ORNL applied its distinctive capabilities in neutron scattering, chemistry, physics, and computation to detailed studies of the magnetic excitations of iron-based superconductors (iron pnictides and

2010 Neutron Review: ORNL Neutron Sciences Progress Report

Energy Technology Data Exchange (ETDEWEB)

Bardoel, Agatha A [ORNL; Counce, Deborah M [ORNL; Ekkebus, Allen E [ORNL; Horak, Charlie M [ORNL; Nagler, Stephen E [ORNL; Kszos, Lynn A [ORNL

2011-06-01

During 2010, the Neutron Sciences Directorate focused on producing world-class science, while supporting the needs of the scientific community. As the instrument, sample environment, and data analysis tools at High Flux Isotope Reactor (HFIR ) and Spallation Neutron Source (SNS) have grown over the last year, so has promising neutron scattering research. This was an exciting year in science, technology, and operations. Some topics discussed are: (1) HFIR and SNS Experiments Take Gordon Battelle Awards for Scientific Discovery - Battelle Memorial Institute presented the inaugural Gordon Battelle Prizes for scientific discovery and technology impact in 2010. Battelle awards the prizes to recognize the most significant advancements at national laboratories that it manages or co-manages. (2) Discovery of Element 117 - As part of an international team of scientists from Russia and the United States, HFIR staff played a pivotal role in the discovery by generating the berkelium used to produce the new element. A total of six atoms of ''ununseptium'' were detected in a two-year campaign employing HFIR and the Radiochemical Engineering Development Center at Oak Ridge National Laboratory (ORNL) and the heavy-ion accelerator capabilities at the Joint Institute for Nuclear Research in Dubna, Russia. The discovery of the new element expands the understanding of the properties of nuclei at extreme numbers of protons and neutrons. The production of a new element and observation of 11 new heaviest isotopes demonstrate the increased stability of super-heavy elements with increasing neutron numbers and provide the strongest evidence to date for the existence of an island of enhanced stability for super-heavy elements. (3) Studies of Iron-Based High-Temperature Superconductors - ORNL applied its distinctive capabilities in neutron scattering, chemistry, physics, and computation to detailed studies of the magnetic excitations of iron-based superconductors (iron

Seismic, high wind, tornado, and probabilistic risk assessment of the high flux isotope reactor

International Nuclear Information System (INIS)

Harris, S.P.; Hashimoto, P.S.; Dizon, J.O.; Hashimoto, P.S.

1989-01-01

Natural phenomena analyses were performed on the High Flux Isotope Reactor (HFIR). Deterministic and probabilistic evaluations were made to determine the risks resulting from earthquakes, high winds, and tornadoes. Analytic methods in conjunction with field evaluations and an earthquake experience data base evaluation methods were used to provide more realistic results in a shorter amount of time. Plant modifications completed in preparation for HFIR restart and potential future enhancements are discussed

Beam dynamics of the Neutralized Drift Compression Experiment-II (NDCX-II),a novel pulse-compressing ion accelerator

International Nuclear Information System (INIS)

Friedman, A.; Barnard, J.J.; Cohen, R.H.; Grote, D.P.; Lund, S.M.; Sharp, W.M.; Faltens, A.; Henestroza, E.; Jung, J.-Y.; Kwan, J.W.; Lee, E.P.; Leitner, M.A.; Logan, B.G.; Vay, J.-L.; Waldron, W.L.; Davidson, R.C.; Dorf, M.; Gilson, E.P.; Kaganovich, I.D.

2009-01-01

Intense beams of heavy ions are well suited for heating matter to regimes of emerging interest. A new facility, NDCX-II, will enable studies of warm dense matter at ∼1 eV and near-solid density, and of heavy-ion inertial fusion target physics relevant to electric power production. For these applications the beam must deposit its energy rapidly, before the target can expand significantly. To form such pulses, ion beams are temporally compressed in neutralizing plasma; current amplification factors of ∼50-100 are routinely obtained on the Neutralized Drift Compression Experiment (NDCX) at LBNL. In the NDCX-II physics design, an initial non-neutralized compression renders the pulse short enough that existing high-voltage pulsed power can be employed. This compression is first halted and then reversed by the beam's longitudinal space-charge field. Downstream induction cells provide acceleration and impose the head-to-tail velocity gradient that leads to the final neutralized compression onto the target. This paper describes the discrete-particle simulation models (1-D, 2-D, and 3-D) employed and the space-charge-dominated beam dynamics being realized.

A cryostat to hold frozen-spin polarized HD targets in CLAS: HDice-II

Energy Technology Data Exchange (ETDEWEB)

Lowry, M.M., E-mail: mlowry@jlab.org [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Bass, C.D. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); D' Angelo, A. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Universita' di Roma ‘Tor Vergata’, and INFN Sezione di Roma ‘Tor Vergata’, Via della Ricerca Scientifica, 1, I-00133 Roma (Italy); Deur, A.; Dezern, G. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Hanretty, C. [University of Virginia, 1400 University Avenue, Charlottesville, VA 22903 (United States); Ho, D. [Carnegie-Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States); Kageya, T.; Kashy, D. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Khandaker, M. [Norfolk State University, 700 Park Avenue, Norfolk, VA 23504 (United States); Laine, V. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Université Blaise Pascal, 34 Avenue Carnot, 63000 Clermont-Ferrand (France); O' Connell, T. [University of Connecticut, 115 N Eagleville Road, Storrs-Mansfield, CT 06269 (United States); Pastor, O. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Peng, P. [University of Virginia, 1400 University Avenue, Charlottesville, VA 22903 (United States); Sandorfi, A.M. [Thomas Jefferson National Accelerator Facility, 12000 Jefferson Avenue, Newport News, VA 23606 (United States); Sokhan, D. [Institut de Physique Nucleaire, Bat 100 – M053, Orsay 91406 (France); and others

2016-04-11

The design, fabrication, operation, and performance of a {sup 3/4}He dilution refrigerator and superconducting magnet system for holding a frozen-spin polarized hydrogen deuteride target in the Jefferson Laboratory CLAS detector during photon beam running is reported. The device operates both vertically (for target loading) and horizontally (for target bombardment). The device proves capable of maintaining a base temperature of 50 mK and a holding field of 1 T for extended periods. These characteristics enabled multi-month polarization lifetimes for frozen spin HD targets having proton polarization of up to 50% and deuteron up to 27%.

Transuranium processing plant

International Nuclear Information System (INIS)

King, L.J.

1983-01-01

The Transuranium Processing Plant (TRU) is a remotely operated, hot-cell, chemical processing facility of advanced design. The heart of TRU is a battery of nine heavily shielded process cells housed in a two-story building. Each cell, with its 54-inch-thick walls of a special high-density concrete, has enough shielding to stop the neutrons and gamma radiation from 1 gram of 252/sub Cf/ and associated fission products. Four cells contain chemical processing equipment, three contain equipment for the preparation and inspection of HFIR targets, and two cells are used for analytical chemistry operations. In addition, there are eight laboratories used for process development, for part of the process-control analyses, and for product finishing operations. Although the Transuranium Processing Plant was built for the purpose of recovering transuranium elements from targets irradiated in the High Flux Isotope Reactor (HFIR), it is also a highly versatile facility which has extensive provisions for changing and modifying equipment. Thus, it was a relatively simple matter to install a Solvent Extraction Test Facility (SETF) in one of the TRU chemical processing cells for use in the evaluation and demonstration of solvent extraction flowsheets for the recovery of fissile and fertile materials from irradiated reactor fuels. The equipment in the SETF has been designed for process development and demonstrations and the particular type of mixer-settler contactors was chosen because it is easy to observe and sample

Transuranium processing plant semiannual report of production, status, and plans for period ending June 30, 1976

Energy Technology Data Exchange (ETDEWEB)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1977-02-01

During the period January 1, 1976, through June 30, 1976, the following amounts of transuranium elements were recovered from ten irradiated HFIR targets: 2 g /sup 243/Am, 50 g /sup 244/Cm, 29 mg /sup 249/Bk, 277 mg /sup 252/Cf, 1.7 mg /sup 253/Es, and 0.5 pg /sup 257/Fm. About 50 mg of high-purity /sup 248/Cm was purified chemically for shipment, and another 75 mg of /sup 248/Cm was separated from /sup 252/Cf. Nineteen HFIR targets, each containing approximately 9 g of curium, were fabricated. There have been no changes during this report period in the chemical processing flowsheets normally used at TRU. Five neutron sources were fabricated, bringing the total fabricated to 84. Six sources that were used previously in various projects have been returned to TRU and are available for reassignment. Special projects included (1) the continued study of /sup 250/Cm production by irradiation of /sup 248/Cm; (2) the production of 0.54 mg of /sup 250/Cf by irradiation of /sup 249/Bk; (3) the separation of approximately 200 pg of /sup 254/Cf from 39-hr /sup 254m/Es that was produced by irradiation of 5 ..mu..g of /sup 253/Es; and (4) the determination of process steps needed to obtain rare-earth fission products in an oxide form from LiCl-based anion exchange raffinate solution.

Commissioning and performance studies of a proton recoil detector at the COMPASS-II experiment

Energy Technology Data Exchange (ETDEWEB)

Joerg, Philipp; Buechele, Maximilian; Fischer, Horst; Gorzellik, Matthias; Grussenmeyer, Tobias; Herrmann, Florian; Koenigsmann, Kay; Kremser, Paul; Schopferer, Sebastian [Physikalisches Institut, Albert-Ludwigs-Universitaet Freiburg (Germany); Collaboration: COMPASS Collaboration

2014-07-01

The COMPASS-II experiment is a fixed target experiment situated at CERN. A tertiary myon beam from the SPS scattered of protons from a liquid hydrogen target is used to measure Deeply Virtual Compton Scattering (DVCS) and Hard Exclusive Meson Production (HEMP). These processes offer a unique way to determine Generalized Parton Distributions, which are related to the total angular momentum of quarks, antiquarks and gluons in the nucleon by Ji's Sum Rule. One of the major parts of the COMPASS-II upgrade is the CAMERA detector. CAMERA is a proton recoil detector surrounding the COMPASS-II liquid hydrogen target. Its purpose is to measure the recoiled target proton in DVCS and HEMP reactions and viz to act as a veto to ensure the exclusivity of the measurement. The talk gives an outline of the detector and its readout electronics. It is focused on the commissioning and performance of the CAMERA detector and gives a brief insight into the ongoing DVCS analysis.

Neutralized Drift Compression Experiment (NDCX) - II Quarterly Report

International Nuclear Information System (INIS)

Kwan, J.W.

2009-01-01

LBNL has received American Recovery and Reinvestment Act (ARRA) funding to construct a new accelerator at Lawrence Berkeley National Laboratory (LBNL) to significantly increase the energy on target, which will allow both the Heavy Ion Fusion (HIF) and Warm Dense Matter (WDM) research communities to explore scientific conditions that have not been available in any other device. For NDCX-II, a new induction linear accelerator (linac) will be constructed at Lawrence Berkeley National Laboratory (LBNL). NDCX-II will produce nano-second long ion beam bunches to hit thin foil targets. The final kinetic energy of the ions arriving at the target varies according to the ion mass. For atomic mass unit of 6 or 7 (Lithium ions), useful kinetic energies range from 1.5 to 5 or more MeV. The expected beam charge in the 1 ns (or shorter) pulse is about 20 nanoCoulombs. The pulse repetition rate will be about once or twice per minute (of course, target considerations will often reduce this rate). Our approach to building the NDCX-II ion accelerator is to make use of the available induction modules and 200 kV pulsers from the retired ATA electron linac at LLNL. Reusing this hardware will maximize the ion energy on target at a minimum cost. Some modification of the cells (e.g., reduce the bore diameter and replace with higher field pulsed solenoids) are needed in order to meet the requirements of this project. The NDCX-II project will include the following tasks: (1) Physics design to determine the required ion current density at the ion source, the injector beam optics, the layout of accelerator cells along the beam line, the voltage waveforms for beam acceleration and compression, the solenoid focusing, the neutralized drift compression and the final focus on target; (2) Engineering design and fabrication of the accelerator components, pulsed power system, diagnostic system, and control and data acquisition system; (3) Conventional facilities; and (4) Installation and integration

Probing HeII Reionization at z>3.5 with Resolved HeII Lyman Alpha Forest Spectra

Science.gov (United States)

Worseck, Gabor

2017-08-01

The advent of GALEX and COS have revolutionized our view of HeII reionization, the final major phase transition of the intergalactic medium. COS spectra of the HeII Lyman alpha forest have confirmed with high confidence the high HeII transmission that signifies the completion of HeII reionization at z 2.7. However, the handful of z>3.5 quasars observed to date show a set of HeII transmission 'spikes' and larger regions with non-zero transmission that suggest HeII reionization was well underway by z=4. This is in striking conflict with predictions from state-of-the-art radiative transfer simulations of a HeII reionization driven by bright quasars. Explaining these measurements may require either faint quasars or more exotic sources of hard photons at z>4, with concomitant implications for HI reionization. However, many of the observed spikes are unresolved in G140L spectra and are significantly impacted by Poisson noise. Current data cannot reliably probe the ionization state of helium at z>3.5.We request 41 orbits to obtain science-grade G130M spectra of the two UV-brightest HeII-transmitting QSOs at z>3.5 to confirm and resolve their HeII transmission spikes as an unequivocal test of early HeII reionization. These spectra are complemented by recently obtained data from 8m telescopes: (1) Echelle spectra of the coeval HI Lya forest to map the underlying density field that modulates the HeII absorption, and (2) Our dedicated survey for foreground QSOs that may source the HeII transmission. Our recent HST programs revealed the only two viable targets to resolve the z>3.5 HeII Lyman alpha forest, and to conclusively solve this riddle.

Status of and plans for the PBFA II Facility

International Nuclear Information System (INIS)

Cook, D.L.

1985-01-01

PBFA II is a 100 TW pulsed power accelerator being constructed for use in the Light Ion Fusion Program. The objective of PBFA II is to accelerate and focus upon an ICF target a lithium beam with sufficicent energy, power, and power density to perform ignition scaling experiments. The technologies used in PBFA II include: (1) primary energy storage and compression with 6 MV, low-inductance Marx generators, (2) pulse forming in water-insulated, water-dielectric lines with self-closing water switches, (3) module synchronization using laser-triggerred, 6 MV multistage gas switches, (4) voltage addition in vacuum using self-magnetically-insulated biconic transmission lines, (5) inductive energy storage and pulse compression using a fast-opening plasma erosion switch, (6) beam formation using a magnetically-insulated ion diode, and (7) space charge and current neutralized beam propagation to the target in a gas-filled cell. Presently, accelerator construction is nearing completion, with the first multimodule shot expected by the end of January 1986

Component and system simulation models for High Flux Isotope Reactor

International Nuclear Information System (INIS)

Sozer, A.

1989-08-01

Component models for the High Flux Isotope Reactor (HFIR) have been developed. The models are HFIR core, heat exchangers, pressurizer pumps, circulation pumps, letdown valves, primary head tank, generic transport delay (pipes), system pressure, loop pressure-flow balance, and decay heat. The models were written in FORTRAN and can be run on different computers, including IBM PCs, as they do not use any specific simulation languages such as ACSL or CSMP. 14 refs., 13 figs

Seismic, high wind, tornado, and probabilistic risk assessments of the High Flux Isotope Reactor

International Nuclear Information System (INIS)

Harris, S.P.; Stover, R.L.; Hashimoto, P.S.; Dizon, J.O.

1989-01-01

Natural phenomena analyses were performed on the High Flux Isotope Reactor (HFIR) Deterministic and probabilistic evaluations were made to determine the risks resulting from earthquakes, high winds, and tornadoes. Analytic methods in conjunction with field evaluations and an earthquake experience data base evaluation methods were used to provide more realistic results in a shorter amount of time. Plant modifications completed in preparation for HFIR restart and potential future enhancements are discussed. 5 figs

Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II ...

Indian Academy of Sciences (India)

Unknown

Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N RAMAN*, Y PITCHAIKANI RAJA and A KULANDAISAMY. Department of Chemistry, VHNSN College, Virudhunagar 626 001, India e-mail: ra_man@123india.com.

Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST Trial

Directory of Open Access Journals (Sweden)

Luis M Ruilope

2006-03-01

Full Text Available Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS blocker and a diuretic are widely used in combination.Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ 12.5 or 25 mg once daily (o.d., or with amlodipine monotherapy (10 mg o.d.. Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and proinflammatory markers than amlodipine alone.

Targeting Hypertension with Valsartan: Lessons Learned from the Valsartan/HCTZ Versus Amlodipine in Stage II Hypertensive Patients (VAST Trial

Directory of Open Access Journals (Sweden)

Luis M Ruilope

2006-03-01

Full Text Available Many patients with hypertension, especially those at increased risk because of additional cardiovascular risk factors, require treatment with more than one antihypertensive agent to achieve target blood pressure (BP goals. Many different classes of antihypertensive agents are available: a renin-angiotensin-aldosterone system (RAAS blocker and a diuretic are widely used in combination. Here we report the results of the recently completed Valsartan/HCTZ versus Amlodipine in STage II hypertensive patients (VAST trial. In this 24-week study, patients with moderate hypertension and at least one other cardiovascular risk factor were treated with a combination of valsartan 160 mg and hydrochlorothiazide (HCTZ 12.5 or 25 mg once daily (o.d., or with amlodipine monotherapy (10 mg o.d.. Overall, valsartan plus HCTZ 25 mg reduced systolic BP significantly more than amlodipine monotherapy, and with fewer adverse events. In addition, combination therapy resulted in a trend towards more favourable outcomes with respect to pro-thrombotic and pro-inflammatory markers than amlodipine alone.

Biologically active new Fe(II, Co(II, Ni(II, Cu(II, Zn(II and Cd(II complexes of N-(2-thienylmethylenemethanamine

Directory of Open Access Journals (Sweden)

C. SPÎNU

2008-04-01

Full Text Available Iron(II, cobalt(II, nickel (II, copper (II, zinc(II and cadmium(II complexes of the type ML2Cl2, where M is a metal and L is the Schiff base N-(2-thienylmethylenemethanamine (TNAM formed by the condensation of 2-thiophenecarboxaldehyde and methylamine, were prepared and characterized by elemental analysis as well as magnetic and spectroscopic measurements. The elemental analyses suggest the stoichiometry to be 1:2 (metal:ligand. Magnetic susceptibility data coupled with electronic, ESR and Mössbauer spectra suggest a distorted octahedral structure for the Fe(II, Co(II and Ni(II complexes, a square-planar geometry for the Cu(II compound and a tetrahedral geometry for the Zn(II and Cd(II complexes. The infrared and NMR spectra of the complexes agree with co-ordination to the central metal atom through nitrogen and sulphur atoms. Conductance measurements suggest the non-electrolytic nature of the complexes, except for the Cu(II, Zn(II and Cd(II complexes, which are 1:2 electrolytes. The Schiff base and its metal chelates were screened for their biological activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and the metal chelates were found to possess better antibacterial activity than that of the uncomplexed Schiff base.

Rotational Characterization of Hayabusa II Target Asteroid (162173) 1999 JU3

OpenAIRE

Moskovitz, Nicholas; Abe, Shinsuke; Pan, Kang-Shian; Osip, David; Pefkou, Dimitra; Melita, Mario; Elias, Mauro; Kitazato, Kohei; Bus, Schelte; DeMeo, Francesca; Binzel, Richard; Abell, Paul

2013-01-01

The Japanese Space Agency's Hayabusa II mission is scheduled to rendezvous with and return a sample from the near-Earth asteroid (162173) 1999 JU3. Previous visible-wavelength spectra of this object show significant variability across multiple epochs which could be the result of a compositionally heterogeneous surface. We present new visible and near-infrared spectra to demonstrate that thermally altered carbonaceous chondrites are plausible compositional analogs, however this is a tentative ...

Mobile group II intron based gene targeting in Lactobacillus plantarum WCFS1.

Science.gov (United States)

Sasikumar, Ponnusamy; Paul, Eldho; Gomathi, Sivasamy; Abhishek, Albert; Sasikumar, Sundaresan; Selvam, Govindan Sadasivam

2016-10-01

The usage of recombinant lactic acid bacteria for delivery of therapeutic proteins to the mucosa has been emerging. In the present study, an attempt was made to engineer a thyA mutant of Lactobacillus plantarum (L. plantarum) using lactococcal group II intron Ll.LtrB for the development of biologically contained recombinant L. plantarum for prevention of calcium oxalate stone disease. The 3 kb Ll.LtrB intron donor cassettes from the source vector pACD4C was PCR amplified, ligated into pSIP series of lactobacillus vector pLp_3050sAmyA, yielding a novel vector pLpACD4C (8.6 kb). The quantitative real-time PCR experiment shows 94-fold increased expression of Ll.LtrB intron and 14-fold increased expression of ltrA gene in recombinant L. plantarum containing pLpACD4C. In order to target the thyA gene, the potential intron RNA binding sites in the thyA gene of L. plantarum was predicted with help of computer algorithm. The insertion location 188|189s of thyA gene (lowest E-0.134) was chosen and the wild type intron Ll.LtrB was PCR modified, yielding a retargeted intron of pLpACDthyA. The retargeted intron was expressed by using induction peptide (sppIP), subsequently the integration of intron in thyA gene was identified by PCR screening and finally ThyA - mutant of L. plantarum (ThyA18) was detected. In vitro growth curve result showed that in the absence of thymidine, colony forming units of mutant ThyA18 was decreased, whereas high thymidine concentration (10 μM) supported the growth of the culture until saturation. In conclusion, ThyA - mutant of L. plantarum (ThyA18) constructed in this study will be used as a biologically contained recombinant probiotic to deliver oxalate decarboxylase into the lumen for treatment of hyperoxaluria and calcium oxalate stone deposition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

26 CFR 1.338-6 - Allocation of ADSP and AGUB among target assets.

Science.gov (United States)

2010-04-01

... allocated among Class II acquisition date assets of target in proportion to the fair market values of such... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Allocation of ADSP and AGUB among target assets... among target assets. (a) Scope—(1) In general. This section prescribes rules for allocating ADSP and...

Validation of a new design of tellurium dioide-irradiated target

Energy Technology Data Exchange (ETDEWEB)

Fllaoui, Aziz; Ghamad, Younes; Zoubir, Brahim; Ayaz, Zinel Abidine; El Morabiti, Aissam; Amayoud, Hafid [Centre National de l' Energie des Sciences et des Techniques Nucleaires, Rabat (Morocco); Chakir, El Mahjoub [Nuclear Physics Department, University Ibn Toufail, Kenitra (Morocco)

2016-10-15

Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO{sub 2}) material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10 - 4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics). To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600 .deg. C with the appearance of deformations on lids beyond 450 .deg. C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes-convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week) at 1.5 MW. The results show that the irradiated targets are

Validation of a New Design of Tellurium Dioxide-Irradiated Target

Directory of Open Access Journals (Sweden)

Aziz Fllaoui

2016-10-01

Full Text Available Production of iodine-131 by neutron activation of tellurium in tellurium dioxide (TeO2 material requires a target that meets the safety requirements. In a radiopharmaceutical production unit, a new lid for a can was designed, which permits tight sealing of the target by using tungsten inert gas welding. The leakage rate of all prepared targets was assessed using a helium mass spectrometer. The accepted leakage rate is ≤ 10−4 mbr.L/s, according to the approved safety report related to iodine-131 production in the TRIGA Mark II research reactor (TRIGA: Training, Research, Isotopes, General Atomics. To confirm the resistance of the new design to the irradiation conditions in the TRIGA Mark II research reactor's central thimble, a study of heat effect on the sealed targets for 7 hours in an oven was conducted and the leakage rates were evaluated. The results show that the tightness of the targets is ensured up to 600°C with the appearance of deformations on lids beyond 450°C. The study of heat transfer through the target was conducted by adopting a one-dimensional approximation, under consideration of the three transfer modes—convection, conduction, and radiation. The quantities of heat generated by gamma and neutron heating were calculated by a validated computational model for the neutronic simulation of the TRIGA Mark II research reactor using the Monte Carlo N-Particle transport code. Using the heat transfer equations according to the three modes of heat transfer, the thermal study of I-131 production by irradiation of the target in the central thimble showed that the temperatures of materials do not exceed the corresponding melting points. To validate this new design, several targets have been irradiated in the central thimble according to a preplanned irradiation program, going from 4 hours of irradiation at a power level of 0.5 MW up to 35 hours (7 h/d for 5 days a week at 1.5 MW. The results show that the irradiated targets are

Neuroprotective Effects and Mechanisms of Curcumin-Cu(II) and -Zn(II) Complexes Systems and Their Pharmacological Implications.

Science.gov (United States)

Yan, Fa-Shun; Sun, Jian-Long; Xie, Wen-Hai; Shen, Liang; Ji, Hong-Fang

2017-12-28

Alzheimer's disease (AD) is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa , is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II) or Zn(II) on hydrogen peroxide (H₂O₂)-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12) cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin-Cu(II) complexes systems possessed enhanced O₂ ·- -scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin-Cu(II) complexes systems were stronger than curcumin-Zn(II) system. Curcumin-Cu(II) or -Zn(II) complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin-Cu(II) complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin-Cu(II) or -Zn(II) complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB) pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin-Cu(II) or -Zn(II) complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.

Complexes of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and dioxouranium(II) with thiophene-2-aldehydethiosemicarbazone

International Nuclear Information System (INIS)

Singh, Balwan; Misra, Harihar

1986-01-01

Metal complexes of thiosemicarbazides have been known for their pharmacological applications. Significant antitubercular, fungicidal and antiviral activities have been reported for thiosemicarbazides and their derivatives. The present study describes the systhesis and characterisation of complexes of Co II , Cu II , Zn II ,Cd II and UO II with thiosemicarbazone obtained by condensing thiophene-2-aldehyde with thiosemicarbazide. 17 refs., 2 tables. (author)

Assembly and Delivery of Rabbit Capsules for Irradiation of Silicon Carbide Cladding Tube Specimens in the High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Koyanagi, Takaaki [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Petrie, Christian M. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-09-01

heat flux configurations have been assembled, welded, evaluated, and delivered to the HFIR along with a complete quality assurance fabrication package. These rabbits contain a wide variety of specimens including monolith tubes, SiC fiber SiC matrix (SiC/SiC) composites, duplex specimens (inner composite, outer monolith), and specimens with a variety of metallic or ceramic coatings on the outer surface. The rabbits are targeted for insertion during HFIR cycle 475, which is scheduled for September 2017.

An Account of Oak Ridge National Laboratory's Thirteen Research Reactors

International Nuclear Information System (INIS)

Rosenthal, Murray Wilford

2009-01-01

The Oak Ridge National Laboratory has built and operated 13 nuclear reactors in its 66-year history. The first was the graphite reactor, the world's first operational nuclear reactor, which served as a plutonium production pilot plant during World War II. It was followed by two aqueous-homogeneous reactors and two red-hot molten-salt reactors that were parts of power-reactor development programs and by eight others designed for research and radioisotope production. One of the eight was an all-metal fast burst reactor used for health physics studies. All of the others were light-water cooled and moderated, including the famous swimming-pool reactor that was copied dozens of times around the world. Two of the reactors were hoisted 200 feet into the air to study the shielding needs of proposed nuclear-powered aircraft. The final reactor, and the only one still operating today, is the High Flux Isotope Reactor (HFIR) that was built particularly for the production of californium and other heavy elements. With the world's highest flux and recent upgrades that include the addition of a cold neutron source, the 44-year-old HFIR continues to be a valuable tool for research and isotope production, attracting some 500 scientific visitors and guests to Oak Ridge each year. This report describes all of the reactors and their histories.

An Account of Oak Ridge National Laboratory's Thirteen Research Reactors

Energy Technology Data Exchange (ETDEWEB)

Rosenthal, Murray Wilford [ORNL

2009-08-01

The Oak Ridge National Laboratory has built and operated 13 nuclear reactors in its 66-year history. The first was the graphite reactor, the world's first operational nuclear reactor, which served as a plutonium production pilot plant during World War II. It was followed by two aqueous-homogeneous reactors and two red-hot molten-salt reactors that were parts of power-reactor development programs and by eight others designed for research and radioisotope production. One of the eight was an all-metal fast burst reactor used for health physics studies. All of the others were light-water cooled and moderated, including the famous swimming-pool reactor that was copied dozens of times around the world. Two of the reactors were hoisted 200 feet into the air to study the shielding needs of proposed nuclear-powered aircraft. The final reactor, and the only one still operating today, is the High Flux Isotope Reactor (HFIR) that was built particularly for the production of californium and other heavy elements. With the world's highest flux and recent upgrades that include the addition of a cold neutron source, the 44-year-old HFIR continues to be a valuable tool for research and isotope production, attracting some 500 scientific visitors and guests to Oak Ridge each year. This report describes all of the reactors and their histories.

Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.

Directory of Open Access Journals (Sweden)

Wendy B Iser

2011-03-01

Full Text Available Insulin/IGF-I-like signaling (IIS has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.

Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants.

Science.gov (United States)

Iser, Wendy B; Wilson, Mark A; Wood, William H; Becker, Kevin; Wolkow, Catherine A

2011-03-09

Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans.

Diffuse Reflectance Spectroscopy of Hidden Objects. Part II: Recovery of a Target Spectrum.

Science.gov (United States)

Pomerantsev, Alexey L; Rodionova, Oxana Ye; Skvortsov, Alexej N

2017-08-01

In this study, we consider the reconstruction of a diffuse reflectance near-infrared spectrum of an object (target spectrum) in case the object is covered by an interfering absorbing and scattering layer. Recovery is performed using a new empirical method, which was developed in our previous study. We focus on a system, which consists of several layers of polyethylene (PE) film and underlayer objects with different spectral features. The spectral contribution of the interfering layer is modeled by a three-component two-parameter multivariate curve resolution (MCR) model, which was built and calibrated using spectrally flat objects. We show that this model is applicable to real objects with non-uniform spectra. Ultimately, the target spectrum can be reconstructed from a single spectrum of the covered target. With calculation methods, we are able to recover quite accurately the spectrum of a target even when the object is covered by 0.7 mm of PE.

The Water Maser in II Zw 96: Scientific Justification

Energy Technology Data Exchange (ETDEWEB)

Wiggins, Brandon Kerry [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-08-06

We propose a VLBI search to image and locate the water emission in II Zw 96. We propose 3 sites within II Zw 96 for VLBI followup (see the proposed target listing below). We request 2.5 hours of on-source integration time with the VLBA per source. The array will achieve ~ 65µJy sensitivity in K band in this time which will be sufficient to detect luminous water maser features.

The Southern H ii Region Discovery Survey (SHRDS): Pilot Survey

Energy Technology Data Exchange (ETDEWEB)

Brown, C.; Dickey, John M. [School of Physical Sciences, Private Bag 37, University of Tasmania, Hobart, TAS, 7001 (Australia); Jordan, C. [International Centre for Radio Astronomy Research, Curtin University, Perth, WA, 6845 (Australia); Anderson, L. D.; Armentrout, W. P. [Department of Physics and Astronomy, West Virginia University, P.O. Box 6315, Morgantown, WV 26506 (United States); Balser, Dana S.; Wenger, Trey V. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22904 (United States); Bania, T. M. [Institute for Astrophysical Research, Department of Astronomy, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States); Dawson, J. R. [Department of Physics and Astronomy and MQ Research Centre in Astronomy, Astrophysics and Astrophotonics, Macquarie University, NSW, 2109 (Australia); Mc Clure-Griffiths, N. M. [Research School of Astronomy and Astrophysics, The Australian National University, Canberra ACT 2611 (Australia)

2017-07-01

The Southern H ii Region Discovery Survey is a survey of the third and fourth quadrants of the Galactic plane that will detect radio recombination line (RRL) and continuum emission at cm-wavelengths from several hundred H ii region candidates using the Australia Telescope Compact Array. The targets for this survey come from the WISE Catalog of Galactic H ii Regions and were identified based on mid-infrared and radio continuum emission. In this pilot project, two different configurations of the Compact Array Broad Band receiver and spectrometer system were used for short test observations. The pilot surveys detected RRL emission from 36 of 53 H ii region candidates, as well as seven known H ii regions that were included for calibration. These 36 recombination line detections confirm that the candidates are true H ii regions and allow us to estimate their distances.

The Southern H ii Region Discovery Survey (SHRDS): Pilot Survey

International Nuclear Information System (INIS)

Brown, C.; Dickey, John M.; Jordan, C.; Anderson, L. D.; Armentrout, W. P.; Balser, Dana S.; Wenger, Trey V.; Bania, T. M.; Dawson, J. R.; Mc Clure-Griffiths, N. M.

2017-01-01

The Southern H ii Region Discovery Survey is a survey of the third and fourth quadrants of the Galactic plane that will detect radio recombination line (RRL) and continuum emission at cm-wavelengths from several hundred H ii region candidates using the Australia Telescope Compact Array. The targets for this survey come from the WISE Catalog of Galactic H ii Regions and were identified based on mid-infrared and radio continuum emission. In this pilot project, two different configurations of the Compact Array Broad Band receiver and spectrometer system were used for short test observations. The pilot surveys detected RRL emission from 36 of 53 H ii region candidates, as well as seven known H ii regions that were included for calibration. These 36 recombination line detections confirm that the candidates are true H ii regions and allow us to estimate their distances.

Mn(II), Zn(II) and VO(II) Schiff

Indian Academy of Sciences (India)

Home; Journals; Journal of Chemical Sciences; Volume 113; Issue 3. Synthesis and characterisation of Cu(II), Ni(II), Mn(II), Zn(II) and VO(II) Schiff base complexes derived from o-phenylenediamine and acetoacetanilide. N Raman Y Pitchaikani Raja A Kulandaisamy. Inorganic Volume 113 Issue 3 June 2001 pp 183-189 ...

Autonomous Collaborative Agents for Onboard Multi-Sensor Re-Targeting, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — In our Phase I effort we developed a prototype software-agent based framework to provide for autonomous re-targeting of sensors hosted on satellites in polar orbits,...

PEP-II RF System Operation and Performance

International Nuclear Information System (INIS)

McIntosh, P.

2005-01-01

The Low Energy Ring (LER) and High Energy Ring (HER) RF systems have operated now on PEP-II since July 1998 and have assisted in breaking all design luminosity records back in June 2001. Luminosity on PEP-II has steadily increased since then as a consequence of larger e+ and e- beam currents being accumulated. This has meant that the RF systems have inevitably been driven harder, not only to achieve these higher stored beam currents, but also to reliably keep the beams circulating whilst at the same time minimizing the number of aborts due to RF system faults. This paper details the current PEP-II RF system configurations for both rings, as well as future upgrade plans spanning the next 3-5 years. Limitations of the current RF system configurations are presented, highlighting improvement projects which will target specific areas within the RF systems to ensure that adequate operating overheads are maintained and reliable operation is assured. The Low Energy Ring (LER) and High Energy Ring (HER) RF systems have operated now on PEP-II since July 1998 and have assisted in breaking all design luminosity records back in June 2001. Luminosity on PEP-II has steadily increased since then as a consequence of larger e+ and e- beam currents being accumulated. This has meant that the RF systems have inevitably been driven harder, not only to achieve these higher stored beam currents, but also to reliably keep the beams circulating whilst at the same time minimizing the number of aborts due to RF system faults. This paper details the current PEP-II RF system configurations for both rings, as well as future upgrade plans spanning the next 3-5 years. Limitations of the current RF system configurations are presented, highlighting improvement projects which will target specific areas within the RF systems to ensure that adequate operating overheads are maintained and reliable operation is assured

Analysis of 6912 unselected somatic hypermutations in human VDJ rearrangements reveals lack of strand specificity and correlation between phase II substitution rates and distance to the nearest 3' activation-induced cytidine deaminase target

DEFF Research Database (Denmark)

Ohm-Laursen, Line; Barington, Torben

2007-01-01

-23*01) from blood B lymphocytes enriched for CD27-positive memory cells. Analyses of 6,912 unique, unselected substitutions showed that in vivo hot and cold spots for the SHM of C and G residues corresponded closely to the target preferences reported for AID in vitro. A detailed analysis of all possible four......-nucleotide motifs present on both strands of the V(H) gene showed significant correlations between the substitution frequencies in reverse complementary motifs, suggesting that the SHM machinery targets both strands equally well. An analysis of individual J(H) and D gene segments showed that the substitution...... rates in G and T residues correlated inversely with the distance to the nearest 3' WRC AID hot spot motif on both the nontranscribed and transcribed strands. This suggests that phase II SHM takes place 5' of the initial AID deamination target and primarily targets T and G residues or, alternatively...

ORNL Neutron Sciences Annual Report for 2007

Energy Technology Data Exchange (ETDEWEB)

Anderson, Ian S [ORNL; Horak, Charlie M [ORNL; Counce, Deborah Melinda [ORNL; Ekkebus, Allen E [ORNL

2008-07-01

This is the first annual report of the Oak Ridge National Laboratory Neutron Sciences Directorate for calendar year 2007. It describes the neutron science facilities, current developments, and future plans; highlights of the year's activities and scientific research; and information on the user program. It also contains information about education and outreach activities and about the organization and staff. The Neutron Sciences Directorate is responsible for operation of the High Flux Isotope Reactor and the Spallation Neutron Source. The main highlights of 2007 were highly successful operation and instrument commissioning at both facilities. At HFIR, the year began with the reactor in shutdown mode and work on the new cold source progressing as planned. The restart on May 16, with the cold source operating, was a significant achievement. Furthermore, measurements of the cold source showed that the performance exceeded expectations, making it one of the world's most brilliant sources of cold neutrons. HFIR finished the year having completed five run cycles and 5,880 MWd of operation. At SNS, the year began with 20 kW of beam power on target; and thanks to a highly motivated staff, we reached a record-breaking power level of 183 kW by the end of the year. Integrated beam power delivered to the target was 160 MWh. Although this is a substantial accomplishment, the next year will bring the challenge of increasing the integrated beam power delivered to 887 MWh as we chart our path toward 5,350 MWh by 2011.

Neuroprotective Effects and Mechanisms of Curcumin–Cu(II and –Zn(II Complexes Systems and Their Pharmacological Implications

Directory of Open Access Journals (Sweden)

Fa-Shun Yan

2017-12-01

Full Text Available Alzheimer’s disease (AD is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa, is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II or Zn(II on hydrogen peroxide (H2O2-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12 cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin–Cu(II complexes systems possessed enhanced O2·–-scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin–Cu(II complexes systems were stronger than curcumin–Zn(II system. Curcumin–Cu(II or –Zn(II complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin–Cu(II complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin–Cu(II or –Zn(II complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin–Cu(II or –Zn(II complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.

DESIGN STUDY FOR A LOW-ENRICHED URANIUM CORE FOR THE HIGH FLUX ISOTOPE REACTOR, ANNUAL REPORT FOR FY 2010

Energy Technology Data Exchange (ETDEWEB)

Cook, David Howard [ORNL; Freels, James D [ORNL; Ilas, Germina [ORNL; Jolly, Brian C [ORNL; Miller, James Henry [ORNL; Primm, Trent [ORNL; Renfro, David G [ORNL; Sease, John D [ORNL; Pinkston, Daniel [ORNL

2011-02-01

This report documents progress made during FY 2010 in studies of converting the High Flux Isotope Reactor (HFIR) from high enriched uranium (HEU) fuel to low enriched uranium (LEU) fuel. Conversion from HEU to LEU will require a change in fuel form from uranium oxide to a uranium-molybdenum alloy. With axial and radial grading of the fuel foil and an increase in reactor power to 100 MW, calculations indicate that the HFIR can be operated with LEU fuel with no degradation in performance to users from the current level. Studies are reported of support to a thermal hydraulic test loop design, the implementation of finite element, thermal hydraulic analysis capability, and infrastructure tasks at HFIR to upgrade the facility for operation at 100 MW. A discussion of difficulties with preparing a fuel specification for the uranium-molybdenum alloy is provided. Continuing development in the definition of the fuel fabrication process is described.

Analysis and modeling of flow-blockage-induced steam explosion events in the high-flux isotope reactor

International Nuclear Information System (INIS)

Taleyarkhan, R.P.; Georgevich, V.; Nestor, C.W.; Gat, U.; Lepard, B.L.; Cook, D.H.; Freels, J.; Chang, S.J.; Luttrell, C.; Gwaltney, R.C.

1994-01-01

This article provides a perspective overview of the analysis and modeling work done to evaluate the threat from steam explosion loads in the High-Flux Isotope Reactor (HFIR) during flow blockage events. The overall work scope included modeling and analysis of core-melt initiation, melt propagation, bounding and best-estimate steam explosion energetics, vessel failure from fracture, bolts failure from exceedance of elastic limits, and, finally, missile evolution and transport. Aluminum ignition was neglected. Evaluations indicated that a thermally driven steam explosion with more than 65 MJ of energy insertion in the core region over several milliseconds would be needed to cause a sufficiently energetic missile with a capacity to cause early confinement failure. This amounts to about 65% of the HFIR core mass melting and participating in a steam explosion. Conservative melt propagation analyses have indicated that at most only 24% of the HFIR core mass could melt during flow blockage events under full-power conditions. 19 refs., 11 figs

'Sleeping reactor' irradiations. The use of a shut-down reactor for the determination of elements with short-lived activation products

International Nuclear Information System (INIS)

Jerde, E.A.; Oak Ridge National Laboratory, TN; Glasgow, D.C.

1999-01-01

Neutron activation analysis utilizing the High Flux Isotope Reactor (HFIR) immediately following SCRAM is a workable solution to obtaining data for ultra-short lived species, principally Al, Ti, Mg, and V. Neutrons are produced in the HFIR core within the beryllium reflector due to gamma-ray bombardment from the spent fuel elements. This neutron flux is not constant, varying by over two orders of magnitude during the first 24 hours. The problems associated with irradiation in a changing neutron flux are removed through the use of a specially tailored activation equation. This activation equation is applicable to any irradiation at HFIR in the firs 24 hours after SCRAM since the fuel elements are identical from cycle to cycle, and the gamma-emitting nuclides responsible for the neutrons reach saturation during the fuel cycle. Reference material tests demonstrate that this method is successful, and detection limit estimates reveal that it should be applicable to materials of widely ranging mass and composition. (author)

Autoimmunity and inflammation are independent of class II transactivator type PIV-dependent class II major histocompatibility complex expression in peripheral tissues during collagen-induced arthritis.

Science.gov (United States)

Waldburger, Jean-Marc; Palmer, Gaby; Seemayer, Christian; Lamacchia, Celine; Finckh, Axel; Christofilopoulos, Panayiotis; Baeten, Dominique; Reith, Walter; Gabay, Cem

2011-11-01

To determine the regulation of class II major histocompatibility complex (MHC) expression in fibroblast-like synoviocytes (FLS) in order to investigate their role as nonprofessional antigen-presenting cells in collagen-induced arthritis (CIA). Expression of class II MHC, class II MHC transactivator (CIITA), and Ciita isoforms PI, PIII, and PIV was examined by real-time quantitative polymerase chain reaction, immunohistochemistry, and flow cytometry in human synovial tissues, arthritic mouse joints, and human and murine FLS. CIA was induced in mice in which isoform PIV of Ciita was knocked out (PIV(-/-) ), in PIV(-/-) mice transgenic for CIITA in the thymus (K14 CIITA), and in their control littermates. HLA-DRA, total CIITA, and CIITA PIII messenger RNA levels were significantly increased in synovial tissue samples from patients with rheumatoid arthritis compared with the levels in tissue from patients with osteoarthritis. Human FLS expressed surface class II MHC via CIITA PIII and PIV, while class II MHC expression in murine FLS was entirely mediated by PIV. Mice with a targeted deletion of CIITA PIV lack CD4+ T cells and were protected against CIA. The expression of CIITA was restored in the thymus of PIV(-/-) K14 CIITA-transgenic mice, which had a normal CD4+ T cell repertoire and normal surface levels of class II MHC on professional antigen-presenting cells, but did not induce class II MHC on FLS. Synovial inflammation and immune responses against type II collagen were similar in PIV(-/-) K14 CIITA-transgenic mice and control mice with CIA, but bone erosion was significantly reduced in the absence of PIV. Overexpression of class II MHC is tightly correlated with CIITA expression in arthritic synovium and in FLS. Selective targeting of Ciita PIV in peripheral tissues abrogates class II MHC expression by murine FLS but does not protect against inflammation and autoimmune responses in CIA. Copyright © 2011 by the American College of Rheumatology.

Adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II), and As(V) on bacterially produced metal sulfides.

Science.gov (United States)

Jong, Tony; Parry, David L

2004-07-01

The adsorption of Pb(II), Cu(II), Cd(II), Zn(II), Ni(II), Fe(II) and As(V) onto bacterially produced metal sulfide (BPMS) material was investigated using a batch equilibrium method. It was found that the sulfide material had adsorptive properties comparable with those of other adsorbents with respect to the specific uptake of a range of metals and, the levels to which dissolved metal concentrations in solution can be reduced. The percentage of adsorption increased with increasing pH and adsorbent dose, but decreased with increasing initial dissolved metal concentration. The pH of the solution was the most important parameter controlling adsorption of Cd(II), Cu(II), Fe(II), Ni(II), Pb(II), Zn(II), and As(V) by BPMS. The adsorption data were successfully modeled using the Langmuir adsorption isotherm. Desorption experiments showed that the reversibility of adsorption was low, suggesting high-affinity adsorption governed by chemisorption. The mechanism of adsorption for the divalent metals was thought to be the formation of strong, inner-sphere complexes involving surface hydroxyl groups. However, the mechanism for the adsorption of As(V) by BPMS appears to be distinct from that of surface hydroxyl exchange. These results have important implications to the management of metal sulfide sludge produced by bacterial sulfate reduction.

Cylindrical target Li-beam-driven hohlraum experiments

International Nuclear Information System (INIS)

Derzon, M.S.; Aubert, J.; Chandler, G.A.

1998-06-01

The authors performed a series of experiments on the Particle Beam Fusion Accelerator II (PBFA II) in May, 1994, and obtained a brightness temperature of 61 ± 2 eV for an ion-beam heated hohlraum. The hohlraum was a 4-mm-diameter, right-circular cylinder with a 1.5-mm-thick gold wall, a low-density CH foam fill, and a 1.5- or 3-mm-diameter diagnostic aperture in the top. The nominal parameters of the radially-incident PBFA II Li ion beam were 9 MeV peak energy (∼10 MeV at the gas cell) at the target at a peak power of 2.5 ± 0.3 TW/cm 2 and a 15 ns pulse width. Azimuthal variations in intensity of a factor of 3, with respect to the mean, were observed. Nonuniformities in thermal x-ray emission across the area of the diagnostic hole were also observed. Time-dependent hole-closure velocities were measured: the time-averaged velocity of ∼2 cm/micros is in good agreement with sound speed estimates. Unfolded x-ray spectra and brightness temperatures as a function of time are reported and compared to simulations. Hole closure corrections are discussed with comparisons between XRD and bolometer measurements. Temperature scaling with power on target is also presented

Hypoxia targeting copper complexes

International Nuclear Information System (INIS)

Dearling, J.L.

1998-11-01

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

Spectroscopy of gluonic states at LAMPF II

International Nuclear Information System (INIS)

Chanowitz, M.S.

1983-08-01

The properties of QCD which imply the existence of gluonic states are reviewed. The problem of discovering the spectrum of gluonic states is discussed in general and illustrated with examples from current data. Higher statistics fixed target experiments, such as could be performed at LAMPF II, are essential for further progress

DISE: A Seed-Dependent RNAi Off-Target Effect That Kills Cancer Cells.

Science.gov (United States)

Putzbach, William; Gao, Quan Q; Patel, Monal; Haluck-Kangas, Ashley; Murmann, Andrea E; Peter, Marcus E

2018-01-01

Off-target effects (OTEs) represent a significant caveat for RNAi caused by substantial complementarity between siRNAs and unintended mRNAs. We now discuss the existence of three types of seed-dependent OTEs (sOTEs). Type I involves unintended targeting through the guide strand seed of an siRNA. Type II is caused by the activity of the seed on the designated siRNA passenger strand when loaded into the RNA-induced silencing complex (RISC). Both type I and II sOTEs will elicit unpredictable cellular responses. By contrast, in sOTE type III the guide strand seed preferentially targets essential survival genes resulting in death induced by survival gene elimination (DISE). In this Opinion article, we discuss DISE as a consequence of RNAi that may preferentially affect cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria

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Daniel Ken Inaoka

2015-07-01

Full Text Available Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM. In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

Structural Insights into the Molecular Design of Flutolanil Derivatives Targeted for Fumarate Respiration of Parasite Mitochondria.

Science.gov (United States)

Inaoka, Daniel Ken; Shiba, Tomoo; Sato, Dan; Balogun, Emmanuel Oluwadare; Sasaki, Tsuyoshi; Nagahama, Madoka; Oda, Masatsugu; Matsuoka, Shigeru; Ohmori, Junko; Honma, Teruki; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu

2015-07-07

Recent studies on the respiratory chain of Ascaris suum showed that the mitochondrial NADH-fumarate reductase system composed of complex I, rhodoquinone and complex II plays an important role in the anaerobic energy metabolism of adult A. suum. The system is the major pathway of energy metabolism for adaptation to a hypoxic environment not only in parasitic organisms, but also in some types of human cancer cells. Thus, enzymes of the pathway are potential targets for chemotherapy. We found that flutolanil is an excellent inhibitor for A. suum complex II (IC50 = 0.058 μM) but less effectively inhibits homologous porcine complex II (IC50 = 45.9 μM). In order to account for the specificity of flutolanil to A. suum complex II from the standpoint of structural biology, we determined the crystal structures of A. suum and porcine complex IIs binding flutolanil and its derivative compounds. The structures clearly demonstrated key interactions responsible for its high specificity to A. suum complex II and enabled us to find analogue compounds, which surpass flutolanil in both potency and specificity to A. suum complex II. Structures of complex IIs binding these compounds will be helpful to accelerate structure-based drug design targeted for complex IIs.

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

International Nuclear Information System (INIS)

Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun; Zhuang, Wen-Fang

2015-01-01

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun, E-mail: majuntongrensh1@126.com; Zhuang, Wen-Fang, E-mail: wenfangzhuangmd@163.com

2015-05-15

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.

Recent progress at RTNS-II

International Nuclear Information System (INIS)

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

1984-01-01

The Rotating Target Neutron Source (RTNS-II) facility produces 14-MeV neutrons for materials damage studies. Initial operation for irradiations, which occurred in 1979, began with a neutron source strength of 10 13 n/s utilizing one of the accelerator-based neutron sources. Details are given on improvements which have resulted in both increased neutron production and neutron source strength and improved control and monitoring. 8 references

Design and Testing for a New Thermosyphon Irradiation Vehicle

Energy Technology Data Exchange (ETDEWEB)

Felde, David K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Carbajo, Juan J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); McDuffee, Joel Lee [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-09-01

The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) requires most materials and all fuel experiments to be placed in a pressure containment vessel to ensure that internal contaminants such as fission products cannot be released into the primary coolant. It also requires that all experiments be capable of withstanding various accident conditions (e.g., loss of coolant) without generating vapor bubbles on the surface of the experiment in the primary coolant. These requirements are intended to artificially increase experiment temperatures by introducing a barrier between the experimental materials and the HFIR coolant, and by reducing heat loads to the HFIR primary coolant, thus ensuring that no boiling can occur. A proposed design for materials irradiation would remove these limitations by providing the required primary containment with an internal cooling flow. This would allow for experiments to be irradiated without concern for coolant contamination (e.g., from cladding failure of advanced fuel pins) or for specimen heat load. This report describes a new materials irradiation experiment design that uses a thermosyphon cooling system to allow experimental materials direct access to a liquid coolant. The new design also increases the range of conditions that can be tested in HFIR. This design will provide a unique capability to validate the performance of current and advanced fuels and materials. Because of limited supporting data for this kind of irradiation vehicle, a test program was initiated to obtain operating data that can be used to (1) qualify the vehicle for operation in HFIR and (2) validate computer models used to perform design- and safety-basis calculations. This report also describes the test facility and experimental data, and it provides a comparison of the experimental data to computer simulations. A total of 51 tests have been completed: four tests with pure steam, 12 tests with argon, and 35 tests with helium. A total

Fragment Screening of Human Kynurenine Aminotransferase-II.

Science.gov (United States)

Jayawickrama, Gayan S; Nematollahi, Alireza; Sun, Guanchen; Church, W Bret

2018-03-01

Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors. Surface plasmon resonance (SPR) was used to screen a fragment library containing 1000 compounds, of which 41 hits were identified. These hits were further evaluated with SPR, and 18 were selected for inhibition studies. From these hits, two fragments, F6037-0164 and F0037-7280, were pursued and determined to have an IC 50 of 524.5 (± 25.6) μM and 115.2 (± 4.5) μM, respectively. This strategy shows the viability of using FBDD in gleaning knowledge about KAT-II inhibition and generating leads for the production of KAT-II inhibitors.

Pharmacological inhibition of dynamin II reduces constitutive protein secretion from primary human macrophages.

Directory of Open Access Journals (Sweden)

Maaike Kockx

Full Text Available Dynamins are fission proteins that mediate endocytic and exocytic membrane events and are pharmacological therapeutic targets. These studies investigate whether dynamin II regulates constitutive protein secretion and show for the first time that pharmacological inhibition of dynamin decreases secretion of apolipoprotein E (apoE and several other proteins constitutively secreted from primary human macrophages. Inhibitors that target recruitment of dynamin to membranes (MiTMABs or directly target the GTPase domain (Dyngo or Dynole series, dose- and time- dependently reduced the secretion of apoE. SiRNA oligo's targeting all isoforms of dynamin II confirmed the involvement of dynamin II in apoE secretion. Inhibition of secretion was not mediated via effects on mRNA or protein synthesis. 2D-gel electrophoresis showed that inhibition occurred after apoE was processed and glycosylated in the Golgi and live cell imaging showed that inhibited secretion was associated with reduced post-Golgi movement of apoE-GFP-containing vesicles. The effect was not restricted to macrophages, and was not mediated by the effects of the inhibitors on microtubules. Inhibition of dynamin also altered the constitutive secretion of other proteins, decreasing the secretion of fibronectin, matrix metalloproteinase 9, Chitinase-3-like protein 1 and lysozyme but unexpectedly increasing the secretion of the inflammatory mediator cyclophilin A. We conclude that pharmacological inhibitors of dynamin II modulate the constitutive secretion of macrophage apoE as a class effect, and that their capacity to modulate protein secretion may affect a range of biological processes.

Synthesis and spectroscopic studies of biologically active tetraazamacrocyclic complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II

Directory of Open Access Journals (Sweden)

Monika Tyagi

2014-01-01

Full Text Available Complexes of Mn(II, Co(II, Ni(II, Pd(II and Pt(II were synthesized with the macrocyclic ligand, i.e., 2,3,9,10-tetraketo-1,4,8,11-tetraazacycoletradecane. The ligand was prepared by the [2 + 2] condensation of diethyloxalate and 1,3-diamino propane and characterized by elemental analysis, mass, IR and 1H NMR spectral studies. All the complexes were characterized by elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic and electron paramagnetic resonance spectral studies. The molar conductance measurements of Mn(II, Co(II and Ni(II complexes in DMF correspond to non electrolyte nature, whereas Pd(II and Pt(II complexes are 1:2 electrolyte. On the basis of spectral studies an octahedral geometry has been assigned for Mn(II, Co(II and Ni(II complexes, whereas square planar geometry assigned for Pd(II and Pt(II. In vitro the ligand and its metal complexes were evaluated against plant pathogenic fungi (Fusarium odum, Aspergillus niger and Rhizoctonia bataticola and some compounds found to be more active as commercially available fungicide like Chlorothalonil.

Lithium ion beam driven hohlraums for PBFA II

International Nuclear Information System (INIS)

Dukart, R.J.

1994-01-01

In our light ion inertial confinement fusion (ICF) program, fusion capsules are driven with an intense x-ray radiation field produced when an intense beam of ions penetrates a radiation case and deposits energy in a foam x-ray conversion region. A first step in the program is to generate and measure these intense fields on the Particle Beam Fusion Accelerator II (PBFA II). Our goal is to generate a 100-eV radiation temperature in lithium ion beam driven hohlraums, the radiation environment which will provide the initial drive temperature for ion beam driven implosion systems designed to achieve high gain. In this paper, we describe the design of such hohlraum targets and their predicted performance on PBFA II as we provide increasing ion beam intensities

The Gerda Phase II detector assembly

Energy Technology Data Exchange (ETDEWEB)

Bode, Tobias; Schoenert, Stefan [Physik-Department E15, Technische Universitaet Muenchen (Germany); Schwingenheuer, Bernhard [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Collaboration: GERDA-Collaboration

2013-07-01

Phase II of the Gerda (Germanium Detector Array) experiment will continue the search for the neutrinoless double beta decay (0νββ) of {sup 76}Ge. Prerequisites for Phase II are an increased target mass and a reduced background index of < 10 {sup -3} cts/(keV.kg.yr). Major hardware upgrades to achieve these requirements are scheduled for 2013. They include the deployment of a new radio pure low mass detector assembly. The structural properties of available radio-pure materials and reduction of mass necessitate a change of the electrical contacting used to bias and read-out the detectors. The detector assembly design and the favored contacting solution are presented.

Mitochondrial fumarate reductase as a target of chemotherapy: from parasites to cancer cells.

Science.gov (United States)

Sakai, Chika; Tomitsuka, Eriko; Esumi, Hiroyasu; Harada, Shigeharu; Kita, Kiyoshi

2012-05-01

Recent research on respiratory chain of the parasitic helminth, Ascaris suum has shown that the mitochondrial NADH-fumarate reductase system (fumarate respiration), which is composed of complex I (NADH-rhodoquinone reductase), rhodoquinone and complex II (rhodoquinol-fumarate reductase) plays an important role in the anaerobic energy metabolism of adult parasites inhabiting hosts. The enzymes in these parasite-specific pathways are potential target for chemotherapy. We isolated a novel compound, nafuredin, from Aspergillus niger, which inhibits NADH-fumarate reductase in helminth mitochondria at nM order. It competes for the quinone-binding site in complex I and shows high selective toxicity to the helminth enzyme. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep indicating that mitochondrial complex I is a promising target for chemotherapy. In addition to complex I, complex II is a good target because its catalytic direction is reverse of succinate-ubiquionone reductase in the host complex II. Furthermore, we found atpenin and flutolanil strongly and specifically inhibit mitochondrial complex II. Interestingly, fumarate respiration was found not only in the parasites but also in some types of human cancer cells. Analysis of the mitochondria from the cancer cells identified an anthelminthic as a specific inhibitor of the fumarate respiration. Role of isoforms of human complex II in the hypoxic condition of cancer cells and fetal tissues is a challenge. This article is part of a Special Issue entitled Biochemistry of Mitochondria, Life and Intervention 2010. Copyright © 2011 Elsevier B.V. All rights reserved.

Irradiation performance of HTGR fertile fuel in HFIR target capsules HT-12 through HT-15. Part I. Experiment description and fission product behavior

International Nuclear Information System (INIS)

Kania, M.J.; Lindemer, T.B.; Morgan, M.T.; Robbins, J.M.

1977-02-01

Sixteen types of Biso-coated designs, on ThO 2 kernels, were irradiated in High Flux Isotope Reactor target capsules HT-12 through HT-15. The report addresses the description of the experiment and extensive postirradiation analyses and experiments to determine fertile-particle burnup, fuel coating failures, and fission product behavior. Several low-temperature isotropic (LTI) pyrocarbon coatings, which ''survived'' according to visual inspection, were shown to have developed permeability during irradiation. These particles were irradiated at temperatures approximately equal to 1250 0 C and to burnups equal to or greater than 8 percent fission per initial heavy-metal atom (FIMA). No evidence of permeability was found in similar particles irradiated at temperatures approximately equal to 1550 0 C and burnups approximately equal to 16 percent FIMA. Failures due to permeability were not detectable by visual inspection but required a more extensive investigation by the 1000 0 C gaseous chlorine leaching technique. Maximum particle surface operating temperatures were found to be approximately 300 0 C in excess of design limits of 900 0 C (low-temperature magazines) and 1250 0 C (high-temperature magazines). The extremes of high temperatures and fast neutron fluences up to 1.6 x 10 22 neutrons/cm 2 produced severe degradation and swelling of the Poco graphite magazines and sample holders

Thermal Safety Analyses for the Production of Plutonium-238 at the High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Hurt, Christopher J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Freels, James D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hobbs, Randy W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Jain, Prashant K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Maldonado, G. Ivan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-08-01

There has been a considerable effort over the previous few years to demonstrate and optimize the production of plutonium-238 (²³⁸Pu) at the High Flux Isotope Reactor (HFIR). This effort has involved resources from multiple divisions and facilities at the Oak Ridge National Laboratory (ORNL) to demonstrate the fabrication, irradiation, and chemical processing of targets containing neptunium-237 (²³⁷Np) dioxide (NpO₂)/aluminum (Al) cermet pellets. A critical preliminary step to irradiation at the HFIR is to demonstrate the safety of the target under irradiation via documented experiment safety analyses. The steady-state thermal safety analyses of the target are simulated in a finite element model with the COMSOL Multiphysics code that determines, among other crucial parameters, the limiting maximum temperature in the target. Safety analysis efforts for this model discussed in the present report include: (1) initial modeling of single and reduced-length pellet capsules in order to generate an experimental knowledge base that incorporate initial non-linear contact heat transfer and fission gas equations, (2) modeling efforts for prototypical designs of partially loaded and fully loaded targets using limited available knowledge of fabrication and irradiation characteristics, and (3) the most recent and comprehensive modeling effort of a fully coupled thermo-mechanical approach over the entire fully loaded target domain incorporating burn-up dependent irradiation behavior and measured target and pellet properties, hereafter referred to as the production model. These models are used to conservatively determine several important steady-state parameters including target stresses and temperatures, the limiting condition of which is the maximum temperature with respect to the melting point. The single pellet model results provide a basis for the safety of the irradiations, followed by parametric analyses in the initial prototypical designs

Rapid molecular evolution across amniotes of the IIS/TOR network.

Science.gov (United States)

McGaugh, Suzanne E; Bronikowski, Anne M; Kuo, Chih-Horng; Reding, Dawn M; Addis, Elizabeth A; Flagel, Lex E; Janzen, Fredric J; Schwartz, Tonia S

2015-06-02

The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network regulates lifespan and reproduction, as well as metabolic diseases, cancer, and aging. Despite its vital role in health, comparative analyses of IIS/TOR have been limited to invertebrates and mammals. We conducted an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes with 18 newly generated transcriptomes from nonavian reptiles and additional available genomes/transcriptomes. We uncovered rapid and extensive molecular evolution between reptiles (including birds) and mammals: (i) the IIS/TOR network, including the critical nodes insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K), exhibit divergent evolutionary rates between reptiles and mammals; (ii) compared with a proxy for the rest of the genome, genes of the IIS/TOR extracellular network exhibit exceptionally fast evolutionary rates; and (iii) signatures of positive selection and coevolution of the extracellular network suggest reptile- and mammal-specific interactions between members of the network. In reptiles, positively selected sites cluster on the binding surfaces of insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and insulin receptor (INSR); whereas in mammals, positively selected sites clustered on the IGF2 binding surface, suggesting that these hormone-receptor binding affinities are targets of positive selection. Further, contrary to reports that IGF2R binds IGF2 only in marsupial and placental mammals, we found positively selected sites clustered on the hormone binding surface of reptile IGF2R that suggest that IGF2R binds to IGF hormones in diverse taxa and may have evolved in reptiles. These data suggest that key IIS/TOR paralogs have sub- or neofunctionalized between mammals and reptiles and that this network may underlie fundamental life history and physiological differences between these amniote sister clades.

Resveratrol: A novel type of topoisomerase II inhibitor.

Science.gov (United States)

Lee, Joyce H; Wendorff, Timothy J; Berger, James M

2017-12-22

Resveratrol, a polyphenol found in various plant sources, has gained attention as a possible agent responsible for the purported health benefits of certain foods, such as red wine. Despite annual multi-million dollar market sales as a nutriceutical, there is little consensus about the physiological roles of resveratrol. One suggested molecular target of resveratrol is eukaryotic topoisomerase II (topo II), an enzyme essential for chromosome segregation and DNA supercoiling homeostasis. Interestingly, resveratrol is chemically similar to ICRF-187, a clinically approved chemotherapeutic that stabilizes an ATP-dependent dimerization interface in topo II to block enzyme activity. Based on this similarity, we hypothesized that resveratrol may antagonize topo II by a similar mechanism. Using a variety of biochemical assays, we find that resveratrol indeed acts through the ICRF-187 binding locus, but that it inhibits topo II by preventing ATPase domain dimerization rather than stabilizing it. This work presents the first comprehensive analysis of the biochemical effects of both ICRF-187 and resveratrol on the human isoforms of topo II, and reveals a new mode for the allosteric regulation of topo II through modulation of ATPase status. Natural polyphenols related to resveratrol that have been shown to impact topo II function may operate in a similar manner. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Non-Surgical Breast-Conserving Treatment (KORTUC-BCT Using a New Radiosensitization Method (KORTUC II for Patients with Stage I or II Breast Cancer

Directory of Open Access Journals (Sweden)

Yasuhiro Ogawa

2015-11-01

-surgical BCT can be performed using KORTUC II, which has three major characteristics: imaging guidance; enzyme-targeting; and targeting of breast cancer stem cells via the CD44 receptor.

Emerging drugs which target the renin-angiotensin-aldosterone system.

Science.gov (United States)

Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

2011-12-01

The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

The exosome component Rrp6 is required for RNA polymerase II termination at specific targets of the Nrd1-Nab3 pathway.

Directory of Open Access Journals (Sweden)

Melanie J Fox

Full Text Available The exosome and its nuclear specific subunit Rrp6 form a 3'-5' exonuclease complex that regulates diverse aspects of RNA biology including 3' end processing and degradation of a variety of noncoding RNAs (ncRNAs and unstable transcripts. Known targets of the nuclear exosome include short (<1000 bp RNAPII transcripts such as small noncoding RNAs (snRNAs, cryptic unstable transcripts (CUTs, and some stable unannotated transcripts (SUTs that are terminated by an Nrd1, Nab3, and Sen1 (NNS dependent mechanism. NNS-dependent termination is coupled to RNA 3' end processing and/or degradation by the Rrp6/exosome in yeast. Recent work suggests Nrd1 is necessary for transcriptome surveillance, regulating promoter directionality and suppressing antisense transcription independently of, or prior to, Rrp6 activity. It remains unclear whether Rrp6 is directly involved in termination; however, Rrp6 has been implicated in the 3' end processing and degradation of ncRNA transcripts including CUTs. To determine the role of Rrp6 in NNS termination globally, we performed RNA sequencing (RNA-Seq on total RNA and perform ChIP-exo analysis of RNA Polymerase II (RNAPII localization. Deletion of RRP6 promotes hyper-elongation of multiple NNS-dependent transcripts resulting from both improperly processed 3' RNA ends and faulty transcript termination at specific target genes. The defects in RNAPII termination cause transcriptome-wide changes in mRNA expression through transcription interference and/or antisense repression, similar to previously reported effects of depleting Nrd1 from the nucleus. Elongated transcripts were identified within all classes of known NNS targets with the largest changes in transcription termination occurring at CUTs. Interestingly, the extended transcripts that we have detected in our studies show remarkable similarity to Nrd1-unterminated transcripts at many locations, suggesting that Rrp6 acts with the NNS complex globally to promote

Irradiation and gamma-ray spectrometric parameters for 129I neutron-activation analysis

International Nuclear Information System (INIS)

Brauer, F.P.; Strebin, R.S. Jr.; Mitzlaff, W.A.; Kaye, J.H.

1983-09-01

This paper describes the influence of reactor neutron irradiation facilities on low-level 129 I analysis methodology. Three reactors are compared - the HFIR at ORNL, the N-Reactor at Hanford, and a 1-MW research reactor at Washington State University, Pullman, WA. Parameters compared include sensitivity for 129 I and natural iodine and interference effects due to high levels of 127 I in irradiated samples. Selection of detector systems for off-site use at HFIR is discussed. A comparison of neutron activation analysis with other sensitive detection methods for measurement of 129 I is given

Effect of Cu(II), Cd(II) and Zn(II) on Pb(II) biosorption by algae Gelidium-derived materials.

Science.gov (United States)

Vilar, Vítor J P; Botelho, Cidália M S; Boaventura, Rui A R

2008-06-15

Biosorption of Pb(II), Cu(II), Cd(II) and Zn(II) from binary metal solutions onto the algae Gelidium sesquipedale, an algal industrial waste and a waste-based composite material was investigated at pH 5.3, in a batch system. Binary Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II) solutions have been tested. For the same equilibrium concentrations of both metal ions (1 mmol l(-1)), approximately 66, 85 and 86% of the total uptake capacity of the biosorbents is taken by lead ions in the systems Pb(II)/Cu(II), Pb(II)/Cd(II) and Pb(II)/Zn(II), respectively. Two-metal results were fitted to a discrete and a continuous model, showing the inhibition of the primary metal biosorption by the co-cation. The model parameters suggest that Cd(II) and Zn(II) have the same decreasing effect on the Pb(II) uptake capacity. The uptake of Pb(II) was highly sensitive to the presence of Cu(II). From the discrete model it was possible to obtain the Langmuir affinity constant for Pb(II) biosorption. The presence of the co-cations decreases the apparent affinity of Pb(II). The experimental results were successfully fitted by the continuous model, at different pH values, for each biosorbent. The following sequence for the equilibrium affinity constants was found: Pb>Cu>Cd approximately Zn.

Neutron energy spectrum influence on irradiation hardening and microstructural development of tungsten

Energy Technology Data Exchange (ETDEWEB)

Fukuda, Makoto, E-mail: makoto.fukuda@qse.tohoku.ac.jp [Tohoku University, Sendai, 980-8579 (Japan); Kiran Kumar, N.A.P.; Koyanagi, Takaaki; Garrison, Lauren M. [Oak Ridge National Laboratory, Oak Ridge, TN, 37831 (United States); Snead, Lance L. [Massachusetts Institute of Technology, Cambridge, MA, 02139 (United States); Katoh, Yutai [Oak Ridge National Laboratory, Oak Ridge, TN, 37831 (United States); Hasegawa, Akira [Tohoku University, Sendai, 980-8579 (Japan)

2016-10-15

Neutron irradiation to single crystal pure tungsten was performed in the mixed spectrum High Flux Isotope Reactor (HFIR). To investigate the influences of neutron energy spectrum, the microstructure and irradiation hardening were compared with previous data obtained from the irradiation campaigns in the mixed spectrum Japan Material Testing Reactor (JMTR) and the sodium-cooled fast reactor Joyo. The irradiation temperatures were in the range of ∼90–∼800 °C and fast neutron fluences were 0.02–9.00 × 10{sup 25} n/m{sup 2} (E > 0.1 MeV). Post irradiation evaluation included Vickers hardness measurements and transmission electron microscopy. The hardness and microstructure changes exhibited a clear dependence on the neutron energy spectrum. The hardness appeared to increase with increasing thermal neutron flux when fast fluence exceeds 1 × 10{sup 25} n/m{sup 2} (E > 0.1 MeV). Irradiation induced precipitates considered to be χ- and σ-phases were observed in samples irradiated to >1 × 10{sup 25} n/m{sup 2} (E > 0.1 MeV), which were pronounced at high dose and due to the very high thermal neutron flux of HFIR. Although the irradiation hardening mainly caused by defects clusters in a low dose regime, the transmutation-induced precipitation appeared to impose additional significant hardening of the tungsten. - Highlights: • The microstructure and irradiation hardening of single crystal pure W irradiated in HFIR was investigated. • The neutron energy spectrum influence was evaluated by comparing the HFIR results with previous work in Joyo and JMTR. • In the dose range up to ∼1 dpa, the neutron energy spectrum influence of irradiation hardening was not clear. • In the dose range above 1 dpa, the neutron energy influence on irradiation hardening and microstructural development was clearly observed. • The irradiation induced precipitates caused significant irradiation hardening of pure W irradiated in HFIR.

Frozen ammonia micropellet generator for Baseball II-T

International Nuclear Information System (INIS)

Denhoy, B.S.

1975-01-01

A ''startup'' plasma at the center of the Baseball II-T magnet was studied. This startup plasma will be used as a target for high energy neutral beams to achieve the required build-up. The target plasma will be created by irradiating a solid pellet with a laser beam. Although a deuterium pellet would be superior because of purity, the development of an ammonia pellet was undertaken because it requires a simpler technology. The ammonia target plasma is physically acceptable for the initial experiment. A frozen ammonia pellet, about 100 μm in diameter, will be irradiated with 300-J CO 2 laser, to produce a density of about 10 13 cm -3 and about 1 kV temperature

MRP II (material requirements planning): one year later.

Science.gov (United States)

Tull, W L; Norman, R L

1994-08-01

This article addresses the continued need for the behavior change process that must be managed long after materiel requirements planning (MRP II) implementation. Mason & Hanger, Pantex Plant is the final assembly and dismantlement facility for all United States nuclear weapons. On October 1, 1990, Mason & Hanger implemented a full production cutover to MRP II. One year later, following class A certification, the MRP II implementation team is still actively managing the change process through education and training programs and overall continuous improvement initiatives. Actual behavior change problems are identified together with the proven solutions implemented in a government-owned, contractor-operated facility environment. Performance measurements ranging from senior management planning to shop floor accomplishments and cost variance reports are shown as normal management tools used to identify target improvement areas.

A Green Bank Telescope Survey of Large Galactic H II Regions

Science.gov (United States)

Anderson, L. D.; Armentrout, W. P.; Luisi, Matteo; Bania, T. M.; Balser, Dana S.; Wenger, Trey V.

2018-02-01

As part of our ongoing H II Region Discovery Survey (HRDS), we report the Green Bank Telescope detection of 148 new angularly large Galactic H II regions in radio recombination line (RRL) emission. Our targets are located at a declination of δ > -45^\\circ , which corresponds to 266^\\circ > {\\ell }> -20^\\circ at b=0^\\circ . All sources were selected from the Wide-field Infrared Survey Explorer Catalog of Galactic H II Regions, and have infrared angular diameters ≥slant 260\\prime\\prime . The Galactic distribution of these “large” H II regions is similar to that of the previously known sample of Galactic H II regions. The large H II region RRL line width and peak line intensity distributions are skewed toward lower values, compared with that of previous HRDS surveys. We discover seven sources with extremely narrow RRLs 100 {pc}, making them some of the physically largest known H II regions in the Galaxy. This survey completes the HRDS H II region census in the Northern sky, where we have discovered 887 H II regions and more than doubled the size of the previously known census of Galactic H II regions.

Retrieval of precipitable water using near infrared channels of Global Imager/Advanced Earth Observing Satellite-II (GLI/ADEOS-II)

International Nuclear Information System (INIS)

Kuji, M.; Uchiyama, A.

2002-01-01

Retrieval of precipitable water (vertically integrated water vapor amount) is proposed using near infrared channels og Global Imager onboard Advanced Earth Observing Satellite-II (GLI/ADEOS-II). The principle of retrieval algorithm is based upon that adopted with Moderate Resolution Imaging Spectroradiometer (MODIS) onboard Earth Observing System (EOS) satellite series. Simulations were carried out with GLI Signal Simulator (GSS) to calculate the radiance ratio between water vapor absorbing bands and non-absorbing bands. As a result, it is found that for the case of high spectral reflectance background (a bright target) such as the land surface, the calibration curves are sensitive to the precipitable water variation. For the case of low albedo background (a dark target) such as the ocean surface, on the contrary, the calibration curve is not very sensitive to its variation under conditions of the large water vapor amount. It turns out that aerosol loading has little influence on the retrieval over a bright target for the aerosol optical thickness less than about 1.0 at 500nm. It is also anticipated that simultaneous retrieval of the water vapor amount using GLI data along with other channels will lead to improved accuracy of the determination of surface geophysical properties, such as vegetation, ocean color, and snow and ice, through the better atmospheric correction

Report of the Fixed-Target Proton-Accelerator Group

International Nuclear Information System (INIS)

Abe, K.; Bunce, G.; Fisk, G.

1982-01-01

The fixed target proton accelerator group divided itself into two roughly equal parts. One sub-group concentrated on a high intensity (10 14 protons/sec) moderate energy (30 GeV) machine while the other worked on a moderate intensity (5 x 10 11 protons/sec) very high energy (20 TeV) machine. For experiments where the total available energy is adequate, the fixed target option added to a anti p p 20 TeV collider ring has several attractive features: (1) high luminosity afforded by intense beams striking thick solid targets; (2) secondary beams of hadrons, photons, and leptons; and (3) the versatility of a fixed target facility, where many experiments can be performed independently. The proposed experiments considered by the subgroup, including neutrino, photon, hadron, and very short lived particle beams were based both on scaled up versions of similar experiments proposed for Tevatron II at Fermilab and on the 400 GeV fixed target programs at Fermilab and CERN

Nuclear reactions and the synthesis of new species

International Nuclear Information System (INIS)

Anon.

1983-01-01

Targets of relatively short-lived, neutron-rich transplutonium isotopes, such as 254 Es, which are produced by the HFIR/TRU, when combined with the capabilities of modern heavy-ion accelerators, offer a unique possibility to expand our knowledge of chemical elements and atomic nuclei toward the limits of nuclear stability. This knowledge should enable us to delineate the forces that eventually terminate the periodic table at its upper end. Specifically, the panel concludes that significant research opportunities exist in several areas, which are highlighted below: Nucleon-transfer reactions between light heavy-ion projectiles (such as 18 O, 22 Ne, or 48 Ca) and 254 Es targets will give access to a completely uncharted region of neutron-rich isotopes. Cold-fusion reactions of 48 Ca projectiles with /sup 254,255/Es targets should yield superheavy nuclei with neutron numbers very close to the predicted closed neutron shell at N = 184

What is LAMPF II

International Nuclear Information System (INIS)

Thiessen, H.A.

1982-08-01

The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H - beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent

What is LAMPF II

Energy Technology Data Exchange (ETDEWEB)

Thiessen, H.A.

1982-08-01

The present conception of LAMPF II is a high-intensity 16-GeV synchrotron injected by the LAMPF 800-MeV H/sup -/ beam. The proton beam will be used to make secondary beams of neutrinos, muons, pions, kaons, antiprotons, and hyperons more intense than those of any existing or proposed accelerator. For example, by taking maximum advantage of a thick target, modern beam optics, and the LAMPF II proton beam, it will be possible to make a negative muon beam with nearly 100% duty factor and nearly 100 times the flux of the existing Stopped Muon Channel (SMC). Because the unique features of the proposed machine are most applicable to beams of the same momentum as LAMPF (that is, < 2 GeV/c), it may be possible to use most of the experimental areas and some of the auxiliary equipment, including spectrometers, with the new accelerator. The complete facility will provide improved technology for many areas of physics already available at LAMPF and will allow expansion of medium-energy physics to include kaons, antiprotons, and hyperons. When LAMPF II comes on line in 1990 LAMPF will have been operational for 18 years and a major upgrade such as this proposal will be reasonable and prudent.

Physicochemical properties of 3,4,5-trimethoxybenzoates of Mn(II, Co(II, Ni(II and Zn(II

Directory of Open Access Journals (Sweden)

W. FERENC

2005-09-01

Full Text Available The complexes of Mn(II, Co(II, Ni(II, Cu(II and Zn(II with 3,4,5-trimethoxybenzoic acid anion of the formula: M(C10H11O52·nH2O, where n = 6 for Ni(II, n = 1 for Mn(II, Co(II, Cu(II, and n = 0 for Zn, have been synthesized and characterized by elemental analysis, IR spectroscopy, X–ray diffraction measurements, thermogravimetry and magnetic studies. They are crystalline compounds characterized by various symmetry. They decompose in various ways when heated in air to 1273 K. At first, they dehydrate in one step and form anhydrous salts. The final products of decomposition are oxides of the respective metals (Mn2O3, Co3O4, NiO, CuO, ZnO. The solubilities of the analysed complexes in water at 293 K are in the orders of 10-2 – 10-4 mol dm-3. The magnetic susceptibilities of the Mn(II, Co(II, Ni(II and Cu(II complexes were measured over the range of 76–303 K and the magnetic moments were calculated. The results show that the 3,4,5-trimethoxybenzoates of Mn(II, Co(II and Ni(II are high-spin complexes but that of Cu(II forms a dimer [Cu2(C10H11O54(H2O2]. The carboxylate groups bind as monodentate or bidentate chelating or bridging ligands.

Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1 Receptor-PKA-Mediated Activation of Proteasome.

Science.gov (United States)

Qin, Xian-Yun; Zhang, Yun-Long; Chi, Ya-Fei; Yan, Bo; Zeng, Xiang-Jun; Li, Hui-Hua; Liu, Ying

2018-01-01

Naive CD4+ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors. The gene mRNA levels were detected by real-time quantitative PCR analysis. The protein levels were measured by ELISA assay or Western blot analysis, respectively. Ang II treatment significantly induced a shift from Th0 to Th1 cell differentiation, which was markedly blocked by angiotensin II type 1 receptor (AT1R) inhibitor Losartan (LST). Moreover, Ang II significantly increased the activities and the expression of proteasome catalytic subunits (β1, β1i, β2i and β5i) in a dose- and time-dependent manner. However, Ang II-induced proteasome activities were remarkably abrogated by LST and PKA inhibitor H-89. Mechanistically, Ang II-induced Th1 differentiation was at least in part through proteasome-mediated degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB. This study for the first time demonstrates that Ang II activates AT1R-PKA-proteasome pathway, which promotes degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB thereby leading to Th1 differentiation. Thus, inhibition of proteasome activation might be a potential therapeutic target for Th1-mediated diseases. © 2018 The Author(s). Published by S. Karger AG, Basel.

Stress-stain relations of irradiated stainless steels below 673 K

International Nuclear Information System (INIS)

Jitsukawa, S.; Hishinuma, A.; Grossbeck, M.L.

1992-01-01

Most specimens, irrespective of thermo-mechnaical treatment, exhibited proof stress levels of above 800 MPa and uniform elongations below 1% after irradiation in the the High Flux Isotope Reactor (HFIR). Only the solution annealed specimens irradiated at a low temperature of 328 k showed uniform elongations larger than 5% and proof stresses smaller than 800 MPa. Irradiation in the High Flux Reactor (HFR) caused more hardening than did irradiation in the HFIR. Ductility loss and change in work hardening characteristics by HFR irradiation were evaluated from reduction of area values. Residual ductility was revealed to be larger than 0.5 in natural strain, and the irradiation was estimated to have a small effect on work hardening characteristics and on fracture stress. The ductility of the irradiated alloys was found to be about 58% of that for the unirradiated alloys, as has been previously reported for irradiation in the HFIR. It was also demonstrated that true stress-strain relations, except for the fracture conditions, could be represented by Swift's type constitutive equation. (orig.)

Synthesis and spectral studies of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) complexes of 4-oxo-4H-1-benzopyran-3-carboxaldehyde hydrazone derivatives

International Nuclear Information System (INIS)

Nawar, N.; Khattab, M.A.; Bekheit, M.M.; El-Kaddah, A.H.

1996-01-01

A few complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) with 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-chlorobenzylhydrazone) (BCBH) and 4-oxo-4H-1-benzopyran-3-(carboxaldehyde-4-methylbenzylhydrazone) (BMBH) have been synthesised and characterized by elemental analysis, molar conductivities, magnetic measurements and infrared (IR) and visible spectral studies. The IR spectra show that BCBH and BMBH behave as bidentate ligands either in the keto or enol form. (author). 24 refs., 2 tabs

Synthesis, Characterization, and Biological Activity of Mn(II, Fe(II, Co(II, Ni(II, Cu(II, Zn(II, and Cd(II Complexes of N-Thiophenoyl-N′-Phenylthiocarbohydrazide

Directory of Open Access Journals (Sweden)

M. Yadav

2013-01-01

Full Text Available Mn(II, Fe(II, Co(II, Ni(II, Cu(II, Zn(II, and Cd(II complex of N-thiophenoyl -N′-phenylthiocarbohydrazide (H2 TPTH have been synthesized and characterized by elemental analysis, magnetic susceptibility measurements, infrared, NMR, electronic, and ESR spectral studies. The complexes were found to have compositions [Mn(H TPTH2], [Co(TPTH (H2O2], [Ni(TPTH (H2O2], [Cu(TPTH], [Zn(H TPTH], [Cd(H TPTH2], and [Fe(H TPTH2(EtOH]. The magnetic and electronic spectral studies suggest square planar geometry for [Cu(TPTH], tetrahedral geometry for [Zn(TPTH] and [Cd(H TPTH2], and octahedral geometry for rest of the complexes. The infrared spectral studies of the 1 : 1 deprotonated complexes suggest bonding through enolic oxygen, thiolato sulfur, and both the hydrazinic nitrogens. Thus, H2TPTH acts as a binegative tetradentate ligand. H2 TPTH and its metal complexes have been screened against several bacteria and fungi.

Target design for materials processing very far from equilibrium

Science.gov (United States)

Barnard, John J.; Schenkel, Thomas

2016-10-01

Local heating and electronic excitations can trigger phase transitions or novel material states that can be stabilized by rapid quenching. An example on the few nanometer scale are phase transitions induced by the passage of swift heavy ions in solids where nitrogen-vacancy color centers form locally in diamonds when ions heat the diamond matrix to warm dense matter conditions at 0.5 eV. We optimize mask geometries for target materials such as silicon and diamond to induce phase transitions by intense ion pulses (e. g. from NDCX-II or from laser-plasma acceleration). The goal is to rapidly heat a solid target volumetrically and to trigger a phase transition or local lattice reconstruction followed by rapid cooling. The stabilized phase can then be studied ex situ. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of crystal targets with micro-structured masks. A simple analytical model, that includes ion heating and radial, diffusive cooling, was developed that agrees closely with the HYDRA simulations. The model gives scaling laws that can guide the design of targets over a wide range of parameters including those for NDCX-II and the proposed BELLA-i. This work was performed under the auspices of the U.S. DOE under contracts DE-AC52-07NA27344 (LLNL), DE-AC02-05CH11231 (LBNL) and was supported by the US DOE Office of Science, Fusion Energy Sciences. LLNL-ABS-697271.

Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II binary complexes of l-methionine in 1,2-propanediol-water mixtures

Directory of Open Access Journals (Sweden)

M. Padma Latha

2007-04-01

Full Text Available Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-methionine in 0.0-60 % v/v 1,2-propanediol-water mixtures maintaining an ionic strength of 0.16 M at 303 K has been studied pH metrically. The active forms of ligand are LH2+, LH and L-. The predominant species detected are ML, MLH, ML2, ML2H, ML2H2 and MLOH. Models containing different numbers of species were refined by using the computer program MINIQUAD 75. The best-fit chemical models were arrived at based on statistical parameters. The trend in variation of complex stability constants with change in the dielectric constant of the medium is explained on the basis of electrostatic and non-electrostatic forces.

Determination of the theoretical feasibility for the transmutation of europium isotopes from high flux isotope reactor control cylinders

International Nuclear Information System (INIS)

Elam, K.R.; Reich, W.J.

1995-09-01

The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) is a 100 MWth light-water research reactor designed and built in the 1960s primarily for the production of transuranic isotopes. The HFIR is equipped with two concentric cylindrical blade assemblies, known as control cylinders, that are used to control reactor power. These control cylinders, which become highly radioactive from neutron exposure, are periodically replaced as part of the normal operation of the reactor. The highly radioactive region of the control cylinders is composed of europium oxide in an aluminum matrix. The spent HFIR control cylinders have historically been emplaced in the ORNL Waste Area Grouping (WAG) 6. The control cylinders pose a potential radiological hazard due to the long lived radiotoxic europium isotopes 152 Eu, 154 Eu, and 155 Eu. In a 1991 health evaluation of WAG 6 (ERD 1991) it was shown that these cylinders were a major component of the total radioactivity in WAG 6 and posed a potential exposure hazard to the public in some of the postulated assessment scenarios. These health evaluations, though preliminary and conservative in nature, illustrate the incentive to investigate methods for permanent destruction of the europium radionuclides. When the cost of removing the control cylinders from WAG 6, performing chemical separations and irradiating the material in HFIR are factored in, the option of leaving the control cylinders in place for decay must be considered. Other options, such as construction of an engineered barrier around the disposal silos to reduce the chance of migration, should also be analyzed

Needs and Requirements for Future Research Reactors (ORNL Perspectives)

Energy Technology Data Exchange (ETDEWEB)

Ilas, Germina [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bryan, Chris [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gehin, Jess C. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-02-10

The High Flux Isotope Reactor (HFIR) is a vital national and international resource for neutron science research, production of radioisotopes, and materials irradiation. While HFIR is expected to continue operation for the foreseeable future, interest is growing in understanding future research reactors features, needs, and requirements. To clarify, discuss, and compile these needs from the perspective of Oak Ridge National Laboratory (ORNL) research and development (R&D) missions, a workshop, titled “Needs and Requirements for Future Research Reactors”, was held at ORNL on May 12, 2015. The workshop engaged ORNL staff that is directly involved in research using HFIR to collect valuable input on the reactor’s current and future missions. The workshop provided an interactive forum for a fruitful exchange of opinions, and included a mix of short presentations and open discussions. ORNL staff members made 15 technical presentations based on their experience and areas of expertise, and discussed those capabilities of the HFIR and future research reactors that are essential for their current and future R&D needs. The workshop was attended by approximately 60 participants from three ORNL directorates. The agenda is included in Appendix A. This document summarizes the feedback provided by workshop contributors and participants. It also includes information and insights addressing key points that originated from the dialogue started at the workshop. A general overview is provided on the design features and capabilities of high performance research reactors currently in use or under construction worldwide. Recent and ongoing design efforts in the US and internationally are briefly summarized, followed by conclusions and recommendations.

F/H Area Effluent Treatment Facility. Phase II. CAC basic data

International Nuclear Information System (INIS)

Collins, W.W.; O'Leary, C.D.

1984-01-01

Project objectives and requirements are listed for both Phase I and II. Schedule is listed with startup targeted for 1989. Storage facilities will be provided for both chemical and radioactive effluents. 8 figs., 19 tabs

Intercomparison of ILAS-II version 1.4 and version 2 target parameters with MIPAS-Envisat measurements

Directory of Open Access Journals (Sweden)

A. Griesfeller

2008-02-01

Full Text Available This paper assesses the mean differences between the two ILAS-II data versions (1.4 and 2 by comparing them with MIPAS measurements made between May and October 2003. For comparison with ILAS-II results, MIPAS data processed at the Institut für Meteorologie und Klimaforschung, Karlsruhe, Germany (IMK in cooperation with the Instituto de Astrofísica de Andalucía (IAA in Granada, Spain, were used. The coincidence criteria of ±300 km in space and ±12 h in time for H₂O, N₂O, and CH₄ and the coincidence criteria of ±300 km in space and ±6 h in time for ClONO₂, O₃, and HNO₃ were used. The ILAS-II data were separated into sunrise (= Northern Hemisphere and sunset (= Southern Hemisphere. For the sunrise data, a clear improvement from version 1.4 to version 2 was observed for H₂O, CH₄, ClONO₂, and O₃. In particular, the ILAS-II version 1.4 mixing ratios of H₂O and CH₄ were unrealistically small, and those of ClONO₂ above altitudes of 30 km unrealistically large. For N₂O and HNO₃, there were no large differences between the two versions. Contrary to the Northern Hemisphere, where some exceptional profiles deviated significantly from known climatology, no such outlying profiles were found in the Southern Hemisphere for both versions. Generally, the ILAS-II version 2 data were in better agreement with the MIPAS data than the version 1.4, and are recommended for quantitative analysis in the stratosphere. For H₂O data in the Southern Hemisphere, further data quality evaluation is necessary.

Recognition elements in rRNA for the tylosin resistance methyltransferase RlmA(II)

DEFF Research Database (Denmark)

Lebars, Isabelle; Husson, Clotilde; Yoshizawa, Satoko

2007-01-01

The methyltransferase RlmA(II) (formerly TlrB) is found in many Gram-positive bacteria, and methylates the N-1 position of nucleotide G748 within the loop of hairpin 35 in 23S rRNA. Methylation of the rRNA by RlmA(II) confers resistance to tylosin and other mycinosylated 16-membered ring macrolide......RNA substrate indicated that multiple contacts occur between RlmA(II) and nucleotides in stem-loops 33, 34 and 35. RlmA(II) appears to recognize its rRNA target through specific surface shape complementarity at the junction formed by these three helices. This means of recognition is highly similar...

India's INDC for transport and 2 C stabilization target

DEFF Research Database (Denmark)

Dhar, Subash; Shukla, Priyadarshi Ramprasad; Pathak, Minal

2017-01-01

Transport sector accounted for 13 % of India's energy-related CO2 emissions. India's Intended Nationally Determined Contributions (INDC) specify an economy wide decarbonization target of 33 to 35 % between 2005 and 2030 and includes announcements for urban transport, intercity transportation...... to model future scenarios for India till year 2050. Three scenarios are explored in this paper: i) a business-As-usual scenario ii) an INDC scenario iii) implementation of INDC in a strong climate regime aiming for the 2 oC target. The assessment shows that CO2 reductions from transport would happen...

cobalt (ii), nickel (ii)

African Journals Online (AJOL)

DR. AMINU

Department of Chemistry Bayero University, P. M. B. 3011, Kano, Nigeria. E-mail: hnuhu2000@yahoo.com. ABSTRACT. The manganese (II), cobalt (II), nickel (II) and .... water and common organic solvents, but are readily soluble in acetone. The molar conductance measurement [Table 3] of the complex compounds in.

Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

International Nuclear Information System (INIS)

He, Jinsong; Wang, Xianming; Guan, Hong; Chen, Weicai; Wang, Ming; Wu, Huisheng; Wang, Zun; Zhou, Ruming; Qiu, Shuibo

2011-01-01

The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m 2 ]; E: epirubicin [90 mg/m 2 ]; F: 5-fluorouracil [600 mg/m 2 ]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

WISDOM-II: Screening against multiple targets implicated in malaria using computational grid infrastructures

Directory of Open Access Journals (Sweden)

Kenyon Colin

2009-05-01

Full Text Available Abstract Background Despite continuous efforts of the international community to reduce the impact of malaria on developing countries, no significant progress has been made in the recent years and the discovery of new drugs is more than ever needed. Out of the many proteins involved in the metabolic activities of the Plasmodium parasite, some are promising targets to carry out rational drug discovery. Motivation Recent years have witnessed the emergence of grids, which are highly distributed computing infrastructures particularly well fitted for embarrassingly parallel computations like docking. In 2005, a first attempt at using grids for large-scale virtual screening focused on plasmepsins and ended up in the identification of previously unknown scaffolds, which were confirmed in vitro to be active plasmepsin inhibitors. Following this success, a second deployment took place in the fall of 2006 focussing on one well known target, dihydrofolate reductase (DHFR, and on a new promising one, glutathione-S-transferase. Methods In silico drug design, especially vHTS is a widely and well-accepted technology in lead identification and lead optimization. This approach, therefore builds, upon the progress made in computational chemistry to achieve more accurate in silico docking and in information technology to design and operate large scale grid infrastructures. Results On the computational side, a sustained infrastructure has been developed: docking at large scale, using different strategies in result analysis, storing of the results on the fly into MySQL databases and application of molecular dynamics refinement are MM-PBSA and MM-GBSA rescoring. The modeling results obtained are very promising. Based on the modeling results, In vitro results are underway for all the targets against which screening is performed. Conclusion The current paper describes the rational drug discovery activity at large scale, especially molecular docking using FlexX software

Homophilic and Heterophilic Interactions of Type II Cadherins Identify Specificity Groups Underlying Cell-Adhesive Behavior

Directory of Open Access Journals (Sweden)

Julia Brasch

2018-05-01

Full Text Available Summary: Type II cadherins are cell-cell adhesion proteins critical for tissue patterning and neuronal targeting but whose molecular binding code remains poorly understood. Here, we delineate binding preferences for type II cadherin cell-adhesive regions, revealing extensive heterophilic interactions between specific pairs, in addition to homophilic interactions. Three distinct specificity groups emerge from our analysis with members that share highly similar heterophilic binding patterns and favor binding to one another. Structures of adhesive fragments from each specificity group confirm near-identical dimer topology conserved throughout the family, allowing interface residues whose conservation corresponds to specificity preferences to be identified. We show that targeted mutation of these residues converts binding preferences between specificity groups in biophysical and co-culture assays. Our results provide a detailed understanding of the type II cadherin interaction map and a basis for defining their role in tissue patterning and for the emerging importance of their heterophilic interactions in neural connectivity. : Type II cadherins are a family of vertebrate cell adhesion proteins expressed primarily in the CNS. Brasch et al. measure binding between adhesive fragments, revealing homophilic and extensive selective heterophilic binding with specificities that define groups of similar cadherins. Structures reveal common adhesive dimers, with residues governing cell-adhesive specificity. Keywords: cell adhesion, crystal structure, hemophilic specificity, heterophilic specificity, neural patterning, synaptic targeting, cadherin

Lithium beam characterization of cylindrical PBFA II hohlraum experiments

International Nuclear Information System (INIS)

Moats, A.R.; Derzon, M.S.; Chandler, G.A.; Haill, T.A.; Johnson, D.J.; Leeper, R.J.; Ruiz, C.L.; Wenger, D.F.

1995-01-01

Sandia National Laboratories is actively engaged in exploring indirect-drive inertial confinement fusion on the Particle Beam Fusion Accelerator (PBFA II) with pulsed-power accelerated lithium ions as the driver. Experiments utilizing cylindrical hohlraum targets were conducted in 1994. Using the incoming ion beam-induced line radiation from titanium wires surrounding these hohlraums, beam profiles during these experiments have been measured and characterized. These data, their comparison/cross-correlation with particle-based beam diagnostics, and an analysis of the beam parameters that most significantly influence target temperature are presented

A three-cell liquid hydrogen target for an extended focal plane polarimeter

International Nuclear Information System (INIS)

Golovanov, L.B.; Chesny, P.; Gheller, J.M.; Guillier, G.; Ladygin, V.P.; Theure, Ph.; Tomasi-Gustafsson, E.

1996-01-01

This article describes the design and working principle of a three-cell liquid hydrogen target produced for the high-energy deuteron polarimeter HYPOM. This target uses liquid helium as a cooling agent. After a general description of the apparatus, tests and operating modes are thoroughly explained. In particular the air controlled self-regulation of helium flow in the cryostat to stabilize the liquid hydrogen level is presented. The main feature of this target is the simplicity of the design as well as its safeness towards any incident. Results of cooling down, filling up of the target and stabilization regime were processed during one experiment of physics at synchrotron Saturne II. (orig.)

Intracellular Zn(II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis

Science.gov (United States)

2016-01-01

Transition metal ions (Zn(II), Cu(II)/(I), Fe(III)/(II), Mn(II)) are essential for life and participate in a wide range of biological functions. Cellular Zn(II) levels must be high enough to ensure that it can perform its essential roles. Yet, since Zn(II) binds to ligands with high avidity, excess Zn(II) can lead to protein mismetallation. The major targets of mismetallation, and the underlying causes of Zn(II) intoxication, are not well understood. Here, we use a forward genetic selection to identify targets of Zn(II) toxicity. In wild-type cells, in which Zn(II) efflux prevents intoxication of the cytoplasm, extracellular Zn(II) inhibits the electron transport chain due to the inactivation of the major aerobic cytochrome oxidase. This toxicity can be ameliorated by depression of an alternate oxidase or by mutations that restrict access of Zn(II) to the cell surface. Conversely, efflux deficient cells are sensitive to low levels of Zn(II) that do not inhibit the respiratory chain. Under these conditions, intracellular Zn(II) accumulates and leads to heme toxicity. Heme accumulation results from dysregulation of the regulon controlled by PerR, a metal-dependent repressor of peroxide stress genes. When metallated with Fe(II) or Mn(II), PerR represses both heme biosynthesis (hemAXCDBL operon) and the abundant heme protein catalase (katA). Metallation of PerR with Zn(II) disrupts this coordination, resulting in depression of heme biosynthesis but continued repression of catalase. Our results support a model in which excess heme partitions to the membrane and undergoes redox cycling catalyzed by reduced menaquinone thereby resulting in oxidative stress. PMID:27935957

Short-lived radionuclides produced on the ORNL 86-inch cyclotron and High-Flux Isotope Reactor

International Nuclear Information System (INIS)

Lamb, E.

1985-01-01

The production of short-lived radionuclides at ORNL includes the preparation of target materials, irradiation on the 86-in. cyclotron and in the High Flux Isotope Reactor (HFIR), and chemical processing to recover and purify the product radionuclides. In some cases the target materials are highly enriched stable isotopes separated on the ORNL calutrons. High-purity 123 I has been produced on the 86-in. cyclotron by irradiating an enriched target of 123 Te in a proton beam. Research on calutron separations has led to a 123 Te product with lower concentrations of 124 Te and 126 Te and, consequently to lower concentrations of the unwanted radionuclides, 124 I and 126 I, in the 123 I product. The 86-in. cyclotron accelerates a beam of protons only but is unique in providing the highest available beam current of 1500 μA at 21 MeV. This beam current produces relatively large quantities of radionuclides such as 123 I and 67 Ga

RTNS-II fusion materials irradiation facility

International Nuclear Information System (INIS)

Heikkinen, D.W.; Tuckerman, D.B.; Davis, J.C.; Massoletti, D.J.; Short, D.W.

1986-01-01

The Rotating Target Neutron Source (RTNS-II) facility provides an intense source of 14-MeV neutrons for the fusion energy programs of Japan and the United States. Each of the two identical accelerator-based neutron sources is capable of providing source strengths in excess of 3 x 10 13 n/s using deuteron beam currents up to 150 mA. The present status of the facility, as well as the various upgrade options, will be described in detail

Cr(III,Mn(II,Fe(III,Co(II,Ni(II,Cu(II and Zn(II Complexes with Diisobutyldithiocarbamato Ligand

Directory of Open Access Journals (Sweden)

Mohammad Tarique

2011-01-01

Full Text Available The synthesis of sulphur and nitrogen containing dithiocarbamato ligand derived from diisobutylamine as well as its coordination compounds with 3d series transition metals is presented. These synthesized compounds were characterized on the basis of elemental analysis, conductometric measurements and IR spectral studies. The analytical data showed the stoichiometry 1:2 and 1:3 for the compounds of the types ML2 {M=Mn(II, Co(II, Ni(II, Cu(II and Zn(II} and M'L3{M'=Cr(III and Fe(III} respectively. The conductometric measurements proved the non-electrolytic behaviour of all the compounds. The bidentate nature of dithiocarbamato moiety was confirmed on the basis of IR spectral data.

Targeting the bone marrow: applications in stem cell transplantation

International Nuclear Information System (INIS)

Orchard, K.; Cooper, M.

2004-01-01

Therapeutic doses of radiation cab be selectively directed to the bone marrow either directly using vectors that bind to myeloid and/or lymphoid specific antigens or indirectly by targeting bone matrix. The combination of an accessible target tissue and relatively radiation sensitive malignant cells favours the use of targeted radiotherapy in the treatment of haematopoietic malignancies. Dose escalation of targeted radiation can increase tumour cell destruction and has led to the use of myelosuppressive and possibly myeloablative doses of targeted radiation. A natural development has been the use of targeted radiation in conditioning prior to haematopoietic stem cell transplantation (HSCT). Several groups are actively exploring the use of targeted radiotherapy in the context of HSCT as treatment for haematological malignancies. Although no randomised trials using targeted radiotherapy in HSCT have been published, phase I and II trials have shown very encouraging results stimulating further clinical research in this field. After more than a decade of translational research the optimal combination of therapeutic radioisotope and vector has not been determined. This review summarises the clinical experience of targeted radiotherapy in HSCT and discusses the problems that still need to be solved to maximise the potential of this new treatment modality in HSCT

Multi-agent target tracking using particle filters enhanced with context data

CSIR Research Space (South Africa)

Claessens, R

2015-05-01

Full Text Available The proposed framework for Multi-Agent Target Tracking supports i) tracking of objects and ii) search and rescue based on the fusion of very heterogeneous data. The system is based on a novel approach to fusing sensory observations, intelligence...

First results from GERDA Phase II

Science.gov (United States)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-09-01

Gerda is designed for a background-free search of 76Ge neutrinoless double-β decay, using bare Ge detectors in liquid Ar. The experiment was upgraded after the successful completion of Phase I to double the target mass and further reduce the background. Newly-designed Ge detectors were installed along with LAr scintillation sensors. Phase II of data-taking started in Dec 2015 with approximately 36 kg of Ge detectors and is currently ongoing. The first results based on 10.8 kg· yr of exposure are presented. The background goal of 10-3 cts/(keV· kg· yr) is achieved and a search for neutrinoless double-β decay is performed by combining Phase I and II data. No signal is found and a new limit is set at T1/20ν > 5.3 \\cdot {1025} yr (90% C.L.).

Transmission of the Neutral Beam Heating Beams at TJ-II; Transmision del Haz de Neutros de Calentamiento en TJ-II

Energy Technology Data Exchange (ETDEWEB)

Fuentes Lopez, C

2007-09-27

Neutral beam injection heating has been development for the TJ-II stellarator. The beam has a port-through power between 700-1500 kW and injection energy 40 keV. The sensibility of the injection system to the changes of several parameters is analysed. Beam transmission is limited by losses processes since beam is born into the ions source until is coming into the fusion machine. For the beam transmission optimization several beam diagnostics have been developed. A carbon fiber composite (CFC) target calorimeter has been installed at TJ-II to study in situ the power density distribution of the neutral beams. The thermographic print of the beam can be recorded and analysed in a reliable way due to the highly anisotropic thermal conductivity of the target material. With the combined thermographic and calorimetric measurements it has been possible to determine the power density distribution of the beam. It has been found that a large beam halo is present, which can be explained by the extreme misalignment of the grids. This kind of halo has a deleterious effect on beam transport and must be minimized in order to improve the plasma heating capability of the beams. (Author) 155 refs.

Dynamic investigation of DNA bending and wrapping by type II topoisomerases

Science.gov (United States)

Shao, Qing; Finzi, Laura; Dunlap, David

2009-11-01

Type II topoisomerases catalyze DNA decatenation and unwinding which is crucial for cell division, and therefore type II topoisomerases are some of the main targets of anti-cancer drugs. A recent crystal structure shows that, during the catalytic cycle, a yeast type II topoimerase can bend a 10 base pair DNA segment by up to 150 degrees. Bacterial gyrase, another type II topoisomerase, can wrap DNA into a tight 180 degree turn. Bending a stiff polymer like DNA requires considerable energy and could represent the rate limiting step in the catalytic (topological) cycle. Using modified deoxyribonucleotides in PCR reactions, stiffer DNA fragments have been produced and used as substrates for topoisomerase II-mediated relaxation of plectonemes introduced in single molecules using magnetic tweezers. The wrapping ability of gyrase decreases for diamino-purine-substituted DNA in which every base pair has three hydrogen-bonds. The overall rate of relaxation of plectonemes by recombinant human topoisomerase II alpha also decreases. These results reveal the dynamic properties of DNA bending and wrapping by type II topisomerases and suggest that A:T base pair melting is a rate determining step for bending and wrapping.

Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II.

Science.gov (United States)

Hong, Seung-Keun; Cha, Mee-Kyung; Choi, Yong-Soo; Kim, Won-Cheol; Kim, Il-Han

2002-04-05

We observed that the transcription of Saccharomyces cerevisiae cytoplasmic thiol peroxidase type II (cTPx II) (YDR453C) is regulated in response to various stresses (e.g. oxidative stress, carbon starvation, and heat-shock). It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress. However, a dramatic loss of transcriptional response to various stresses in yeast mutant strains lacking both Msn2p and Msn4p suggests that the transcription factors act as a principal transcriptional activator. In addition to two Yap1p response elements (YREs), TTACTAA and TTAGTAA, the presence of two stress response elements (STREs) (CCCCT) in the upstream sequence of cTPx II also suggests that Msn2p/Msn4p could control stress-induced expression of cTPx II. Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter. The transcriptional activity of the cTPx II promoter was exponentially increased after postdiauxic growth. The transcriptional activity of the cTPx II promoter is greatly increased by rapamycin. Deletion of Tor1, Tor2, Ras1, and Ras2 resulted in a considerable induction when compared with their parent strains, suggesting that the transcription of cTPx II is under negative control of the Ras/cAMP and target of rapamycin signaling pathways. Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways. Furthermore, the accumulation of cTPx II upon exposure to oxidative stress and during the postdiauxic shift suggests an important antioxidant role in stationary phase yeast cells.

Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments

NARCIS (Netherlands)

Wubbolts, R.; Fernandez-Borja, M.; Jordens, I.; Reits, E.; Dusseljee, S.; Echeverri, C.; Vallee, R. B.; Neefjes, J.

1999-01-01

MHC class II molecules exert their function at the cell surface by presenting to T cells antigenic fragments that are generated in the endosomal pathway. The class II molecules are targetted to early lysosomal structures, termed MIIC, where they interact with antigenic fragments and are subsequently

Fixed Target Collisions at STAR

Energy Technology Data Exchange (ETDEWEB)

Meehan, Kathryn C.

2016-12-15

The RHIC Beam Energy Scan (BES) program was proposed to look for the turn-off of signatures of the quark gluon plasma (QGP), search for a possible QCD critical point, and study the nature of the phase transition between hadronic and partonic matter. Previous results have been used to claim that the onset of deconfinement occurs at a center-of-mass energy of 7 GeV. Data from lower energies are needed to test if this onset occurs. The goal of the STAR Fixed-Target Program is to extend the collision energy range in BES II to energies that are likely below the onset of deconfinement. Currently, STAR has inserted a gold target into the beam pipe and conducted test runs at center-of-mass energies of 3.9 and 4.5 GeV. Tests have been done with both Au and Al beams. First physics results from a Coulomb potential analysis of Au + Au fixed-target collisions are presented and are found to be consistent with results from previous experiments. Furthermore, the Coulomb potential, which is sensitive to the Z of the projectile and degree of baryonic stopping, will be compared to published results from the AGS.

Targeting the Brain with Nanomedicine.

Science.gov (United States)

Rueda, Felix; Cruz, Luis J

2017-01-01

Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Computer augumented modelling studies of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-glutamic acid in 1,2-propanediol–water mixtures

Directory of Open Access Journals (Sweden)

MAHESWARA RAO VEGI

2008-12-01

Full Text Available Chemical speciation of Pb(II, Cd(II, Hg(II, Co(II, Ni(II, Cu(II and Zn(II complexes of L-glutamic acid was studied at 303 K in 0–60 vol. % 1,2-propanediol–water mixtures, whereby the ionic strength was maintained at 0.16 mol dm-3. The active forms of the ligand are LH3+, LH2 and LH–. The predominant detected species were ML, ML2, MLH, ML2H and ML2H2. The trend of the variation in the stability constants with changing dielectric constant of the medium is explained based on the cation stabilizing nature of the co-solvents, specific solvent–water interactions, charge dispersion and specific interactions of the co-solvent with the solute. The effect of systematic errors in the concentrations of the substances on the stability constants is in the order alkali > > acid > ligand > metal. The bioavailability and transportation of metals are explained based on distribution diagrams and stability constants.

EPOXYEICOSATRIENOIC ACID ANALOG ATTENUATES ANGIOTENSIN II HYPERTENSION AND KIDNEY INJURY

Directory of Open Access Journals (Sweden)

Md. Abdul Hye Khan

2014-09-01

Full Text Available Epoxyeicosatrienoic acids (EETs contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end-organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II-induced hypertension. EET-B was administered in drinking water for 14 days (10mg/kg/d and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension.

Synthesis and characterization of heterobimetallic complexes of the type [Cu(pn2][MCl4] where M = Co(II, Ni(II, Cu(II, Zn(II, Cd(II, and Hg(II

Directory of Open Access Journals (Sweden)

Seema Yadav

2016-11-01

Full Text Available A series of new bimetallic transition metal complexes of the type [Cu(pn2] [MCl4] have been synthesized (where M = Co(II, Ni(II, Cu(II, Zn(II, Cd(II and Hg(II, pn = 1,3-diaminopropane and characterized by elemental analysis, molar conductance, TGA, IR and electronic spectra. All the compounds are 1:1 electrolyte in DMF. The Cu(II ion is square-planar while metal ions in the anionic moiety acquire their usual tetrahedral arrangement. On the basis of these studies it is concluded that anionic moiety is electrically stabilized by its cationic counterpart.

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

Directory of Open Access Journals (Sweden)

Reini F Luco

2008-05-01

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

An updated Type II supernova Hubble diagram

Science.gov (United States)

Gall, E. E. E.; Kotak, R.; Leibundgut, B.; Taubenberger, S.; Hillebrandt, W.; Kromer, M.; Burgett, W. S.; Chambers, K.; Flewelling, H.; Huber, M. E.; Kaiser, N.; Kudritzki, R. P.; Magnier, E. A.; Metcalfe, N.; Smith, K.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.

2018-03-01

We present photometry and spectroscopy of nine Type II-P/L supernovae (SNe) with redshifts in the 0.045 ≲ z ≲ 0.335 range, with a view to re-examining their utility as distance indicators. Specifically, we apply the expanding photosphere method (EPM) and the standardized candle method (SCM) to each target, and find that both methods yield distances that are in reasonable agreement with each other. The current record-holder for the highest-redshift spectroscopically confirmed supernova (SN) II-P is PS1-13bni (z = 0.335-0.012+0.009), and illustrates the promise of Type II SNe as cosmological tools. We updated existing EPM and SCM Hubble diagrams by adding our sample to those previously published. Within the context of Type II SN distance measuring techniques, we investigated two related questions. First, we explored the possibility of utilising spectral lines other than the traditionally used Fe IIλ5169 to infer the photospheric velocity of SN ejecta. Using local well-observed objects, we derive an epoch-dependent relation between the strong Balmer line and Fe IIλ5169 velocities that is applicable 30 to 40 days post-explosion. Motivated in part by the continuum of key observables such as rise time and decline rates exhibited from II-P to II-L SNe, we assessed the possibility of using Hubble-flow Type II-L SNe as distance indicators. These yield similar distances as the Type II-P SNe. Although these initial results are encouraging, a significantly larger sample of SNe II-L would be required to draw definitive conclusions. Tables A.1, A.3, A.5, A.7, A.9, A.11, A.13, A.15 and A.17 are also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/611/A25

High Flux Isotope Reactor cold neutron source reference design concept

International Nuclear Information System (INIS)

Selby, D.L.; Lucas, A.T.; Hyman, C.R.

1998-05-01

In February 1995, Oak Ridge National Laboratory's (ORNL's) deputy director formed a group to examine the need for upgrades to the High Flux Isotope Reactor (HFIR) system in light of the cancellation of the Advanced neutron Source Project. One of the major findings of this study was that there was an immediate need for the installation of a cold neutron source facility in the HFIR complex. In May 1995, a team was formed to examine the feasibility of retrofitting a liquid hydrogen (LH 2 ) cold source facility into an existing HFIR beam tube. The results of this feasibility study indicated that the most practical location for such a cold source was the HB-4 beam tube. This location provides a potential flux environment higher than the Institut Laue-Langevin (ILL) vertical cold source and maximizes the space available for a future cold neutron guide hall expansion. It was determined that this cold neutron beam would be comparable, in cold neutron brightness, to the best facilities in the world, and a decision was made to complete a preconceptual design study with the intention of proceeding with an activity to install a working LH 2 cold source in the HFIR HB-4 beam tube. During the development of the reference design the liquid hydrogen concept was changed to a supercritical hydrogen system for a number of reasons. This report documents the reference supercritical hydrogen design and its performance. The cold source project has been divided into four phases: (1) preconceptual, (2) conceptual design and testing, (3) detailed design and procurement, and (4) installation and operation. This report marks the conclusion of the conceptual design phase and establishes the baseline reference concept

High flux isotope reactor cold source preconceptual design study report

International Nuclear Information System (INIS)

Selby, D.L.; Bucholz, J.A.; Burnette, S.E.

1995-12-01

In February 1995, the deputy director of Oak Ridge National Laboratory (ORNL) formed a group to examine the need for upgrades to the High Flux Isotope Reactor (HFIR) system in light of the cancellation of the Advanced Neutron Source Project. One of the major findings of this study was that there was an immediate need for the installation of a cold neutron source facility in the HFIR complex. The anticipated cold source will consist of a cryogenic LH 2 moderator plug, a cryogenic pump system, a refrigerator that uses helium gas as a refrigerant, a heat exchanger to interface the refrigerant with the hydrogen loop, liquid hydrogen transfer lines, a gas handling system that includes vacuum lines, and an instrumentation and control system to provide constant system status monitoring and to maintain system stability. The scope of this project includes the development, design, safety analysis, procurement/fabrication, testing, and installation of all of the components necessary to produce a working cold source within an existing HFIR beam tube. This project will also include those activities necessary to transport the cold neutron beam to the front face of the present HFIR beam room. The cold source project has been divided into four phases: (1) preconceptual, (2) conceptual design and research and development (R and D), (3) detailed design and procurement, and (4) installation and operation. This report marks the conclusion of the preconceptual phase and establishes the concept feasibility. The information presented includes the project scope, the preliminary design requirements, the preliminary cost and schedule, the preliminary performance data, and an outline of the various plans for completing the project

Needs and Requirements for Future Research Reactors (ORNL Perspectives)

International Nuclear Information System (INIS)

Ilas, Germina; Bryan, Chris; Gehin, Jess C.

2016-01-01

The High Flux Isotope Reactor (HFIR) is a vital national and international resource for neutron science research, production of radioisotopes, and materials irradiation. While HFIR is expected to continue operation for the foreseeable future, interest is growing in understanding future research reactors features, needs, and requirements. To clarify, discuss, and compile these needs from the perspective of Oak Ridge National Laboratory (ORNL) research and development (R&D) missions, a workshop, titled ''Needs and Requirements for Future Research Reactors'', was held at ORNL on May 12, 2015. The workshop engaged ORNL staff that is directly involved in research using HFIR to collect valuable input on the reactor's current and future missions. The workshop provided an interactive forum for a fruitful exchange of opinions, and included a mix of short presentations and open discussions. ORNL staff members made 15 technical presentations based on their experience and areas of expertise, and discussed those capabilities of the HFIR and future research reactors that are essential for their current and future R&D needs. The workshop was attended by approximately 60 participants from three ORNL directorates. The agenda is included in Appendix A. This document summarizes the feedback provided by workshop contributors and participants. It also includes information and insights addressing key points that originated from the dialogue started at the workshop. A general overview is provided on the design features and capabilities of high performance research reactors currently in use or under construction worldwide. Recent and ongoing design efforts in the US and internationally are briefly summarized, followed by conclusions and recommendations.

Small Diameter Bomb Increment II (SDB II)

Science.gov (United States)

2015-12-01

Selected Acquisition Report (SAR) RCS: DD-A&T(Q&A)823-439 Small Diameter Bomb Increment II (SDB II) As of FY 2017 President’s Budget Defense... Bomb Increment II (SDB II) DoD Component Air Force Joint Participants Department of the Navy Responsible Office References SAR Baseline (Production...Mission and Description Small Diameter Bomb Increment II (SDB II) is a joint interest United States Air Force (USAF) and Department of the Navy

Synthesis and structural characterization of nickel(II), cobalt(II), Zinc(II), manganese(II), cadmium(II) and uranium(VI) complexes of α-oximinoacetoacet-o/p-anisidide thiosemicarbazone

International Nuclear Information System (INIS)

Patel, P.S.; Patel, M.M.; Ray, R.M.

1993-01-01

A few metal complexes of α-oximinoacetoacet-o/p-anisidide thiosemicarbazones (OAOATS)/(OAPATS) with Ni(II), Co(II), Zn(II), Mn(II), Hg(II), Cd(II) and UO 2 (II) have been prepared and characterized by elemental analyses, conductivity, differential scanning calorimetry study, thermogravimetric analyses and infrared and electronic spectral measurements in conjunction with magnetic susceptibility measurements at room temperature. They have also been tested for their antimicrobial activities. (author). 24 refs., 2 tabs

Research applications of the Livermore RTNS-II neutron sources

International Nuclear Information System (INIS)

Davis, J.C.

1978-01-01

The Lawrence Livermore Laboratory has completed construction of the Rotating Target Neutron Source-II (RTNS-II) Facility. These sources, built and operated for the Office of Fusion Energy of the Department of Energy, will be operated by LLL as a national facility for the study of materials damage processes induced by 14-MeV neutrons. Design strength of the sources is 4 x 10 13 n/s with a maximum flux of 1 X 10 13 n/cm 2 s. The 400 keV, 150 mA D + accelerators and 5000 rpm titanium--tritide target assemblies were built using experience gained with LLL's RTNS-I neutron source. The RTNS-I source, producing 6 x 10 12 n/s, is currently the most intense 14-MeV source available. RTNS-I has been used for fusion reactor materials studies for the past six years. The experimental program for the new sources will be oriented toward fundamental measurements of high energy neutron-induced effects. The data produced will be used to develop models of damage processes to help guide materials selection for future fusion reactors

Analysis and modeling of flow blockage-induced steam explosion events in the High-Flux Isotope Reactor

International Nuclear Information System (INIS)

Taleyarkhan, R.P.; Georgevich, V.; Lestor, C.W.; Gat, U.; Lepard, B.L.; Cook, D.H.; Freels, J.; Chang, S.J.; Luttrell, C.; Gwaltney, R.C.; Kirkpatrick, J.

1993-01-01

This paper provides a perspective overview of the analysis and modeling work done to evaluate the threat from steam explosion loads in the High-Flux Isotope Reactor during flow blockage events. The overall workscope included modeling and analysis of core melt initiation, melt propagation, bounding and best-estimate steam explosion energetics, vessel failure from fracture, bolts failure from exceedance of elastic limits, and finally, missile evolution and transport. Aluminum ignition was neglected. Evaluations indicated that a thermally driven steam explosion with more than 65 MJ of energy insertion in the core region over several miliseconds would be needed to cause a sufficiently energetic missile with a capacity to cause early confinement failure. This amounts to about 65% of the HFIR core mass melting and participating in a steam explosion. Conservative melt propagation analyses have indicated that at most only 24% of the HFIR core mass could melt during flow blockage events under full-power conditions. Therefore, it is judged that the HFIR vessel and top head structure will be able to withstand loads generated from thermally driven steam explosions initiated by any credible flow blockage event. A substantial margin to safety was demonstrated

Radiation effects on reactor pressure vessel supports

International Nuclear Information System (INIS)

Johnson, R.E.

1996-05-01

The purpose of this report is to present the findings from the work done in accordance with the Task Action Plan developed to resolve the Nuclear Regulatory Commission (NRC) Generic Safety Issue No. 15, (GSI-15). GSI-15 was established to evaluate the potential for low-temperature, low-flux-level neutron irradiation to embrittle reactor pressure vessel (RPV) supports to the point of compromising plant safety. An evaluation of surveillance samples from the High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory (ORNL) had suggested that some materials used for RPV supports in pressurized-water reactors could exhibit higher than expected embrittlement rates. However, further tests designed to evaluate the applicability of the HFIR data to reactor RPV supports under operating conditions led to the conclusion that RPV supports could be evaluated using traditional method. It was found that the unique HFIR radiation environment allowed the gamma radiation to contribute significantly to the embrittlement. The shielding provided by the thick steel RPV shell ensures that degradation of RPV supports from gamma irradiation is improbable or minimal. The findings reported herein were used, in part, as the basis for technical resolution of the issue

Establishing a Cost Basis for Converting the High Flux Isotope Reactor from High Enriched to Low Enriched Uranium Fuel

International Nuclear Information System (INIS)

Primm, Trent; Guida, Tracey

2010-01-01

Under the auspices of the Global Threat Reduction Initiative Reduced Enrichment for Research and Test Reactors Program, the National Nuclear Security Administration/Department of Energy (NNSA/DOE) has, as a goal, to convert research reactors worldwide from weapons grade to non-weapons grade uranium. The High Flux Isotope Reactor (HFIR) at Oak Ridge National Lab (ORNL) is one of the candidates for conversion of fuel from high enriched uranium (HEU) to low enriched uranium (LEU). A well documented business model, including tasks, costs, and schedules was developed to plan the conversion of HFIR. Using Microsoft Project, a detailed outline of the conversion program was established and consists of LEU fuel design activities, a fresh fuel shipping cask, improvements to the HFIR reactor building, and spent fuel operations. Current-value costs total $76 million dollars, include over 100 subtasks, and will take over 10 years to complete. The model and schedule follows the path of the fuel from receipt from fuel fabricator to delivery to spent fuel storage and illustrates the duration, start, and completion dates of each subtask to be completed. Assumptions that form the basis of the cost estimate have significant impact on cost and schedule.

Flightless I (Drosophila) homolog facilitates chromatin accessibility of the estrogen receptor α target genes in MCF-7 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Jeong, Kwang Won, E-mail: kwjeong@gachon.ac.kr

2014-04-04

Highlights: • H3K4me3 and Pol II binding at TFF1 promoter were reduced in FLII-depleted MCF-7 cells. • FLII is required for chromatin accessibility of the enhancer of ERalpha target genes. • Depletion of FLII causes inhibition of proliferation of MCF-7 cells. - Abstract: The coordinated activities of multiple protein complexes are essential to the remodeling of chromatin structure and for the recruitment of RNA polymerase II (Pol II) to the promoter in order to facilitate the initiation of transcription in nuclear receptor-mediated gene expression. Flightless I (Drosophila) homolog (FLII), a nuclear receptor coactivator, is associated with the SWI/SNF-chromatin remodeling complex during estrogen receptor (ER)α-mediated transcription. However, the function of FLII in estrogen-induced chromatin opening has not been fully explored. Here, we show that FLII plays a critical role in establishing active histone modification marks and generating the open chromatin structure of ERα target genes. We observed that the enhancer regions of ERα target genes are heavily occupied by FLII, and histone H3K4me3 and Pol II binding induced by estrogen are decreased in FLII-depleted MCF-7 cells. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments showed that depletion of FLII resulted in reduced chromatin accessibility of multiple ERα target genes. These data suggest FLII as a key regulator of ERα-mediated transcription through its role in regulating chromatin accessibility for the binding of RNA Polymerase II and possibly other transcriptional coactivators.

Flightless I (Drosophila) homolog facilitates chromatin accessibility of the estrogen receptor α target genes in MCF-7 breast cancer cells

International Nuclear Information System (INIS)

Jeong, Kwang Won

2014-01-01

Highlights: • H3K4me3 and Pol II binding at TFF1 promoter were reduced in FLII-depleted MCF-7 cells. • FLII is required for chromatin accessibility of the enhancer of ERalpha target genes. • Depletion of FLII causes inhibition of proliferation of MCF-7 cells. - Abstract: The coordinated activities of multiple protein complexes are essential to the remodeling of chromatin structure and for the recruitment of RNA polymerase II (Pol II) to the promoter in order to facilitate the initiation of transcription in nuclear receptor-mediated gene expression. Flightless I (Drosophila) homolog (FLII), a nuclear receptor coactivator, is associated with the SWI/SNF-chromatin remodeling complex during estrogen receptor (ER)α-mediated transcription. However, the function of FLII in estrogen-induced chromatin opening has not been fully explored. Here, we show that FLII plays a critical role in establishing active histone modification marks and generating the open chromatin structure of ERα target genes. We observed that the enhancer regions of ERα target genes are heavily occupied by FLII, and histone H3K4me3 and Pol II binding induced by estrogen are decreased in FLII-depleted MCF-7 cells. Furthermore, formaldehyde-assisted isolation of regulatory elements (FAIRE)-quantitative polymerase chain reaction (qPCR) experiments showed that depletion of FLII resulted in reduced chromatin accessibility of multiple ERα target genes. These data suggest FLII as a key regulator of ERα-mediated transcription through its role in regulating chromatin accessibility for the binding of RNA Polymerase II and possibly other transcriptional coactivators

Deep functional analysis of synII, a 770 kb synthetic yeast chromosome

Science.gov (United States)

Gao, Feng; Gong, Jianhui; Abramczyk, Dariusz; Walker, Roy; Zhao, Hongcui; Chen, Shihong; Liu, Wei; Luo, Yisha; Müller, Carolin A.; Paul-Dubois-Taine, Adrien; Alver, Bonnie; Stracquadanio, Giovanni; Mitchell, Leslie A.; Luo, Zhouqing; Fan, Yanqun; Zhou, Baojin; Wen, Bo; Tan, Fengji; Wang, Yujia; Zi, Jin; Xie, Zexiong; Li, Bingzhi; Yang, Kun; Richardson, Sarah M.; Jiang, Hui; French, Christopher E.; Nieduszynski, Conrad A.; Koszul, Romain; Marston, Adele L.; Yuan, Yingjin; Wang, Jian; Bader, Joel S.; Dai, Junbiao; Boeke, Jef D.; Xu, Xun; Cai, Yizhi; Yang, Huanming

2017-01-01

Herein we report the successful design, construction and characterization of a 770 kb synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels, including phenomics, transcriptomics, proteomics, chromosome segregation and replication analysis to provide a thorough and comprehensive analysis of a synthetic chromosome. Our “Trans-Omics” analyses reveal a modest but potentially significant pervasive up-regulation of translational machinery observed in synII is mainly caused by the deletion of 13 tRNAs. By both complementation assays and SCRaMbLE, we targeted and debuged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the HOG response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. PMID:28280153

Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

International Nuclear Information System (INIS)

Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne

2012-01-01

Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id + tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id + single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id + fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id + tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id + scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

Energy Technology Data Exchange (ETDEWEB)

Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne, E-mail: bjarne.bogen@medisin.uio.no [Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo (Norway)

2012-10-30

Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id{sup +} tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id{sup +} single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id{sup +} fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id{sup +} tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id{sup +} scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag

International Nuclear Information System (INIS)

Xue Yongjie; Hou Haobo; Zhu Shujing

2009-01-01

Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01 M NaNO 3 . In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84 mM in the single element system and 0.21 mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH 50 (the pH at which 50% adsorption occurs) was found to follow the sequence Zn > Cu > Pb > Cd in single-element systems, but Pb > Cu > Zn > Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems

Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag

Energy Technology Data Exchange (ETDEWEB)

Xue Yongjie [School of Resource and Environment Science, Wuhan University, Hubei, Wuhan (China); Wuhan Kaidi Electric Power Environmental Protection Co. Ltd., Hubei, Wuhan (China)], E-mail: xueyj@mail.whut.edu.cn; Hou Haobo; Zhu Shujing [School of Resource and Environment Science, Wuhan University, Hubei, Wuhan (China)

2009-02-15

Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01 M NaNO{sub 3}. In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84 mM in the single element system and 0.21 mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH{sub 50} (the pH at which 50% adsorption occurs) was found to follow the sequence Zn > Cu > Pb > Cd in single-element systems, but Pb > Cu > Zn > Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems.

Competitive adsorption of copper(II), cadmium(II), lead(II) and zinc(II) onto basic oxygen furnace slag.

Science.gov (United States)

Xue, Yongjie; Hou, Haobo; Zhu, Shujing

2009-02-15

Polluted and contaminated water can often contain more than one heavy metal species. It is possible that the behavior of a particular metal species in a solution system will be affected by the presence of other metals. In this study, we have investigated the adsorption of Cd(II), Cu(II), Pb(II), and Zn(II) onto basic oxygen furnace slag (BOF slag) in single- and multi-element solution systems as a function of pH and concentration, in a background solution of 0.01M NaNO(3). In adsorption edge experiments, the pH was varied from 2.0 to 13.0 with total metal concentration 0.84mM in the single element system and 0.21mM each of Cd(II), Cu(II), Pb(II), and Zn(II) in the multi-element system. The value of pH(50) (the pH at which 50% adsorption occurs) was found to follow the sequence Zn>Cu>Pb>Cd in single-element systems, but Pb>Cu>Zn>Cd in the multi-element system. Adsorption isotherms at pH 6.0 in the multi-element systems showed that there is competition among various metals for adsorption sites on BOF slag. The adsorption and potentiometric titrations data for various slag-metal systems were modeled using an extended constant-capacitance surface complexation model that assumed an ion-exchange process below pH 6.5 and the formation of inner-sphere surface complexes at higher pH. Inner-sphere complexation was more dominant for the Cu(II), Pb(II) and Zn(II) systems.

Targeting Renin–Angiotensin System Against Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Abadi Kahsu Gebre

2018-04-01

Full Text Available Renin Angiotensin System (RAS is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer’s disease (AD, and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD. Angiotensin II (AngII via AT1 receptor is reported to increase brain Aβ level via different mechanisms including increasing amyloid precursor protein (APP mRNA, β-secretase activity, and presenilin expression. Similarly, it was associated with tau phosphorylation, and reactive oxygen species generation. However, these effects are counterbalanced by Ang II mediated AT2 signaling. The protective effect observed with angiotensin receptor blockers (ARBs and angiotensin converting enzyme inhibitors (ACEIs could be as the result of inhibition of Ang II signaling. ARBs also offer additional benefit by shifting the effect of Ang II toward AT2 receptor. To conclude, targeting RAS in the brain may benefit patients with AD though it still requires further in depth understanding.

IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer.

Science.gov (United States)

Mal, Chittabrata; Aftabuddin, Md; Kundu, Sudip

2018-03-16

Growing evidences suggest that microRNAs (miRNAs) can efficiently regulate gene expression at intracellular and extracellular levels. It has been previously reported that plant/food-derived miRNAs are highly enriched in human serum or serum from phytophagous animals, and they are responsible for regulating mammalian gene expression. Thus, miRNAs could function as active signaling molecules, which carry information across distinct species or even kingdoms. However, the mode of miRNA shuttling among various organisms is still a mystery to unravel. The intra and inter kingdom miRNA transfer has boosted up the hypothesis about the potential impact of plant or animal miRNAs on each other. To our knowledge, the software for analyzing cross-kingdom miRNA-targets is lacking. We have developed a web-tool "IIKmTA: Inter and Intra Kingdom miRNA-Target Analyzer" utilizing a database; the data of which have been collected from another web server. Here, user can analyze the targeting potential of (i) plant miRNAs on animal UTRs (Untranslated regions), and vice versa (i.e., inter kingdom), (ii) plant miRNAs on plant UTRs and animal miRNAs on animal UTRs (i.e., intra kingdom). Further, user can analyze (i) miRNAs to targets, (ii) targets to miRNAs, and (iii) miRNA sets targeting sets of targets. For a wide variety of animal and plant species, IIKmTA can identify the miRNA binding sites in the probable target UTRs. Moreover, GC% and AU% of miRNAs will be calculated. All the results can be saved as .csv file. Recent researches identified miRNAs in plants and human secretions and their role in regulating the human genes. Such findings indicate the therapeutic role of secretory miRNAs of such plants which exhibits medicinal value and in near future many diseases may be treated by consumption of these plant miRNAs through food. Using our newly developed database and analyzing tool, one can easily determine the different relationships between miRNAs and their targets across kingdoms

Preparation of Schiff s base complexes of Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) and their spectroscopic, magnetic, thermal, and antifungal studies

International Nuclear Information System (INIS)

Parekh, H.M.; Patel, M.N.

2006-01-01

The potassium salt of salicylidene-DL-alanine (KHL), bis(benzylidene)ethylenediamine (A 1 ), thiophene-o-carboxaldene-p-toluidine (A 2 ), and its metal complexes of the formula [(M II (L)(A)(H 2 O)] (M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II); A = A 1 or A 2 ) are prepared. They are characterized by elemental analysis, magnetic susceptibility measurements, thermogravimetric analysis, and infrared and electronic spectral studies. The electronic spectral and magnetic moment data suggest an octahedral geometry for the complexes. All of these complexes, metal nitrates, fungicides (bavistin and emcarb), and ligands are screened for their antifungal activity against Aspergillus niger, Fusarium oxysporum, and Aspergillus flavus using a plate poison technique. The complexes show higher activity than those of the free ligands, metal nitrate, and the control (DMSO) and moderate activity against bavistin and emcarb [ru

Pulsed laser deposition of II-VI and III-V semiconductor materials

Energy Technology Data Exchange (ETDEWEB)

Mele, A.; Di Palma, T.M.; Flamini, C.; Giardini Guidoni, A. [Rome, Univ. `La Sapienza` (Italy). Dep. di Chimica

1998-12-01

Pulsed laser irradiation of a solid target involves electronic excitation and heating, followed by expansion from the target of the elliptical gas cloud (plume) which can be eventually condensed on a suitable substrate. Pulsed laser ablation has been found to be a valuable technique to prepare II-VI and III-V thin films of semiconductor materials. Pulsed laser ablation deposition is discussed in the light of the results of an investigation on CdS, CdSe, CdTe and CdSe/CdTe multilayers and AIN, GaN and InN together with Al-Ga-In-N heterostructures. [Italiano] L`irradiazione di un target solido, mediante un fascio laser impulsato, genera una serie di processi che possono essere schematizzati come segue: riscaldamento ed eccitazione elettronica del target, da cui consegue l`espulsione di materiale sotto forma di una nube gassosa di forma ellissoidale (plume), che espande e puo` essere fatta depositare su un opportuno substrato. L`ablazione lasersi e` rivelata una tecnica valida per preparare film sottili di composti di elementi del II-VI e del III-V gruppo della tavola periodica. La deposizione via ablazione laser viene discussa alla luce dei risultati ottenuti nella preparazione di film di CdS, CdSe, CdTe e di film multistrato di CdSe/CdTe, di film di AIN, GaN, InN e di eterostrutture di Al-Ga-In-N.

Evidence for $\\pi K$ -atoms with DIRAC-II

CERN Document Server

Allkofer, Yves

2008-01-01

DIRAC-II is a fixed-target experiment at the CERN Proton Synchroton (PS) which has been designed to search for piK atoms, a bound state of a pi±K± pair, and measure their lifetime. These atoms are observed through an excess of low energetic piK pairs over the background, detected in the two spectrometer arms. This excess comes from the ionization of piK atoms in the target and can be related to their mean life. The piK S-wave scattering length combination |a1/2 - a3/2| (for isospin 1/2 and 3/2) can be related to the latter. The aim of the upgraded DIRAC-II experiment is a measurement of the scattering length combination |a1/2 - a3/2| with a precision of 5%. piK atoms have not been observed so far. The original DIRAC experiment was designed to measure the scattering lengths of pipi atoms. So far, close to 15 000 atoms have been detected, leading to a precision on |a0 - a2| which is better than 10%. In chiral perturbation theories (ChPT) the pipi scattering lengths have been calculated with 2% precision a...

Cu(II) AND Zn(II)

African Journals Online (AJOL)

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SYNTHESIS OF 2,2-DIMETHYL-4-PHENYL-[1,3]-DIOXOLANE USING ZEOLITE. ENCAPSULATED Co(II), Cu(II) AND Zn(II) COMPLEXES. B.P. Nethravathi1, K. Rama Krishna Reddy2 and K.N. Mahendra1*. 1Department of Chemistry, Bangalore University, Bangalore-560001, India. 2Department of Chemistry, Government ...

Transuranium processing plant report of production, status, and plans for the period October 1, 1978-September 30, 1980

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1981-08-01

During this period, transuranium elements were obtained from 26 irradiated HFIT targets. The products included 86 mg of 249 Bk, 686 mg of 252 Cf, 3.1 mg of 253 Es, and an estimated 1.4 pg of 257 Fm. In addition, about 326 mg of high-purity 248 Cm was separated from previously purified 252 Cf. One hundred seven product shipments were made from TRU; recipients and the amounts of nuclides shipped are listed in a table. Forty-two standard and two special HFIR targets were fabricated. During the next 18 months, production totals of 110 mg of 249 Bk, 1200 mg of 252 Cf, 5.5 mg of 253 Es, and 2 pg of 257 Fm are anticipated. Also, a total of 225 mg of 248 Cm is expected to be made available. During this report period, a charcoal adsorber system for radioiodine removal was installed, tested, and placed in service. This system serves as a backup to the Hopcalite-charcoal system for adsorption of 131 I from the VOG stream. Seven 252 Cf neutron sources were fabricated during this report period. A total of 100 neutron sources have been fabricated previously at TRU. The original and current contents ( 252 Cf and 248 Cm) of the existing sources and the individuals to whom the sources are currently loaned are listed in a table. In addition to neutron sources, nine fission sources were prepared by electroplating 252 Cf onto platinum disks or foils.Special projects during this report period included (1) purification of two batches of isotopically pure 240 Pu, (2) fabrication of two special HFIR targets, (3) repurification of the residues of the einsteinium product from Campaign 56, (4) production of approx. 235 μg of 250 Cf by irradiation of 249 Bk, (5) radiography of 28 irradiated, stainless steel alloy, fracture-strain specimens, and (6) preparations for the production of 40 μg of 245 Es by irradiation of 253 Es

IGORR 1: Proceedings of the 1. meeting of the International Group On Research Reactors

Energy Technology Data Exchange (ETDEWEB)

West, C D [comp.

1990-05-01

Descriptions of the ongoing projects presented at this Meeting were concerned with: New Research Reactor FRM-II at Munich; MITR-II reactor; The Advanced. Neutron Source (ANS) Project; The high Flux Reactor Petten, Status and Prospects; The High Flux Beam Reactor Instrumentation Upgrade; BER-II Upgrade; The BR2 Materials Testing Reactor Past, Ongoing and Under-Study Upgrades; The ORPHEE, Reactor Current Status and Proposed Enhancement of Experimental Variabilities; Construction of the Upgraded JRR-3; Status of the University of Missouri-Columbia Research Reactor Upgrade; the Reactor and Cold Neutron Facility at NIST; Upgrade of Materials Irradiation Facilities in HFIR; Backfitting of the FRG Reactors; University Research Reactors in the United States; and Organization of the ITER Project - Sharing of Informational Procurements. Topics of interest were: Thermal-hydraulic tests and correlations, Corrosion tests and analytical models , Multidimensional kinetic analysis for small cores, Fuel plates fabrication, Fuel plates stability, Fuel irradiation, Burnable poison irradiation, Structural materials irradiation, Neutron guides irradiation, Cold Source materials irradiation, Cold Source LN{sub 2} test, Source LH2-H{sub 2}O reaction (H or D), Instrumentation upgrading and digital control system, Man-machine interface.

IGORR 1: Proceedings of the 1. meeting of the International Group On Research Reactors

International Nuclear Information System (INIS)

West, C.D.

1990-05-01

Descriptions of the ongoing projects presented at this Meeting were concerned with: New Research Reactor FRM-II at Munich; MITR-II reactor; The Advanced. Neutron Source (ANS) Project; The high Flux Reactor Petten, Status and Prospects; The High Flux Beam Reactor Instrumentation Upgrade; BER-II Upgrade; The BR2 Materials Testing Reactor Past, Ongoing and Under-Study Upgrades; The ORPHEE, Reactor Current Status and Proposed Enhancement of Experimental Variabilities; Construction of the Upgraded JRR-3; Status of the University of Missouri-Columbia Research Reactor Upgrade; the Reactor and Cold Neutron Facility at NIST; Upgrade of Materials Irradiation Facilities in HFIR; Backfitting of the FRG Reactors; University Research Reactors in the United States; and Organization of the ITER Project - Sharing of Informational Procurements. Topics of interest were: Thermal-hydraulic tests and correlations, Corrosion tests and analytical models , Multidimensional kinetic analysis for small cores, Fuel plates fabrication, Fuel plates stability, Fuel irradiation, Burnable poison irradiation, Structural materials irradiation, Neutron guides irradiation, Cold Source materials irradiation, Cold Source LN 2 test, Source LH2-H 2 O reaction (H or D), Instrumentation upgrading and digital control system, Man-machine interface

Displacement cross sections and PKA spectra: tables and applications

International Nuclear Information System (INIS)

Doran, D.G.; Graves, N.J.

1976-12-01

Damage energy cross sections to 20 MeV are given for aluminum, vanadium, chromium, iron, nickel, copper, zirconium, niobium, molybdenum, tantalum, tungsten, lead, and 18Cr10Ni stainless steel. They are based on ENDF/B-IV nuclear data and the Lindhard energy partition model. Primary knockon atom (PKA) spectra are given for aluminum, iron, niobium, tantalum, and lead for neutron energies up to 15 MeV at approximately one-quarter lethargy intervals. The contributions of various reactions to both the displacement cross sections (taken to be proportional to the damage energy cross sections) and the PKA spectra are presented graphically. Spectral-averaged values of the displacement cross sections are given for several spectra, including approximate maps for the Experimental Breeder Reactor-II (EBR-II) and several positions in the Fast Test Reactor (FTR). Flux values are included to permit estimation of displacement rates. Graphs show integral PKA spectra for the five metals listed above for neutron spectra corresponding to locations in the EBR-II, the High Flux Isotope Reactor (HFIR), and a conceptual fusion reactor (UWMAK-I). Detailed calculations are given only for cases not previously documented. Uncertainty estimates are included

Maintenance management at the High Flux Isotope Reactor

International Nuclear Information System (INIS)

Farrar, M.B.

1982-02-01

Maintenance procedures are described for mechanical and electrical equipment; nuclear and process instrumentation; operational maintenance; equipment and systems inspections; and HFIR quality assurance

Spectroscopic and thermal degradation behavior of Mg(II, Ca(II, Ba(II and Sr(II complexes with paracetamol drug

Directory of Open Access Journals (Sweden)

Moamen S. Refat

2017-05-01

Full Text Available Complexes of Mg(II, Ca(II, Ba(II and Sr(II with paracetamol drug were synthesized and characterized by elemental analysis, conductivity, UV–Vis, IR, and 1H NMR spectroscopy and thermal analysis, as well as screened for antimicrobial activity. The IR spectral data suggested that the ligand behaves as paracetamol behaves as a neutral bidentate ligand coordinated to the metal ions via the lone pair of electrons of nitrogen and carbonyl-O atoms of the amide group. From the microanalytical data, the stoichiometry of the complexes reacts with Mg(II, Ca(II, Ba(II and Sr(II by molar ratios (2:1 (paracetamol:metal ion. The thermal behavior (TG/DTG of the complexes was studied. The ligand and their metal complexes were screened against both of antibacterial and fungicidal activities.

Some Remarks on Prediction of Drug-Target Interaction with Network Models.

Science.gov (United States)

Zhang, Shao-Wu; Yan, Xiao-Ying

2017-01-01

System-level understanding of the relationships between drugs and targets is very important for enhancing drug research, especially for drug function repositioning. The experimental methods used to determine drug-target interactions are usually time-consuming, tedious and expensive, and sometimes lack reproducibility. Thus, it is highly desired to develop computational methods for efficiently and effectively analyzing and detecting new drug-target interaction pairs. With the explosive growth of different types of omics data, such as genome, pharmacology, phenotypic, and other kinds of molecular networks, numerous computational approaches have been developed to predict Drug-Target Interactions (DTI). In this review, we make a survey on the recent advances in predicting drug-target interaction with network-based models from the following aspects: i) Available public data sources and benchmark datasets; ii) Drug/target similarity metrics; iii) Network construction; iv) Common network algorithms; v) Performance comparison of existing network-based DTI predictors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transuranium Processing Plant semiannual report of production, status, and plans for period ending June 30, 1977

International Nuclear Information System (INIS)

King, L.J.; Bigelow, J.E.; Collins, E.D.

1977-12-01

During the period January 1, 1977, through June 30, 1977, the following amounts of transuranium elements were recovered from 12 irradiated HFIR targets: 0.1g 243 Am, 21g 244 Cm, 29.5 mg 249 Bk, 288 mg 252 Cf, 1.48 mg 253 Es, and 0.7 pg 257 Fm. One batch of high-purity 248 Cm (approximately 50 mg) was separated from 252 Cf. Twenty-three shipments were made from TRU during the period; recipients and the amounts of nuclides are tabulated. Five HFIR targets, each containing 8 to 9 g of curium, were fabricated. During the next 18 months, we expect to obtain totals of 92 mg of 249 Bk, 910 mg of 252 Cf, 3.8 mg of 253 Es (in a mixture of isotopes), 615 μg of high-purity 253 Es, and 1.6 pg of 257 Fm; we also expect to make available 250 mg of high-purity 248 Cm. No process or equipment changes were made during this report period. Five neutron sources were fabricated during this report period, bringing the total fabricated to date to 97. Two sources that had previously been returned to TRU were reassigned. Special projects included the following: (1) the enrichment of the 244 Pu concentration in 100 mg of plutonium by irradiation to burn out the lighter isotopes, (2) the separation of 245 pg of 254 Cf from 39-hr /sup 254m/Es that was produced by irradiation of 5 μg of 253 Es, and (3) an experimental separation of cerium from the other rare-earth elements in a TRU process waste solution. The values that we are currently using for transuranium element decay data and for cross-section data in planning irradiation-processing cycles, calculating production forecasts, and assaying products are tabulated in the Appendix

The metacompiler system META-II/X

International Nuclear Information System (INIS)

Kneis, W.

1975-03-01

It is the objective of this work to demonstrate by the properties of the META-II/X system and concrete compiler implementation for IML that a simple and universally applicable symbol processor allows to develop in a very easy manner precompilers for problem oriented languages. The main feature consists in the fact that no auxiliary routines coded manually had to be added for special implementation. The translation of IML is exclusively defined by the compiler description written in the META language. As a whole, META-II/X proves to be a system which is relatively convenient to handle in automating the translation of explicit languages. The decisive point is the choise of an assembler language as target language allowing to transfer to the assembler level references not completely resolved. Implementation includes the possibility of an uncomplicated transfer of the whole system inclusive of the internal compiler representations. (orig.) [de

Angiotensin II increases CTGF expression via MAPKs/TGF-{beta}1/TRAF6 pathway in atrial fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Gu, Jun [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Liu, Xu, E-mail: xkliuxu@yahoo.cn [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Wang, Quan-xing, E-mail: shmywqx@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Tan, Hong-wei [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China); Guo, Meng [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University School of medicine, Shanghai (China)

2012-10-01

The activation of transforming growth factor-{beta}1(TGF-{beta}1)/Smad signaling pathway and increased expression of connective tissue growth factor (CTGF) induced by angiotensin II (AngII) have been proposed as a mechanism for atrial fibrosis. However, whether TGF{beta}1/non-Smad signaling pathways involved in AngII-induced fibrogenetic factor expression remained unknown. Recently tumor necrosis factor receptor associated factor 6 (TRAF6)/TGF{beta}-associated kinase 1 (TAK1) has been shown to be crucial for the activation of TGF-{beta}1/non-Smad signaling pathways. In the present study, we explored the role of TGF-{beta}1/TRAF6 pathway in AngII-induced CTGF expression in cultured adult atrial fibroblasts. AngII (1 {mu}M) provoked the activation of P38 mitogen activated protein kinase (P38 MAPK), extracellular signal-regulated kinase 1/2(ERK1/2) and c-Jun NH(2)-terminal kinase (JNK). AngII (1 {mu}M) also promoted TGF{beta}1, TRAF6, CTGF expression and TAK1 phosphorylation, which were suppressed by angiotensin type I receptor antagonist (Losartan) as well as p38 MAPK inhibitor (SB202190), ERK1/2 inhibitor (PD98059) and JNK inhibitor (SP600125). Meanwhile, both TGF{beta}1 antibody and TRAF6 siRNA decreased the stimulatory effect of AngII on TRAF6, CTGF expression and TAK1 phosphorylation, which also attenuated AngII-induced atrial fibroblasts proliferation. In summary, the MAPKs/TGF{beta}1/TRAF6 pathway is an important signaling pathway in AngII-induced CTGF expression, and inhibition of TRAF6 may therefore represent a new target for reversing Ang II-induced atrial fibrosis. -- Highlights: Black-Right-Pointing-Pointer MAPKs/TGF{beta}1/TRAF6 participates in AngII-induced CTGF expression in atrial fibroblasts. Black-Right-Pointing-Pointer TGF{beta}1/TRAF6 participates in AngII-induced atrial fibroblasts proliferation. Black-Right-Pointing-Pointer TRAF6 may represent a new target for reversing Ang II-induced atrial fibrosis.

Postirradiation evaluations of capsules HANS-1 and HANS-2 irradiated in the HFIR target region in support of fuel development for the advanced neutron source

International Nuclear Information System (INIS)

Hofman, G.L.; Snelgrove, J.L.; Copeland, G.L.

1995-08-01

This report describes the design, fabrication, irradiation, and evaluation of two capsule tests containing U 3 Si 2 fuel particles in contact with aluminum. The tests were in support of fuel qualification for the Advanced Neutron Source (ANS) reactor, a high-powered research reactor that was planned for the Oak Ridge National Laboratory. At the time of these tests, the fuel consisted of U 3 Si 2 , containing highly enriched uranium dispersed in aluminum at a volume fraction of ∼0.15. The extremely high thermal flux in the target region of the High Flux Isotope Reactor provided up to 90% burnup in one 23-d cycle. Temperatures up to 450 degrees C were maintained by gamma heating. Passive SiC temperature monitors were employed. The very small specimen size allowed only microstructural examination of the fuel particles but also allowed many specimens to be tested at a range of temperatures. The determination of fission gas bubble morphology by microstructural examination has been beneficial in developing a fuel performance model that allows prediction of fuel performance under these extreme conditions. The results indicate that performance of the reference fuel would be satisfactory under the ANS conditions. In addition to U 3 Si 2 , particles of U 3 Si, UAl 2 , UAl x , and U 3 O 8 were tested

New Therapeutic Targets in Soft Tissue Sarcoma

Science.gov (United States)

Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C.; Lazar, Alexander J

2012-01-01

Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

Paralog-divergent Features May Help Reduce Off-target Effects of Drugs: Hints from Glucagon Subfamily Analysis

Directory of Open Access Journals (Sweden)

Zhining Sa

2017-08-01

Full Text Available Side effects from targeted drugs remain a serious concern. One reason is the nonselective binding of a drug to unintended proteins such as its paralogs, which are highly homologous in sequences and have similar structures and drug-binding pockets. To identify targetable differences between paralogs, we analyzed two types (type-I and type-II of functional divergence between two paralogs in the known target protein receptor family G-protein coupled receptors (GPCRs at the amino acid level. Paralogous protein receptors in glucagon-like subfamily, glucagon receptor (GCGR and glucagon-like peptide-1 receptor (GLP-1R, exhibit divergence in ligands and are clinically validated drug targets for type 2 diabetes. Our data showed that type-II amino acids were significantly enriched in the binding sites of antagonist MK-0893 to GCGR, which had a radical shift in physicochemical properties between GCGR and GLP-1R. We also examined the role of type-I amino acids between GCGR and GLP-1R. The divergent features between GCGR and GLP-1R paralogs may be helpful in their discrimination, thus enabling the identification of binding sites to reduce undesirable side effects and increase the target specificity of drugs.

Target conception for the Munich fission fragment accelerator

CERN Document Server

Maier, H J; Gross, M L; Grossmann, R; Kester, O; Thirolf, P

1999-01-01

For the new high-flux reactor FRM II, the fission fragment accelerator MAFF is under design. MAFF will supply intense mass-separated radioactive ion beams of very neutron-rich nuclei with energies around the Coulomb barrier. A central part of this accelerator is the ion source with the fission target, which is operated at a neutron flux of 1.5x10 sup 1 sup 4 cm sup - sup 2 s sup - sup 1. The target consists of typically 1 g of sup 2 sup 3 sup 5 U dispersed in a cylindrical graphite matrix, which is encapsulated in a Re container. To enable diffusion and extraction of the fission products, the target has to be maintained at a temperature of up to 2400 deg. C during operation. It has to stand this temperature for at least one reactor cycle of 1250 h. Comprehensive tests are required to study the long-term behaviour of the involved materials at these conditions prior to operation in the reactor. The present paper gives details of the target conception and the projected tests.

The PIP-II Reference Design Report

Energy Technology Data Exchange (ETDEWEB)

Lebedev, Valeri, [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); et al.

2015-06-01

The Proton Improvement Plan-II (PIP-II) is a high-intensity proton facility being developed to support a world-leading neutrino program over the next two decades at Fermilab. PIP-II is an integral part of the U.S. Intensity Frontier Roadmap as described in the Particle Physics Project Prioritization Panel (P5) report of May 2014 [1]. As an immediate goal PIP-II is focused on upgrades to the Fermilab accelerator complex capable of providing a beam power in excess of 1 MW on target at the initiation of LBNF [1,2] operations. PIP-II is a part of a longer-term concept for a sustained campaign of upgrades and improvements to achieve multi-MW capabilities at Fermilab. PIP-II is based on three major thrusts. They are (1) the recently completed upgrades to the Recycler and Main Injector (MI) for the NOvA experiment, (2) the Proton Improvement Plan [3] currently underway, and (3) the Project X Reference Design [4]. Note that: The Proton Improvement Plan (PIP) consolidates a set of improvements to the existing Linac, Booster, and Main Injector (MI) aimed at supporting 15 Hz Booster beam operation. In combination, the NOvA upgrades and PIP create a capability of delivering 700 kW beam power from the Main Injector at 120 GeV; The scope of the Project X Reference Design Report was aimed well beyond PIP. It described a complete concept for a multi-MW proton facility that could support a broad particle physics program based on neutrino, kaon, muon, and nucleon experiments [5,6]. The Project X conceptual design has evolved over a number of years, incorporating continuous input on physics research goals and advances in the underlying technology development programs [7,8,9]. PIP-II, to high degree, inherits these goals as the goals for future developments and upgrades. This document (PIP-II Reference Design Report) describes an initial step in the development of the Fermilab accelerating complex. The plan described in this Report balances the far-term goals of the Laboratory

Cd(II), Cu(II)

African Journals Online (AJOL)

user

Depending on the way goethite was pretreated with oxalic acid, affinity for Cd(II) varied ...... Effects and mechanisms of oxalate on Cd(II) adsorption on goethite at different ... precipitation, surfactant mediation, hydrothermal and micro-emulsion.

Late-onset Bartter syndrome type II.

Science.gov (United States)

Gollasch, Benjamin; Anistan, Yoland-Marie; Canaan-Kühl, Sima; Gollasch, Maik

2017-10-01

Mutations in the ROMK1 potassium channel gene ( KCNJ1 ) cause antenatal/neonatal Bartter syndrome type II (aBS II), a renal disorder that begins in utero , accounting for the polyhydramnios and premature delivery that is typical in affected infants, who develop massive renal salt wasting, hypokalaemic metabolic alkalosis, secondary hyperreninaemic hyperaldosteronism, hypercalciuria and nephrocalcinosis. This BS type is believed to represent a disorder of the infancy, but not in adulthood. We herein describe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations, consisting of a novel c.197T > A (p.I66N) and a previously reported c.875G > A (p.R292Q) KCNJ1 mutation. We implemented and evaluated the performance of two different bioinformatics-based approaches of targeted massively parallel sequencing [next generation sequencing (NGS)] in defining the molecular diagnosis. Our results demonstrate that aBS II may be suspected in patients with a late-onset phenotype. Our experimental approach of NGS-based mutation screening combined with Sanger sequencing proved to be a reliable molecular approach for defining the clinical diagnosis in our patient, and results in important differential diagnostic and therapeutic implications for patients with BS. Our results could have a significant impact on the diagnosis and methodological approaches of genetic testing in other patients with clinical unclassified phenotypes of nephrocalcinosis and congenital renal electrolyte abnormalities.

Determining the cortical target of transcranial magnetic stimulation.

Science.gov (United States)

Thielscher, A; Wichmann, F A

2009-10-01

Determining the cortical region that is effectively targeted by TMS to induce a reproducible behavioral effect is a non-trivial problem. In mapping experiments, a grid of coil positions is used to systematically assess the TMS effect on, e.g. muscle responses or error rates. The center-of-mass (CoM) of the response distribution is projected onto the cortex to determine the likely target site, implicitly assuming the existence of a single, contiguous target. The mapping results, however, often contain several local maxima. These could either stem from measurement noise, or hint towards a distributed target region. Critically, the calculation of a CoM, by design, treats multiple maxima as if they were noise. Here, a stringent hierarchical sigmoidal model fitting approach is developed that determines the cortical target(s) from TMS mapping based on electric field calculations. Monte-Carlo simulations are used to assess the significance and the goodness-of-fit of the sigmoidal fits, and to obtain confidence regions around the calculated targets. The approach was applied to mapping data on visual suppression (N=7). In all subjects, we reliably identified two or three neighboring targets commonly contributing to the suppression effect (average distance+/-SD: 7.7+/-2.3 mm). This demonstrates that (i) the assumption of a single CoM is not generally valid and (ii) the combination of TMS mapping with the fitting approach has a cortical resolution of TMS.

Early biomarkers of brain injury and cerebral hypo- and hyperoxia in the SafeBoosC II trial

DEFF Research Database (Denmark)

Plomgaard, Anne M.; Alderliesten, Thomas; Austin, Topun

2017-01-01

Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both the inte......Background The randomized clinical trial, SafeBoosC II, examined the effect of monitoring of cerebral oxygenation by near-infrared spectroscopy combined with a guideline on treatment when cerebral oxygenation was out of the target range. Data on cerebral oxygenation was collected in both......, and the biomarkers of brain injury from birth till term equivalent age that was collected as secondary and explorative outcomes in the SafeBoosC II trial. Methods Cerebral oxygenation was continuously monitored during the first 72h of life in 166 extremely preterm infants. Cranial ultrasound was performed at day 1...

Sequestration of Cu(II), Ni(II), and Co(II) by ethyleneimine immobilized on silica

International Nuclear Information System (INIS)

Arakaki, Luiza N.H.; Alves, Ana Paula M.; Silva Filho, Edson C. da; Fonseca, Maria G.; Oliveira, Severino F.; Espinola, Jose Geraldo P.; Airoldi, Claudio

2007-01-01

Thermodynamic data on interaction of Cu(II), Ni(II), and Co(II) with silica modified with ethyleneimine are obtained by calorimetric titration. The amount of ethyleneimine anchored on silica surface was estimated to be 0.70 mmol g -1 . The enthalpies of binding Ni(II), Cu(II) and Co(II), are -3.59 ± 0.001, -4.88 ± 0.001, and -7.75 ± 0.003 kJ mol -1 , respectively

PROSTVAC® targeted immunotherapy candidate for prostate cancer.

Science.gov (United States)

Shore, Neal D

2014-01-01

Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

MHC class II tetramers made from isolated recombinant α and β chains refolded with affinity-tagged peptides

DEFF Research Database (Denmark)

Braendstrup, Peter; Justesen, Sune Frederik Lamdahl; Osterbye, Thomas

2013-01-01

Targeting CD4+ T cells through their unique antigen-specific, MHC class II-restricted T cell receptor makes MHC class II tetramers an attractive strategy to identify, validate and manipulate these cells at the single cell level. Currently, generating class II tetramers is a specialized undertaking...... effectively limiting their use and emphasizing the need for improved methods of production. Using class II chains expressed individually in E. coli as versatile recombinant reagents, we have previously generated peptide-MHC class II monomers, but failed to generate functional class II tetramers. Adding...... a monomer purification principle based upon affinity-tagged peptides, we here provide a robust method to produce class II tetramers and demonstrate staining of antigen-specific CD4+ T cells. We also provide evidence that both MHC class II and T cell receptor molecules largely accept affinity-tagged peptides...

Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes.

Science.gov (United States)

Zhao, Lue Ping; Carlsson, Annelie; Larsson, Helena Elding; Forsander, Gun; Ivarsson, Sten A; Kockum, Ingrid; Ludvigsson, Johnny; Marcus, Claude; Persson, Martina; Samuelsson, Ulf; Örtqvist, Eva; Pyo, Chul-Woo; Bolouri, Hamid; Zhao, Michael; Nelson, Wyatt C; Geraghty, Daniel E; Lernmark, Åke

2017-11-01

It is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies. Utilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D. In the training set, estimated risk scores were significantly different between patients and controls (P = 8.12 × 10 -92 ), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a "biological validation" by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA-2A (Z-score = 3.628, P < 0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high-risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime. Through both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high-risk subjects for prevention research in high-risk populations. Copyright © 2017 John Wiley & Sons, Ltd.

CALCULATIONS FOR A MERCURY JET TARGET IN A SOLENOID MAGNET CAPTURE SYSTEM

International Nuclear Information System (INIS)

GALLARDO, J.; KAHN, S.; PALMER, R.B.; THIEBERGER, P.; WEGGEL, R.J.; MCDONALD, K.

2001-01-01

A mercury jet is being considered as the production target for a muon storage ring facility to produce an intense neutrino beam. A 20 T solenoid magnet that captures pions for muon production surrounds the mercury target. As the liquid metal jet enters or exits the field eddy currents are induced. We calculate the effects that a liquid metal jet experiences in entering and exiting the magnetic field for the magnetic configuration considered in the Neutrino Factory Feasibility Study II

Solid-phase extraction of Mn(II), Co(II), Ni(II), Cu(II), Cd(II) and Pb(II) ions from environmental samples by flame atomic absorption spectrometry (FAAS)

Energy Technology Data Exchange (ETDEWEB)

Duran, Celal [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey); Gundogdu, Ali [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey); Bulut, Volkan Numan [Department of Chemistry, Giresun Faculty of Art and Science, Karadeniz Technical University, 28049 Giresun (Turkey); Soylak, Mustafa [Department of Chemistry, Faculty of Art and Science, Erciyes University, 38039 Kayseri (Turkey)]. E-mail: soylak@erciyes.edu.tr; Elci, Latif [Department of Chemistry, Faculty of Art and Science, Pamukkale University, 20020 Denizli (Turkey); Sentuerk, Hasan Basri [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey); Tuefekci, Mehmet [Department of Chemistry, Faculty of Art and Science, Karadeniz Technical University, 61080 Trabzon (Turkey)

2007-07-19

A new method using a column packed with Amberlite XAD-2010 resin as a solid-phase extractant has been developed for the multi-element preconcentration of Mn(II), Co(II), Ni(II), Cu(II), Cd(II), and Pb(II) ions based on their complex formation with the sodium diethyldithiocarbamate (Na-DDTC) prior to flame atomic absorption spectrometric (FAAS) determinations. Metal complexes sorbed on the resin were eluted by 1 mol L{sup -1} HNO{sub 3} in acetone. Effects of the analytical conditions over the preconcentration yields of the metal ions, such as pH, quantity of Na-DDTC, eluent type, sample volume and flow rate, foreign ions etc. have been investigated. The limits of detection (LOD) of the analytes were found in the range 0.08-0.26 {mu}g L{sup -1}. The method was validated by analyzing three certified reference materials. The method has been applied for the determination of trace elements in some environmental samples.

Global track finder for Belle II experiment

Energy Technology Data Exchange (ETDEWEB)

Trusov, Viktor; Feindt, Michael; Heck, Martin; Kuhr, Thomas; Goldenzweig, Pablo [Karlsruhe Institute of Technology, IEKP (Germany); Collaboration: Belle II-Collaboration

2015-07-01

We present an implementation of a method based on the Legendre transformation for reconstruction charged particle tracks in the central drift chamber of the Belle II experiment. The method is designed for fast track finding and restoring circular patterns of track hits in transverse plane. It is done by searching for common tangents to drift circles of hits in the conformal space. With known transverse trajectories longitudinal momentum estimation performed by assigning stereo hits followed by determination of the track parameters. The method includes algorithms responsible for track quality estimation and reduction of rate of fakes. The work is targeting at increasing the efficiency and reducing the execution time because the computing power available to the experiment is limited. The algorithm is developed within the Belle II software environment with using Monte-Carlo simulation for probing its efficiency.

Status of the Gerda phase II experiment

Energy Technology Data Exchange (ETDEWEB)

Lazzaro, Andrea [Physik-Department and Excellence Cluster Universe, Technische Universitaet Muenchen (Germany); Collaboration: GERDA-Collaboration

2016-07-01

The Gerda experiment searches for the neutrinoless double beta decay (0νββ) in {sup 76}Ge. The first phase of the experiment collected 21.6 kg. yr of exposure with a background index (BI) of 0.01 cts/(keV . kg . yr). No signal was observed and a lower limit for the 0νββ half-life was set to T{sup 0νββ}{sub 1/2} < 2.1 . 10{sup 25} yr (90% C.L). The apparatus has now been upgraded to the Phase II configuration. In Phase II 38 kg of HPGe detectors will be operated to reach an exposure of 100 kg . yr. The goal of Gerda Phase II is to lower the BI to 10{sup -3} cts/(keV . kg . y), in order to reach the sensitivity for T{sup 0νββ}{sub 1/2} = O(10{sup 26}) yr. The additional target mass is constituted of 30 custom made BEGe detectors with higher energy resolution and better pulse shape discrimination performance. The detectors are operated in new radio-pure low-mass holders. The liquid argon surrounding the detectors has been instrumented to veto the background events which produce scintillation light. In this talk the current status and the performance of the Gerda Phase II are presented.

Identification of miRNAs associated with recurrence of stage II colorectal cancer

DEFF Research Database (Denmark)

Christensen, Lise Lotte; Tobiasen, Heidi; Schepeler, Troels

2011-01-01

Colorectal cancer (CRC) is one of the leading causes of cancer deaths. Twenty-five percent of the patients radically treated for a stage II CRC (no lymph node or distant metastasis) later develop recurrence and dies from the disease. MicroRNAs (miRNAs) are aberrantly expressed or mutated in human...... target prediction and transcript profiling. Initially, miRNA over-expression in HCT116 cells was followed by transcriptional profiling of transfected cells using GeneChip Human Exon 1.0 ST Arrays. Three in silico predicted miRNA targets showing differential mRNA expression upon miRNA up-regulation were...... cancers, and function either as tumour suppressors or oncogenes. Additionally, they also appear to have both diagnostic and prognostic significance. The aim of the present study was to identify miRNAs associated with recurrence of stage II CRC, followed up by an investigation of how these potential...

Probability of success for phase III after exploratory biomarker analysis in phase II.

Science.gov (United States)

Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver

2017-05-01

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.

Expression, purification and characterization of enoyl-ACP reductase II, FabK, from Porphyromonas gingivalis

Energy Technology Data Exchange (ETDEWEB)

Hevener, Kirk E.; Mehboob, Shahila; Boci, Teuta; Truong, Kent; Santarsiero, Bernard D.; Johnson, Michael E. (UIC)

2012-10-25

The rapid rise in bacterial drug resistance coupled with the low number of novel antimicrobial compounds in the discovery pipeline has led to a critical situation requiring the expedient discovery and characterization of new antimicrobial drug targets. Enzymes in the bacterial fatty acid synthesis pathway, FAS-II, are distinct from their mammalian counterparts, FAS-I, in terms of both structure and mechanism. As such, they represent attractive targets for the design of novel antimicrobial compounds. Enoyl-acyl carrier protein reductase II, FabK, is a key, rate-limiting enzyme in the FAS-II pathway for several bacterial pathogens. The organism, Porphyromonas gingivalis, is a causative agent of chronic periodontitis that affects up to 25% of the US population and incurs a high national burden in terms of cost of treatment. P. gingivalis expresses FabK as the sole enoyl reductase enzyme in its FAS-II cycle, which makes this a particularly appealing target with potential for selective antimicrobial therapy. Herein we report the molecular cloning, expression, purification and characterization of the FabK enzyme from P. gingivalis, only the second organism from which this enzyme has been isolated. Characterization studies have shown that the enzyme is a flavoprotein, the reaction dependent upon FMN and NADPH and proceeding via a Ping-Pong Bi-Bi mechanism to reduce the enoyl substrate. A sensitive assay measuring the fluorescence decrease of NADPH as it is converted to NADP{sup +} during the reaction has been optimized for high-throughput screening. Finally, protein crystallization conditions have been identified which led to protein crystals that diffract x-rays to high resolution.

SCORPION II persistent surveillance system update

Science.gov (United States)

Coster, Michael; Chambers, Jon

2010-04-01

This paper updates the improvements and benefits demonstrated in the next generation Northrop Grumman SCORPION II family of persistent surveillance and target recognition systems produced by the Xetron Campus in Cincinnati, Ohio. SCORPION II reduces the size, weight, and cost of all SCORPION components in a flexible, field programmable system that is easier to conceal and enables integration of over fifty different Unattended Ground Sensor (UGS) and camera types from a variety of manufacturers, with a modular approach to supporting multiple Line of Sight (LOS) and Beyond Line of Sight (BLOS) communications interfaces. Since 1998 Northrop Grumman has been integrating best in class sensors with its proven universal modular Gateway to provide encrypted data exfiltration to Common Operational Picture (COP) systems and remote sensor command and control. In addition to feeding COP systems, SCORPION and SCORPION II data can be directly processed using a common sensor status graphical user interface (GUI) that allows for viewing and analysis of images and sensor data from up to seven hundred SCORPION system gateways on single or multiple displays. This GUI enables a large amount of sensor data and imagery to be used for actionable intelligence as well as remote sensor command and control by a minimum number of analysts.

Cold moderators at ORNL

International Nuclear Information System (INIS)

Lucas, A. T.

1997-09-01

The Advanced Neutron Source (ANS) cold moderators were not an 'Oak Ridge first', but would have been the largest both physically and in terms of cold neutron flux. Two cold moderators were planned each 410 mm in diameter and containing about 30L of liquid deuterium. They were to be completely independent of each other. A modular system design was used to provide greater reliability and serviceability. When the ANS was terminated, upgrading of the resident High Flux Isotope Reactor (HFIR) was examined and an initial study was made into the feasibility of adding a cold source. Because the ANS design was modular, it was possible to use many identical design features. Sub-cooled liquid at 4 bar abs was initially chosen for the HFIR design concept, but this was subsequently changed to 15 bar abs to operate above the critical pressure. As in the ANS, the hydrogen will operate at a constant pressure throughout the temperature range and a completely closed loop with secondary containment was adopted. The heat load of 2 kW made the heat flux comparable with that of the ANS. Subsequent studies into the construction of cryogenic moderators for the proposed new Synchrotron Neutron source indicated that again many of the same design concepts could be used. By connecting the two cold sources together in series, the total heat load of 2 kW is very close to that of the HFIR allowing a very similar supercritical hydrogen system to be configured. The two hydrogen moderators of the SNS provide a comparable heat load to the HFIR moderator. It is subsequently planned to connect the two in series and operate from a single cold loop system, once again using supercritical hydrogen. The spallation source also provided an opportunity to re-examine a cold pellet solid methane moderator operating at 20K.

High Flux Isotope Reactor cold neutron source reference design concept

Energy Technology Data Exchange (ETDEWEB)

Selby, D.L.; Lucas, A.T.; Hyman, C.R. [and others

1998-05-01

In February 1995, Oak Ridge National Laboratory`s (ORNL`s) deputy director formed a group to examine the need for upgrades to the High Flux Isotope Reactor (HFIR) system in light of the cancellation of the Advanced neutron Source Project. One of the major findings of this study was that there was an immediate need for the installation of a cold neutron source facility in the HFIR complex. In May 1995, a team was formed to examine the feasibility of retrofitting a liquid hydrogen (LH{sub 2}) cold source facility into an existing HFIR beam tube. The results of this feasibility study indicated that the most practical location for such a cold source was the HB-4 beam tube. This location provides a potential flux environment higher than the Institut Laue-Langevin (ILL) vertical cold source and maximizes the space available for a future cold neutron guide hall expansion. It was determined that this cold neutron beam would be comparable, in cold neutron brightness, to the best facilities in the world, and a decision was made to complete a preconceptual design study with the intention of proceeding with an activity to install a working LH{sub 2} cold source in the HFIR HB-4 beam tube. During the development of the reference design the liquid hydrogen concept was changed to a supercritical hydrogen system for a number of reasons. This report documents the reference supercritical hydrogen design and its performance. The cold source project has been divided into four phases: (1) preconceptual, (2) conceptual design and testing, (3) detailed design and procurement, and (4) installation and operation. This report marks the conclusion of the conceptual design phase and establishes the baseline reference concept.

Heysham II/Torness AGR core integrity

International Nuclear Information System (INIS)

Birch, A.L.; Hampson, J.D.

1985-01-01

The design and construction process for the Heysham II/Torness AGR core structures is presented. The design intent utilizing all past experience in designing and building AGR core structures is described. The major aspects of the design criteria and the design conditions are outlined to demonstrate how the integrity of the Heysham II/Torness core is assured. Since no recognized codes of practice for graphite core design exist, the National Nuclear Corporation (NNC) have conceived design criteria utilizing reserve factors based on their design experience. Target reserve factors are defined for particular loading conditions including the ultimate 'safe-shutdown earthquake'. The substantial programme of computer analysis and RandD work to substantiate the design, including seismic qualification, is described. In keeping with their responsibility for the detailed core structure design and the fuel path geometry (guide tube system), NNC attach great importance to design/manufacture/construction liaison, which is demonstrated in the quality assurance section. (author)

Self-similarity of hard cumulative processes in fixed target experiment for BES-II at STAR

International Nuclear Information System (INIS)

Tokarev, M.V.; Aparin, A.A.; Zborovsky, I.

2014-01-01

Search for signatures of phase transition in Au + Au collisions is in the heart of the heavy ion program at RHIC. Systematic study of particle production over a wide range of collision energy revealed new phenomena such as the nuclear suppression effect expressed by nuclear modification factor, the constituent quark number scaling for elliptic flow, the 'ridge effect' in - fluctuations, etc. To determine the phase boundaries and location of the critical point of nuclear matter, the Beam Energy Scan (BES-I) program at RHIC has been suggested and performed by STAR and PHENIX Collaborations. The obtained results have shown that the program (BES-II) should be continued. In this paper a proposal to use hard cumulative processes in BES Phase-II program is outlined. Selection of the cumulative events is assumed to enrich data sample by a new type of collisions characterized by higher energy density and more compressed matter. This would allow finding clearer signatures of phase transition, location of a critical point and studying extreme conditions in heavy ion collisions.

Average [O II] nebular emission associated with Mg II absorbers: dependence on Fe II absorption

Science.gov (United States)

Joshi, Ravi; Srianand, Raghunathan; Petitjean, Patrick; Noterdaeme, Pasquier

2018-05-01

We investigate the effect of Fe II equivalent width (W2600) and fibre size on the average luminosity of [O II] λλ3727, 3729 nebular emission associated with Mg II absorbers (at 0.55 ≤ z ≤ 1.3) in the composite spectra of quasars obtained with 3 and 2 arcsec fibres in the Sloan Digital Sky Survey. We confirm the presence of strong correlations between [O II] luminosity (L_{[O II]}) and equivalent width (W2796) and redshift of Mg II absorbers. However, we show L_{[O II]} and average luminosity surface density suffer from fibre size effects. More importantly, for a given fibre size, the average L_{[O II]} strongly depends on the equivalent width of Fe II absorption lines and found to be higher for Mg II absorbers with R ≡W2600/W2796 ≥ 0.5. In fact, we show the observed strong correlations of L_{[O II]} with W2796 and z of Mg II absorbers are mainly driven by such systems. Direct [O II] detections also confirm the link between L_{[O II]} and R. Therefore, one has to pay attention to the fibre losses and dependence of redshift evolution of Mg II absorbers on W2600 before using them as a luminosity unbiased probe of global star formation rate density. We show that the [O II] nebular emission detected in the stacked spectrum is not dominated by few direct detections (i.e. detections ≥3σ significant level). On an average, the systems with R ≥ 0.5 and W2796 ≥ 2 Å are more reddened, showing colour excess E(B - V) ˜ 0.02, with respect to the systems with R < 0.5 and most likely trace the high H I column density systems.

T-REX on-demand redox targeting in live cells.

Science.gov (United States)

Parvez, Saba; Long, Marcus J C; Lin, Hong-Yu; Zhao, Yi; Haegele, Joseph A; Pham, Vanha N; Lee, Dustin K; Aye, Yimon

2016-12-01

This protocol describes targetable reactive electrophiles and oxidants (T-REX)-a live-cell-based tool designed to (i) interrogate the consequences of specific and time-resolved redox events, and (ii) screen for bona fide redox-sensor targets. A small-molecule toolset comprising photocaged precursors to specific reactive redox signals is constructed such that these inert precursors specifically and irreversibly tag any HaloTag-fused protein of interest (POI) in mammalian and Escherichia coli cells. Syntheses of the alkyne-functionalized endogenous reactive signal 4-hydroxynonenal (HNE(alkyne)) and the HaloTag-targetable photocaged precursor to HNE(alkyne) (also known as Ht-PreHNE or HtPHA) are described. Low-energy light prompts photo-uncaging (t 1/2 <1-2 min) and target-specific modification. The targeted modification of the POI enables precisely timed and spatially controlled redox events with no off-target modification. Two independent pathways are described, along with a simple setup to functionally validate known targets or discover novel sensors. T-REX sidesteps mixed responses caused by uncontrolled whole-cell swamping with reactive signals. Modification and downstream response can be analyzed by in-gel fluorescence, proteomics, qRT-PCR, immunofluorescence, fluorescence resonance energy transfer (FRET)-based and dual-luciferase reporters, or flow cytometry assays. T-REX targeting takes 4 h from initial probe treatment. Analysis of targeted redox responses takes an additional 4-24 h, depending on the nature of the pathway and the type of readouts used.

The Anti-Adipogenic Potential of COUP-TFII Is Mediated by Downregulation of the Notch Target Gene Hey1.

Directory of Open Access Journals (Sweden)

Ilse Scroyen

Full Text Available Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII belongs to the steroid/thyroid hormone receptor superfamily and may contribute to the pathogenesis of obesity. It has not conclusively been established, however, whether its role is pro- or anti-adipogenic.Gene silencing of Coup-tfII in 3T3-F442A preadipocytes resulted in enhanced differentiation into mature adipocytes. This was associated with upregulation of the Notch signaling target gene Hey1. A functional role of Hey1 was confirmed by gene silencing in 3T3-F442A preadipocytes, resulting in impaired differentiation. In vivo, de novo fat pad formation in NUDE mice was significantly stimulated following injection of preadipocytes with Coup-tfII gene silencing, but impaired with Hey1 gene silencing. Moreover, expression of Coup-tfII was lower and that of Hey1 higher in isolated adipocytes of obese as compared to lean adipose tissue.These in vitro and in vivo data support an anti-adipogenic role of COUP-TFII via downregulating the Notch signaling target gene Hey1.

Structural information on the coordination compounds formed by manganese(II), cobalt(II), nickel(II), zinc(II), cadmium(II) and mercury(II) thiocyanates with 4-cyanopyridine N-oxide from their magnetic moments, electronic and infrared spectra

Science.gov (United States)

Ahuja, I. S.; Yadava, C. L.; Singh, Raghuvir

1982-05-01

Coordination compounds formed by the interaction of 4-cyanopyridine. N-oxide (4-CPO), a potentially bidentate ligand, with manganese(II), cobalt(II), nickel(II), zinc(II), cadmium(II) and rnercury(II) thiocyanates have been prepared and characterized from their elemental analyses, magnetic susceptibilities, electronic and infrared spectral studies down to 200 cm -1 in the solid state. The compounds isolated are: Mn(4-CPO) 2(NCS) 2, Co(4-CPO) 2(NCS) 2,Ni(4-CPO) 2(NCS) 2,Zn(4-CPO) 2(NCS) 2, Cd(4-CPO)(NCS) 2 and Hg(4-CPO) 2(SCN) 2. It is shown that 4-CPO acts as a terminal N-oxide oxygen bonded monodentate ligand in all the metal(II) thiocyanate complexes studied. Tentative stereochemistries of the complexes in the solid state are discussed. The ligand field parameters 10 Dq, B, β and λ calculated for the manganese(II), cobalt(II) and nickel(II) complexes are consistent with their proposed stereochemistries.

Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy.

Science.gov (United States)

Bostad, Monica; Olsen, Cathrine Elisabeth; Peng, Qian; Berg, Kristian; Høgset, Anders; Selbo, Pål Kristian

2015-05-28

The cancer stem cell (CSC) marker CD133 is an attractive target to improve antitumor therapy. We have used photochemical internalization (PCI) for the endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin (PCIAC133-saporin). PCI employs an endocytic vesicle-localizing photosensitizer, which generates reactive oxygen species upon light-activation causing a rupture of the vesicle membranes and endosomal escape of entrapped drugs. Here we show that AC133-saporin co-localizes with the PCI-photosensitizer TPCS2a, which upon light exposure induces cytosolic release of AC133-saporin. PCI of picomolar levels of AC133-saporin in colorectal adenocarcinoma WiDr cells blocked cell proliferation and induced 100% inhibition of cell viability and colony forming ability at the highest light doses, whereas no cytotoxicity was obtained in the absence of light. Efficient PCI-based CD133-targeting was in addition demonstrated in the stem-cell-like, triple negative breast cancer cell line MDA-MB-231 and in the aggressive malignant melanoma cell line FEMX-1, whereas no enhanced targeting was obtained in the CD133-negative breast cancer cell line MCF-7. PCIAC133-saporin induced mainly necrosis and a minimal apoptotic response based on assessing cleavage of caspase-3 and PARP, and the TUNEL assay. PCIAC133-saporin resulted in S phase arrest and reduced LC3-II conversion compared to control treatments. Notably, co-treatment with Bafilomycin A1 and PCIAC133-saporin blocked LC3-II conversion, indicating a termination of the autophagic flux in WiDr cells. For the first time, we demonstrate laser-controlled targeting of CD133 in vivo. After only one systemic injection of AC133-saporin and TPCS2a, a strong anti-tumor response was observed after PCIAC133-saporin. The present PCI-based endosomal escape technology represents a minimally invasive strategy for spatio-temporal, light-controlled targeting of CD133+ cells in localized primary tumors or metastasis. Copyright © 2015

Characterization of the minimum domain required for targeting budding yeast myosin II to the site of cell division

Directory of Open Access Journals (Sweden)

Tolliday Nicola J

2006-06-01

Full Text Available Abstract Background All eukaryotes with the exception of plants use an actomyosin ring to generate a constriction force at the site of cell division (cleavage furrow during mitosis and meiosis. The structure and filament forming abilities located in the C-terminal or tail region of one of the main components, myosin II, are important for localising the molecule to the contractile ring (CR during cytokinesis. However, it remains poorly understood how myosin II is recruited to the site of cell division and how this recruitment relates to myosin filament assembly. Significant conservation between species of the components involved in cytokinesis, including those of the CR, allows the use of easily genetically manipulated organisms, such as budding yeast (Saccharomyces cerevisiae, in the study of cytokinesis. Budding yeast has a single myosin II protein, named Myo1. Unlike most other class II myosins, the tail of Myo1 has an irregular coiled coil. In this report we use molecular genetics, biochemistry and live cell imaging to characterize the minimum localisation domain (MLD of budding yeast Myo1. Results We show that the MLD is a small region in the centre of the tail of Myo1 and that it is both necessary and sufficient for localisation of Myo1 to the yeast bud neck, the pre-determined site of cell division. Hydrodynamic measurements of the MLD, purified from bacteria or yeast, show that it is likely to exist as a trimer. We also examine the importance of a small region of low coiled coil forming probability within the MLD, which we call the hinge region. Removal of the hinge region prevents contraction of the CR. Using fluorescence recovery after photobleaching (FRAP, we show that GFP-tagged MLD is slightly more dynamic than the GFP-tagged full length molecule but less dynamic than the GFP-tagged Myo1 construct lacking the hinge region. Conclusion Our results define the intrinsic determinant for the localization of budding yeast myosin II and show

Design Study for a Low-Enriched Uranium Core for the High Flux Isotope Reactor, Annual Report for FY 2008

Energy Technology Data Exchange (ETDEWEB)

Primm, Trent [ORNL; Chandler, David [ORNL; Ilas, Germina [ORNL; Miller, James Henry [ORNL; Sease, John D [ORNL; Jolly, Brian C [ORNL

2009-03-01

This report documents progress made during FY 2008 in studies of converting the High Flux Isotope Reactor (HFIR) from highly enriched uranium (HEU) fuel to low-enriched uranium (LEU) fuel. Conversion from HEU to LEU will require a change in fuel form from uranium oxide to a uranium-molybdenum alloy. With axial and radial grading of the fuel foil and an increase in reactor power to 100 MW, calculations indicate that the HFIR can be operated with LEU fuel with no degradation in reactor performance from the current level. Results of selected benchmark studies imply that calculations of LEU performance are accurate. Scoping experiments with various manufacturing methods for forming the LEU alloy profile are presented.

Deep functional analysis of synII, a 770-kilobase synthetic yeast chromosome.

Science.gov (United States)

Shen, Yue; Wang, Yun; Chen, Tai; Gao, Feng; Gong, Jianhui; Abramczyk, Dariusz; Walker, Roy; Zhao, Hongcui; Chen, Shihong; Liu, Wei; Luo, Yisha; Müller, Carolin A; Paul-Dubois-Taine, Adrien; Alver, Bonnie; Stracquadanio, Giovanni; Mitchell, Leslie A; Luo, Zhouqing; Fan, Yanqun; Zhou, Baojin; Wen, Bo; Tan, Fengji; Wang, Yujia; Zi, Jin; Xie, Zexiong; Li, Bingzhi; Yang, Kun; Richardson, Sarah M; Jiang, Hui; French, Christopher E; Nieduszynski, Conrad A; Koszul, Romain; Marston, Adele L; Yuan, Yingjin; Wang, Jian; Bader, Joel S; Dai, Junbiao; Boeke, Jef D; Xu, Xun; Cai, Yizhi; Yang, Huanming

2017-03-10

Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by loxP -mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain. Copyright © 2017, American Association for the Advancement of Science.

Synthesis and Biological Evaluation of Ru(II) and Pt(II) Complexes Bearing Carboxyl Groups as Potential Anticancer Targeted Drugs.

Science.gov (United States)

Martínez, Ma Ángeles; Carranza, M Pilar; Massaguer, Anna; Santos, Lucia; Organero, Juan A; Aliende, Cristina; de Llorens, Rafael; Ng-Choi, Iteng; Feliu, Lidia; Planas, Marta; Rodríguez, Ana M; Manzano, Blanca R; Espino, Gustavo; Jalón, Félix A

2017-11-20

The synthesis and characterization of Pt(II) (1 and 2) and Ru(II) arene (3 and 4) or polypyridine (5 and 6) complexes is described. With the aim of having a functional group to form bioconjugates, one uncoordinated carboxyl group has been introduced in all complexes. Some of the complexes were selected for their potential in photodynamic therapy (PDT). The molecular structures of complexes 2 and 5, as well as that of the sodium salt of the 4'-(4-carboxyphenyl)-2,2':6',2″-terpyridine ligand (cptpy), were determined by X-ray diffraction. Different techniques were used to evaluate the binding capacity to model DNA molecules, and MTT cytotoxicity assays were performed against four cell lines. Compounds 3, 4, and 5 showed little tendency to bind to DNA and exhibited poor biological activity. Compound 2 behaves as bonded to DNA probably through a covalent interaction, although its cytotoxicity was very low. Compound 1 and possibly 6, both of which contain a cptpy ligand, were able to intercalate with DNA, but toxicity was not observed for 6. However, compound 1 was active in all cell lines tested. Clonogenic assays and apoptosis induction studies were also performed on the PC-3 line for 1. The photodynamic behavior for complexes 1, 5, and 6 indicated that their nuclease activity was enhanced after irradiation at λ = 447 nm. The cell viability was significantly reduced only in the case of 5. The different behavior in the absence or presence of light makes complex 5 a potential prodrug of interest in PDT. Molecular docking studies followed by molecular dynamics simulations for 1 and the counterpart without the carboxyl group confirmed the experimental data that pointed to an intercalation mechanism. The cytotoxicity of 1 and the potential of 5 in PDT make them good candidates for subsequent conjugation, through the carboxyl group, to "selected peptides" which could facilitate the selective vectorization of the complex toward receptors that are overexpressed in

Macrocyclic receptor showing extremely high Sr(II)/Ca(II) and Pb(II)/Ca(II) selectivities with potential application in chelation treatment of metal intoxication.

Science.gov (United States)

Ferreirós-Martínez, Raquel; Esteban-Gómez, David; Tóth, Éva; de Blas, Andrés; Platas-Iglesias, Carlos; Rodríguez-Blas, Teresa

2011-04-18

Herein we report a detailed investigation of the complexation properties of the macrocyclic decadentate receptor N,N'-Bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (H(2)bp18c6) toward different divalent metal ions [Zn(II), Cd(II), Pb(II), Sr(II), and Ca(II)] in aqueous solution. We have found that this ligand is especially suited for the complexation of large metal ions such as Sr(II) and Pb(II), which results in very high Pb(II)/Ca(II) and Pb(II)/Zn(II) selectivities (in fact, higher than those found for ligands widely used for the treatment of lead poisoning such as ethylenediaminetetraacetic acid (edta)), as well as in the highest Sr(II)/Ca(II) selectivity reported so far. These results have been rationalized on the basis of the structure of the complexes. X-ray crystal diffraction, (1)H and (13)C NMR spectroscopy, as well as theoretical calculations at the density functional theory (B3LYP) level have been performed. Our results indicate that for large metal ions such as Pb(II) and Sr(II) the most stable conformation is Δ(δλδ)(δλδ), while for Ca(II) our calculations predict the Δ(λδλ)(λδλ) form being the most stable one. The selectivity that bp18c6(2-) shows for Sr(II) over Ca(II) can be attributed to a better fit between the large Sr(II) ions and the relatively large crown fragment of the ligand. The X-ray crystal structure of the Pb(II) complex shows that the Δ(δλδ)(δλδ) conformation observed in solution is also maintained in the solid state. The Pb(II) ion is endocyclically coordinated, being directly bound to the 10 donor atoms of the ligand. The bond distances to the donor atoms of the pendant arms (2.55-2.60 Å) are substantially shorter than those between the metal ion and the donor atoms of the crown moiety (2.92-3.04 Å). This is a typical situation observed for the so-called hemidirected compounds, in which the Pb(II) lone pair is stereochemically active. The X-ray structures of the Zn(II) and Cd(II) complexes show that

Comprehensive diagnostic set for intense lithium ion hohlraum experiments on PBFA II

International Nuclear Information System (INIS)

Leeper, R.J.; Bailey, J.E.; Carlson, A.L.

1994-01-01

A review of the comprehensive diagnostic package developed at Sandia National Laboratories for intense lithium ion hohlraum target experiments on PBFA II will be presented. This package contains an extensive suite of x-ray spectral and imaging diagnostics that enable measurements of target radiation smoothing, hydro-motion, and temperature. The x-ray diagnostics include time-integrated and time-resolved pinhole cameras, energy-resolved 1-D streaked imaging diagnostics that enable measurements of target radiation smoothing, hydro-motion, and temperature. The x-ray diagnostics include time-integrated and time-resolved pinhole cameras, energy-resolved 1-D streaked imaging diagnostics, time-integrated and time-resolved grazing incidence spectrographs, a transmission grating spectrography, an elliptical crystal spectrograph, a bolometer array, an eleven element x-ray diode (XRD) array, and an eleven element PIN diode detector array. A hohlraum temperature measurement technique under development is a shock breakout diagnostic that measures the radiation pressure at the hohlraum wall. The incident Li beam symmetry and an estimate of incident Li beam power density are measured from ion beam-induced characteristic x-ray line and neutron emissions. An attempt to measure the Li beam intensity directly on target used Rutherford scattered ions into an ion movie camera and a magnetic spectrograph. The philosophy used in designing all the diagnostics in the set has emphasized redundant and independent measurements of fundamental physical quantities relevant to the performance of the target. Details of each diagnostic, its integration, data reduction procedures, and recent PBFA-II data will be discussed

Fabrication of control rods for the High Flux Isotope Reactor

International Nuclear Information System (INIS)

Sease, J.D.

1998-01-01

The High Flux Isotope Reactor (HFIR) is a research-type nuclear reactor that was designed and built in the early 1960s and has been in continuous operation since its initial criticality in 1965. Under current plans, the HFIR is expected to continue in operation until 2035. This report updates ORNL/TM-9365, Fabrication Procedure for HFIR Control Plates, which was mainly prepared in the early 1970's but was not issued until 1984, and reflects process changes, lessons learned in the latest control rod fabrication campaign, and suggested process improvements to be considered in future campaigns. Most of the personnel involved with the initial development of the processes and in part campaigns have retired or will retire soon. Because their unlikely availability in future campaigns, emphasis has been placed on providing some explanation of why the processes were selected and some discussions about the importance of controlling critical process parameters. Contained in this report is a description of the function of control rods in the reactor, the brief history of the development of control rod fabrication processes, and a description of procedures used in the fabrication of control rods. A listing of the controlled documents and procedures used in the last fabrication campaigns is referenced in Appendix A

Fabrication of control rods for the High Flux Isotope Reactor

Energy Technology Data Exchange (ETDEWEB)

Sease, J.D.

1998-03-01

The High Flux Isotope Reactor (HFIR) is a research-type nuclear reactor that was designed and built in the early 1960s and has been in continuous operation since its initial criticality in 1965. Under current plans, the HFIR is expected to continue in operation until 2035. This report updates ORNL/TM-9365, Fabrication Procedure for HFIR Control Plates, which was mainly prepared in the early 1970's but was not issued until 1984, and reflects process changes, lessons learned in the latest control rod fabrication campaign, and suggested process improvements to be considered in future campaigns. Most of the personnel involved with the initial development of the processes and in part campaigns have retired or will retire soon. Because their unlikely availability in future campaigns, emphasis has been placed on providing some explanation of why the processes were selected and some discussions about the importance of controlling critical process parameters. Contained in this report is a description of the function of control rods in the reactor, the brief history of the development of control rod fabrication processes, and a description of procedures used in the fabrication of control rods. A listing of the controlled documents and procedures used in the last fabrication campaigns is referenced in Appendix A.

TNF Receptor Type II as an Emerging Drug Target for the Treatment of Cancer, Autoimmune Diseases, and Graft-Versus-Host Disease: Current Perspectives and In Silico Search for Small Molecule Binders

Directory of Open Access Journals (Sweden)

Faraz Shaikh

2018-06-01

Full Text Available There is now compelling evidence that TNF receptor type II (TNFR2 is predominantly expressed on CD4+Foxp3+ regulatory T cells (Tregs and myeloid-derived suppressor cells (MDSCs, and plays a major role in the expansion and function of Tregs and MDSCs. Consequently, targeting of TNFR2 by either antagonists or agonists may represent a novel strategy in the treatment of cancer and autoimmune diseases, by downregulating or upregulating suppressor cell activity. The advance in the understanding of complex structure of TNFR2 and its binding with TNF at molecular levels offers opportunity for structure-guided drug discovery. This article reviews the current evidences regarding the decisive role of TNFR2 in immunosuppressive function of Tregs and MDSCs, and the current effort to develop novel TNFR2-targeting therapeutic agents in the treatment of cancer, autoimmune diseases, and graft-versus-host disease. To shed light on the potential TNFR2-targeting small molecules, we for the first time performed virtual screening of 400,000 natural compounds against the two TNF-binding sites, regions 3 and 4, of TNFR2. Our result showed that the top hits at region 4 had slightly higher docking energies than those at region 3. Nevertheless, free energy calculation from the TNF–TNFR2 molecular dynamics simulation revealed that the binding strength of TNF in region 3 is only one-tenth of that in region 4. This suggests that region 3 is a potentially more viable binding site to be targeted by small molecules than region 4. Therefore, the effectiveness in targeting region 3 of TNFR2 deserves further investigation.

Solid Phase Extraction of Trace Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) Ions in Beverages on Functionalized Polymer Microspheres Prior to Flame Atomic Absorption Spectrometric Determinations.

Science.gov (United States)

Berber, Hale; Alpdogan, Güzin

2017-01-01

In this study, poly(glycidyl methacrylate-methyl methacrylate-divinylbenzene) was synthesized in the form of microspheres, and then functionalized by 2-aminobenzothiazole ligand. The sorption properties of these functionalized microspheres were investigated for separation, preconcentration and determination of Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) ions using flame atomic absorption spectrometry. The optimum pH values for quantitative sorption were 2 - 4, 5 - 8, 6 - 8, 4 - 6, 2 - 6 and 2 - 3 for Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II), respectively, and also the highest sorption capacity of the functionalized microspheres was found to be for Cu(II) with the value of 1.87 mmol g -1 . The detection limits (3σ; N = 6) obtained for the studied metals in the optimal conditions were observed in the range of 0.26 - 2.20 μg L -1 . The proposed method was successfully applied to different beverage samples for the determination of Al(III), Fe(II), Co(II), Cu(II), Cd(II) and Pb(II) ions, with the relative standard deviation of <3.7%.

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

Science.gov (United States)

Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Prevalence of diabetic retinopathy in type II diabetic patients in a ...

African Journals Online (AJOL)

Prevalence of diabetic retinopathy in type II diabetic patients in a health facility in Karachi, Pakistan. ... Conclusion: DR is prevalent in the target population and, therefore, emphasis should be on the education of the local population of New Karachi Township on how to attain euglycemic state with regular medication, diet and ...

Commercial Applications at FRM II Based on Neutron Irradiations

Energy Technology Data Exchange (ETDEWEB)

Gerstenberg, H.; Draack, A.; Kastenmuller, A. [Technische Universitaet Muenchen, Munchen (Germany)

2013-07-01

Due to its design as a heavy water moderated reactor with a very compact core FRM II, Germany's most modern and most powerful research reactor, offers excellent conditions for basic research using beam tubes. On the other hand it is equipped with various irradiation facilities to be used mainly for industrial purposes. From the very beginning of reactor operation a dedicated department had been implemented in order to provide a neutron irradiation service to interested parties on a commercial basis. As of today the most widely used application is Si doping. The semiautomatic doping facility accepts ingots with diameters between 125 mm and 200 mm and a maximum height of 500 mm. The irradiation channel is located deep in the heavy water tank and exhibits a ratio of thermal/fast neutron flux density of > 1000. This value allows the doping of Si to a target resistivity as high as 1100 Ωcm within the tight limits regarding accuracy and homogeneity specified by the customer. Typically the throughput of Si doped in FRM II sums up to about 15 t/year. Another topic of growing importance is the use of FRM II aiming the production of radioisotopes mainly for the radiopharmaceutical industry. The maybe most challenging example is the production of Lu-177 n. c. a. based on the irradiation of Yb{sub 2}O{sub 3} to a high fluence of thermal neutrons of typically 1.5E20 cm{sup -2}. The Lu-177 activity delivered to the customer is in the range of 750 GBq. With respect to further processing it turned out to be a highly advantageous to have the laboratories of ITG, the company extracting the Lu-177 from the freshly irradiated Yb{sub 2}O{sub 3} on site FRM II. Further irradiation facilities are available at FRM II in order to allow the activation of samples for analytical purposes or to irradiate samples for geochronological investigations using the fission track technique. Finally a project on the future installation of a facility dedicated to the irradiation of U-targets for

Non-target adjacent stimuli classification improves performance of classical ERP-based brain computer interface

Science.gov (United States)

Ceballos, G. A.; Hernández, L. F.

2015-04-01

Objective. The classical ERP-based speller, or P300 Speller, is one of the most commonly used paradigms in the field of Brain Computer Interfaces (BCI). Several alterations to the visual stimuli presentation system have been developed to avoid unfavorable effects elicited by adjacent stimuli. However, there has been little, if any, regard to useful information contained in responses to adjacent stimuli about spatial location of target symbols. This paper aims to demonstrate that combining the classification of non-target adjacent stimuli with standard classification (target versus non-target) significantly improves classical ERP-based speller efficiency. Approach. Four SWLDA classifiers were trained and combined with the standard classifier: the lower row, upper row, right column and left column classifiers. This new feature extraction procedure and the classification method were carried out on three open databases: the UAM P300 database (Universidad Autonoma Metropolitana, Mexico), BCI competition II (dataset IIb) and BCI competition III (dataset II). Main results. The inclusion of the classification of non-target adjacent stimuli improves target classification in the classical row/column paradigm. A gain in mean single trial classification of 9.6% and an overall improvement of 25% in simulated spelling speed was achieved. Significance. We have provided further evidence that the ERPs produced by adjacent stimuli present discriminable features, which could provide additional information about the spatial location of intended symbols. This work promotes the searching of information on the peripheral stimulation responses to improve the performance of emerging visual ERP-based spellers.

Anti-Inflammatory Inhibitors Targeting Jak and Ikk Have An Anabolic Effect on Type II Collagen Turnover ex Vivo

DEFF Research Database (Denmark)

Kjelgaard-Petersen, Cecilie Freja; Bay-Jensen, Anne-Christine; Karsdal, M.A.

2016-01-01

be beneficial for the selection of novel anti-inflammatory treatments for RA and iOA. Objectives The aim of this study was to investigate the direct effect of the anti-inflammatory inhibitors R406 (the active metabolite of Fostamatinib), Tofacitinib, TPCA-1 and SB203580 on the cartilage ECM turnover. Methods...... Full depth bovine cartilage ex vivo cultures were cultured for 3 weeks with OSM [10 ng/mL] and TNFα [2 ng/mL] (O+T) or together with R406, Tofacitinib or TPCA-1 at 10 μM and a two-fold dilution to 0.16 μM. SB203580 was tested at 3 μM, 1 μM and 0.3 μM. As negative control, untreated explants were...... R406, the Jak inhibitor Tofacitinib, and the IKK inhibitor TPCA-1 inhibited the release of ARGS or AGNx1, while the p38 inhibitor, SB203580, had no effect. The turnover of type II collagen was measured by the formation of type II collagen (ProC2) and MMP-mediated degradation of type II collagen (C2M...

Operational limit of a planar DC magnetron cluster source due to target erosion

International Nuclear Information System (INIS)

Rai, A.; Mutzke, A.; Bandelow, G.; Schneider, R.; Ganeva, M.; Pipa, A.V.; Hippler, R.

2013-01-01

The binary collision-based two dimensional SDTrimSP-2D model has been used to simulate the erosion process of a Cu target and its influence on the operational limit of a planar DC magnetron nanocluster source. The density of free metal atoms in the aggregation region influences the cluster formation and cluster intensity during the target lifetime. The density of the free metal atoms in the aggregation region can only be predicted by taking into account (i) the angular distribution of the sputtered flux from the primary target source and (ii) relative downwards shift of the primary source of sputtered atoms during the erosion process. It is shown that the flux of the sputtered atoms smoothly decreases with the target erosion

An RNA polymerase II-and AGO4-associated protein acts in RNA-directed DNA methylation

KAUST Repository

Gao, Zhihuan

2010-04-21

DNA methylation is an important epigenetic mark in many eukaryotes. In plants, 24-nucleotide small interfering RNAs (siRNAs) bound to the effector protein, Argonaute 4 (AGO4), can direct de novo DNA methylation by the methyltransferase DRM2 (refs 2, 4-6). Here we report a new regulator of RNA-directed DNA methylation (RdDM) in Arabidopsis: RDM1. Loss-of-function mutations in the RDM1 gene impair the accumulation of 24-nucleotide siRNAs, reduce DNA methylation, and release transcriptional gene silencing at RdDM target loci. RDM1 encodes a small protein that seems to bind single-stranded methyl DNA, and associates and co-localizes with RNA polymerase II (Pol II, also known as NRPB), AGO4 and DRM2 in the nucleus. Our results indicate that RDM1 is a component of the RdDM effector complex and may have a role in linking siRNA production with pre-existing or de novo cytosine methylation. Our results also indicate that, although RDM1 and Pol V (also known as NRPE) may function together at some RdDM target sites in the peri-nucleolar siRNA processing centre, Pol II rather than Pol V is associated with the RdDM effector complex at target sites in the nucleoplasm. © 2010 Macmillan Publishers Limited. All rights reserved.

Synthesis, Spectral Characterization and Antioxidant Activity of Tin(II-Morin Complex

Directory of Open Access Journals (Sweden)

Shahabuddin Memon

2012-12-01

Full Text Available The study focuses on the interaction between morin and Tin(II and the resulting complex was characterized through various analytical techniques by comparing it with morin. The complexation was confirmed at first by UV-Vis study, which shows that addition of Tin(II to morin may produce bathochromic shifts indicative of complex formation. IR spectral studies indicated that carbonyl has involved in coordination with Tin(II. Moreover, 1H-NMR studies validated that in conjunction with carbonyl, 3-OH of morin is more appropriate to be involved in complexation by replacement of its proton. Scavenging activities of morin and its Tin(II complex on DPPH• radical showed the inhibitory rates of 65% and 49%, respectively. In addition, the reducing capacity of morin was outstanding at 0.5 and 2.0 mg/ml concentrations relative to Tin(II complex. Overall, the study potentially shows the strong impact in order to design the anticancer drugs jointly from its cytotoxic potential and antioxidant activities, thereby selectively targeting the cancerous cells in result increasing their therapeutic index as well as extra advantages over other anticancer drugs.

Magnetite Dissolution Performance of HYBRID-II Decontamination Process

International Nuclear Information System (INIS)

Kim, Seonbyeong; Lee, Woosung; Won, Huijun; Moon, Jeikwon; Choi, Wangkyu

2014-01-01

In this study, we conducted the magnetite dissolution performance test of HYBRID-II (Hydrazine Based Reductive metal Ion Decontamination with sulfuric acid) as a part of decontamination process development. Decontamination performance of HYBRID process was successfully tested with the results of the acceptable decontamination factor (DF) in the previous study. While following-up studies such as the decomposition of the post-decontamination HYBRID solution and corrosion compatibility on the substrate metals of the target reactor coolant system have been continued, we also seek for an alternate version of HYBRID process suitable especially for decommissioning. Inspired by the relationship between the radius of reacting ion and the reactivity, we replaced the nitrate ion in HYBRID with bigger sulfate ion to accommodate the dissolution reaction and named HYBRID-II process. As a preliminary step for the decontamination performance, we tested the magnetite dissolution performance of developing HYBRID-II process and compared the results with those of HYBRID process. HYBRID process developed previously is known have the acceptable decontamination performance, but the relatively larger volume of secondary waste induced by anion exchange resin to treat nitrate ion is the one of the problems related in the development of HYBRID process to be applicable. Therefore we alternatively devised HYBRID-II process using sulfuric acid and tested its dissolution of magnetite in numerous conditions. From the results shown in this study, we can conclude that HYBRID-II process improves the decontamination performance and potentially reduces the volume of secondary waste. Rigorous tests with metal oxide coupons obtained from reactor coolant system will be followed to prove the robustness of HYBRID-II process in the future

The NDCX-II engineering design

Energy Technology Data Exchange (ETDEWEB)

Waldron, W.L., E-mail: WLWaldron@lbl.gov [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Abraham, W.J.; Arbelaez, D. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Friedman, A. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Galvin, J.E. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Gilson, E.P. [Princeton Plasma Physics Laboratory, Princeton, NJ 08543 (United States); Greenway, W.G. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Grote, D.P. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Jung, J.-Y.; Kwan, J.W.; Leitner, M.; Lidia, S.M.; Lipton, T.M.; Reginato, L.L.; Regis, M.J.; Roy, P.K. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Sharp, W.M. [Lawrence Livermore National Laboratory, Livermore, CA 94550 (United States); Stettler, M.W.; Takakuwa, J.H.; Volmering, J. [Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); and others

2014-01-01

The Neutralized Drift Compression Experiment (NDCX-II) is a user facility located at Lawrence Berkeley National Laboratory which is uniquely designed for ion-beam-driven high energy density laboratory physics and heavy ion fusion research. Construction was completed in March 2012 and the facility is now in the commissioning phase. A significant amount of engineering was carried out in order to meet the performance parameters required for a wide range of target heating experiments while making the most cost-effective use of high-value hardware available from a decommissioned high current electron induction accelerator. The technical challenges and design of this new ion induction accelerator facility are described.

Magnetic compression/magnetized target fusion (MAGO/MTF)

International Nuclear Information System (INIS)

Kirkpatrick, R.C.; Lindemuth, I.R.

1997-03-01

Magnetized Target Fusion (MTF) was reported in two papers at the First Symposium on Current Trends in International Fusion Research. MTF is intermediate between two very different mainline approaches to fusion: Inertial Confinement Fusion (ICF) and magnetic confinement fusion (MCF). The only US MTF experiments in which a target plasma was compressed were the Sandia National Laboratory ''Phi targets''. Despite the very interesting results from that series of experiments, the research was not pursued, and other embodiments of MTF concept such as the Fast Liner were unable to attract the financial support needed for a firm proof of principle. A mapping of the parameter space for MTF showed the significant features of this approach. The All-Russian Scientific Research Institute of Experimental Physics (VNIIEF) has an on-going interest in this approach to thermonuclear fusion, and Los Alamos National Laboratory (LANL) and VNIIEF have done joint target plasma generation experiments relevant to MTF referred to as MAGO (transliteration of the Russian acronym for magnetic compression). The MAGO II experiment appears to have achieved on the order of 200 eV and over 100 KG, so that adiabatic compression with a relatively small convergence could bring the plasma to fusion temperatures. In addition, there are other experiments being pursued for target plasma generation and proof of principle. This paper summarizes the previous reports on MTF and MAGO and presents the progress that has been made over the past three years in creating a target plasma that is suitable for compression to provide a scientific proof of principle experiment for MAGO/MTF

The adaptor protein CrkII regulates IGF-1-induced biological behaviors of pancreatic ductal adenocarcinoma.

Science.gov (United States)

Liu, Rui; Wang, Qing; Xu, Guangying; Li, Kexin; Zhou, Lingli; Xu, Baofeng

2016-01-01

Recently, the adaptor protein CrkII has been proved to function in initiating signals for proliferation and invasion in some malignancies. However, the specific mechanisms underlying insulin-like growth factor 1 (IGF-1)-CrkII signaling-induced proliferation of pancreatic ductal adenocarcinoma (PDAC) were not unraveled. In this work, PDAC tissues and cell lines were subjected to in vitro and in vivo assays. Our findings showed that CrkII was abundantly expressed in PDAC tissues and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When cells were subjected to si-CrkII, si-CrkII inhibited IGF-1-mediated PDAC cell growth. In vitro, we demonstrated the upregulation of CrkII, p-Erk1/2, and p-Akt occurring in IGF-1-treated PDAC cells. Conversely, si-CrkII affected upregulation of CrkII, p-Erk1/2, and p-Akt. In addition, cell cycle and in vivo assay identified that knockdown of CrkII inhibited the entry of G1 into S phase and the increase of PDAC tumor weight. In conclusion, CrkII mediates IGF-1 signaling and further balanced PDAC biological behaviors via Erk1/2 and Akt pathway, which indicates that CrkII gene and protein may act as an effective target for the treatment of PDAC.

Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart

NARCIS (Netherlands)

Nederlof, Rianne; Eerbeek, Otto; Hollmann, Markus W.; Southworth, Richard; Zuurbier, Coert J.

2014-01-01

Mitochondrially bound hexokinase II (mtHKII) has long been known to confer cancer cells with their resilience against cell death. More recently, mtHKII has emerged as a powerful protector against cardiac cell death. mtHKII protects against ischaemia-reperfusion (IR) injury in skeletal muscle and

Characterization of insulin-like-growth factor II (IGF II mRNA positive hepatic altered foci and IGF II expression in hepatocellular carcinoma during diethylnitrosamine-induced hepatocarcinogenesis in rats

Directory of Open Access Journals (Sweden)

Mukherjee Biswajit

2005-08-01

Full Text Available Abstract Background Insulin-like-growth factor II (IGF II has been implicated in the pathogenesis of neoplasm of different tissues, including liver of rats and men. This growth factor is believed to exert its effect during cellular proliferation. During the process of development of hepatocellular carcinoma (HCC, different hepatic altered foci appear. They are believed to be the putative precursors of HCC in rats and in men. Thus, to study the role of the gene in a defined model of hepatocarcinogenesis was the target to elucidate its role in various cancer phenotypes during the entire development stage of cancer, right from earlier preneoplastic lesions to HCC Methods Antisense in situ hybridization technique was used here to characterize the type(s of foci in which IGF II mRNA had expressed during the development of hepatocarcinogenesis-induced by diethylnitrosamine and promoted by phenobarbital in rats. Various focal lesions have been categorized depending on the stages and sizes along with IGF II expression patterns in them. Immunohistochemical detection for proliferating cell nuclear antigen (PCNA was made to detect the role of the gene in preneoplastic and neoplastic cellular proliferation. Results IGF II expression was located in the glycogen-storage acidophilic cell foci maximally followed by mixed cell lesions and the least in basophilic lesions. The expression of IGF II was found to be predominant in the HCC. The expression of gene was also located at the peripheral cells of spongiosis hepatis which are believed to be the precursor of ito cell carcinoma. It was noted that there is a direct correlation between IGF II expression and Immunohistochemical detection for PCNA. Conclusion It may be concluded that IGF II gene expression plays an important role during the development of neoplasia and the gene expresses in the sequence of events leading from glycogen-rich-acidophilic lesions to glycogen poor basophilic lesions to HCC with an

Synthesis, characterization and thermal studies of nickel (II), copper (II), zinc (II) and cadmium (II) complexes with some mixed ligands

International Nuclear Information System (INIS)

Mitra, Samiran; Kundu, Parimal; Singh, Rajkumar Bhubon

1998-01-01

Dichloro-(DCA) and trichloroacetate(TCA) -cyclic ligand morpholine (Morph)/thiomorpholine (Tmorph)/methylmorpholine (Mmorph)/dimethyl-piperazine (DMP) complexes of nickel (II), copper (II), zinc (II) and cadmium (II) with the compositions [Ni(tmorph) 2 (DCA) 2 ], [Ni(tmorph) 2 (TCA) 2 ].2H 2 O, [Cu(DMP) 2 (TCA) 2 ],[ML 2 X 2 ].nH 2 O where M=Zn II or Cd II , L=Morph, DMP or tmorph and X=DCA or TCA and n=O except in case of [Cd (Morph) 2 (TCA) 2 ] where n=1 have been synthesised. Some intermediate complexes have been isolated by temperature arrest technique (pyrolysis) and characterised. Configurational and conformational changes have been studied by elemental analyses, IR and electronic spectra, magnetic moment data (in the case of Ni(II) and Cu(II) complexes) and thermal analysis. E a * , ΔH, and ΔS for the decomposition reaction of these complexes are evaluated and the stability of the complexes with respect to activation energy has also been compared. The linear correlation has been found between E a * and ΔS for the decomposition of the complexes. (author)

Stimulation of topoisomerase II mediated DNA cleavage at specific sequence elements by the 2-nitroimidazole Ro 15-0216

International Nuclear Information System (INIS)

Sorensen, B.S.; Jensen, P.S.; Andersen, A.H.; Christiansen, K.; Alsner, J.; Thomsen, B.; Westergaard, O.

1990-01-01

The effect of the 2-nitroimidazole Ro 15-0216 upon the interaction between purified topoisomerase II and its DNA substrate was investigated. The cleavage reaction in the presence of this DNA-nonintercalative drug took place with the hallmarks of a regular topoisomerase II mediated cleavage reaction, including covalent linkage of the enzyme to the cleaved DNA. In the presence of Ro 15-0216, topoisomerase II mediated cleavage was extensively stimulated at major cleavage sites of which only one existed in the 4363 base pair pBR322 molecule. The sites stimulated by Ro 15-0216 shared a pronounced sequence homology, indicating that a specific nucleotide sequence is crucial for the action of this drug. The effect of Ro 15-0216 thus differs from that of the clinically important topoisomerase II targeted agents such as mAMSA, VM26, and VP16, which enhance enzyme-mediated cleavage at a multiple number of sites. In contrast to the previous described drugs, Ro 15-0216 did not exert any inhibitory effect on the enzyme's catalytic activity. This observation might be ascribed to the low stability of the cleavage complexes formed in the presence of Ro 15-0216 as compared to the stability of the ones formed in the presence of traditional topoisomerase II targeted drugs

Peptide deformylase as an antibacterial drug target: target validation and resistance development.

Science.gov (United States)

Apfel, C M; Locher, H; Evers, S; Takács, B; Hubschwerlen, C; Pirson, W; Page, M G; Keck, W

2001-04-01

New inhibitors of peptide deformylase (PDF) which are very potent against the isolated enzyme and show a certain degree of antibacterial activity have recently been synthesized by our group. Several lines of experimental evidence indicate that these inhibitors indeed interfere with the target enzyme in the bacterial cell. (i) The inhibition of Escherichia coli growth could be counteracted by overexpression of PDF from different organisms, including E. coli, Streptococcus pneumoniae, and Haemophilus influenzae. Conversely, reduced expression of PDF in S. pneumoniae resulted in an increased susceptibility to the inhibitors. (ii) Proteome analysis on two-dimensional gels revealed a shift for many proteins towards lower pI in the presence of PDF inhibitors, as would be expected if the proteins still carry their N-formyl-Met terminus. (iii) PDF inhibitors show no antimicrobial activity against E. coli under conditions that make growth independent of formylation and deformylation. The antibacterial activity in E. coli was characterized as bacteriostatic. Furthermore, the development of resistance in E. coli was observed to occur with high frequency (10(-7)). Resistant mutants show a reduced growth rate, and DNA sequence analysis revealed mutations in their formyl transferase gene. Taking all these aspects into account, we conclude that PDF may not be an optimal target for broad-spectrum antibacterial agents.

Competition from Cu(II), Zn(II) and Cd(II) in Pb(II) binding to Suwannee River Fulvic Acid

NARCIS (Netherlands)

Chakraborty, P.; Chakrabarti, C.L.

2008-01-01

This is a study of trace metal competition in the complexation of Pb(II) by well-characterized humic substances, namely Suwannee River Fulvic Acid (SRFA) in model solutions. It was found that Cu(II) seems to compete with Pb(II) for strong binding sites of SRFA when present at the same concentration

Long-Lifetime Low-Scatter Neutron Polarization Target

International Nuclear Information System (INIS)

Richardson, Jonathan M.

2004-01-01

Polarized neutrons scattering is an important technology for characterizing magnetic and other materials. Polarized helium three (P-3He) is a novel technology for creating polarized beams and, perhaps more importantly, for the analysis of polarization in highly divergent scattered beams. Analysis of scattered beams requires specialized targets with complex geometries to ensure accurate results. Special materials and handling procedures are required to give the targets a long useful lifetime. In most cases, the targets must be shielded from stray magnetic fields from nearby equipment. SRL has developed and demonstrated hybrid targets made from glass and aluminum. We have also developed and calibrated a low-field NMR system for measuring polarization lifetimes. We have demonstrated that our low-field system is able to measure NMR signals in the presence of conducting (metallic) cell elements. We have also demonstrated a non-magnetic valve that can be used to seal the cells. We feel that these accomplishments in Phase I are sufficient to ensure a successful Phase II program. The commercial market for this technology is solid. There are over nine neutron scattering centers in the US and Canada and over 22 abroad. Currently, the US plans to build a new $1.4B scattering facility called the Spallation Neutron Source (SNS). The technology developed in this project will allow SRL to supply targets to both existing and future facilities. SRL is also involved with the application of P-3He to medical imaging

Secondary metabolites of Cynodon dactylon as an antagonist to angiotensin II type1 receptor: Novel in silico drug targeting approach for diabetic retinopathy

Science.gov (United States)

Jananie, R. K.; Priya, V.; Vijayalakshmi, K.

2012-01-01

Objectives: To study the ability of the secondary metabolites of Cynodon dactylon to serve as an antagonist to angiotensin II type 1 receptor (AT1); activation of this receptor plays a vital role in diabetic retinopathy (DR). Materials and Methods: In silico methods are mainly harnessed to reduce time, cost and risk associated with drug discovery. Twenty-four compounds were identified as the secondary metabolites of hydroalcoholic extract of C. dactylon using the GCMS technique. These were considered as the ligands or inhibitors that would serve as an antagonist to the AT1. The ACD/Chemsketch tool was used to generate 3D structures of the ligands. A molecular file format converter tool was used to convert the generated data to the PDB format (Protein Data Bank) and was used for docking studies. The AT1 structure was retrieved from the Swissprot data base and PDB and visualized using the Rasmol tool. Domain analysis was carried from the Pfam data base; following this, the active site of the target protein was identified using a Q-site finder tool. The ability of the ligands to bind with the active site of AT1 was studied using the Autodocking tool. The docking results were analyzed using the WebLab viewer tool. Results: Sixteen ligands showed effective binding with the target protein; diazoprogesteron, didodecyl phthalate, and 9,12-octadecadienoyl chloride (z,z) may be considered as compounds that could be used to bind with the active site sequence of AT1. Conclusions: The present study shows that the metabolites of C. dactylon could serve as a natural antagonist to AT1 that could be used to treat diabetic retinopathy. PMID:22368412

Synthesis, investigation and spectroscopic characterization of piroxicam ternary complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with glycine and DL-phenylalanine

Science.gov (United States)

Mohamed, Gehad G.; El-Gamel, Nadia E. A.

2004-11-01

The ternary piroxicam (Pir; 4-hydroxy-2-methyl- N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with various amino acids (AA) such as glycine (Gly) or DL-phenylalanine (PhA) were prepared and characterized by elemental analyses, molar conductance, IR, UV-Vis, magnetic moment, diffuse reflectance and X-ray powder diffraction. The UV-Vis spectra of Pir and the effect of metal chelation on the different interligand transitions are discussed in detailed manner. IR and UV-Vis spectra confirm that Pir behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine- N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its carboxylic group, in addition PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its carboxylic and amino groups. All the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. The molar conductance data reveal that most of these chelates are non electrolytes, while Fe(III)-Pir-Gly, Co(II)-, Ni(II)-, Cu(II)- and Zn(II)-Pir-PhA cheletes were 1:1 electrolytes. X-ray powder diffraction is used as a new tool to estimate the crystallinity of chelates as well as to elucidate their geometrical structures.

Around the laboratories: Rutherford: Successful tests on bubble chamber target technique; Stanford (SLAC): New storage rings proposal; Berkeley: The HAPPE project to examine cosmic rays with superconducting magnets; The 60th birthday of Professor N.N. Bogolyubov; Argonne: Performance of the automatic film measuring system POLLY II

CERN Multimedia

1969-01-01

Around the laboratories: Rutherford: Successful tests on bubble chamber target technique; Stanford (SLAC): New storage rings proposal; Berkeley: The HAPPE project to examine cosmic rays with superconducting magnets; The 60th birthday of Professor N.N. Bogolyubov; Argonne: Performance of the automatic film measuring system POLLY II

Coordination compounds of cobalt(II), nickel(II), copper(II), and zinc(II) with pantothenic acid

Energy Technology Data Exchange (ETDEWEB)

Shabilalov, A.A.; Yunuskhodzhaev, A.N.; Khodzhaev, O.F.; Azizov, M.A.

1986-11-01

The compounds Ni(PANA - H)/sub 2/ x 4H/sub 2/O (PANA stands for pantothenic acid, and - H indicates a deprotonated ligand), Cu(PANA - H)/sub 2/ x 2H/sub 2/O, Zn(PANA - H)/sub 2/ x H/sub 2/O, Co(PANA - H)Cl x H/sub 2/O, and Ni(PANA - H)Cl x 3H/sub 2/O have been synthesized on the basis of pantothenic acid and Co(II), Ni(II), Cu(II), and Zn(II) salts in aqueous media. The compounds have been identified by elemental and x-ray diffraction analysis. Some physicochemical properties (solubility, melting point, molar conductivity) of the compounds obtained have been studied. The structure of the compounds isolated has been established on the basis of an analysis of their IR, ESR, and electronic spectra, as well as derivatograms.

PBFA II lithium beam characterization from inner-shell x-ray images

International Nuclear Information System (INIS)

Moats, A.R.; Derzon, M.S.; Chandler, G.A.; Dukart, R.J.; Haill, T.A.

1994-01-01

The Particle Beam Fusion Accelerator (PBFA II) is not driving targets with ICF-relevant lithium ion beams. During the most recent lithium beam target series, time-integrated x-ray pinhole cameras viewed the ion-induced inner-shell x-ray fluorescence from the central gold cone target and a titanium-coated strip. Ion beam profiles at a nominal 10 mm radius and fixed azimuthal direction were obtained from images of the Ti K α , fluorescence of a Ti-coated Al diagnostic wire. The gold cone gave us beam profiles at a nominal 3 mm radius and at all azimuthal angles from the Au L α fluorescence. From these profiles, we obtained the ion beam vertical focus position, full-width-at-half-maximum, and the degree of azimuthal uniformity for the lithium target shots. For these initial results, beam steering problems were evident. Azimuthal uniformity was measured from the ion beam footprint on the outer Au case (predominantly Au L α ) of the hohlraum target and were found to be in the same range (up to 30%) as for previous proton beam target series. We then present plans for Li beam diagnostics for an upcoming target experimental series

Drug-Target Interaction Prediction through Label Propagation with Linear Neighborhood Information.

Science.gov (United States)

Zhang, Wen; Chen, Yanlin; Li, Dingfang

2017-11-25