Results from In-pile experiments on LWR fuel rod behavior under LOCA conditions with unirradiated rods

International Nuclear Information System (INIS)

Sepold, L.; Karb, E.H.; Pruessmann, M.

1981-06-01

This report summarizes the results of the FR2-in-pile tests at KfK (Kernforschungszentrum Karlsruhe) with unirradiated test rods. The in-pile tests with the objective of investigating the influence of a nuclear environment on the mechanisms of fuel rod failure were being performed with irradiated and unirradiated single rods of a PWR design in the DK loop of the FR2 reactor. The main parameter of the test program was the burnup, ranging from 2.500 to 35.000 MWd/t. The program with unirradiated specimens comprised the series A and B with a total of 14 tests. (orig.) [de

Progress in chemical processing of LEU targets for 99Mo production - 1997

International Nuclear Information System (INIS)

Vandegrift, G.F.; Conner, C.; Sedlet, J.; Wygmans, D.G.; Wu, D.; Iskander, F.; Landsberger, S.

1997-01-01

Presented here are recent experimental results of our continuing development activities associated with converting current processes for producing fission-product 99 Mo from targets using high-enriched uranium (HEU) to low-enriched uranium (LEU). Studies were focused in four areas: (1) measuring the chemical behavior of iodine, rhodium, and silver in the LEU-modified Cintichem process, (2) performing experiments and calculations to assess the suitability of zinc fission barriers for LEU metal foil targets, (3) developing an actinide separations method for measuring alpha contamination of the purified 99 Mo product, and (4) developing a cooperation with Sandia National Laboratories and Los Alamos National Laboratory that will lead to approval by the U.S. Federal Drug Administration for production of 99 Mo from LEU targets. Experimental results continue to show the technical feasibility of converting current HEU processes to LEU. (author)

Induction of lethal mutations in the x-chromosome of unirradiated Drosophila oocytes after fertilization by irradiated spermatozoa

International Nuclear Information System (INIS)

Shaposhnikov, M.V.; Zainullin, V.G.

2003-01-01

Full text: In primary study on Drosophila it was found that irradiated male X-chromosomes induce recessive lethals in unirradiated female homologues (Abeleva et al., 1961, Radiobiologya. 1:123-126). The same effects were obtained in Drosophila in some recent investigations. The mechanisms of these effects is unknown. However it may be responsible for low-dose radiation effects as it induce mutations in unirradiated DNA. We assume that this effect may be a result of activation of error prone repair in response to preliminary DNA lesions in irradiated chromosome. In this research we analyse the frequencies of the recessive lethal mutations in the X-chromosome of Drosophila females mated with irradiated Basc males. We used acute irradiation with a dose rate of 10 Gy. For testing our hypothesis we use the mus209 and mei-41 mutant females. Mus209 is a PCNA gene homologue and mei-41 is a homologue of ATM gene. These genes are involved in post-replication DNA repair which may be error prone repair in Drosophila. It was obtained the tendency to decreasing the mutation rate at the mei-41[D5] background and decreasing mutation rate in mus209[B1] background in comparison with wild type strains CS (p<0.05). The obtained results demonstrate the possible role of mus209[B1] and mei-41[D5] genes in the inducing of mutations in the unirradiated X-chromosome in the presence of irradiated homologue

Non-targeted mutagenesis of unirradiated lambda phage in Escherichia coli

International Nuclear Information System (INIS)

Wood, R.D.; Hutchinson, F.

1984-01-01

Non-targeted mutagenesis of lambda phage by ultraviolet light is the increase over background mutagenesis when non-irradiated phage are grown in irradiated Escherichia coli host cells. Such mutagenesis is caused by different processes from targeted mutagenesis, in which mutations in irradiated phage are correlated with photoproducts in the phage DNA. Non-irradiated phage grown in heavily irradiated uvr + host cells showed non-targeted mutations, which were 3/4 frameshifts, whereas targeted mutations were 2/3 transitions. For non-targeted mutagenesis in heavily irradiated host cells, there were one or two mutant phage per mutant burst. From the results of a series of experiments with various mutant host cells, a major pathway of non-targeted mutagenesis by ultraviolet light was proposed which acts in addition to ''SOS induction''. This pathway involves binding of the enzyme DNA polymerase I to damaged genomic DNA, and low polymerase activity leads to frameshift mutations during semiconservative DNA replication. The data suggest that this process will play a much smaller role in ultraviolet mutagenesis of the bacterial genome than it does in the mutagenesis of lambda phage. (author)

Non-targeted mutagenesis of unirradiated lambda phage in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Wood, R.D.; Hutchinson, F. (Yale Univ., New Haven, CT (USA). Dept. of Molecular Biophysics and Biochemistry)

1984-03-05

Non-targeted mutagenesis of lambda phage by ultraviolet light is the increase over background mutagenesis when non-irradiated phage are grown in irradiated Escherichia coli host cells. Such mutagenesis is caused by different processes from targeted mutagenesis, in which mutations in irradiated phage are correlated with photoproducts in the phage DNA. Non-irradiated phage grown in heavily irradiated uvr/sup +/ host cells showed non-targeted mutations, which were 3/4 frameshifts, whereas targeted mutations were 2/3 transitions. For non-targeted mutagenesis in heavily irradiated host cells, there were one or two mutant phage per mutant burst. From the results of a series of experiments with various mutant host cells, a major pathway of non-targeted mutagenesis by ultraviolet light was proposed which acts in addition to ''SOS induction''. This pathway involves binding of the enzyme DNA polymerase I to damaged genomic DNA, and low polymerase activity leads to frameshift mutations during semiconservative DNA replication. The data suggest that this process will play a much smaller role in ultraviolet mutagenesis of the bacterial genome than it does in the mutagenesis of lambda phage.

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

Molecular dynamics study on interfacial thermal conductance of unirradiated and irradiated SiC/C

International Nuclear Information System (INIS)

Wang, Qingyu; Wang, Chenglong; Zhang, Yue; Li, Taosheng

2014-01-01

SiC f /SiC composite materials have been considered as candidate structural materials for several types of advanced nuclear reactors. Both experimental and computer simulations studies have revealed the degradation of thermal conductivity for this material after irradiation. The objective of this study is to investigate the effect of SiC/graphite interface structure and irradiation on the interfacial thermal conductance by using molecular dynamics simulation. Five SiC/graphite composite models were created with different interface structures, and irradiation was introduced near the interfaces. Thermal conductance was calculated by means of reverse-NEMD method. Results show that there is a positive correlation between the interfacial energy and interfacial C–Si bond quantity, and irradiated models showed higher interfacial energy compared with their unirradiated counterparts. Except the model with graphite atom plane parallel to the interface, the interfacial thermal conductance of unirradiated and irradiated (1000 eV) models, increases as the increase of interfacial energy, respectively. For all irradiated models, lattice defects are of importance in impacting the interfacial thermal conductance depending on the interface structure. For the model with graphite layer parallel to the interface, the interfacial thermal conductance increased after irradiation, for the other models the interfacial thermal conductance decreased. The vibrational density of states of atoms in the interfacial region was calculated to analyze the phonon mismatch at the interface

Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

Science.gov (United States)

Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

2015-01-01

The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

A highway accident involving unirradiated nuclear fuel in Springfield, Massachusetts, on December 16, 1991

International Nuclear Information System (INIS)

Carlson, R.W.; Fischer, L.E.

1992-06-01

In the early morning of Dec. 16, 1991, a severe accident occurred when a passenger vehicle traveling in the wrong direction collided with a tractor trailer carrying 24 unirradiated nuclear fuel assemblies in 12 containers on Interstate I-91 in Springfield, Massachusetts. The purpose of this report is to document the mechanical circumstances of the severe accident, confirm the nature and quantity of the radioactive materials involved, and assess the physical environment to which the containers were exposed and the response of the containers and their contents. The report consists of five major sections. The first section describes the circumstances and conditions of the accident and the finding of facts. The second describes the containers, the unirradiated nuclear fuel assemblies, and the tie down arrangement used for the trailer. The third describes the damage sustained during the accident to the tractor, trailer, containers, and unirradiated nuclear fuel assemblies. The fourth evaluates the accident environment and its effects on the containers and their contents. The final section gives conclusions derived from the analysis and fact finding investigation. During this severe accident, only minor injuries occurred, and at no time was the public health and safety at risk

Stress corrosion crack growth in unirradiated zircaloy

International Nuclear Information System (INIS)

Pettersson, K.

1978-10-01

Experimental techniques suitable for the determination of stress corrosion crack growth rates in irradiated Zircaloy tube have been developed. The techniques have been tested on unirradiated. Zircaloy and it was found that the results were in good agreement with the results of other investigations. Some of the results were obtained at very low stress intensities and the crack growth rates observed, gave no indication of the existance of a K sub(ISCC) for iodine induced stress corrosion cracking in Zircaloy. This is of importance both for fuel rod behavior after a power ramp and for long term storage of spent Zircaloy-clad fuel. (author)

Unirradiated cladding rip-propagation tests

International Nuclear Information System (INIS)

Hu, W.L.; Hunter, C.W.

1981-04-01

The size of cladding rips which develop when a fuel pin fails can affect the subassembly cooling and determine how rapidly fuel escapes from the pin. The object of the Cladding Rip Propagation Test (CRPT) was to quantify the failure development of cladding so that a more realistic fuel pin failure modeling may be performed. The test results for unirradiated 20% CS 316 stainless steel cladding show significantly different rip propagation behavior at different temperatures. At room temperature, the rip growth is stable as the rip extension increases monotonically with the applied deformation. At 500 0 C, the rip propagation becomes unstable after a short period of stable rip propagation. The rapid propagation rate is approximately 200 m/s, and the critical rip length is 9 mm. At test temperatures above 850 0 C, the cladding exhibits very high failure resistances, and failure occurs by multiple cracking at high cladding deformation. 13 figures

High Temperature Tensile Properties of Unirradiated and Neutron Irradiated 20 Cr-35 Ni Austenitic Steel

Energy Technology Data Exchange (ETDEWEB)

Roy, R B; Solly, B

1966-12-15

The tensile properties of an unirradiated and neutron irradiated (at 40 deg C) 20 % Cr, 35 % Ni austenitic steel have been studied at 650 deg C, 750 deg C and 820 deg C. The tensile elongation and mode of fracture (transgranular) of unirradiated specimens tested at room temperature and 650 deg C are almost identical. At 750 deg C and 820 deg C the elongation decreases considerably and a large part of the total elongation is non-uniform. Furthermore, the mode of fracture at these temperatures is intergranular and microscopic evidence suggests that fracture is caused by formation and linkup of grain boundary cavities. YS and UTS decrease monotonically with temperature. Irradiated specimens show a further decrease in ductility and an increase in the tendency to grain boundary cracking. Irradiation has no significant effect on the YS, but the UTS are reduced. The embrittlement of the irradiated specimens is attributed to the presence of He and Li atoms produced during irradiation and the possible mechanisms are discussed. Prolonged annealing of irradiated and unirradiated specimens at 650 deg C appears to have no significant effect on tensile properties.

Thermogravimetric studies of the thermo-oxidative stability of irradiated and unirradiated polyethylene

International Nuclear Information System (INIS)

Novakovic, L.; Gal, O.; Markovic, V.; Stannett, V.T.

1985-01-01

In part one of this series the effects of a phenolic, an amine and a thioester antioxidant on the thermo-oxidative stability of irradiated and unirradiated low-density polyethylene was reported. In this paper the effects of combined phenolic and thioester stabilizers are described. Isothermal thermogravimetric analysis was used to study the systems. Pronounced synergism was observed with the induction periods, the time when the initial weight loss begins and the 5% weight loss. At about 50% of each stabilizer increases greater than twofold were observed both with the unirradiated and irradiated polymers. The rate constants for oxygen uptake were decreased. However, the rates of degradation at 5% weight loss fell between the values of the two pure stabilizers with no pronounced synergism in either case. In the absence of oxygen little effect of either antioxidant or their mixtures was observed. The corresponding activation energies were somewhat higher, however, with the irradiated samples containing antioxidants. Dynamic thermogravimetry was used for this study. A kinetic analysis indicated that there were somewhat different modes of degradation at lower- and higher-temperature ranges. (author)

Characterization of un-irradiated and irradiated reactor graphite; Karakterizacija neozracenog i ozracenog reaktorskog grafita

Energy Technology Data Exchange (ETDEWEB)

Marinkovic, S [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Yugoslavia)

1965-11-15

This report contains three parts: characterization of Yugoslav nuclear graphite development of methods and obtained results, characterization of un-irradiated and irradiated domestic nuclear graphite; calculation of electrical conductivity changes due to vacancies in the graphite crystal lattice.

Plant-scale anodic dissolution of unirradiated N-Reactor fuel

International Nuclear Information System (INIS)

Gay, E.C.; Miller, W.E.; Laidler, J.J.

1995-01-01

Anodic dissolution tests were made with unirradiated N-Reactor fuel to determine the fuel segment length, diameter, and shape required for high throughput electrorefiner treatment for ultimate disposal in a geologic repository. Based on these tests, a conceptual design was produced of an electrorefiner for a full-scale plant to process N-Reactor spent fuel. In this design, the diameter of an electrode assembly is about 0.6 m (25 in.). Eight of these assemblies in an electrorefiner would accommodate a 1.333-metric-ton batch of N-Reactor fuel. Electrorefining would proceed at a rate of 40 kg uranium per hour

Progress in converting 99Mo production from high-to-low-enriched uranium - 1999

International Nuclear Information System (INIS)

Snelgrove, J.L.; Vandegrift, G.F.; Conner, C.; Wiencek, T.C.; Hofman, G.L.

1999-01-01

Over this past year, extraordinary progress has been made in executing our charter to assist in converting Mo-99 production worldwide from HEU to LEU. Building on the successful development of the experimental LEU-foil target, we have designed a new, economical irradiation target. We have also successfully demonstrated, in collaboration with BATAN in Indonesia, that LEU can be substituted for HEU in the Cintichem target without loss of product yield or purity; in fact, conversion may make economic sense. We are interacting with a number of commercial producers - we have begun active collaborations with the CNEA and ANSTO; we are working to define the scope of collaborations with MDS Nordion and Mallinckrodt; and IRE has offered its services to irradiate and test a target at the appropriate time. Conversion of the CNEA process is on schedule. Other papers presented at this meeting will present specific results on the demonstration of the LEU-modified Cintichem process, the development of the new target, and progress in converting the CNEA process. (author)

Dissolution experiments of unirradiated uranium dioxide pellets

International Nuclear Information System (INIS)

Ollila, K.

1985-01-01

The purpose of this study was to measure the dissolution rate of uranium from unirradiated uranium dioxide pellets in deionized water and natural groundwater. Moreover, the solubility limit of uranium in natural groundwater was measured. Two different temperatures, 25 and 60 deg C were used. The low oxygen content of deep groundwater was simulated. The dissolution rate of uranium varied from 10 -7 to 10 -8 g cm -2 d -1 . The rate in reionized water was one order of magnitude lower than in groundwater. No great difference was observed between the natural groundwaters with different composition. Temperature seems to have effect on the dissolution rate. The solubility limit of uranium in natural groundwater in reducing conditions, at 25 deg C, varied from 20 to 600 μg/l and in oxidizing conditions, at 60 deg C, from 4 to 17 mg/l

The dissolution of unirradiated UO2 fuel pellets under simulated disposal conditions

International Nuclear Information System (INIS)

Ollila, K.; Leino-Forsman, H.

1993-03-01

The dissolution behaviour of unirradiated UO 2 pellets was studied as a function of water composition under oxidizing and reducing conditions at 25 deg C. The waters included deionized water as the reference water, sodium bicarbonate solutions with varying bicarbonate content, and two different synthetic groundwaters. The release of uranium was measured during static batch dissolution experiments of long duration (3-4 years)

New type of metal targets

International Nuclear Information System (INIS)

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

2014-01-01

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

Plant-scale anodic dissolution of unirradiated N-Reactor fuel

International Nuclear Information System (INIS)

Gay, E.C.; Miller, W.E.; Laidler, J.J.

1995-01-01

Anodic dissolution tests were made with unirradiated N-Reactor fuel to determine the fuel segment length, diameter, and shape required for high throughput electro-refiner treatment for ultimate disposal in a geologic repository. Based on these tests, a conceptual design was produced of an electro-refiner for a full-scale plant to process N-Reactor spent fuel. In this design, the diameter of an electrode assembly is about 0.6 m (25 in.). Eight of these assemblies in an electro-refiner would accommodate a 1.333-metric-ton batch of N-Reactor fuel. Electrorefining would proceed at a rate of 40 kg uranium per hour. (author)

Chromosome dosimetry: the influence of culture media on the proliferation of irradiated and unirradiated human lymphocytes

International Nuclear Information System (INIS)

Purrott, R.J.; Lloyd, D.C.; Vulpis, N.

1981-01-01

The proliferation of phytohaemagglutinin stimulated human lymphocytes in four types of synthetic culture medium has been studied using the fluorescence plus Giemsa staining technique to determine cell cycle status. 48 hour cultures of unirradiated cells containing Ham's F10 or RPMI 1640 media yielded significant numbers of second cycle metaphases. Cultures containing Eagle's MEM or TC 199 media, however, required longer incubation times to produce appreciable numbers of second division cells. Intrinsic differences between donors in the rate of proliferation had little effect on the relative ranking of the media. Radiation induced mitotic delay of about 1 hour per Gray was observed for each medium. The relevance of these results to the accuracy of radiation dose estimation by chromosome aberration analysis is discussed. (author)

An analysis of facial nerve function in irradiated and unirradiated facial nerve grafts

International Nuclear Information System (INIS)

Brown, Paul D.; Eshleman, Jeffrey S.; Foote, Robert L.; Strome, Scott E.

2000-01-01

, the irradiated graft group had a greater proportion of patients with pathologic evidence of nerve invasion (p = 0.007) and unfavorable type of nerve graft (p = 0.04). Although the irradiated graft cohort had more potentially negative prognostic factors, there was no difference in functional outcome (H-B Grade III or IV) between irradiated and unirradiated graft patients. H-B Grades III, IV, V, and VI were the best postoperative facial nerve functions achieved in 35%, 39%, 13%, and 13% of patients, respectively. The patient with preoperative radiotherapy never recovered any facial nerve function (H-B Grade VI). Median time to best facial nerve function after surgery was longer in the irradiated patients (13.1 vs. 10.8 months), but this was not statistically significant (p 0.10). Presence of preoperative facial nerve palsy (p = 0.005), duration of preoperative palsy (p = 0.003), and age greater than 60 years at the time of grafting (p = 0.04) were all negative prognostic factors for achieving a functional facial nerve on univariate analysis. Analysis of age as a continuous variable (p = 0.12) and pathologic evidence of nerve invasion (p 0.1) revealed a trend toward negative prognostic factors. Gender, number of previous operations in the parotid bed, extent of surgery at the time of nerve grafting, and type of grafting procedure were not significant prognostic factors. Whether radiotherapy was delivered less than 6 weeks after nerve grafting or more than 6 weeks had no impact on achievement of a functional facial nerve. Conclusion: Negative prognostic factors for achieving a functional facial nerve in our series include the presence of preoperative facial nerve palsy, duration of preoperative palsy, and age greater than 60 years. Radiotherapy was not a negative prognostic factor. Comparing irradiated and unirradiated grafts revealed no difference in best facial nerve function achieved, despite the presence of a greater proportion of negative prognostic factors in the

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

Comparison of the growth of Listeria monocytogenes in unirradiated and irradiated cook-chill roast beef and gravy at refrigeration temperatures

International Nuclear Information System (INIS)

Grant, I.R.; Nixon, C.R.; Patterson, M.F.

1993-01-01

Specific growth rates of two strains of Listeria monocytogenes in unirradiated and irradiated (2 kGy) roast beef and gravy stored at 5° and 10°C were found to be similar. However, exponential growth of L. monocytogenes after irradiation was preceded by an extended lag period of 6–9 d at 5°C and 3–4 d at 10°C, compared with lag periods of 1–2 d and <0.1 d in unirradiated beef and gravy stored similarly

The influence of Boron on creep-rupture behaviour of austenitic unstabilized and Nb-stabilized stainless steel X8CrNi 1613 in unirradiated and irradiated condition

International Nuclear Information System (INIS)

Sen, Susant Kumar.

1976-10-01

The present study deals with influence of boron on creep-rupture behaviour in unirradiated condition at 650 0 C along with precipitation behaviour, heat-treatment and recrystallization of unstabilized and stabilized steel. The results of creep-rupture tests on unirradiated specimens show that boron exerts a beneficial effect on the rupture life and ductility. Boron losses its beneficial effect on creep properties in unstabilized steel by prolong creeping. The magnitude of beneficial effect of Boron on creep properties depends upon the initial boron distribution which influences the number, size and distribution of the precipitates. Boron promotes the precipitation of type M 23 C 6 Carbides in the grain as well as at the grain boundary. Boron segregates in atomic form during slow cooling from austenitizing temperature. The recrystallization will be delayed by the presence of boron. The results of creep tests at 650 0 C shows that boron exerts a beneficial effect on creep life of irradiated steels. (orig./GSC) [de

Food and Drug Administration process validation activities to support 99Mo production at Sandia National Laboratories

International Nuclear Information System (INIS)

McDonald, M.J.; Bourcier, S.C.; Talley, D.G.

1997-01-01

Prior to 1989 99 Mo was produced in the US by a single supplier, Cintichem Inc., Tuxedo, NY. Because of problems associated with operating its facility, in 1989 Cintichem elected to decommission the facility rather than incur the costs for repair. The demise of the 99 Mo capability at Cintichem left the US totally reliant upon a single foreign source, Nordion International, located in Ottawa Canada. In 1992 the DOE purchased the Cintichem 99 Mo Production Process and Drug Master File (DMF). In 1994 the DOE funded Sandia National Laboratories (SNL) to produce 99 Mo. Although Cintichem produced 99 Mo and 99m Tc generators for many years, there was no requirement for process validation which is now required by the Food and Drug Administration (FDA). In addition to the validation requirement, the requirements for current Good manufacturing Practices were codified into law. The purpose of this paper is to describe the process validation being conducted at SNL for the qualification of SNL as a supplier of 99 Mo to US pharmaceutical companies

Response of unirradiated and irradiated PWR fuel rods tested under power-cooling-mismatch conditions

International Nuclear Information System (INIS)

MacDonald, P.E.; Quapp, W.J.; Martinson, Z.R.; McCardell, R.K.; Mehner, A.S.

1978-01-01

This report summarizes the results from the single-rod power-cooling-mismatch (PCM) and irradiation effects (IE) tests conducted to date in the Power Burst Facility (PBF) at the U.S. DOE Idaho National Engineering Laboratory. This work was performed for the U.S. NRC under contact to the Department of Energy. These tests are part of the NRC Fuel Behavior Program, which is designed to provide data for the development and verification of analytical fuel behavior models that are used to predict fuel response to abnormal or postulated accident conditions in commercial LWRs. The mechanical, chemical and thermal response of both previously unirradiated and previously irradiated LWR-type fuel rods tested under power-cooling-mismatch condition is discussed. A brief description of the test designs is presented. The results of the PCM thermal-hydraulic studies are summarized. Primary emphasis is placed on the behavior of the fuel and cladding during and after stable film boiling. (orig.) [de

A review of the rates of reaction of unirradiated uranium in gaseous atmospheres

International Nuclear Information System (INIS)

Pearce, R.J.

1989-10-01

The review collates available quantitative rate data for the reaction of unirradiated uranium in dry and moist air, steam and carbon dioxide based atmospheres at temperatures ranging from room temperature to above the melting point of uranium. Reactions in nitrogen and carbon monoxide are also considered. The aim of the review is to provide a compilation of base data for the hazard analysis of fault conditions relating to Magnox fuel. (author)

Scintillation activity in an unirradiated single crystal of 3-hydroxyxanthine

International Nuclear Information System (INIS)

Cooke, D.W.; Jahan, M.S.; Alexander, C. Jr.

1976-01-01

A method of growing single crystals (approximately 4mm long) of 3-hydroxyxanthine is described. Observed scintillations occurring in an unirradiated single crystal of this potent oncogen as the temperature is lowered from 300 to 90 K are shown. It was found that these scintillations occur upon heating or cooling and do not diminish in activity as the number of heating and cooling cycles increase. It was found that a short duration u.v. exposure would terminate the scintillation activity and various attempts (such as annealing and pressure changes) to rejuvenate them were unsuccessful. With these observations in mind speculation is made concerning the mechanisms associated with the production of purine N-oxide derivatives. (U.K.)

Thermogravimetric studies of the thermo-oxidative stability of irradiated and unirradiated polyethylene. 2. Combined antioxidants

Energy Technology Data Exchange (ETDEWEB)

Novakovic, L; Gal, O; Markovic, V; Stannett, V T

1985-01-01

In part one of this series the effects of a phenolic, an amine and a thioester antioxidant on the thermo-oxidative stability of irradiated and unirradiated low-density polyethylene was reported. In this paper the effects of combined phenolic and thioester stabilizers are described. Isothermal thermogravimetric analysis was used to study the systems. Pronounced synergism was observed with the induction periods, the time when the initial weight loss begins and the 5% weight loss. At about 50% of each stabilizer increases greater than twofold were observed both with the unirradiated and irradiated polymers. The rate constants for oxygen uptake were decreased. However, the rates of degradation at 5% weight loss fell between the values of the two pure stabilizers with no pronounced synergism in either case. In the absence of oxygen little effect of either antioxidant or their mixtures was observed. The corresponding activation energies were somewhat higher, however, with the irradiated samples containing antioxidants. Dynamic thermogravimetry was used for this study. A kinetic analysis indicated that there were somewhat different modes of degradation at lower- and higher-temperature ranges. (author).

Histochemical differentiation between unirradiated and gamma-irradiated tissue in commercial use of some irradiated vegetables

International Nuclear Information System (INIS)

Foa, E.

1978-01-01

The use of gamma irradiation as a commercial method for the preservation of fruits and vegetables calls for methods of differentiation between unirradiated and irradiated products. A new approach to studying the influence of gamma irradiation on vegetable tissue at the cellular level by histochemical techniques has been developed by the authors and already applied to a number of fruits and vegetables. The possibility of evidencing radiation effects in the polysaccharide components of the cell wall suggested that these detected differences could be applied to differentiate irradiated from unirradiated tomatoes and potatoes. Some work done to determine changes in the cell wall polysaccharides of gamma-irradiated potatoes and tomatoes and to relate these changes to some other factors, such as storage time and vegetable variety, is reported here. While significant differences have been found in the optical densities of the total polysaccharides of the cell wall as a function of irradiation and of the other variables mentioned, it is not yet possible to use these values as a means of reliable differentiation. (author)

Truck accident involving unirradiated nuclear fuel

International Nuclear Information System (INIS)

Carlson, R.W.; Fischer, L.E.

1993-01-01

In the early morning of Dec. 16, 1991, a severe accident occurred when a passenger vehicle traveling in the wrong direction collided with a tractor trailer carrying 24 unirradiated nuclear fuel assemblies in 12 containers on Interstate I-91 in Springfield, Massachusetts. This paper documents the mechanical circumstances of the accident and assesses the physical environment to which the containers were exposed and the response of the containers and their contents. The accident involved four impacts where the truck was struck by the car, impacted on the center guardrail, impacted on the outer concrete barrier and came to rest against the center guardrail. The impacts were followed by a fire that began in the engine compartment, spread to the tractor and cab, and eventually spread to the trailer and payload. The fire lasted for about three hours and the packages were involved in the fire for about two hours. As a result of the fire, the tractor-trailer was completely destroyed and the packages were exposed to flames with temperatures between 1,300 F and 1,800 F. The fuel assemblies remained intact during the accident and there was no release of any radioactive material during the accident. This was a very severe accident; however, the injuries were minor and at no time was the public health and safety at risk

Oxide particle size distribution from shearing irradiated and unirradiated LWR fuels in Zircaloy and stainless steel cladding: significance for risk assessment

Energy Technology Data Exchange (ETDEWEB)

Davis, W. Jr.; West, G.A.; Stacy, R.G.

1979-03-22

Sieve fractionation was performed with oxide particles dislodged during shearing of unirradiated or irradiated fuel bundles or single rods of UO/sub 2/ or 96 to 97% ThO/sub 2/--3 to 4% UO/sub 2/. Analyses of these data by nonlinear least-squares techniques demonstrated that the particle size distribution is lognormal. Variables involved in the numerical analyses include lognormal median size, lognormal standard deviation, and shear cut length. Sieve-fractionation data are presented for unirradiated bundles of stainless-steel-clad or Zircaloy-2-clad UO/sub 2/ or ThO/sub 2/--UO/sub 2/ sheared into lengths from 0.5 to 2.0 in. Data are also presented for irradiated single rods (sheared into lengths of 0.25 to 2.0 in.) of Zircaloy-2-clad UO/sub 2/ from BWRs and of Zircaloy-4-clad UO/sub 2/ from PWRs. Median particle sizes of UO/sub 2/ from shearing irradiated stainless-steel-clad fuel ranged from 103 to 182 ..mu..m; particle sizes of ThO/sub 2/--UO/sub 2/, under these same conditions, ranged from 137 to 202 ..mu..m. Similarly, median particle sizes of UO/sub 2/ from shearing unirradiated Zircaloy-2-clad fuel ranged from 230 to 957 ..mu..m. Irradiation levels of fuels from reactors ranged from 9,000 to 28,000 MWd/MTU. In general, particle sizes from shearing these irradiated fuels are larger than those from the unirradiated fuels; however, unirradiated fuel from vendors was not available for performing comparative shearing experiments. In addition, variations in particle size parameters pertaining to samples of a single vendor varied as much as those between different vendors. The fraction of fuel dislodged from the cladding is nearly proportional to the reciprocal of the shear cut length, until the cut length attains some minimum value below which all fuel is dislodged. Particles of fuel are generally elongated with a long-to-short axis ratio usually less than 3. Using parameters of the lognormal distribution estimates can be made of fractions of dislodged fuel having

Tensile and fracture toughness properties of copper alloys and their HIP joints with austenitic stainless steel in unirradiated and neutron irradiated condition

International Nuclear Information System (INIS)

Taehtinen, S.; Pyykkoenen, M.; Singh, B.N.; Toft, P.

1998-03-01

The tensile strength and ductility of unirradiated CuAl25 IG0 and CuCrZr alloys decreased continuously with increasing temperature up to 350 deg C. Fracture toughness of unirradiated CuAl25 IG0 alloy decreased continuously with increasing temperature from 20 deg C to 350 deg C whereas the fracture toughness of unirradiated CuCrZr alloy remained almost constant at temperatures up to 100 deg C, was decreased significantly at 200 deg C and slightly increased at 350 deg C. Fracture toughness of HIP joints were lower than that of corresponding copper alloy and fracture path in HIP joint specimen was always within copper alloy side of the joint. Neutron irradiation to a dose level of 0.3 dpa resulted in hardening and reduction in uniform elongation to about 2-4% at 200 deg C in both copper alloys. At higher temperatures softening was observed and uniform elongation increased to about 5% and 16% for CuAl25 IG0 and CuCrZr alloys, respectively. Fracture toughness of CuAl25 IG0 alloy reduced markedly due to neutron irradiation in the temperature range from 20 deg C to 350 deg C. The fracture toughness of the irradiated CuCrZr alloy also decreased in the range from 20 deg C to 350 deg C, although it remained almost unaffected at temperatures below 200 deg C and decreased significantly at 350 deg C when compared with that of unirradiated CuCrZr alloy. (orig.)

The effect of compressive stress on the Young's modulus of unirradiated and irradiated nuclear graphites

International Nuclear Information System (INIS)

Oku, T.; Usui, T.; Ero, M.; Fukuda, Y.

1977-01-01

The Young's moduli of unirradiated and high temperature (800 to 1000 0 C) irradiated graphites for HTGR were measured by the ultrasonic method in the direction of applied compressive stress during and after stressing. The Young's moduli of all the tested graphites decreased with increasing compressive stress both during and after stressing. In order to investigate the reason for the decrease in Young's modulus by applying compressive stress, the mercury pore diameter distributions of a part of the unirradiated and irradiated specimens were measured. The change in pore distribution is believed to be associated with structural changes produced by irradiation and compressive stressing. The residual strain, after removing the compressive stress, showed a good correlation with the decrease in Young's modulus caused by the compressive stress. The decrease in Young's modulus by applying compressive stress was considered to be due to the increase in the mobile dislocation density and the growth or formation of cracks. The results suggest, however, that the mechanism giving the larger contribution depends on the brand of graphite, and in anisotropic graphite it depends on the direction of applied stress and the irradiation conditions. (author)

Sperm quantity and size variation in un-irradiated and irradiated males of the malaria mosquito Anopheles arabiensis Patton

NARCIS (Netherlands)

Helinski, M.; Knols, B.G.J.

2009-01-01

Anopheles mosquitoes are important candidates for genetic control strategies. However, little is known about sperm quality and quantity as determinants of male reproductive success. In this study, sperm quantity and length variation were assessed in testes of un-irradiated and irradiated Anopheles

Erythrokinetics in mice bearing tumours in either preirradiated or unirradiated tissue

International Nuclear Information System (INIS)

Jirtle, R.L.; Clifton, K.H.

1978-01-01

Experiments were designed to clarify the causes of anaemia in hosts bearing tumours in either unirradiated or preirradiated tissue. Isotopic methods are described which enable the estimation of erythrocyte destruction and production rates, and the potential red cell life spans in tumour-bearing animals. In this experimental system, anaemia (a) is in large part due to accelerated random erythrocyte loss, (b) is exacerbated as tumours grow by a progressive reduction in the potential erythrocyte life span due to intrinsic erythrocyte defects. (c) is accompanied by an increase in erythrocyte production of six- to ten-fold and (d) is postponed in onset and decreased in magnitude by preirradiation of the tumour transplant site. (author)

Erythrokinetics in mice bearing tumours in either preirradiated or unirradiated tissue

Energy Technology Data Exchange (ETDEWEB)

Jirtle, R L; Clifton, K H [Wisconsin Univ., Madison (USA). Div. of Clinical Oncology

1978-11-01

Experiments were designed to clarify the causes of anaemia in hosts bearing tumours in either unirradiated or preirradiated tissue. Isotopic methods are described which enable the estimation of erythrocyte destruction and production rates, and the potential red cell life spans in tumour-bearing animals. In this experimental system, anaemia (a) is in large part due to accelerated random erythrocyte loss, (b) is exacerbated as tumours grow by a progressive reduction in the potential erythrocyte life span due to intrinsic erythrocyte defects. (c) is accompanied by an increase in erythrocyte production of six- to ten-fold and (d) is postponed in onset and decreased in magnitude by preirradiation of the tumour transplant site.

Target-type probability combining algorithms for multisensor tracking

Science.gov (United States)

Wigren, Torbjorn

2001-08-01

Algorithms for the handing of target type information in an operational multi-sensor tracking system are presented. The paper discusses recursive target type estimation, computation of crosses from passive data (strobe track triangulation), as well as the computation of the quality of the crosses for deghosting purposes. The focus is on Bayesian algorithms that operate in the discrete target type probability space, and on the approximations introduced for computational complexity reduction. The centralized algorithms are able to fuse discrete data from a variety of sensors and information sources, including IFF equipment, ESM's, IRST's as well as flight envelopes estimated from track data. All algorithms are asynchronous and can be tuned to handle clutter, erroneous associations as well as missed and erroneous detections. A key to obtain this ability is the inclusion of data forgetting by a procedure for propagation of target type probability states between measurement time instances. Other important properties of the algorithms are their abilities to handle ambiguous data and scenarios. The above aspects are illustrated in a simulations study. The simulation setup includes 46 air targets of 6 different types that are tracked by 5 airborne sensor platforms using ESM's and IRST's as data sources.

The influence of late-stage pupal irradiation and increased irradiated: un-irradiated male ratio on mating competitiveness of the malaria mosquito Anopheles arabiensis Patton.

Science.gov (United States)

Helinski, M E H; Knols, B G J

2009-06-01

Competitiveness of released males in genetic control programmes is of critical importance. In this paper, we explored two scenarios to compensate for the loss of mating competitiveness after pupal stage irradiation in males of the malaria mosquito Anopheles arabiensis. First, competition experiments with a higher ratio of irradiated versus un-irradiated males were performed. Second, pupae were irradiated just prior to emergence and male mating competitiveness was determined. Males were irradiated in the pupal stage with a partially or fully-sterilizing dose of 70 or 120 Gy, respectively. Pupae were irradiated aged 20-26 h (young) as routinely performed, or the pupal stage was artificially prolonged by cooling and pupae were irradiated aged 42-48 h (old). Irradiated males competed at a ratio of 3:1:1 to un-irradiated males for mates in a large cage design. At the 3:1 ratio, the number of females inseminated by males irradiated with 70 Gy as young pupae was similar to the number inseminated by un-irradiated males for the majority of the replicates. At 120 Gy, significantly fewer females were inseminated by irradiated than by un-irradiated males. The irradiation of older pupae did not result in a significantly improved male mating competitiveness compared to the irradiation of young pupae. Our findings indicate that the loss of competitiveness after pupal stage irradiation can be compensated for by a threefold increase of irradiated males, but only for the partially-sterilizing dose. In addition, cooling might be a useful tool to facilitate handling processes of large numbers of mosquitoes in genetic control programmes.

Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes

Science.gov (United States)

Yin, Xiaoming; Tian, Wenqian; Wang, Longxiao; Wang, Jingdong; Zhang, Shuyu; Cao, Jianping; Yang, Hongying

2015-01-01

Traditional radiation biology states that radiation causes damage only in cells traversed by ionizing radiation. But radiation-induced bystander effect (RIBE), which refers to the biological responses in unirradiated cells when the neighboring cells are exposed to radiation, challenged this old dogma and has become a new paradigm of this field. By nature, RIBEs are the consequences of intercellular communication between irradiated and unirradiated cells. However, there are still some important questions remain unanswered such as whether RIBE is dependent on radiation quality, what are the determining factors if so, etc. Using a transwell co-culture system, we found that HaCaT keratinocytes irradiated with α-particles but not X-rays could induce bystander micronucleus formation in unirradiated WS1 fibroblasts after co-culture. More importantly, the activation of TGF-β1-Smad2 pathway and the consistent decrease of miR-21 level in α-irradiated HaCaT cells were essential to the micronucleus induction in bystander WS1 cells. On the other hand, X-irradiation did not induce bystander effect in unirradiated WS1 cells, accompanied by lack of Smad2 activation and consistent decrease of miR-21 in X-irradiated HaCaT cells. Taken together, these results suggest that the radiation quality-dependence of bystander effect may be associated with the TGF-β1-Smad2 pathway and miR-21 in irradiated cells. PMID:26080011

Special Analysis for the Disposal of the INL Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) Waste Stream at the Area 5 Radioactive Waste Management Site

Energy Technology Data Exchange (ETDEWEB)

Shott, Gregory [National Security Technologies, LLC, Las Vegas, NV (United States)

2017-03-21

This special analysis (SA) evaluates whether the Idaho National Laboratory (INL) Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) waste stream (INEL167203QR1, Revision 0) is suitable for shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS) on the Nevada National Security Site (NNSS). Disposal of the INL Waste Associated with the Unirradiated LWBR waste meets all U.S. Department of Energy (DOE) Manual DOE M 435.1-1, “Radioactive Waste Management Manual,” Chapter IV, Section P performance objectives (DOE 1999). The INL Waste Associated with the Unirradiated LWBR waste stream is recommended for acceptance with the condition that the total uranium-233 (²³3U) inventory be limited to 2.7E13 Bq (7.2E2 Ci).

Special Analysis for the Disposal of the Idaho National Laboratory Unirradiated Light Water Breeder Reactor Rods and Pellets Waste Stream at the Area 5 Radioactive Waste Management Site, Nevada National Security Site, Nye County, Nevada

Energy Technology Data Exchange (ETDEWEB)

None

2014-08-31

The purpose of this special analysis (SA) is to determine if the Idaho National Laboratory (INL) Unirradiated Light Water Breeder Reactor (LWBR) Rods and Pellets waste stream (INEL103597TR2, Revision 2) is suitable for disposal by shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS). The INL Unirradiated LWBR Rods and Pellets waste stream consists of 24 containers with unirradiated fabricated rods and pellets composed of uranium oxide (UO2) and thorium oxide (ThO2) fuel in zirconium cladding. The INL Unirradiated LWBR Rods and Pellets waste stream requires an SA because the 229Th, 230Th, 232U, 233U, and 234U activity concentrations exceed the Nevada National Security Site (NNSS) Waste Acceptance Criteria (WAC) Action Levels.

Oxide particle size distribution from shearing irradiated and unirradiated LWR fuels in Zircaloy and stainless steel cladding: significance for risk assessment

International Nuclear Information System (INIS)

Davis, W. Jr.; West, G.A.; Stacy, R.G.

1979-01-01

Sieve fractionation was performed with oxide particles dislodged during shearing of unirradiated or irradiated fuel bundles or single rods of UO 2 or 96 to 97% ThO 2 --3 to 4% UO 2 . Analyses of these data by nonlinear least-squares techniques demonstrated that the particle size distribution is lognormal. Variables involved in the numerical analyses include lognormal median size, lognormal standard deviation, and shear cut length. Sieve-fractionation data are presented for unirradiated bundles of stainless-steel-clad or Zircaloy-2-clad UO 2 or ThO 2 --UO 2 sheared into lengths from 0.5 to 2.0 in. Data are also presented for irradiated single rods (sheared into lengths of 0.25 to 2.0 in.) of Zircaloy-2-clad UO 2 from BWRs and of Zircaloy-4-clad UO 2 from PWRs. Median particle sizes of UO 2 from shearing irradiated stainless-steel-clad fuel ranged from 103 to 182 μm; particle sizes of ThO 2 --UO 2 , under these same conditions, ranged from 137 to 202 μm. Similarly, median particle sizes of UO 2 from shearing unirradiated Zircaloy-2-clad fuel ranged from 230 to 957 μm. Irradiation levels of fuels from reactors ranged from 9,000 to 28,000 MWd/MTU. In general, particle sizes from shearing these irradiated fuels are larger than those from the unirradiated fuels. In addition, variations in particle size parameters pertaining to samples of a single vendor varied as much as those between different vendors. The fraction of fuel dislodged from the cladding is nearly proportional to the reciprocal of the shear cut length, until the cut length attains some minimum value below which all fuel is dislodged. Particles of fuel are generally elongated with a long-to-short axis ratio usually less than 3. Using parameters of the lognormal distribution deduced from experimental data, realistic estimates can be made of fractions of dislodged fuel having dimensions less than specified values

Gas generation during waste treatment of acidic solutions from the dissolution of irradiated LEU targets for ⁹⁹Mo production

Energy Technology Data Exchange (ETDEWEB)

Bakel, Allen J. [Argonne National Lab. (ANL), Argonne, IL (United States); Conner, Cliff [Argonne National Lab. (ANL), Argonne, IL (United States); Quigley, Kevin [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-01-01

The goal of the Reduced Enrichment for Research and Test Reactors Program is to limit the use of high-enriched uranium (HEU) in research and test reactors by substituting low-enriched uranium (LEU) wherever possible. The work reported here documents our work to develop the calcining technologies and processes that will be needed for ⁹⁹Mo production using LEU foil targets and the Modified Cintichem Process. The primary concern with the conversion to LEU from HEU targets is that it would result in a five- to six-fold increase in the total uranium. This increase results in more liquid waste from the process. We have been working to minimize the increase in liquid waste and to minimize the impact of any change in liquid waste. Direct calcination of uranium-rich nitric acid solutions generates NO₂ gas and UO₃ solid. We have proposed two processes for treating the liquid waste from a Modified Cintichem Process with a LEU foil. One is an optimized direct calcination process that is similar to the process currently in use. The other is a uranyl oxalate precipitation process. The specific goal of the work reported here was to characterize and compare the chemical reactions that occur during these two processes. In particular, the amounts and compositions of the gaseous and solid products were of interest. A series of experiments was carried out to show the effects of temperature and the redox potential of the reaction atmosphere. The primary products of the direct calcination process were mixtures of U₃O₈ and UO₃ solids and NO₂ gas. The primary products of the oxalate precipitation process were mixtures of U₃O₈ and UO₂ solid and CO₂ gas. Higher temperature and a reducing atmosphere tended to favor quadrivalent over hexavalent uranium in the solid product. These data will help producers to decide between the two processes. In addition, the data can be used

Safety Analysis Report for Packaging: The unirradiated fuel shipping container USA/9853/AF

International Nuclear Information System (INIS)

1991-01-01

The HFBR Unirradiated Fuel Shipping Container was designed and fabricated at the Oak Ridge National Laboratory in 1978 for the transport of fuel for the High Flux Beam Reactor (HFBR) for Brookhaven National Laboratory. The package has been evaluated analytically, as well as the comparison to tests on similar packages, to demonstrate compliance with the applicable regulations governing packages in which radioactive and fissile materials are transported. The contents of this Safety Analysis Report for Packaging (SARP) are based on Regulatory Guide 7.9 (proposed Revision 2 - May 1986), 10 CFR Part 71, DOE Order 1540.2, DOE Order 5480.3, and 49 CFR Part 173

Thermal studies on unirradiated and γ-irradiated polymer of allyl diglycol carbonate

International Nuclear Information System (INIS)

Kalsi, P.C.; Pandey, A.K.; Iyer, R.H.; Singh Mudher, K.D.

1995-01-01

The thermal decomposition of unirradiated and γ-irradiated (5.93-15.5 MRad dose range) allyl diglycol carbonate polymer (trade name, CR-39) was studied by thermogravimetry (TG) and differential thermal analysis (DTA). These studies indicate four main decomposition steps in CR-39 polymer in air. Assessment of the influence of radiation dose on the above range shows that while the 5.93 MRad γ-irradiated polymer CR-39 degrades in three steps, the 15.5 MRad γ-irradiated polymer degrades in only two steps. The kinetics of the different stages of degradation were also evaluated from the TG curves. Irradiation enhances the decomposition rate and the effect increases further with increasing radiation dose. The activation energy values calculated for all the decomposition stages decrease on irradiation

An Effort to Improve U Foil Fabrication Technology of Roll-casting for Fission Mo Target

Energy Technology Data Exchange (ETDEWEB)

Kim, Chang Kyu; Woo, Yun Myeong; Kim, Ki Hwan; Oh, Jong Myeong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Sim, Moon Soo [Chungnam University, Green Energy Technology, Daejeon (Korea, Republic of)

2010-10-15

Mo-99 isotope has been produced mainly by extracting fission products of {sup 235}U. The targets for irradiating in reactor have used as stainless tube coated with highly enriched UO{sub 2} at the inside surface and highly enriched UAlx plate cladded with aluminum. In connection with non-proliferation policy the RERTR program developed a new process of Mo-99 using low enriched uranium (LEU) instead of highly enriched uranium (HEU). LEU should be put about five times more quantity than HEU because the {sup 235}U contents of LEU and HEU are 20% and higher than 90%, respectively. Accordingly pure uranium metal foil target was adopted as a promising target material due to high uranium density. ANL and BATAN developed a Cintichem process using uranium metal foil target of 130 {mu}m in thickness jointly and the RERTR program is trying to disseminate the new process world-widely. However, uranium foil is made by lots of times rolling work on uranium plate, which is laborious and tedious. In order to avoid this difficulty KAERI developed a new process of making foil directly from uranium melt by roll casting. This process is very much simple, productive, and cost-effective. But the outside surface of foil is generally very rough. A typical transverse cross section had a minimum thickness of 65 {mu}m and a maximum thickness of 205 {mu}m. This roughness could affect (1) target fabrication, where the U foil, or the Ni foil might be damaged during drawing, and (2) irradiation behavior, where gaps between the target walls and the U metal might affect cooling of the target

A comparison of the iraddiated tensile properties of a high-manganese austenitic steel and type 316 stainless steel

International Nuclear Information System (INIS)

Klueh, R.L.; Grossbeck, M.L.

1984-01-01

The USSR steel EP-838 is a high-manganese, low-nickel steel that also has lower chromium and molybdenum than type 316 stainless steel. Tensile specimens of 20%-cold-worked EP-838 and type 316 stainless steel were irradiated in the High Flux Isotope Reactor (HFIR) at the coolant temperature (approx.=50 0 C). A displacement damage level of 5.2 dpa was reached for the EP-838 and up to 9.5 dpa for the type 316 stainless steel. Tensile tests at room temperature and 300 0 C on the two steels indicated that the irradiation led to increased strength and decreased ductility compared to the unirradiated steels. Although the 0.2% yield stress of the type 316 stainless steel in the unirradiated condition was greater than that for the EP-838, after irradiation there was essentially no difference between the strength or ductility of the two steels. The results indicate that the replacement of the majority of the nickel by manganese and a reduction of chromium and molybdenum in an austenitic stainless steel of composition near that for type 316 stainless steel has little effect on the irradiated and unirradiated tensile properties at low temperatures. (orig.)

Damage and failure of unirradiated and irradiated fuel rods tested under film boiling conditions

International Nuclear Information System (INIS)

Mehner, A.S.; Hobbins, R.R.; Seiffert, S.L.; MacDonald, P.E.; McCardell, R.K.

1979-01-01

Power-cooling-mismatch experiments are being conducted as part of the Thermal Fuels Behavior Program in the Power Burst Facility at the Idaho National Engineering Laboratory to evaluate the behavior of unirradiated and previously irradiated light water reactor fuel rods tested under stable film boiling conditions. The observed damage that occurs to the fuel rod cladding and the fuel as a result of film boiling operation is reported. Analyses performed as a part of the study on the effects of operating failed fuel rods in film boiling, and rod failure mechanisms due to cladding embrittlement and cladding melting upon being contacted by molten fuel are summarized

Membrane Targeting of P-type ATPases in Plant Cells

International Nuclear Information System (INIS)

Harper, Jeffrey F.

2004-01-01

How membrane proteins are targeted to specific subcellular locations is a very complex and poorly understood area of research. Our long-term goal is to use P-type ATPases (ion pumps), in a model plant system Arabidopsis, as a paradigm to understand how members of a family of closely related membrane proteins can be targeted to different subcellular locations. The research is divided into two specific aims. The first aim is focused on determining the targeting destination of all 10 ACA-type calcium pumps (Arabidopsis Calcium ATPase) in Arabidopsis. ACAs represent a plant specific-subfamily of plasma membrane-type calcium pumps. In contrast to animals, the plant homologs have been found in multiple membrane systems, including the ER (ACA2), tonoplast (ACA4) and plasma membrane (ACA8). Their high degree of similarity provides a unique opportunity to use a comparative approach to delineate the membrane specific targeting information for each pump. One hypothesis to be tested is that an endomembrane located ACA can be re-directed to the plasma membrane by including targeting information from a plasma membrane isoform, ACA8. Our approach is to engineer domain swaps between pumps and monitor the targeting of chimeric proteins in plant cells using a Green Fluorescence Protein (GFP) as a tag. The second aim is to test the hypothesis that heterologous transporters can be engineered into plants and targeted to the plasma membrane by fusing them to a plasma membrane proton pump. As a test case we are evaluating the targeting properties of fusions made between a yeast sodium/proton exchanger (Sod2) and a proton pump (AHA2). This fusion may potentially lead to a new strategy for engineering salt resistant plants. Together these aims are designed to provide fundamental insights into the biogenesis and function of plant cell membrane systems

Reactor Materials Program electrochemical potential measurements by ORNL with unirradiated and irradiated stainless steel specimens

Energy Technology Data Exchange (ETDEWEB)

Baumann, E.W.; Caskey, G.R. Jr.

1993-07-01

Effect of irradiation of stainless steel on electrochemical potential (ECP) was investigated by measurements in dilute HNO{sub 3} and H{sub 2}O{sub 2} solutions, conditions simulating reactor moderator. The electrodes were made from unirradiated/irradiated, unsensitized/sensitized specimens from R-reactor piping. Results were inconclusive because of budgetary restrictions. The dose rate may have been too small to produce a significant radiolytic effect. Neither the earlier CERT corrosion susceptibility tests nor the present ECP measurements showed a pronounced effect of irradiation on susceptibility of the stainless steel to IGSCC; this is confirmed by the absence in the stainless steel of the SRS reactor tanks (except for the C Reactor tank knuckle area).

Reactor Materials Program electrochemical potential measurements by ORNL with unirradiated and irradiated stainless steel specimens

International Nuclear Information System (INIS)

Baumann, E.W.; Caskey, G.R. Jr.

1993-07-01

Effect of irradiation of stainless steel on electrochemical potential (ECP) was investigated by measurements in dilute HNO 3 and H 2 O 2 solutions, conditions simulating reactor moderator. The electrodes were made from unirradiated/irradiated, unsensitized/sensitized specimens from R-reactor piping. Results were inconclusive because of budgetary restrictions. The dose rate may have been too small to produce a significant radiolytic effect. Neither the earlier CERT corrosion susceptibility tests nor the present ECP measurements showed a pronounced effect of irradiation on susceptibility of the stainless steel to IGSCC; this is confirmed by the absence in the stainless steel of the SRS reactor tanks (except for the C Reactor tank knuckle area)

Programmable type III-A CRISPR-Cas DNA targeting modules.

Directory of Open Access Journals (Sweden)

H Travis Ichikawa

Full Text Available The CRISPR-Cas systems provide invader defense in a wide variety of prokaryotes, as well as technologies for many powerful applications. The Type III-A or Csm CRISPR-Cas system is one of the most widely distributed across prokaryotic phyla, and cleaves targeted DNA and RNA molecules. In this work, we have constructed modules of Csm systems from 3 bacterial species and heterologously expressed the functional modules in E. coli. The modules include a Cas6 protein and a CRISPR locus for crRNA production, and Csm effector complex proteins. The expressed modules from L. lactis, S. epidermidis and S. thermophilus specifically eliminate invading plasmids recognized by the crRNAs of the systems. Characteristically, activation of plasmid targeting activity depends on transcription of the plasmid sequence recognized by the crRNA. Activity was not observed when transcription of the crRNA target sequence was blocked, or when the opposite strand or a non-target sequence was transcribed. Moreover, the Csm module can be programmed to recognize plasmids with novel target sequences by addition of appropriate crRNA coding sequences to the module. These systems provide a platform for investigation of Type III-A CRISPR-Cas systems in E. coli, and for introduction of programmable transcription-activated DNA targeting into novel organisms.

Kinetics of thermal decomposition of γ-irradiated and unirradiated complexes of mandelhydroxamic acid

International Nuclear Information System (INIS)

Hassan, R.M.; Farid, T.; El-Bellihi, A.A.

1992-01-01

The thermal decomposition of γ-irradiated and unirradiated complexes of mandelhydroxamic acid (HMA), Co (HMA) 2 .1/2H 2 O, Mn (HMA) 2 .2H 2 O, Ba (HMA) 2 .2H 2 O and Cd (HMA) 2 .2H 2 O have been studied thermogravimetrically (under isothermal conditions). The thermal dehydration of each complex occured in one step, while the decomposition of dehydrated complexes occured in two steps. The kinetic parameters for dehydration were computed by different models. The thermal dehydration is regulated by random nucleation A 3 for Co-, Mn-, and Cd-complexes and by phase-boundary (R 3 ) for Ba-complex. The effect of γ-irradiation on the kinetic parameters of thermal decomposition is discussed. Radiation did not modify the mechanism of the reaction but accelarated the dehydration steps in the case of Mn- and Co-complexes. (author) 7 refs.; 1 fig.; 4 tabs

Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition

Science.gov (United States)

Datsenko, Kirill A.; Jackson, Ryan N.; Wiedenheft, Blake; Severinov, Konstantin; Brouns, Stan J. J.

2013-01-01

Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts are processed into small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids by complementary base pairing. However, to avoid autoimmunity it is essential that these RNA-guides exclusively target invading DNA and not complementary DNA sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous work on the Type III-A CRISPR system from Staphylococcus epidermidis has demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self versus non-self discrimination. This self-avoidance mechanism relies on sensing base pairing between the RNA-guide and sequences flanking the target DNA. To determine if the RNA-guide participates in self versus non-self discrimination in the Type I-E system from Escherichia coli we altered base pairing potential between the RNA-guide and the flanks of DNA targets. Here we demonstrate that Type I-E systems discriminate self from non-self through a base pairing-independent mechanism that strictly relies on the recognition of four unchangeable PAM sequences. In addition, this work reveals that the first base pair between the guide RNA and the PAM nucleotide immediately flanking the target sequence can be disrupted without affecting the interference phenotype. Remarkably, this indicates that base pairing at this position is not involved in foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism of avoiding self sequences and preventing autoimmunity is fundamentally different from that employed by Type III-A systems. We propose the exclusive targeting of PAM-flanked sequences to be termed a target versus non-target discrimination mechanism. PMID:24039596

Flow sheet development for the dissolution of unirradiated Mark 42 fuel tubes in F-Canyon, Part II

International Nuclear Information System (INIS)

Murray, A.M.

1999-01-01

Two dissolution flow sheets were tested for the desorption of unirradiated Mark 42 fuel tubes. Both the aluminum (from the can, cladding, and fuel core) and the plutonium oxide (PuO 2 ) are dissolved simultaneously, i.e., a co-dissolution flow sheet. In the first series of tests, 0.15 and 0.20 molar (M) potassium fluoride (KF) solutions were used and the dissolution extended over several days. In the other series of tests, solutions with higher concentrations of fluoride (0.25 to 0.30 M) were used. Calcium fluoride (CaF 2 ) was used in those tests as the fluoride source

Evaluation of staphylococcus aureus growth in unirradiated and irradiated cured meats using the Gompertz equation

International Nuclear Information System (INIS)

Szczawinski, J.; Szczawinska, M.

1993-01-01

1. Sodium nitrite, in concentration of 156 mg/kg, exerted little (from practical point of view) inhibitory effect on S. aureus in cured meat. Its addition caused lag time extension, increase of exponential growth rate, decrease of generation time and maximum population density of staphylococci in samples of cured meat stored at 20 C. 2. Growth curves of Staphylococcus aureus in unirradiated and irradiated (50 kGy) meats cured without sodium nitrite were similar. 3. Irradiation of meat cured with 156 mg/kg sodium nitrite with increasing doses of ionizing radiation (0, 10, 30, 50 kGy) progressively decreased growth rates and lag time and increased generation time and maximum population densities of Staphylococcus aureus in samples inoculated after radiation treatment and incubated at 20 C. (orig.)

Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation

DEFF Research Database (Denmark)

Napoletano, Chiara; Zizzari, Ilaria G; Rughetti, Aurelia

2012-01-01

NAc or Tn)-carrying tumor-associated antigens to improve DC performance. MGL expressed by ex vivo-generated iDCs from healthy donors was engaged by a 60-mer MUC1(9Tn) -glycopeptide as a Tn-carrying tumor-associated antigen, and an anti-MGL antibody, as a specific MGL binder. We demonstrated that MGL......Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner....... Targeting of these receptors is becoming an efficient strategy of delivering antigens in DC-based anticancer immunotherapy. Here we investigated the role of the macrophage galactose type C-lectin receptor (MGL), expressed by immature DCs (iDCs), as a molecular target for a-N-acetylgalactosamine (Gal...

Waste Treatment of Acidic Solutions from the Dissolution of Irradiated LEU Targets for 99-Mo Production

Energy Technology Data Exchange (ETDEWEB)

Bakel, Allen J. [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Conner, Cliff [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Quigley, Kevin [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division

2016-10-01

One of the missions of the Reduced Enrichment for Research and Test Reactors (RERTR) program (and now the National Nuclear Security Administrations Material Management and Minimization program) is to facilitate the use of low enriched uranium (LEU) targets for ⁹⁹Mo production. The conversion from highly enriched uranium (HEU) to LEU targets will require five to six times more uranium to produce an equivalent amount of ⁹⁹Mo. The work discussed here addresses the technical challenges encountered in the treatment of uranyl nitrate hexahydrate (UNH)/nitric acid solutions remaining after the dissolution of LEU targets. Specifically, the focus of this work is the calcination of the uranium waste from ⁹⁹Mo production using LEU foil targets and the Modified Cintichem Process. Work with our calciner system showed that high furnace temperature, a large vent tube, and a mechanical shield are beneficial for calciner operation. One- and two-step direct calcination processes were evaluated. The high-temperature one-step process led to contamination of the calciner system. The two-step direct calcination process operated stably and resulted in a relatively large amount of material in the calciner cup. Chemically assisted calcination using peroxide was rejected for further work due to the difficulty in handling the products. Chemically assisted calcination using formic acid was rejected due to unstable operation. Chemically assisted calcination using oxalic acid was recommended, although a better understanding of its chemistry is needed. Overall, this work showed that the two-step direct calcination and the in-cup oxalic acid processes are the best approaches for the treatment of the UNH/nitric acid waste solutions remaining from dissolution of LEU targets for ⁹⁹Mo production.

Bakery products from irradiated and unirradiated eggs - detection of irradiation in a processed food

International Nuclear Information System (INIS)

Pfordt, J.; Grabowski, H.U. von

1995-01-01

The detection of radiation-specific degradation products in fat has become an established method which has successfully been applied to egg products. This study is making evident the detectability of irradiated eggs as an ingredient of specified processed foods. Tart layers were produced from both irradiated and non-irradiated liquid whole egg. When the fat components were isolated from the tart layers and investigated by GC/MS, the presence of irradiated eggs could clearly be shown. While the radiation-induced hydrocarbons and 2-alkylcyclobutanones could not be found in unirradiated samples, tart layers from irradiated eggs contained these substances. Especially for the hydrocarbons a satisfying correlation between radiation dose and concentration could be observed. The concentrations of radiation-induced compounds were generally lower in the tart layers than in the liquid egg samples they had been produced from. (orig.) [de

Targeting intensive versus conventional glycaemic control for type 1 diabetes mellitus

DEFF Research Database (Denmark)

Kähler, Pernille; Grevstad, Berit; Almdal, Thomas

2014-01-01

OBJECTIVE: To assess the benefits and harms of targeting intensive versus conventional glycaemic control in patients with type 1 diabetes mellitus. DESIGN: A systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: The Cochrane Library, MEDLINE......, EMBASE, Science Citation Index Expanded and LILACS to January 2013. STUDY SELECTION: Randomised clinical trials that prespecified different targets of glycaemic control in participants at any age with type 1 diabetes mellitus were included. DATA EXTRACTION: Two authors independently assessed studies...... for inclusion and extracted data. RESULTS: 18 randomised clinical trials included 2254 participants with type 1 diabetes mellitus. All trials had high risk of bias. There was no statistically significant effect of targeting intensive glycaemic control on all-cause mortality (risk ratio 1.16, 95% CI 0.65 to 2...

Effect of helium pressure on the response of unirradiated UO2 subjected to thermal transients

International Nuclear Information System (INIS)

Fenske, G.R.; Chapello, P.M.; Emerson, J.E.; Poeppel, R.B.

1983-01-01

The effect of helium pressure on the transient response of unirradiated depleted UO 2 subjected to simulated hypothetical loss-of-flow accidents in a gas-cooled fast reactor was examined by use of the direct electrical heating technique. Transient tests were performed at pressures ranging from 7 to 10 X 10 5 Pa(7 to 10 atm) to 7 to 8 MPa (70 to 80 atm) on radially restrained and unrestrained fuel segments. The average heating rates ranged from about17 to 240 J/g x s. The results indicate that while the mechanical integrity of the fuel segment was independent of the test pressure, the rapid ejection of molten fuel from pellet interfaces of unrestrained fuel, observed at the lower pressures, was delayed or suppressed at the higher pressures

Properties of unirradiated fuel element graphites H-451 and SO818. [Bulk density, tensile properties, thermal expansion, thermal conductivity

Energy Technology Data Exchange (ETDEWEB)

Engle, G.B.; Johnson, W.R.

1976-10-08

Nuclear graphites H-451, lot 440 (Great Lakes Carbon Corporation (GLCC)), and SO818 (Airco Speer Division, Air Reduction Corporation (AS)) are described, and physical, mechanical, and chemical property data are presented for the graphites in the unirradiated state. A summary of the mean values of the property data and of data on TS-1240 and H-451, lot 426, is tabulated. A direct comparison of H-451, lot 426, chosen for Fort St. Vrain (FSV) fuel reload production, TS-1240, and SO818 may be made from the table. (auth)

Direct Down-scale Experiments of Concentration Column Designs for SHINE Process

Energy Technology Data Exchange (ETDEWEB)

Youker, Amanda J. [Argonne National Lab. (ANL), Argonne, IL (United States); Stepinski, Dominique C. [Argonne National Lab. (ANL), Argonne, IL (United States); Vandegrift, George F. [Argonne National Lab. (ANL), Argonne, IL (United States)

2017-05-01

Argonne is assisting SHINE Medical Technologies in their efforts to become a domestic Mo-99 producer. The SHINE accelerator-driven process uses a uranyl-sulfate target solution for the production of fission-product Mo-99. Argonne has developed a molybdenum recovery and purification process for this target solution. The process includes an initial Mo recovery column followed by a concentration column to reduce the product volume from 15-25 L to < 1 L prior to entry into the LEU Modified Cintichem (LMC) process for purification.1 This report discusses direct down-scale experiments of the plant-scale concentration column design, where the effects of loading velocity and temperature were investigated.

Macrophage galactose-type C-type lectin receptor for DC targeting of antitumor glycopeptide vaccines

DEFF Research Database (Denmark)

Nuti, M; Zizzari, I; Napoletano, C

2011-01-01

e13528 Background: Dendritic cells (DCs) are the most potent antigen presenting cells and are employed in cancer vaccination. Several receptors are being studied in order to identif strategies to increase DCs activating capacity. The C-type lectin macrophage galactose type C-type lectin (MGL...... of IFNg and IL-2 secretion by both CD8 and CD4 T cells. CONCLUSIONS: These results demonstrate that MGL engagement profoundly affects DC plasticity inducing and directing a Th1 immune response. Moreover, MGL receptor expressed on human DC can be targeted by glycopeptide based vaccines with adjuvant...

Overview and Critical Assessment of the Tensile Properties of unirradiated and irradiated EUROFER97

Energy Technology Data Exchange (ETDEWEB)

Lucon, E.; Vandermeulen, W.

2007-10-15

Material research represents a crucial issue for the assessment of fusion as a future viable source of energy. Structural materials, in particular, need to show a superior mechanical and chemical behaviour to guarantee the safe operation of the reactor during its whole lifetime, while retaining low activation characteristics to minimise the environmental impact of the produced waste. In this context, specific efforts have been focused for the last twenty years in Europe, Japan and the US, on developing suitable Reduced Activation Ferritic Martensitic (RAFM) steels as candidate structural materials. EUROFER97 has recently emerged in Europe as the reference material for the DEMO design. In the framework of the Long-Term Programme of EFDA (European Fusion Development Agreement), a coordinated effort has been launched aimed at providing a critical assessment of the mechanical and microstructural properties of EUROFER97 in the unirradiated and irradiated conditions, based on the results accumulated since the late 90ies within numerous EFDA tasks.

Storage for the Fast Flux Test Facility unirradiated fuel in the Plutonium Finishing Plant Complex, Hanford Site, Richland, Washington

International Nuclear Information System (INIS)

1992-01-01

This Environmental Assessment evaluates the proposed action to relocate and store unirradiated Fast Flux Test Facility fuel in the Plutonium Finishing Plant Complex on the Hanford Site, Richland, Washington. The US Department of Energy has decided to cease fuel fabrication activities in the 308 Building in the 300 Area. This decision was based on a safety concern over the ability of the fuel fabrication portion of the 308 Building to withstand a seismic event. The proposed action to relocate and store the fuel is based on the savings that could be realized by consolidating security costs associated with storage of the fuel. While the 308 Building belowgrade fuel storage areas are not at jeopardy by a seismic event, the US Department of Energy is proposing to cease storage operations along with the related fabrication operations. The US Department of Energy proposes to remove the unirradiated fuel pins and fuel assemblies from the 308 Building and store them in Room 192A, within the 234-5Z Building, a part of the Plutonium Finishing Plant Complex, located in the 200 West Area. Minor modifications to Room 192A would be required to accommodate placement of the fuel. The US Department of Energy estimates that removing all of the fuel from the 308 Building would save $6.5 million annually in security expenditures for the Fast Flux Test Facility. Environmental impacts of construction, relocation, and operation of the proposed action and alternatives were evaluated. This evaluation concluded that the proposed action would have no significant impacts on the human environment

Interaction of spermine with DNA, vitamin C and bovine serum albumin in the unirradiated and gamma irradiated states

International Nuclear Information System (INIS)

Upadhyay, S.N.; Lal, C.; Bhardwaj, R.; Chaturvedi, S.; Chaudhury, N.K.

2006-01-01

Structural deformability of spermine with radiation dose (maximum 10 Gy) has been proved. Complex formation of spermine with DNA, vitamin C and BSA took place. Calibration and radiation-induced absorption changes in spermine by ninhydrin reagent has been followed quantitatively. Interaction of vitamin C with DNA and their radiation-induced changes have been reported. Interaction of spermine with DNA in the unirradiated and gamma irradiated states in 10 -3 M phosphate buffer and water have been compared. Addition of spermine and vitamin C to DNA makes DNA structure more condensed. Bovine serum albumin also binds with spermine and protects it from radiation-induced degradation. (author)

Solubility of unirradiated UO2 fuel in aqueous solutions. Comparison between experimental and calculated (EQ3/6) data

International Nuclear Information System (INIS)

Ollila, K.

1995-11-01

The solubility behaviour of unirradiated UO 2 pellets was studied under oxic (air-saturated) and anoxic (N 2 ) conditions in deionized water, in sodium bicarbonate solutions with varying bicarbonate content (60 - 600 ppm), in Allard groundwater simulating granitic fresh groundwater conditions, and in bentonite water simulating the effects of bentonite on granitic fresh groundwater (25 deg C). The release of uranium was measured during static batch dissolution experiments of long duration (2-6 years). A comparison was made with the theoretical solubility data calculated with the geochemical code EQ3/6 in order to evaluate solubility (steady state) limiting factors. (orig.) (26 refs., 32 figs., 13 tabs.)

Toxin production by Clostridium Botulinum type B (proteolitic) in radurized raw fish

International Nuclear Information System (INIS)

Suhadi, F.

1978-01-01

The earliest toxin production by three proteolytic strains of Cl. botulinum type B was determined in irradiated and unirradiated raw fish (Rastrelliger sp., Euthynnus sp., and Scomberomorus sp.) under the storage temperatures of 20, 10, and 5degC. The estimation of maximum storage life was evaluated by an untrained panel on uninoculated fish samples and in parellel the total bacterial counts were also determined. Percentage data of the toxic samples were analyzed according to a fully randomized design involving factorial treatments. In unirradiated samples with inoculum levels of 10 2 -10 6 spores per gram and stored at 20degC, the earliest toxin production was detected after the samples were spoiled. While in irradiated samples toxin were detected before the end of the storage life or after the samples were spoiled, depending on the levels of inoculum. In general, both in unirradiated and irradiated samples inoculated with 10 2 -10 6 spores per gram and stored at 10degC, the earlieast toxin production was detected after the samples were spoiled. While the samples were stored at 5degC, no toxic samples were found up to 30 days of storage when the experiment were terminated. The percentage of toxic samples was shown highly effected by type B strains, fish species, inoculum levels and storage time, when the storage temperature is 20degC. But no significant difference was found after treatment with irradiation doses. In general the interaction effects between those treatments on the percentage of toxic samples showed no significant difference. (author)

A new type industrial total station based on target automatic collimation

Science.gov (United States)

Lao, Dabao; Zhou, Weihu; Ji, Rongyi; Dong, Dengfeng; Xiong, Zhi; Wei, Jiang

2018-01-01

In the case of industrial field measurement, the present measuring instruments work with manual operation and collimation, which give rise to low efficiency for field measurement. In order to solve the problem, a new type industrial total station is presented in this paper. The new instrument can identify and trace cooperative target automatically, in the mean time, coordinate of the target is measured in real time. For realizing the system, key technology including high precision absolutely distance measurement, small high accuracy angle measurement, target automatic collimation with vision, and quick precise controlling should be worked out. After customized system assemblage and adjustment, the new type industrial total station will be established. As the experiments demonstrated, the coordinate accuracy of the instrument is under 15ppm in the distance of 60m, which proved that the measuring system is feasible. The result showed that the total station can satisfy most industrial field measurement requirements.

Targeting dysfunctional beta-cell signaling for the potential treatment of type 1 diabetes mellitus.

Science.gov (United States)

Fenske, Rachel J; Kimple, Michelle E

2018-03-01

Since its discovery and purification by Frederick Banting in 1921, exogenous insulin has remained almost the sole therapy for type 1 diabetes mellitus. While insulin alleviates the primary dysfunction of the disease, many other aspects of the pathophysiology of type 1 diabetes mellitus are unaffected. Research aimed towards the discovery of novel type 1 diabetes mellitus therapeutics targeting different cell signaling pathways is gaining momentum. The focus of these efforts has been almost entirely on the impact of immunomodulatory drugs, particularly those that have already received FDA-approval for other autoimmune diseases. However, these drugs can often have severe side effects, while also putting already immunocompromised individuals at an increased risk for other infections. Potential therapeutic targets in the insulin-producing beta-cell have been largely ignored by the type 1 diabetes mellitus field, save the glucagon-like peptide 1 receptor. While there is preliminary evidence to support the clinical exploration of glucagon-like peptide 1 receptor-based drugs as type 1 diabetes mellitus adjuvant therapeutics, there is a vast space for other putative therapeutic targets to be explored. The alpha subunit of the heterotrimeric G z protein (Gα z ) has been shown to promote beta-cell inflammation, dysfunction, death, and failure to replicate in the context of diabetes in a number of mouse models. Genetic loss of Gα z or inhibition of the Gα z signaling pathway through dietary interventions is protective against the development of insulitis and hyperglycemia. The multifaceted effects of Gα z in regards to beta-cell health in the context of diabetes make it an ideal therapeutic target for further study. It is our belief that a low-risk, effective therapy for type 1 diabetes mellitus will involve a multidimensional approach targeting a number of regulatory systems, not the least of which is the insulin-producing beta-cell. Impact statement The expanding

Radiation enhanced reactivation of irradiated human adenovirus type 2 in human cells

International Nuclear Information System (INIS)

Jeeves, W.P.

1981-04-01

Radiation-enhanced reactivation (ER) of a radiation-damaged mammalian virus is the term given to the observation that the survival of irradiated virus can be enhanced by irradiation of an appropriate host cell prior to infection. In this work, both UV-enhanced reactivation (UVER) and gamma-ray-enhanced reactivation (γRER) of irradiated human adenovirus type 2 (AD 2) were studied in a variety of normal and DNA repair-deficient human fibroblast host cell strains. In order to examine the lesion specificity of ER in human cells, experiments were performed using UV-irradiated and γ-irradiated virus. The investigation was carried out using a sensitive technique of indirect immunofluorescence, according to which irradiated and unirradiated cell cultures were infected with irradiated or unirradiated AD 2 and were subsequently examined for the presence of viral structural antigens ('V' Ag) at a fixed time after infection

Electrochemical corrosion studies on copper-base waste package container materials in unirradiated 0.1 N NaNO3 at 95 degrees C

International Nuclear Information System (INIS)

Akkaya, M.; Verink, E.D. Jr.; Van Konynenburg, R.A.

1988-05-01

Three candidate materials were investigated in this study in terms of their electrochemical corrosion behavior in unirradiated 0.1 N NaNO 3 solutions at 95 degrees C. Anodic polarization experiments were conducted to determine the passive current densities, pitting potentials, and other parameters, together with Cyclic Current Reversal Voltammetry tests to evaluate the stability and protectiveness of the passive oxides formed. X-ray diffraction and Auger Electron Spectroscopy were used for identification of the corrosion products as well as Scanning Electron Microscopy for the surface morphology studies. 2 refs., 22 figs., 2 tabs

Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise

DEFF Research Database (Denmark)

Kristensen, Dorte Enggaard; Albers, Peter Hjorth; Prats, Clara

2015-01-01

are expressed in a fibre type-dependent manner and that fibre type-specific activation of AMPK and downstream targets is dependent on exercise intensity. Pools of type I and II fibres were prepared from biopsies of m. vastus lateralis from healthy men before and after two exercise trials; A) continuous cycling......AMP-activated protein kinase (AMPK) is a regulator of energy homeostasis during exercise. Studies suggest muscle fibre type-specific AMPK expression. However, fibre type-specific regulation of AMPK and downstream targets during exercise has not been proven. We hypothesized that AMPK subunits...... (CON) 30 min at 69 ± 1% VO2peak or B) interval cycling (INT) 30 min with 6 × 1.5 min high-intense bouts peaking at 95 ± 2% VO2peak . In type I vs. II fibres a higher β1 AMPK (+215%) and lower γ3 AMPK expression (-71%) was found. α1 , α2 , β2 and γ1 AMPK expression was similar between fibre types...

Yield of opportunistic targeted screening for type 2 diabetes in primary care: the diabscreen study.

NARCIS (Netherlands)

Klein Woolthuis, E.P.; Grauw, W.J.C. de; Gerwen, W.H.E.M. van; Hoogen, H.J.M. van den; Lisdonk, E.H. van de; Metsemakers, J.F.M.; Weel, C. van

2009-01-01

PURPOSE: In screening for type 2 diabetes, guidelines recommend targeting high-risk individuals. Our objectives were to assess the yield of opportunistic targeted screening for type 2 diabetes in primary care and to assess the diagnostic value of various risk factors. METHODS: In 11 family practices

Type 1 Diabetes--Reaping the Rewards of a Targeted Research Investment.

Science.gov (United States)

Fradkin, Judith E; Wallace, Julie A; Akolkar, Beena; Rodgers, Griffin P

2016-02-01

The Diabetes Control and Complications Trial (DCCT) precipitated a major research effort to develop new approaches to achieve near-normal glycemic control in real-world settings in people with type 1 diabetes. Toward that end, a unique funding stream from the U.S. Congress-the Special Statutory Funding Program for Type 1 Diabetes Research-has provided nearly $2.5 billion for research into the prevention, cure, and treatment of type 1 diabetes since 1998. This funding generated a targeted, sustained investment in type 1 diabetes research with six specific goals: identifying new therapeutic targets through the understanding of disease etiology and pathogenesis, preventing or reversing the disease, developing cell replacement therapy, improving management and care, preventing or reducing the complications, and attracting new talent and applying new technologies to type 1 diabetes research. This Perspective describes exciting results that have emerged from the investment and further advances on the horizon, including artificial pancreas technologies, new therapies for diabetic retinopathy, and breakthroughs in laboratory production of β-cells. The recent program extension enables us to build on this foundation and pursue key new initiatives to harness emerging technologies and develop the next generation of type 1 diabetes researchers. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

The alpha-cell as target for type 2 diabetes therapy

DEFF Research Database (Denmark)

Christensen, Mikkel; Bagger, Jonatan I; Vilsboll, Tina

2011-01-01

for type 2 diabetes. Several lines of preclinical evidence have paved the way for the development of drugs, which suppress glucagon secretion or antagonize the glucagon receptor. In this review, the physiological actions of glucagon and the role of glucagon in type 2 diabetic pathophysiology are outlined...... antagonists are confronted with several safety issues. At present, available pharmacological agents based on the glucose-dependent glucagonostatic effects of GLP-1 represent the most favorable way to apply constraints to the alpha-cell in type 2 diabetes.......-coupled receptors in the hepatocytes. Type 2 diabetic patients are characterized by elevated glucagon levels contributing decisively to hyperglycemia in these patients. Accumulating evidence demonstrates that targeting the pancreatic alpha-cell and its main secretory product glucagon is a possible treatment...

Therapeutic Target Achievement in Type 2 Diabetic Patients after Hyperglycemia, Hypertension, Dyslipidemia Management

Directory of Open Access Journals (Sweden)

Ah Young Kang

2011-06-01

Full Text Available BackgroundOur study group established "3H care" in 2002. The meaning of "3H care" attain and maintain adequate controls over hypertension, hyperlipidemia, and hyperglycemia in type 2 diabetic patients. This study evaluated the achievement of target goals after one year or more of "3H care" by specialists in our diabetic clinic.MethodsThis was a retrospective study of 200 type 2 diabetic patients who received "3H care" for one year or more in our diabetic clinic. We evaluated achievement of target goals for metabolic controls as suggested by the American Diabetes Association.ResultsOverall, 200 type 2 diabetes patients were enrolled, of whom 106 were males (53% and 94 were females (47%. After one year of "3H care," the mean HbA1c was 7.2±1.5% and the percentage of patients achieving glycemic control (HbA1c <7% was 51.8%. However only 32.2% of hypertensive patients achieved the recommended target. After one year of "3H care," the percentages of those who achieved the target value for dyslipidemia were 80.0% for total cholesterol, 66.3% for low density lipoprotein cholesterol, 57.9% for triglyceride, and 51.8% for high density lipoprotein cholesterol. The percentage that achieved all three targets level was only 4.4% after one year and 14.8% after two years.ConclusionThe results of this study demonstrate that only a minor proportion of patients with type 2 diabetes achieved the recommended goals despite the implementation of "3H care." It is our suggestion that better treatment strategies and methods should be used to control hypertension, hyperlipidemia and hyperglycemia.

Lift-based up-ender and methods using same to manipulate a shipping container containing unirradiated nuclear fuel

Science.gov (United States)

Nilles, Michael J.

2017-08-01

A shipping container containing an unirradiated nuclear fuel assembly is lifted off the ground by operating a crane to raise a lifting tool comprising a winch. The lifting tool is connected with the shipping container by a rigging line connecting with the shipping container at a lifting point located on the shipping container between the top and bottom of the shipping container, and by winch cabling connecting with the shipping container at the top of the shipping container. The shipping container is reoriented by operating the winch to adjust the length of the winch cabling so as to rotate the shipping container about the lifting point. Shortening the winch cabling rotates the shipping container about the lifting point from a horizontal orientation to a vertical orientation, while lengthening the winch cabling rotates the shipping container about the lifting point from the vertical orientation to the horizontal orientation.

The alpha-cell as target for type 2 diabetes therapy

DEFF Research Database (Denmark)

Christensen, Mikkel; Bagger, Jonatan I; Vilsboll, Tina

2011-01-01

-coupled receptors in the hepatocytes. Type 2 diabetic patients are characterized by elevated glucagon levels contributing decisively to hyperglycemia in these patients. Accumulating evidence demonstrates that targeting the pancreatic alpha-cell and its main secretory product glucagon is a possible treatment....... Furthermore, potential advantages and limitations of antagonizing the glucagon receptor or suppressing glucagon secretion in the treatment of type 2 diabetes are discussed with a focus on already marketed drugs and drugs in clinical development. It is concluded that the development of novel glucagon receptor...

The reaction of unirradiated and irradiated nuclear graphites with water vapor in helium

International Nuclear Information System (INIS)

Imai, Hisashi; Nomura, Shinzo; Kurosawa, Takeshi; Fujii, Kimio; Sasaki, Yasuichi

1980-10-01

Nuclear graphites more than 10 brands were oxidized with water vapor in helium and then some selected graphites were irradiated with fast neutron in the Japan Materials Testing Reactor to clarify the effect of radiation damage of graphite on their reaction behaviors. The reaction was carried out under a well defined condition in the temperature range 800 -- 1000 0 C at concentrations of water vapor 0.38 -- 1.30 volume percent in helium flow of total pressure of 1 atm. The chemical reactivity of graphite irradiated at 1000 +- 50 0 C increased linearly with neutron fluence until irradiation of 3.2 x 10 21 n/cm 2 . The activation energy for the reaction was found to decrease with neutron fluence for almost all the graphites, except for a few ones. The order of reaction increased from 0.5 for the unirradiated graphite to 1.0 for the graphite irradiated up to 6.0 x 10 20 n/cm 2 . Experiment was also performed to study a superposed effect between the influence of radiation damage of graphite and the catalytic action of barium on the reaction rate, as well as the effect of catalyser of barium. It was shown that these effects were not superposed upon each other, although barium had a strong catalytic action on the reaction. (author)

Effect of fast-neutron irradiation on plastic deformation of Type 304 stainless steel

International Nuclear Information System (INIS)

Yamada, H.

1978-01-01

Plastic deformation of EBR-II-irradiated Type 304 stainless steel was investigated by a stress-relaxation method. The stress-strain-rate relationships for the irradiated specimens at room temperature are concave upward, which are similar to those for the unirradiated specimens. However, concave downward behavior in the stress-strain-rate relationships were observed at much lower temperatures for the irradiated specimens in contrast to the unirradiated specimens. These results were analyzed succccessfully using Hart's mechanical equation-of-state concept. It was found that the hardness sigma*, which is the minimum stress necessary for the dislocation to overcome obstacles without thermal activation, increases linearly with fast-neutron fluence. This increase in sigma* is consistent with so-called ''irradiation hardening.'' In addition, resistance to dislocation glide, which is quantitatively measured in terms of sigma 0 , was observed to decrease linearly with fast-neutron fluence. The decrease in sigma 0 can be attributed to a decrease of solute drag due to irradiation-induced solute segregation

Evidence for induction of DNA double strand breaks in the bystander response to targeted soft X-rays in CHO cells

International Nuclear Information System (INIS)

Kashino, Genro; Prise, Kevin M.; Schettino, Giuseppe; Folkard, Melvyn; Vojnovic, Borivoj; Michael, Barry D.; Suzuki, Keiji; Kodama, Seiji; Watanabe, Masami

2004-01-01

This study investigated the role of DNA double strand breaks and DNA base damage in radiation-induced bystander responses in Chinese hamster ovary (CHO) cell lines. Two CHO repair-deficient clones, xrs5 (DNA double strand break repair-deficient) and EM9 (DNA base excision repair-deficient) were used in addition to the wild type (CHO). The Gray Cancer Institute ultrasoft X-ray microprobe is a powerful tool for investigating the bystander response, because it permits the irradiation of only a single nucleus of a cell, as reported previously. In order to investigate the bystander effect in each repair-deficient cell line, we irradiated a single cell within a population and scored the formation of micronuclei. When a single nucleus in the population was targeted with 1 Gy, elevated numbers of micronuclei were induced in the neighbouring unirradiated cells in the EM9 and xrs5 cell lines, whereas induction was not observed in CHO. The induction of micronuclei in xrs5 was significantly higher than that in EM9. Under these conditions, the surviving fraction in the neighbouring cells was significantly lower in xrs5 than in the other cell lines, showing a higher cell killing effect in xrs5. To confirm that bystander factors secreted from irradiated cells caused these effects, we carried out medium transfer experiments using conventional X-irradiation. Medium conditioned for 24 h with irradiated cells was transferred to unirradiated cells and elevated induction of micronuclei was observed in xrs5. These results suggest that DNA double strand breaks rather than base damage are caused by factors secreted in the medium from irradiated cells

Radiation-induced genomic instability and bystander effects: inter-related inflammatory-type non-targeted effects of exposure to ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Wright, E.G. (Molecular and Cellular Pathology Laboratories, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, Dundee, Scotland (United Kingdom))

2008-12-15

The dogma that genetic alterations are restricted to directly irradiated cells has been challenged by observations in which effects of ionizing radiation, characteristically associated with the consequences of energy deposition in the cell nucleus, arise in non-irradiated cells. These, so called, untargeted effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that have communicated with neighbouring irradiated cells (radiation-induced bystander effects). There are also reports of long-range signals in vivo, known as clastogenic factors, with the capacity to induce damage in unirradiated cells. Clastogenic factors may be related to the inflammatory responses that have been implicated in some of the pathological consequences of radiation exposures. The phenotypic expression of untargeted effects reflects a balance between the type of signals produced and the responses of cell populations to such signals, both of which may be significantly influenced by cell type and genotype. There is accumulating evidence that untargeted effects in vitro involve inter-cellular signalling, production of cytokines and free radical generation. These are also features of inflammatory responses in vivo that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. At present it is far from clear how untargeted effects contribute to overall cellular radiation responses and in vivo consequences but it is possible that the various untargeted effects may reflect inter-related aspects of a non-specific inflammatory-type response to radiation-induced stress and injury and be involved in a variety of the pathological consequences of radiation exposures. (orig.)

Radiation-induced genomic instability and bystander effects: inter-related inflammatory-type non-targeted effects of exposure to ionizing radiation

International Nuclear Information System (INIS)

Wright, E.G.

2008-01-01

The dogma that genetic alterations are restricted to directly irradiated cells has been challenged by observations in which effects of ionizing radiation, characteristically associated with the consequences of energy deposition in the cell nucleus, arise in non-irradiated cells. These, so called, untargeted effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that have communicated with neighbouring irradiated cells (radiation-induced bystander effects). There are also reports of long-range signals in vivo, known as clastogenic factors, with the capacity to induce damage in unirradiated cells. Clastogenic factors may be related to the inflammatory responses that have been implicated in some of the pathological consequences of radiation exposures. The phenotypic expression of untargeted effects reflects a balance between the type of signals produced and the responses of cell populations to such signals, both of which may be significantly influenced by cell type and genotype. There is accumulating evidence that untargeted effects in vitro involve inter-cellular signalling, production of cytokines and free radical generation. These are also features of inflammatory responses in vivo that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. At present it is far from clear how untargeted effects contribute to overall cellular radiation responses and in vivo consequences but it is possible that the various untargeted effects may reflect inter-related aspects of a non-specific inflammatory-type response to radiation-induced stress and injury and be involved in a variety of the pathological consequences of radiation exposures. (orig.)

Predicting the Types of Ion Channel-Targeted Conotoxins Based on AVC-SVM Model.

Science.gov (United States)

Xianfang, Wang; Junmei, Wang; Xiaolei, Wang; Yue, Zhang

2017-01-01

The conotoxin proteins are disulfide-rich small peptides. Predicting the types of ion channel-targeted conotoxins has great value in the treatment of chronic diseases, epilepsy, and cardiovascular diseases. To solve the problem of information redundancy existing when using current methods, a new model is presented to predict the types of ion channel-targeted conotoxins based on AVC (Analysis of Variance and Correlation) and SVM (Support Vector Machine). First, the F value is used to measure the significance level of the feature for the result, and the attribute with smaller F value is filtered by rough selection. Secondly, redundancy degree is calculated by Pearson Correlation Coefficient. And the threshold is set to filter attributes with weak independence to get the result of the refinement. Finally, SVM is used to predict the types of ion channel-targeted conotoxins. The experimental results show the proposed AVC-SVM model reaches an overall accuracy of 91.98%, an average accuracy of 92.17%, and the total number of parameters of 68. The proposed model provides highly useful information for further experimental research. The prediction model will be accessed free of charge at our web server.

The non-targeted effects of radiation are perpetuated by exosomes

Energy Technology Data Exchange (ETDEWEB)

Al-Mayah, Ammar; Bright, Scott; Chapman, Kim [Genomic Instability Group, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom); Irons, Sarah [Insect Virus Research Group, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom); Luo, Ping [Izon Science Ltd., The Oxford Science Park, Magdalen Centre, Robert Robinson Avenue, Oxford OX4 4GA (United Kingdom); Carter, David [Chromatin and non-coding RNA, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom); Goodwin, Edwin [The New Mexico Consortium, Los Alamos, NM 87544 (United States); Kadhim, Munira, E-mail: mkadhim@brookes.ac.uk [Genomic Instability Group, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP (United Kingdom)

2015-02-15

Highlights: • Radiation induces a DNA damaging process in bystander cells through cell–cell signalling. • Exosome RNA and protein molecules play crucial roles in bystander effects. • Cell progeny inherit the ability to secret bystander effect-inducing exosomes. • This mechanism is most likely accountable for the propagation of GI. - Abstract: Exosomes contain cargo material from endosomes, cytosol, plasma membrane and microRNA molecules, they are released by a number of non-cancer and cancer cells into both the extracellular microenvironment and body fluids such as blood plasma. Recently we demonstrated radiation-induced non-targeted effects [NTE: genomic instability (GI) and bystander effects (BE)] are partially mediated by exosomes, particularly the RNA content. However the mechanistic role of exosomes in NTE is yet to be fully understood. The present study used MCF7 cells to characterise the longevity of exosome-induced activity in the progeny of irradiated and unirradiated bystander cells. Exosomes extracted from conditioned media of irradiated and bystander progeny were added to unirradiated cells. Analysis was carried out at 1 and 20/24 population doublings following medium/exosome transfer for DNA/chromosomal damage. Results confirmed exosomes play a significant role in mediating NTE of ionising radiation (IR). This effect was remarkably persistent, observed >20 doublings post-irradiation in the progeny of bystander cells. Additionally, cell progeny undergoing a BE were themselves capable of inducing BE in other cells via exosomes they released. Furthermore we investigated the role of exosome cargo. Culture media from cells exposed to 2 Gy X-rays was subjected to ultracentrifugation and four inoculants prepared, (a) supernatants with exosomes removed, and pellets with (b) exosome proteins denatured, (c) RNA degraded, and (d) a combination of protein–RNA inactivation. These were added to separate populations of unirradiated cells. The BE was

The non-targeted effects of radiation are perpetuated by exosomes

International Nuclear Information System (INIS)

Al-Mayah, Ammar; Bright, Scott; Chapman, Kim; Irons, Sarah; Luo, Ping; Carter, David; Goodwin, Edwin; Kadhim, Munira

2015-01-01

Highlights: • Radiation induces a DNA damaging process in bystander cells through cell–cell signalling. • Exosome RNA and protein molecules play crucial roles in bystander effects. • Cell progeny inherit the ability to secret bystander effect-inducing exosomes. • This mechanism is most likely accountable for the propagation of GI. - Abstract: Exosomes contain cargo material from endosomes, cytosol, plasma membrane and microRNA molecules, they are released by a number of non-cancer and cancer cells into both the extracellular microenvironment and body fluids such as blood plasma. Recently we demonstrated radiation-induced non-targeted effects [NTE: genomic instability (GI) and bystander effects (BE)] are partially mediated by exosomes, particularly the RNA content. However the mechanistic role of exosomes in NTE is yet to be fully understood. The present study used MCF7 cells to characterise the longevity of exosome-induced activity in the progeny of irradiated and unirradiated bystander cells. Exosomes extracted from conditioned media of irradiated and bystander progeny were added to unirradiated cells. Analysis was carried out at 1 and 20/24 population doublings following medium/exosome transfer for DNA/chromosomal damage. Results confirmed exosomes play a significant role in mediating NTE of ionising radiation (IR). This effect was remarkably persistent, observed >20 doublings post-irradiation in the progeny of bystander cells. Additionally, cell progeny undergoing a BE were themselves capable of inducing BE in other cells via exosomes they released. Furthermore we investigated the role of exosome cargo. Culture media from cells exposed to 2 Gy X-rays was subjected to ultracentrifugation and four inoculants prepared, (a) supernatants with exosomes removed, and pellets with (b) exosome proteins denatured, (c) RNA degraded, and (d) a combination of protein–RNA inactivation. These were added to separate populations of unirradiated cells. The BE was

Interleukin-1 beta targeted therapy for type 2 diabetes

DEFF Research Database (Denmark)

Maedler, K.; Dharmadhikari, G.; Schumann, D.M.

2009-01-01

Since having been cloned in 1984, IL-1beta has been the subject of over 22,000 citations in Pubmed, among them over 800 reviews. This is because of its numerous effects. IL-1beta is a regulator of the body's inflammatory response and is produced after infection, injury, and antigenic challenge. I....... We highlight recent clinical studies and experiments in animals and isolated islets using IL-1beta as a potential target for the therapy of type 2 diabetes Udgivelsesdato: 2009/9...

DNA targeting by the type I-G and type I-A CRISPR–Cas systems of Pyrococcus furiosus

Science.gov (United States)

Elmore, Joshua; Deighan, Trace; Westpheling, Jan; Terns, Rebecca M.; Terns, Michael P.

2015-01-01

CRISPR–Cas systems silence plasmids and viruses in prokaryotes. CRISPR–Cas effector complexes contain CRISPR RNAs (crRNAs) that include sequences captured from invaders and direct CRISPR-associated (Cas) proteins to destroy corresponding invader nucleic acids. Pyrococcus furiosus (Pfu) harbors three CRISPR–Cas immune systems: a Cst (Type I-G) system with an associated Cmr (Type III-B) module at one locus, and a partial Csa (Type I-A) module (lacking known invader sequence acquisition and crRNA processing genes) at another locus. The Pfu Cmr complex cleaves complementary target RNAs, and Csa systems have been shown to target DNA, while the mechanism by which Cst complexes silence invaders is unknown. In this study, we investigated the function of the Cst as well as Csa system in Pfu strains harboring a single CRISPR–Cas system. Plasmid transformation assays revealed that the Cst and Csa systems both function by DNA silencing and utilize similar flanking sequence information (PAMs) to identify invader DNA. Silencing by each system specifically requires its associated Cas3 nuclease. crRNAs from the 7 shared CRISPR loci in Pfu are processed for use by all 3 effector complexes, and Northern analysis revealed that individual effector complexes dictate the profile of mature crRNA species that is generated. PMID:26519471

Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation.

Directory of Open Access Journals (Sweden)

Hongkai Ji

Full Text Available The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP, global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs. We further document that a Myc core signature (MCS set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells.

Preparation of chromatographic and solid-solvent extraction 99mTc generators using gel-type targets

International Nuclear Information System (INIS)

Le Van So

2000-01-01

We have studied two types of targets zirconium-molybdate (ZrMo) and titanium-molybdate (TiMo) prepared by precipitating reaction between ammonium-molybdate and zirconium-chloride or titanium-chloride solutions, respectively. Other types of targets were also prepared by co-precipitating ZrMo or TiMo with hydrous manganese-dioxide, hydrous silica, and hydrous titanium-dioxide or by impregnated ZrMo or TiMo with Iodate anions. The results on extraction of Tc-99m from neutron irradiated TiMo solid phase using solvents such as MEK, aceton, ethylic ether, chloroform, etc showed that separation yield (SY) of Tc-99m in case of aceton extraction was from 70% to 80% and in other cases non higher than 40%. The Tc-99m elution curves and column kinetic in case of aceton extraction (after evaporation of aceton and recovery of Tc-99m in 0,9% NaCl solution) was superior than in case chromatographic generator using saline eluant. As result obtained, two types of generators were successfully prepared and put into use: Chromatographic generator using titanium-molybdate target as packing material and saline as eluant. Solid-solvent extraction 99m Tc generator using titanium-molybdate target (as solid phase) and aceton as extracting solvent. (author)

Bacterial flora-typing with targeted, chip-based Pyrosequencing

Directory of Open Access Journals (Sweden)

El-Sayed Yasser Y

2007-11-01

Full Text Available Abstract Background The metagenomic analysis of microbial communities holds the potential to improve our understanding of the role of microbes in clinical conditions. Recent, dramatic improvements in DNA sequencing throughput and cost will enable such analyses on individuals. However, such advances in throughput generally come at the cost of shorter read-lengths, limiting the discriminatory power of each read. In particular, classifying the microbial content of samples by sequencing the Results We describe a method for identifying the phylogenetic content of bacterial samples using high-throughput Pyrosequencing targeted at the 16S rRNA gene. Our analysis is adapted to the shorter read-lengths of such technology and uses a database of 16S rDNA to determine the most specific phylogenetic classification for reads, resulting in a weighted phylogenetic tree characterizing the content of the sample. We present results for six samples obtained from the human vagina during pregnancy that corroborates previous studies using conventional techniques. Next, we analyze the power of our method to classify reads at each level of the phylogeny using simulation experiments. We assess the impacts of read-length and database completeness on our method, and predict how we do as technology improves and more bacteria are sequenced. Finally, we study the utility of targeting specific 16S variable regions and show that such an approach considerably improves results for certain types of microbial samples. Using simulation, our method can be used to determine the most informative variable region. Conclusion This study provides positive validation of the effectiveness of targeting 16S metagenomes using short-read sequencing technology. Our methodology allows us to infer the most specific assignment of the sequence reads within the phylogeny, and to identify the most discriminative variable region to target. The analysis of high-throughput Pyrosequencing on human flora

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus.

Science.gov (United States)

Guan, Jing; Wang, Wanying; Sun, Baolin

2017-01-01

CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCC mec ). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5' tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCC mec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive

Characterization of un-irradiated MIMAS MOX fuel by Raman spectroscopy and EPMA

Science.gov (United States)

Talip, Zeynep; Peuget, Sylvain; Magnin, Magali; Tribet, Magaly; Valot, Christophe; Vauchy, Romain; Jégou, Christophe

2018-02-01

In this study, Raman spectroscopy technique was implemented to characterize un-irradiated MIMAS (MIcronized - MASter blend) MOX fuel samples with average 7 wt.% Pu content and different damage levels, 13 years after fabrication, one year after thermal recovery and soon after annealing, respectively. The impacts of local Pu content, deviation from stoichiometry and self-radiation damage on Raman spectrum of the studied MIMAS MOX samples were assessed. MIMAS MOX fuel has three different phases Pu-rich agglomerate, coating phase and uranium matrix. In order to distinguish these phases, Raman results were associated with Pu content measurements performed by Electron Microprobe Analysis. Raman results show that T2g frequency significantly shifts from 445 to 453 cm-1 for Pu contents increasing from 0.2 to 25 wt.%. These data are satisfactorily consistent with the calculations obtained with Gruneisen parameters. It was concluded that the position of the T2g band is mainly controlled by Pu content and self-radiation damage. Deviation from stoichiometry does not have a significant influence on T2g band position. Self-radiation damage leads to a shift of T2g band towards lower frequency (∼1-2 cm-1 for the UO2 matrix of damaged sample). However, this shift is difficult to quantify for the coating phase and Pu agglomerates given the dispersion of high Pu concentrations. In addition, 525 cm-1 band, which was attributed to sub-stoichiometric structural defects, is presented for the first time for the self-radiation damaged MOX sample. Thanks to the different oxidation resistance of each phase, it was shown that laser induced oxidation could be alternatively used to identify the phases. It is demonstrated that micro-Raman spectroscopy is an efficient technique for the characterization of heterogeneous MOX samples, due to its low spatial resolution.

[Relationship among weblog authors' target audience, contents, and types of interpersonal communication].

Science.gov (United States)

Miura, Asako; Matsumura, Naohiro; Kitayama, Satoshi

2008-12-01

Weblogs are one of the most popular personal websites in Japan, where entries are made in journal style and displayed in reverse chronological order. This study examined the relationship between weblog authors' target audience (i.e., orientation) and the actual situations depicted in their weblogs by combining a questionnaire survey of the authors with an analysis of their weblog content data. Based on a questionnaire survey of 736 Japanese weblog authors, their target audience was divided into four clusters: (a) general public, (b) self, (c) self and offline friends, and (d) various others. To assess the actual situations depicted in their weblogs, the amount of happy and unhappy emotional expression in their writing and the frequency of interpersonal communication (comments, bookmarks, and trackbacks) were calculated from their log data. The results suggested that weblog authors wrote different types of content and used different types of communication depending on their audience, whereas the weblog content itself still showed the diary-like characteristic of personal daily-life records.

High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Philip J. Barter

2013-09-01

Full Text Available High density lipoproteins (HDLs have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic β cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

Tensile and electrical properties of unirradiated and irradiated Hycon 3HP{trademark} CuNiBe

Energy Technology Data Exchange (ETDEWEB)

Zinkle, S.J.; Eatherly, W.S. [Oak Ridge National Lab., TN (United States)

1996-10-01

The unirradiated tensile properties of two different heats of Hycon 3HP{trademark} CuNiBe (HT Temper) have been measured over the temperature range of 20-500{degrees}C for longitudinal and long transverse orientations. The room temperature electrical conductivity has also been measured for both heats. Both heats exhibited a very good combination of strength and conductivity at room temperature. The strength remained relatively high at all test temperatures, with a yield strength of 420-520 MPa at 500{degrees}C. However, low levels of ductility (<5% uniform elongation) were observed at test temperatures above 200-250{degrees}C, due to flow localization adjacent to grain boundaries. Fission neutron irradiation to a dose of {approximately}0.7 dpa at temperatures between 100 and 240{degrees}C produced a slight increase in strength and a significant decrease in ductility. The measured tensile elongation increased with increasing irradiation temperature, with a uniform elongation of {approximately}3.3% observed at 240{degrees}C. The electrical conductivity decreased slightly following irradiation, due to the presence of defect clusters and Ni, Zn, Co transmutation products. The data indicate that CuNiBe alloys have irradiated tensile and electrical properties comparable or superior to CuCrZr and oxide dispersion strengthened copper at temperatures <250{degrees}C, and may be suitable for certain fusion energy structural applications.

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.

A new type of active actinide target for studying fission and (n,xn) reactions

International Nuclear Information System (INIS)

Belier, G.; Aupiais, J.; Varignon, C.; Vayre, S.

2011-01-01

A new type of active target for the detection of fission of actinides has been developed, it is based on α spectrometry through liquid scintillation. The target uses the liquid-liquid extraction in order to mix the actinide with the liquid organic scintillator. The actinide to be detected is inside the detector itself which maximises the efficiency of the detector. The use of an organic scintillator allows the identification of the particles emitted. Indeed, the time delay for the transfer of the energy deposited in the solvent towards the scintillating molecules depends on the type of the energy deposits: instantaneous fluorescence is obtained for direct excitation while delayed fluorescence is obtained for energy deposits through ionization. By discriminating the different slow and quick components of the photomultiplier signal it is then possible to identify the particle: beta, alpha or fission products. This target has been tested with Cf 252 irradiated with 18 MeV neutrons, the experimental data show different peaks corresponding to alpha decay (97%), spontaneous fission (3%), beta decay and recoil protons due to neutron emissions. (A.C.)

AMPK activation: a therapeutic target for type 2 diabetes?

Directory of Open Access Journals (Sweden)

Coughlan KA

2014-06-01

Full Text Available Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly – some of which (for example, metformin and thiazolidinediones are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D. Keywords: adenosine monophosphate-activated protein kinase, type 2 diabetes, insulin resistance, drug therapy

Targeting VEGF-B as a novel treatment for insulin resistance and type 2 diabetes.

Science.gov (United States)

Hagberg, Carolina E; Mehlem, Annika; Falkevall, Annelie; Muhl, Lars; Fam, Barbara C; Ortsäter, Henrik; Scotney, Pierre; Nyqvist, Daniel; Samén, Erik; Lu, Li; Stone-Elander, Sharon; Proietto, Joseph; Andrikopoulos, Sofianos; Sjöholm, Ake; Nash, Andrew; Eriksson, Ulf

2012-10-18

The prevalence of type 2 diabetes is rapidly increasing, with severe socioeconomic impacts. Excess lipid deposition in peripheral tissues impairs insulin sensitivity and glucose uptake, and has been proposed to contribute to the pathology of type 2 diabetes. However, few treatment options exist that directly target ectopic lipid accumulation. Recently it was found that vascular endothelial growth factor B (VEGF-B) controls endothelial uptake and transport of fatty acids in heart and skeletal muscle. Here we show that decreased VEGF-B signalling in rodent models of type 2 diabetes restores insulin sensitivity and improves glucose tolerance. Genetic deletion of Vegfb in diabetic db/db mice prevented ectopic lipid deposition, increased muscle glucose uptake and maintained normoglycaemia. Pharmacological inhibition of VEGF-B signalling by antibody administration to db/db mice enhanced glucose tolerance, preserved pancreatic islet architecture, improved β-cell function and ameliorated dyslipidaemia, key elements of type 2 diabetes and the metabolic syndrome. The potential use of VEGF-B neutralization in type 2 diabetes was further elucidated in rats fed a high-fat diet, in which it normalized insulin sensitivity and increased glucose uptake in skeletal muscle and heart. Our results demonstrate that the vascular endothelium can function as an efficient barrier to excess muscle lipid uptake even under conditions of severe obesity and type 2 diabetes, and that this barrier can be maintained by inhibition of VEGF-B signalling. We propose VEGF-B antagonism as a novel pharmacological approach for type 2 diabetes, targeting the lipid-transport properties of the endothelium to improve muscle insulin sensitivity and glucose disposal.

In vivo tumor targeting of gold nanoparticles: effect of particle type and dosing strategy.

Science.gov (United States)

Puvanakrishnan, Priyaveena; Park, Jaesook; Chatterjee, Deyali; Krishnan, Sunil; Tunnell, James W

2012-01-01

Gold nanoparticles (GNPs) have gained significant interest as nanovectors for combined imaging and photothermal therapy of tumors. Delivered systemically, GNPs preferentially accumulate at the tumor site via the enhanced permeability and retention effect, and when irradiated with near infrared light, produce sufficient heat to treat tumor tissue. The efficacy of this process strongly depends on the targeting ability of the GNPs, which is a function of the particle's geometric properties (eg, size) and dosing strategy (eg, number and amount of injections). The purpose of this study was to investigate the effect of GNP type and dosing strategy on in vivo tumor targeting. Specifically, we investigated the in vivo tumor-targeting efficiency of pegylated gold nanoshells (GNSs) and gold nanorods (GNRs) for single and multiple dosing. We used Swiss nu/nu mice with a subcutaneous tumor xenograft model that received intravenous administration for a single and multiple doses of GNS and GNR. We performed neutron activation analysis to quantify the gold present in the tumor and liver. We performed histology to determine if there was acute toxicity as a result of multiple dosing. Neutron activation analysis results showed that the smaller GNRs accumulated in higher concentrations in the tumor compared to the larger GNSs. We observed a significant increase in GNS and GNR accumulation in the liver for higher doses. However, multiple doses increased targeting efficiency with minimal effect beyond three doses of GNPs. These results suggest a significant effect of particle type and multiple doses on increasing particle accumulation and on tumor targeting ability.

Fusarium growth on culture media made of tissue juice from irradiated and unirradiated potato tubers

International Nuclear Information System (INIS)

Taczanowski, M.

1994-01-01

Fusarium Sulphureum Schlecht is one of the tuber pathogens causing potato storage disease knowing as dry rot. Because irradiation can disturb the tissue defence mechanism against the pathogen, it was decided to carry out experiments on influence of the treatment on subsequent tuber tissue reaction to a maceration process. The maceration as a physical stress was a substitute for the pathogen activity. Tubers of two potato varieties were tested: Mila -a resistant variety to Fusarium and Atol - susceptible one. Tubers of both varieties were irradiated with a dose of 105 kGy. Unirradiated tubers were taken as a control. A day after irradiation the cortex tissue was macerated using an ordinary rasper and the resulted tissue pulp was strained through medical gauze to obtain crude juice. The juice was clarified by centrifugation and then added to dissolved PDA. The volume ratio of juice to PDA was 1:1. The prepared media were dispensed into Petri dishes. Small pieces of the Fusarium culture were put on the surface of the medium at the centre of each Petri dish. Subsequent growth of the fungus was assessed by measurement of culture diameters every 24 hours. Linear functions of the Fusarium growth were obtained for Mila control and Atol control. In the case of Mila, the Fusarium found more favourable conditions for its growth in the presence of juice from irradiated tubers than from the control ones. Making the same comparison for Atol, no difference was detected. (author)

The Analysis of the General Performance and Mechanical Behavior of Unirradiated FeCrAl Alloys Before and After Welding

Energy Technology Data Exchange (ETDEWEB)

Gussev, Maxim N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2016-06-03

The present report summarizes and discusses the preliminary results for the in-depth characterization of the modern, nuclear-grade FeCrAl alloys currently under development. The alloys were designed for enhanced radiation tolerance and weldability, and the research is currently being pursued by the Department of Energy (DOE) Nuclear Energy Enabling Technologies (NEET) program. Last year, seven candidate FeCrAl alloys with well-controlled chemistry and microstructures were designed and produced; welding was performed under well-controlled conditions. The structure and general performance of unirradiated alloys were assessed using standardized and advanced microstructural characterization techniques and mechanical testing. The primary objective is to identify the best candidate alloy, or at a minimum to identify the contributing factors that increase the weldability and radiation tolerance of FeCrAl alloys, therefore enabling future generations of FeCrAl alloys to deliver better performance parameters. This report is structured so as to describe these critical assessments of the weldability; radiation tolerance will be reported on in later reports from this program.

Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts

International Nuclear Information System (INIS)

Rude, J.M.; Friedberg, E.C.

1977-01-01

Rates of semiconservative DNA synthesis have been investigated in asynchronous xeroderma pigmentosum (XP), XP variant, and normal human skin fibroblasts using the technique of cellular autoradiography. In unirradiated cells, no differences in DNA synthesis rates were detected among the three cell strains. Exposure to UV radiation caused the rate of DNA synthesis to decrease for at least three hours in all three cell strains. In the normal cell strain, recovery of the DNA synthetic rate occurred at later times following a UV fluence of 5 J/m 2 . At this same UV fluence, recovery was absent in classical XP cells during a 24 h post-irradiation period while it was slower than normal in XP variant cells. When the UV fluence to classical XP and XP variant cells was reduced so that survival in all three cell strains was approximately the same (25%), recovery of the DNA synthetic rate was similar in all three cell strains. These results are discussed in terms of current models of DNA replication in UV-irradiated cells and indicate: (1) that pyrimidine dimers are very effective blocks to DNA synthesis and (2) that there is no inherent defect in semiconservative DNA synthesis in either classical XP or XP variant cells which is independent of a defect in DNA repair capacity

Perceived Changes in Well-Being: The Role of Chronological Age, Target Age, and Type of Measure

Science.gov (United States)

Okun, Morris A.; Dittburner, Julie L.; Huff, Barbara P.

2006-01-01

The goal of this study is to investigate whether perceived changes in one's well-being from the present to the future are related to chronological age, target age, and type of measure (psychological well-being versus life satisfaction). Young adults (N = 114) rated their current well-being and their future well-being at one of three target ages…

Urokinase-type plasminogen activator: a new target for male contraception?

Science.gov (United States)

Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

2015-01-01

Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development.

Social comparisons in adults with type 2 diabetes: Patients' reasons for target selection.

Science.gov (United States)

Arigo, Danielle; Cornell, Max; Smyth, Joshua M

2018-07-01

To examine reasons for selecting a social comparison target (i.e. a specific other for relative self-evaluation), and their influence on affect and motivation for self-care, in type 2 diabetes (T2DM). Adults with T2DM (n = 180, M A1c  = 7.6%) chose to read about one of four targets. Participants rated five reasons for their choice (strongly disagree - strongly agree), and rated affect and self-care motivation before and after reading. To boost confidence in my ability to manage diabetes was rated highest overall (ps motivation (p motivation only among those who chose better-off targets (p = 0.01). Patients' reasons for a particular comparison are associated with short-term changes in affect and self-care motivation, and warrant greater empirical and clinical attention.

Target cell cyclophilins facilitate human papillomavirus type 16 infection.

Science.gov (United States)

Bienkowska-Haba, Malgorzata; Patel, Hetalkumar D; Sapp, Martin

2009-07-01

Following attachment to primary receptor heparan sulfate proteoglycans (HSPG), human papillomavirus type 16 (HPV16) particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB) facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

Target cell cyclophilins facilitate human papillomavirus type 16 infection.

Directory of Open Access Journals (Sweden)

Malgorzata Bienkowska-Haba

2009-07-01

Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

Radiation induced synthesis of In{sub 2}O{sub 3} nanoparticles - Part II: Synthesis of In{sub 2}O{sub 3} nanoparticles by thermal decomposition of un-irradiated and γ-irradiated indium acetylacetonate

Energy Technology Data Exchange (ETDEWEB)

Al-Resheedi, Ajayb Saud; Alhokbany, Norah Saad [Department of Chemistry, College of Science, King Saud University, KSU, (Saudi Arabia); Mahfouz, Refaat Mohammed, E-mail: rmhfouz@science.au.edu.eg [Chemistry Department, Faculty of Science, Assiut University, AUN, (Egypt)

2015-09-15

Pure cubic phase, In{sub 2}O{sub 3} nanoparticles with porous structure were synthesized by solid state thermal oxidation of un-irradiated and γ-irradiated indium acetyl acetonate in presence and absence of sodium dodecyl sulphate as surfactant. The as- synthesized In{sub 2}O{sub 3} nanoparticles were characterized by X-ray diffraction (XRD), fourier transformation infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transition electron microscopy (TEM) and thermogravimetry (TG). The shapes and morphologies of as- synthesized In{sub 2}O{sub 3} nanoparticles were highly affected by γ-irradiation of indium acetyl acetonate precursor and by addition of sodium dodecyl sulphate as surfactant. Calcination of un-irradiated indium acetyl acetonate precursor to 4 hours of 600 °C leads to the formation of spherical- shaped accumulative and merged In{sub 2}O{sub 3} nanoparticles with porous structure, whereas irregular porous architectures composed of pure In{sub 2}O{sub 3} nanoparticles were obtained by using γ-irradiated indium acetylacetonate precursor. The as- prepared In{sub 2}O{sub 3} nano products exhibit photoluminescence emission (PL) property and display thermal stability in a wide range of temperature (25-800 °C) which suggest possible applications in nanoscale optoelectronic devices. (author)

Water flow experiments and analyses on the cross-flow type mercury target model with the flow guide plates

CERN Document Server

Haga, K; Kaminaga, M; Hino, R

2001-01-01

A mercury target is used in the spallation neutron source driven by a high-intensity proton accelerator. In this study, the effectiveness of the cross-flow type mercury target structure was evaluated experimentally and analytically. Prior to the experiment, the mercury flow field and the temperature distribution in the target container were analyzed assuming a proton beam energy and power of 1.5 GeV and 5 MW, respectively, and the feasibility of the cross-flow type target was evaluated. Then the average water flow velocity field in the target mock-up model, which was fabricated from Plexiglass for a water experiment, was measured at room temperature using the PIV technique. Water flow analyses were conducted and the analytical results were compared with the experimental results. The experimental results showed that the cross-flow could be realized in most of the proton beam path area and the analytical result of the water flow velocity field showed good correspondence to the experimental results in the case w...

How are metabolic control targets of patients with Type 1 diabetes mellitus achieved in daily practice in the area with high diabetes prevalence?

Science.gov (United States)

Kekäläinen, Päivi; Tirkkonen, Hilkka; Laatikainen, Tiina

2016-05-01

We assessed the prevalence of Type 1 diabetes mellitus and determined how the targets established in the guidelines for patients with Type 1 diabetes mellitus were achieved in clinical practice in North Karelia, Finland. All adult Type 1 diabetes mellitus patients (n=1075) were identified from the regional electronic patient database. The data for HbA1c and LDL cholesterol measurements during the years 2013 and 2014 were obtained from medical records. The prevalence of Type 1 diabetes mellitus in the adult population in North Karelia was 0.8%, which is among the highest worldwide. HbA1c and LDL cholesterol were measured in 93% and 90% of participants, respectively. Nineteen percent of patients reached the HbA1c target of diabetes achieved glycaemic control targets compared with 13-16% of younger patients with diabetes. Glycaemic control was in line with the recommendations in only one-fifth of Type 1 diabetes mellitus patients and less than half of them had LDL cholesterol levels within the target range. Interestingly, older Type 1 diabetes mellitus patients met the glycaemic control target more often than younger patients with diabetes. The targets established for patients with Type 1 diabetes mellitus are not achieved satisfactorily in daily practice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessment of erosion of the ITER divertor targets during type I ELMs

Science.gov (United States)

Federici, G.; Loarte, A.; Strohmayer, G.

2003-09-01

This paper presents the results of a preliminary assessment conducted to estimate the thermal response and erosion lifetime of the ITER divertor targets clad either with carbon-fibre composite or tungsten during type I ELMs. The one-dimensional thermal/erosion model, used for the analyses, is briefly described. It includes all the key surface heat transfer processes such as evaporation, melting, and radiation, and their interaction with the bulk thermal response, and it is based on an implicit finite-difference scheme, which allows for temperature-dependent material properties. The cases analysed clarify the influence of several ELM parameters on the heat transfer and erosion processes at the target (i.e. characteristic plasma ELM energy loss from the pedestal, fraction of the energy reaching the divertor, broadening of the strike-points during ELMs, duration and waveform of the ELM heat load) and design/material parameters (i.e. inclination of the target, type and thickness of the armour material, and for tungsten only, fraction of the melt layer loss). Comparison is made between cases where all ELMs are characterized by the same fixed averaged parameters, and cases where instead the characteristic parameters of each ELM are evaluated in a random fashion by using a standard Monte Carlo technique, based on distributions of some of the variables of interest derived from experiments in today's machines. Although uncertainties rule out providing firm quantitative predictions, the results of this study are useful to illustrate trends. Based on the results, the implications on the design and operation are discussed and priorities are determined for the R&D needed to reduce the remaining uncertainties.

Assessment of erosion of the ITER divertor targets during type I ELMs

International Nuclear Information System (INIS)

Federici, G; Loarte, A; Strohmayer, G

2003-01-01

This paper presents the results of a preliminary assessment conducted to estimate the thermal response and erosion lifetime of the ITER divertor targets clad either with carbon-fibre composite or tungsten during type I ELMs. The one-dimensional thermal/erosion model, used for the analyses, is briefly described. It includes all the key surface heat transfer processes such as evaporation, melting, and radiation, and their interaction with the bulk thermal response, and it is based on an implicit finite-difference scheme, which allows for temperature-dependent material properties. The cases analysed clarify the influence of several ELM parameters on the heat transfer and erosion processes at the target (i.e. characteristic plasma ELM energy loss from the pedestal, fraction of the energy reaching the divertor, broadening of the strike-points during ELMs, duration and waveform of the ELM heat load) and design/material parameters (i.e. inclination of the target, type and thickness of the armour material, and for tungsten only, fraction of the melt layer loss). Comparison is made between cases where all ELMs are characterized by the same fixed averaged parameters, and cases where instead the characteristic parameters of each ELM are evaluated in a random fashion by using a standard Monte Carlo technique, based on distributions of some of the variables of interest derived from experiments in today's machines. Although uncertainties rule out providing firm quantitative predictions, the results of this study are useful to illustrate trends. Based on the results, the implications on the design and operation are discussed and priorities are determined for the R and D needed to reduce the remaining uncertainties

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

Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation.

Science.gov (United States)

Bald, Tobias; Landsberg, Jennifer; Lopez-Ramos, Dorys; Renn, Marcel; Glodde, Nicole; Jansen, Philipp; Gaffal, Evelyn; Steitz, Julia; Tolba, Rene; Kalinke, Ulrich; Limmer, Andreas; Jönsson, Göran; Hölzel, Michael; Tüting, Thomas

2014-06-01

Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell-poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4(R24C) mice, which imitate human immune cell-poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies. Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell-poor tumors to cellular immune surveillance. ©2014 American Association for Cancer Research.

Targeted delivery of curcumin for treating type 2 diabetes.

Science.gov (United States)

Maradana, Muralidhara Rao; Thomas, Ranjeny; O'Sullivan, Brendan J

2013-09-01

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Rude' e, J.M.; Friedberg, E.C.

1977-03-01

Rates of semiconservative DNA synthesis have been investigated in asynchronous xeroderma pigmentosum (XP), XP variant, and normal human skin fibroblasts using the technique of cellular autoradiography. In unirradiated cells, no differences in DNA synthesis rates were detected among the three cell strains. Exposure to uv radiation caused the rate of DNA synthesis to decrease for at least three hours in all three cell strains. In the normal cell strain, recovery of the DNA synthetic rate occurred at later times following a uv fluence of 5 J/m2. At this same uv fluence, recovery was absent in classical XP cells during a 24 h post-irradiation period while it was slower than normal in XP variant cells. When the uv fluence to classical XP and XP variant cells was reduced so that survival in all three cell strains was approximately the same (25%), recovery of the DNA synthetic rate was similar in all three cell strains. These results are discussed in terms of current models of DNA replication in uv-irradiated cells and indicate: (1) that pyrimidine dimers are very effective blocks to DNA synthesis and (2) that there is no inherent defect in semi-conservative DNA synthesis in either classical XP or XP variant cells which is independent of a defect in DNA repair capacity.

Small D-type asteroids in the NEO population: new targets for space missions

Science.gov (United States)

Barucci, Maria Antonietta; Perna, D.; Popescu, M.; Fornasier, S.; Doressoundiram, A.; Lantz, C.; Merlin, F.; Fulchignoni, M.; Dotto, E.; Kanuchova, S.

2018-06-01

In the framework of the Near Earth Objects (NEOs) observational campaign carried out within the NEOShield-2 project, we identify nine new small D-type asteroids with estimated diameter less than 600 m. The link with meteorites for this class of asteroids is weak and the best fit obtained is with the Tagish Lake meteorite for seven of them. D-type asteroids are believed to contain the most pristine material of the Solar system and could have delivered the pre-biotic material to the Earth. Our results double the known sample of the D-types in the NEO population and triple the candidates of this class for a sample-return mission (at very low ΔV). Our finding increases considerably the number of targets for sample-return mission. A sample-return mission to a D-type asteroid will provide a major progress in understanding the early history of the Solar system and to investigate the origin of life on the Earth.

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

A new type of liquid-3He target system using small mechanical refrigerators

International Nuclear Information System (INIS)

Kato, S.; Kobayashi, K.; Maruyama, K.; Okuno, H.; Konno, O.; Suda, T.; Maki, T.; Asami, H.; Koizumi, T.

1991-04-01

A new type of liquid- 3 He target has been developed for photoabsorption experiments at intermediate energies. Using the cooling power of liquid 4 He at reduced vapour pressure, 3 He gas is liquefied into a cylindrical target cell of 180 ml and is maintained at 2.0 K during the experiment. Evaporated 4 He gas is evacuated by a rotary pump and returned into the 4 He bath in the cryostat, where two small mechanical refrigerators with cooling capacities of 3 W at 4.3 K and 10 W at 20 K are operated for the purpose of 4 He recondensation. A maintenance-free operation of more than 1,000 hours has become possible by adopting the 4 He circulation system. (author)

Targeting nocturnal hypertension in type 2 diabetes mellitus.

Science.gov (United States)

Rossen, Niklas Blach; Knudsen, Søren Tang; Fleischer, Jesper; Hvas, Anne-Mette; Ebbehøj, Eva; Poulsen, Per Løgstrup; Hansen, Klavs Würgler

2014-11-01

Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; Pdiabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention. © 2014 American Heart Association, Inc.

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.

RNA and DNA Targeting by a Reconstituted Thermus thermophilus Type III-A CRISPR-Cas System.

Directory of Open Access Journals (Sweden)

Tina Y Liu

Full Text Available CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated systems are RNA-guided adaptive immunity pathways used by bacteria and archaea to defend against phages and plasmids. Type III-A systems use a multisubunit interference complex called Csm, containing Cas proteins and a CRISPR RNA (crRNA to target cognate nucleic acids. The Csm complex is intriguing in that it mediates RNA-guided targeting of both RNA and transcriptionally active DNA, but the mechanism is not well understood. Here, we overexpressed the five components of the Thermus thermophilus (T. thermophilus Type III-A Csm complex (TthCsm with a defined crRNA sequence, and purified intact TthCsm complexes from E. coli cells. The complexes were thermophilic, targeting complementary ssRNA more efficiently at 65°C than at 37°C. Sequence-independent, endonucleolytic cleavage of single-stranded DNA (ssDNA by TthCsm was triggered by recognition of a complementary ssRNA, and required a lack of complementarity between the first 8 nucleotides (5' tag of the crRNA and the 3' flanking region of the ssRNA. Mutation of the histidine-aspartate (HD nuclease domain of the TthCsm subunit, Cas10/Csm1, abolished DNA cleavage. Activation of DNA cleavage was dependent on RNA binding but not cleavage. This leads to a model in which binding of an ssRNA target to the Csm complex would stimulate cleavage of exposed ssDNA in the cell, such as could occur when the RNA polymerase unwinds double-stranded DNA (dsDNA during transcription. Our findings establish an amenable, thermostable system for more in-depth investigation of the targeting mechanism using structural biology methods, such as cryo-electron microscopy and x-ray crystallography.

RNA and DNA Targeting by a Reconstituted Thermus thermophilus Type III-A CRISPR-Cas System.

Science.gov (United States)

Liu, Tina Y; Iavarone, Anthony T; Doudna, Jennifer A

2017-01-01

CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) systems are RNA-guided adaptive immunity pathways used by bacteria and archaea to defend against phages and plasmids. Type III-A systems use a multisubunit interference complex called Csm, containing Cas proteins and a CRISPR RNA (crRNA) to target cognate nucleic acids. The Csm complex is intriguing in that it mediates RNA-guided targeting of both RNA and transcriptionally active DNA, but the mechanism is not well understood. Here, we overexpressed the five components of the Thermus thermophilus (T. thermophilus) Type III-A Csm complex (TthCsm) with a defined crRNA sequence, and purified intact TthCsm complexes from E. coli cells. The complexes were thermophilic, targeting complementary ssRNA more efficiently at 65°C than at 37°C. Sequence-independent, endonucleolytic cleavage of single-stranded DNA (ssDNA) by TthCsm was triggered by recognition of a complementary ssRNA, and required a lack of complementarity between the first 8 nucleotides (5' tag) of the crRNA and the 3' flanking region of the ssRNA. Mutation of the histidine-aspartate (HD) nuclease domain of the TthCsm subunit, Cas10/Csm1, abolished DNA cleavage. Activation of DNA cleavage was dependent on RNA binding but not cleavage. This leads to a model in which binding of an ssRNA target to the Csm complex would stimulate cleavage of exposed ssDNA in the cell, such as could occur when the RNA polymerase unwinds double-stranded DNA (dsDNA) during transcription. Our findings establish an amenable, thermostable system for more in-depth investigation of the targeting mechanism using structural biology methods, such as cryo-electron microscopy and x-ray crystallography.

Facilitation of syngeneic stem cell engraftment by anti-class I monoclonal antibody pretreatment of unirradiated recipients

International Nuclear Information System (INIS)

Voralia, M.; Semeluk, A.; Wegmann, T.G.

1987-01-01

We have established a murine model of syngeneic bone marrow transplantation based on the use of monoclonal antibody as the sole conditioning regimen in unirradiated recipients. Administration of a single injection of monoclonal antibody directed against major histocompatibility complex-encoded class I determinants facilitated permanent hemopoietic stem cell engraftment without any apparent side-effects. Whereas untreated hosts exhibited a maximal chimerism of 15% at donor cell doses of up to 12 X 10(7) bone marrow cells, pretreatment by 2 mg of anti-class I antibody one week prior to transplantation of 3 X 10(7) syngeneic bone marrow cells resulted in a mean donor representation of about 80%. The antibody can be given up to four weeks prior to transplantation, and the degree of donor engraftment observed is a function of the dose of antibody administered. The fact that specific antibody enhanced engraftment in two strain combinations indicates that antibody is the active agent in facilitating engraftment and that facilitation is not strain-restricted. Anti-class I antibodies of the IgG2a, but not IgG1, isotype are effective in promoting engraftment. Although the isotype requirement suggests a role for antibody-mediated cytotoxicity in promoting stem cell engraftment, the extensive time-frame of facilitation suggests that other effects of the antibody may also be involved. The model of syngeneic bone marrow transplantation we describe here will be useful in studying the mechanisms regulating stem cell engraftment and may have potential clinical application as an approach to autologous marrow transplantation

PROPERTIES OF 42 SOLAR-TYPE KEPLER TARGETS FROM THE ASTEROSEISMIC MODELING PORTAL

Energy Technology Data Exchange (ETDEWEB)

Metcalfe, T. S.; Mathur, S. [Space Science Institute, 4750 Walnut Street Suite 205, Boulder, CO 80301 (United States); Creevey, O. L. [Institut d' Astrophysique Spatiale, Université Paris XI, UMR 8617, CNRS, Batiment 121, F-91405 Orsay Cedex (France); Doğan, G.; Christensen-Dalsgaard, J.; Karoff, C.; Trampedach, R. [Stellar Astrophysics Centre, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C (Denmark); Xu, H. [Computational and Information Systems Laboratory, NCAR, P.O. Box 3000, Boulder, CO 80307 (United States); Bedding, T. R.; Benomar, O. [Sydney Institute for Astronomy (SIfA), School of Physics, University of Sydney, NSW 2006 (Australia); Chaplin, W. J.; Campante, T. L.; Davies, G. R. [School of Physics and Astronomy, University of Birmingham, Birmingham B15 2TT (United Kingdom); Brown, B. P. [Department of Astronomy and Center for Magnetic Self Organization in Laboratory and Astrophysical Plasmas, University of Wisconsin, Madison, WI 53706 (United States); Buzasi, D. L. [Department of Chemistry and Physics, Florida Gulf Coast University, Fort Myers, FL 33965 (United States); Çelik, Z. [Ege University, Department of Astronomy and Space Sciences, Bornova, 35100, Izmir (Turkey); Cunha, M. S. [Centro de Astrofísica e Faculdade de Ciências, Universidade do Porto, Rua das Estrelas, 4150-762, Porto (Portugal); Deheuvels, S. [Université de Toulouse, UPS-OMP, IRAP, Toulouse (France); Derekas, A. [Konkoly Observatory, MTA CSFK, H-1121 Budapest, Konkoly Thege M. út 15-17 (Hungary); Mauro, M. P. Di [INAF-IAPS Istituto di Astrofisica e Planetologia Spaziali, Via del Fosso del Cavaliere 100, I-00133 Roma (Italy); and others

2014-10-01

Recently the number of main-sequence and subgiant stars exhibiting solar-like oscillations that are resolved into individual mode frequencies has increased dramatically. While only a few such data sets were available for detailed modeling just a decade ago, the Kepler mission has produced suitable observations for hundreds of new targets. This rapid expansion in observational capacity has been accompanied by a shift in analysis and modeling strategies to yield uniform sets of derived stellar properties more quickly and easily. We use previously published asteroseismic and spectroscopic data sets to provide a uniform analysis of 42 solar-type Kepler targets from the Asteroseismic Modeling Portal. We find that fitting the individual frequencies typically doubles the precision of the asteroseismic radius, mass, and age compared to grid-based modeling of the global oscillation properties, and improves the precision of the radius and mass by about a factor of three over empirical scaling relations. We demonstrate the utility of the derived properties with several applications.

Study on the behavior of unirradiated light water reactor fuel with iodine-127 under the reactivity initiated accident (RIA) conditions

International Nuclear Information System (INIS)

Sasajima, Hideo; Yanagisawa, Kazuaki; Kanazawa, Hiroyuki

1988-07-01

In a light water reactor fuel, a stress arised from pellet-cladding interaction (PCI) will have possibility to cause stress corrosion claddling (PCI failure) under an environment of corrosive fission product ; line iodine. A pulse irradiation experiment by NSRR was carried out to examine whether or not an unirradiated NSRR standard fuel rod in which 1.3 mg (33 x 10 -6 g/cm 2 ) of iodine was artificially filled could cause the PCI failure. Obtained results are: (1) The fuel rods with iodine did not fail both at deposited energy levels of 268 and 280 cal/g · UO 2 . On the other hand, the fuel rods without iodine failed at the same energy levels due to thinning of the cladding wall thickness. Within this experimental scope, PCI-failure did not occur on iodine filled fuel rods. (2) At a periphery of the fuel pellet of iodine filled rod, an uniform torus ring was formed. The torus ring consisted of an equi-axed large grains at 268 cal/g · UO 2 and a columnar ones at 280 cal/g · UO 2 . The torus ring was not formed in the fuel without iodine. (author)

A type III-B CRISPR-Cas effector complex mediating massive target DNA destruction.

Science.gov (United States)

Han, Wenyuan; Li, Yingjun; Deng, Ling; Feng, Mingxia; Peng, Wenfang; Hallstrøm, Søren; Zhang, Jing; Peng, Nan; Liang, Yun Xiang; White, Malcolm F; She, Qunxin

2017-02-28

The CRISPR (clustered regularly interspaced short palindromic repeats) system protects archaea and bacteria by eliminating nucleic acid invaders in a crRNA-guided manner. The Sulfolobus islandicus type III-B Cmr-α system targets invading nucleic acid at both RNA and DNA levels and DNA targeting relies on the directional transcription of the protospacer in vivo. To gain further insight into the involved mechanism, we purified a native effector complex of III-B Cmr-α from S. islandicus and characterized it in vitro. Cmr-α cleaved RNAs complementary to crRNA present in the complex and its ssDNA destruction activity was activated by target RNA. The ssDNA cleavage required mismatches between the 5΄-tag of crRNA and the 3΄-flanking region of target RNA. An invader plasmid assay showed that mutation either in the histidine-aspartate acid (HD) domain (a quadruple mutation) or in the GGDD motif of the Cmr-2α protein resulted in attenuation of the DNA interference in vivo. However, double mutation of the HD motif only abolished the DNase activity in vitro. Furthermore, the activated Cmr-α binary complex functioned as a highly active DNase to destroy a large excess DNA substrate, which could provide a powerful means to rapidly degrade replicating viral DNA. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment.

Directory of Open Access Journals (Sweden)

Ruben R Bender

2016-06-01

Full Text Available Receptor-targeted lentiviral vectors (LVs can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance. Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4 was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.

The effect of sedimentation background of depression target stratum containing mineral in Erlian basin, Ulanqab to uranium mineralization type

International Nuclear Information System (INIS)

Kang Shihu; Jiao Yangquan; Men Hong; Kuang Wenzhan

2012-01-01

The ore bearing stratum in depression of Ulanqab contains target stratum of lower cretaceous Saihan formation, upper cretaceous Erlian formation, paleogene system etc. The uranium mineralization type which have found by now contains sandstone type, mudstone type and coal petrography. The genetic type of mineral deposit contains paleovalley-type, reformed type after superposition with sedimentation and diagenesis by sedimentation. Uranium mineralization of both the natural type and genetic type have close relationship with its ore bearing stratum. Different geological background forms different sedimentary system combination, and different sedimentary system combination forms different uranium mineralization type. (authors)

Nitric oxide mediated bystander responses induced by microbeam targeted cells

International Nuclear Information System (INIS)

Shao, C.; Prise, K.M.; Folkard, M.; Michael, B.D.

2003-01-01

Considerable evidence has recently been accumulated in support of the existence of a 'bystander effect', which cells having received no irradiation show biological consequences from their vicinal irradiated cells. The application of microbeams is providing new insights into the radiation-induced bystander effect. The present study found that when a fraction of radioresistant human glioblastoma cells were individually targeted with a precise number of helium ions generated from the Gray Cancer Institute Charged Particle Microbeam, micronucleus (MN) induction significantly exceeded the expected value that was calculated from the number of MN observed when all of the cells were targeted assuming no bystander effect occurring. Even when only a single cell within a population was hit by one helium ion, the MN induction in the population could be increased by 16%. These results provide direct evidence of radiation-induced bystander effect. Moreover, MN was effectively induced in the unirradiated primary human fibroblasts and glioblastoma cells either co-cultured with irradiated cells or treated with the medium harvested from irradiated cells, indicating a signal molecule was produced from the irradiated cells. However, when c-PTIO, a nitric oxide (NO)-specific scavenger, was present in the medium during and after irradiation until MN analysis, the production of MN in all of the above cases was reduced to low levels. Consequently, NO plays an important role in the radiation-induced bystander effect

Multi-targeted and aggressive treatment of patients with type 2 diabetes at high risk

DEFF Research Database (Denmark)

Gaede, P; Pedersen, O

2005-01-01

Results from many single risk factor intervention trials and the multi-targeted Steno-2 trial in the last few years have provided a strong case that management of type 2 diabetes in all age groups requires a structured and intensified approach that is far more than just glucocentric, an approach...... addressing additional cardiovascular risk factors including hypertension, dyslipidaemia, sedentary behaviour, smoking and dietary habits causing insulin resistance and pro-inflammation. This type of integrated therapy applied for almost 8 years to high-risk type 2 diabetic patients has cut the relative risk......-driven polypharmacy and simple but focused behaviour modelling with continuous education, motivation and trouble-shooting for treatment barriers identified for the patient and the care giver. It is high time we transfer these experiences and major health benefits gained in the 'green house' of controlled clinical...

The Pseudomonas syringae type III effector HopG1 targets mitochondria, alters plant development, and suppresses plant innate immunity

Science.gov (United States)

Block, Anna; Guo, Ming; Li, Guangyong; Elowsky, Christian; Clemente, Thomas E.; Alfano, James R.

2009-01-01

Summary The bacterial plant pathogen Pseudomonas syringae uses a type III protein secretion system to inject type III effectors into plant cells. Primary targets of these effectors appear to be effector-triggered immunity (ETI) and pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI). The type III effector HopG1 is a suppressor of ETI that is broadly conserved in bacterial plant pathogens. Here we show that HopG1 from P. syringae pv. tomato DC3000 also suppresses PTI. Interestingly, HopG1 localizes to plant mitochondria, suggesting that its suppression of innate immunity may be linked to a perturbation of mitochondrial function. While HopG1 possesses no obvious mitochondrial signal peptide, its N-terminal two-thirds was sufficient for mitochondrial localization. A HopG1-GFP fusion lacking HopG1’s N-terminal 13 amino acids was not localized to the mitochondria reflecting the importance of the N-terminus for targeting. Constitutive expression of HopG1 in Arabidopsis thaliana, Nicotiana tabacum (tobacco) and Lycopersicon esculentum (tomato) dramatically alters plant development resulting in dwarfism, increased branching and infertility. Constitutive expression of HopG1 in planta leads to reduced respiration rates and an increased basal level of reactive oxygen species. These findings suggest that HopG1’s target is mitochondrial and that effector/target interaction promotes disease by disrupting mitochondrial functions. PMID:19863557

Role of biologics targeting type 2 airway inflammation in asthma : What have we learned so far?

NARCIS (Netherlands)

Parulekar, Amit D.; Diamant, Zuzana; Hanania, Nicola A.

Purpose of reviewSevere asthma is a heterogeneous syndrome that can be classified into distinct phenotypes and endotypes. In the type 2 (T2)-high endotype, multiple cytokines are produced that lead to eosinophilic inflammation. These cytokines and their receptors are targets for biologic therapies

The performance of a fiber optic displacement sensor for different types of probes and targets

International Nuclear Information System (INIS)

Yasin, M; Harun, S W; Abdul-Rashid, H A; Kusminarto; Karyono; Ahmad, H

2008-01-01

A simple fiber optic displacement sensor is presented using a multimode plastic bundled fiber and the intensity modulation technique. The performance of the sensor is compared for different types of probes and targets. The probe with the largest receiving core diameter demonstrates the highest linearity range, and increasing the number of receiving cores increases the sensitivity of the sensor. With a stainless steel target and the concentric bundled fiber with 16 receiving fibers as a probe, the sensitivity of the sensor is found to be 0.0220 mV/μm over 150 to 550 μm range and – 0.0061 mV/μm over 1100 to 2000 μm range. The target with a higher reflectivity shows a higher sensitivity. The linearity range for the front slope is almost similar for all targets tested. However, for the back slope, lower reflectivity objects have a relatively higher linearity range with the highest range of 1600 μm being obtained using plastic and aluminum targets. The simplicity of the design, high degree of sensitivity, dynamic range, non-contact measurement and low cost of the fabrication make it suitable for applications in industries for position control and micro displacement measurement in the hazardous regions

Progress towards discovery of antifibrotic drugs targeting synthesis of type I collagen

KAUST Repository

Fritz, Dillon Jeffery; Cai, Le; Stefanovic, Lela; Stefanovic, Branko

2011-01-01

Type I collagen is the most abundant protein in human body. Fibrosis is characterized by excessive synthesis of type I collagen in parenchymal organs. It is a leading cause of morbidity and mortality worldwide, about 45% of all natural deaths are attributable to some fibroproliferative disease. There is no cure for fibrosis. To find specific antifibrotic therapy targeting type I collagen, critical molecular interactions regulating its synthesis must be elucidated. Type I and type III collagen mRNAs have a unique sequence element at the 5' end, the 5' stem-loop. This stem-loop is not found in any other mRNA. We cloned LARP6 as the protein which binds collagen 5' stem-loop with high affinity and specificity. Mutation of the 5' stem-loop or knock down of LARP6 greatly diminishes collagen expression. Mice with mutation of the 5' stem-loop are resistant to development of liver fibrosis. LARP6 associates collagen mRNAs with filaments composed of nonmuscle myosin; disruption of these filaments abolishes synthesis of type I collagen. Thus, LARP6 dependent collagen synthesis is the specific mechanism of high collagen expression seen in fibrosis. We developed fluorescence polarization (FP) method to screen for drugs that can inhibit binding of LARP6 to 5' stem-loop RNA. FP is high when LARP6 is bound, but decreases to low levels when the binding is competed out. Thus, by measuring decrease in FP it is possible to identify chemical compounds that can dissociate LARP6 from the 5' stem-loop. The method is simple, fast and suitable for high throughput screening. © 2011 Bentham Science Publishers Ltd.

Progress towards discovery of antifibrotic drugs targeting synthesis of type I collagen

KAUST Repository

Fritz, Dillon Jeffery

2011-08-01

Type I collagen is the most abundant protein in human body. Fibrosis is characterized by excessive synthesis of type I collagen in parenchymal organs. It is a leading cause of morbidity and mortality worldwide, about 45% of all natural deaths are attributable to some fibroproliferative disease. There is no cure for fibrosis. To find specific antifibrotic therapy targeting type I collagen, critical molecular interactions regulating its synthesis must be elucidated. Type I and type III collagen mRNAs have a unique sequence element at the 5\\' end, the 5\\' stem-loop. This stem-loop is not found in any other mRNA. We cloned LARP6 as the protein which binds collagen 5\\' stem-loop with high affinity and specificity. Mutation of the 5\\' stem-loop or knock down of LARP6 greatly diminishes collagen expression. Mice with mutation of the 5\\' stem-loop are resistant to development of liver fibrosis. LARP6 associates collagen mRNAs with filaments composed of nonmuscle myosin; disruption of these filaments abolishes synthesis of type I collagen. Thus, LARP6 dependent collagen synthesis is the specific mechanism of high collagen expression seen in fibrosis. We developed fluorescence polarization (FP) method to screen for drugs that can inhibit binding of LARP6 to 5\\' stem-loop RNA. FP is high when LARP6 is bound, but decreases to low levels when the binding is competed out. Thus, by measuring decrease in FP it is possible to identify chemical compounds that can dissociate LARP6 from the 5\\' stem-loop. The method is simple, fast and suitable for high throughput screening. © 2011 Bentham Science Publishers Ltd.

Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

Directory of Open Access Journals (Sweden)

M J Pont

Full Text Available Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage-restricted expression as potential targets for immunotherapy of hematological cancers.

Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes

DEFF Research Database (Denmark)

Sørensen, Rikke Kruse; Vienberg, Sara Gry; Vind, Birgitte F

2017-01-01

obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes. CONCLUSIONS....../INTERPRETATION: Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure...... that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established. METHODS...

Metallogenic geologic prerequisites of sandstone-type uranium deposits and target area selection. Taking Erlian and Ordos basins as examples

International Nuclear Information System (INIS)

Chen Fazheng

2002-01-01

Sandstone-type uranium deposit is the main target of recent uranium prospecting and exploration. According to the metallogenic characteristics, sandstone-type uranium deposits are divided into three groups: paleo-channel type, interlayer oxidation zone type and phreatic interlayer oxidation type. The author makes an analysis on the geologic prerequisites of the three types of uranium deposits, the similarities and difference, and preliminarily summarizes genetic models of different types of uranium deposits. Finally, taking Erlian and Ordos basins as examples, the author makes an evaluation and a strategic analysis on the uranium metallogenic prospect of the above two basins

Uranium exploration target selection for proterozoic iron oxide/breccia complex type deposits in India

International Nuclear Information System (INIS)

Dwivedy, K.K.; Sinha, K.K.

1997-01-01

Multimetal iron oxide/breccia complex (IOBC) type deposits exemplified by Olympic Dam in Australia, fall under low grade, large tonnage deposits. A multidisciplinary integrated exploration programme consisting of airborne surveys, ground geological surveys, geophysical and geochemical investigations and exploratory drilling, supported adequately by the state of the art analytical facilities, data processing using various software and digital image processing has shown moderate success in the identification of target areas for this type of deposits in the Proterozoic terrains of India. Intracratonic, anorogenic, continental rift to continental margin environment have been identified in a very wide spectrum of rock associations. The genesis and evolution of such associations during the Middle Proterozoic period have been reviewed and applied for target selection in the (i) Son-Narmada rift valley zone; (ii) areas covered by Dongargarh Supergroup of rocks in Madhya Pradesh; (iii) areas exposing ferruginous breccia in the western part of the Singhbhum Shear Zone (SSZ) around Lotapahar; (iv) Siang Group of rocks in Arunachal Pradesh; (v) Crystalline rocks of Garo Hills around Anek; and (vi) Chhotanagpur Gneissic complex in the Bahia-Ulatutoli tract of Ranchi Plateau. Of theses six areas, the Son-Narmada rift area appears to be the most promising area for IOBC type deposits. Considering occurrences of the uranium anomalies near Meraraich, Kundabhati, Naktu and Kudar and positive favourability criteria observed in a wide variety of rocks spatially related to the rifts and shears, certain sectors in Son-Narmada rift zone have been identified as promising for intense subsurface exploration. 20 refs, 4 figs, 1 tab

Tensile properties of unirradiated path A PCA

International Nuclear Information System (INIS)

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

1983-01-01

The tensile properties of PCA in the Al (solution annealed), A3 (25%-cold worked), and B2 (aged, cold worked, and reaged) conditions were determined from room temperature to 600 0 C. The tensile behavior of PCA-A1 and -A3 was generally similar to that of titanium-modified type 316 stainless steel with similar microstructures. The PCA-B2 was weaker than PCA-A3, especially above 500 0 C, but demonstrated slightly better ducility

Regulating the effects of GPR21, a novel target for type 2 diabetes

Science.gov (United States)

Leonard, Siobhán; Kinsella, Gemma K.; Benetti, Elisa; Findlay, John B. C.

2016-05-01

Type 2 diabetes is a chronic metabolic disorder primarily caused by insulin resistance to which obesity is a major contributor. Expression levels of an orphan G protein-coupled receptor (GPCR), GPR21, demonstrated a trend towards a significant increase in the epididymal fat pads of wild type high fat high sugar (HFHS)-fed mice. To gain further insight into the potential role this novel target may play in the development of obesity-associated type 2 diabetes, the signalling capabilities of the receptor were investigated. Overexpression studies in HEK293T cells revealed GPR21 to be a constitutively active receptor, which couples to Gαq type G proteins leading to the activation of mitogen activated protein kinases (MAPKs). Overexpression of GPR21 in vitro also markedly attenuated insulin signalling. Interestingly, the effect of GPR21 on the MAPKs and insulin signalling was reduced in the presence of serum, inferring the possibility of a native inhibitory ligand. Homology modelling and ligand docking studies led to the identification of a novel compound that inhibited GPR21 activity. Its effects offer potential as an anti-diabetic pharmacological strategy as it was found to counteract the influence of GPR21 on the insulin signalling pathway.

A study on density, porosity and grain size of unirradiated ROX fuels and simulated ROX fuels

International Nuclear Information System (INIS)

Yanagisawa, Kazuaki; Shirasu, Noriko; Ohmichi, Toshihiko

1999-05-01

The unirradiated ROX fuels made of (1) 23wt%PuO 2 -17wt%SZR-56wt%Al 2 O 3 -4wt%MgO (ROX-SZR) and (2) 20wt%PuO 2 -29wt%ThO 2 -48wt%Al 2 O 3 -3wt%MgO (ROX-ThO 2 ) were fabricated by JAERI. Additionally, 9 simulated ROX fuels (used UO 2 instead of PuO 2 ) were fabricated by NFI. Densities, porosity and grain sizes of those were studied. Obtained results are: (1) ROX fuels: The estimated theoretical density (TD) was 5.6g/cc for the ROX-SZR and 6.2g/cc for the ROX-ThO 2 . Those were about half of that in UO 2 (10.96g/cc). As-fabricated density determined was 4.6g/cc (82%TD) for the former and 5.2g/cc (83%TD) for the latter. The %TD of those was low than that of UO 2 (95%TD). One of main reason is that the ROX fuels were sintered at temperature of 1,400degC while UO 2 was sintered at temperature of 1,700degC. The average pore diameter was about 3 μm and the porosity was 17-18%, implying that the ROX fuels were resulted in containing a lot of small pores 2 . As-fabricated density determined in the present study was about 4.5-5.5g/cc. The %TD of the simulated ROX fuels ranged about 94-98%TD. They were in the same as that of UO 2 because as high sintering temperature of 1,750degC as UO 2 . The average pore diameter was about 4-8 μm and the porosity was <6%. Grain size was revealed to be about 1-4 μm. (author)

Effect of umuC mutations on targeted and untargeted ultraviolet mutagenesis in bacteriophage lambda

International Nuclear Information System (INIS)

Maenhaut-Michel, G.; Caillet-Fauquet, P.

1984-01-01

Mutagenesis of phage lambda towards clear-plaque (c + → c) results in two classes of mutants that can be distinguished genetically and morphologically. Indirect mutagenesis, i.e. mutagenesis of unirradiated phage lambdac + stimulated by the ultraviolet irradiation of the Escherichia coli host, results in mixed bursts (c/c + ) of turbid wild-type and clear=plaque mutant phages. Pure bursts of lambdac mutants are induced by irradiation of the phage genome. Irradiation of both phages and host bacteria stimulates the production of the two classes of mutant clones. It is shown that three different mutant alleles of the E. coli umuC gene only prevent the appearance of pure bursts of clear-plaque mutants, while mixed bursts are produced at least as frequently in umuC mutants as in the umuC + parent. (author)

Development of Techniques for Small Scale Indigenous 99Mo Production Using LEU Targets at ICN Pitesti-Romania [Country report: Romania

International Nuclear Information System (INIS)

2015-01-01

Initiation of the IAEA Coordinated Research Project (CRP) “Development Techniques for Small Scale Indigenous 99 Mo Production Using LEU Fission or Neutron Activation” during 2005 allowed Member States to participate through their research organization on contractor arrangement to accomplish the CRP objectives. Among these, the participating research organization Institute for Nuclear Research Pitesti Romania (ICN), was the beneficiary of financial support and Argonne National Laboratory assistance provided by US Department of Energy to the CRP for development of techniques for fission 99 Mo production based on LEU modified CINTICHEM process. The Agency’s role in this field was to assist in the transfer and adaptation of existing technology in order to disseminate a technique, which advances international non-proliferation objectives and promotes sustainable development needs, while also contributing to extend the production capacity for addressing supply shortages from the latest years. The Institute for Nuclear Research, considering the existing good conditions of infrastructure of the research reactor with suitable irradiation conditions for radioisotopes, a post irradiation laboratory with direct transfer of irradiated targets from the reactor and handling of high radioactive sources, and simultaneously the existence of an expanding internal market, decided to undertake the necessary steps in order to produce fission molybdenum. The Institute intends to develop the capability to respond to the domestic needs in cooperation with the IFINN–HH from Bucharest, which is able to perform the last step consisting in the loading of fission molybdenum on chromatography generators and dispensing to the final client. The primary scope of the project is the development of the necessary technological steps and chemical processing steps in order to be able to cover the entire process for fission molybdenum production at the required standard of purity

Precession electron diffraction for SiC grain boundary characterization in unirradiated TRISO fuel

International Nuclear Information System (INIS)

Lillo, T.M.; Rooyen, I.J. van; Wu, Y.Q.

2016-01-01

Highlights: • SiC grain orientation determined by TEM-based precession electron diffraction. • Orientation data improved with increasing TEM sample thickness. • Fraction of low angle grain boundaries lower from PED data than EBSD data. • Fractions of high angle and CSL-related boundaries similar to EBSD data. - Abstract: Precession electron diffraction (PED), a transmission electron microscopy-based technique, has been evaluated for the suitability for evaluating grain boundary character in the SiC layer of tristructural isotropic (TRISO) fuel. This work reports the effect of transmission electron microscope (TEM) lamella thickness on the quality of data and establishes a baseline comparison to SiC grain boundary characteristics, in an unirradiated TRISO particle, determined previously using a conventional electron backscatter diffraction (EBSD) scanning electron microscope (SEM)-based technique. In general, it was determined that the lamella thickness produced using the standard focused ion beam (FIB) fabrication process (∼80 nm), is sufficient to provide reliable PED measurements, although thicker lamellae (∼120 nm) were found to produce higher quality orientation data. Also, analysis of SiC grain boundary character from the TEM-based PED data showed a much lower fraction of low-angle grain boundaries compared to SEM-based EBSD data from the SiC layer of a TRISO-coated particle made using the same fabrication parameters and a SiC layer deposited at a slightly lower temperature from a surrogate TRISO particle. However, the fractions of high-angle and coincident site lattice (CSL)-related grain boundaries determined by PED are similar to those found using SEM-based EBSD. Since the grain size of the SiC layer of TRSIO fuel can be as small as 250 nm (Kirchhofer et al., 2013), depending on the fabrication parameters, and since grain boundary fission product precipitates in irradiated TRISO fuel can be nano-sized, the TEM-based PED orientation data

Original geochemical types and epigenetic alteration of rocks in prospecting target stratum for uranium deposit in the southeast of Songliao basin

International Nuclear Information System (INIS)

Lin Jinrong; Tian Hua; Dong Wenming; Xia Yuliang; Qi Daneng; Yao Shancong; Zheng Jiwei

2009-01-01

By comprehensive analysis on informations of regional geology and evaluating drillhole works of uranium resources in the southeast of Songliao basin, lithofacies-palaeogeography features, lithologies and sandbody characteristics of target layes in Quantou formation, Yaojia formation and Sifangtai formation have been basically found out. By research on geochemical environment of rocks in target layez, types of original geochemistry and epigenetic alteration have been identified and classified. The types of original geochemistry have been divided into types of original oxidation and original reduction, and the types of epigenetic alteration have been divided into types of reduction by oil-gas and coalbed gas and epigenetic oxidation. By comparative study on mineral and chemical characteristics of original geochemistry and epigenetic oxidation, identification marks for oil-gas and coalbed gas reduced epigenetic oxidation have been proposed. It is proposed that uranium was strongly pre-concentrated in original sandstone that bearing carboniferous matter, and reduction by oil-gas and coalbed gas made uranium superimpose and concentrate in alterated rocks. (authors)

Dependence of Au- production upon the target work function in a plasma-sputter-type negative ion source

International Nuclear Information System (INIS)

Okabe, Yushirou; Sasao, Mamiko; Fujita, Junji; Yamaoka, Hitoshi; Wada, Motoi.

1991-01-01

A method to measure the work function of the target surface in a plasma-sputter-type negative ion source has been developed. The method can determine the work function by measuring the photoelectric current induced by two lasers (He-Ne, Ar + laser). The dependence of Au - production upon the work function of the target surface in the ion source was studied using this method. The time variation of the target work function and Au - production rate were measured during the cesium coverage decrease due to the plasma ion sputtering. The observed minimum work function of a cesiated gold surface in an Ar plasma was 1.3 eV. At the same time, the negative ion production rate (Au - current/target current) took the maximum value. The negative ion production rate indicated the same dependence on the incident ion energy as that of the sputtering rate when the work function was constant. (author)

Comparison of ring compression testing to three point bend testing for unirradiated ZIRLO cladding

Energy Technology Data Exchange (ETDEWEB)

None, None

2015-04-01

Safe shipment and storage of nuclear reactor discharged fuel requires an understanding of how the fuel may perform under the various conditions that can be encountered. One specific focus of concern is performance during a shipment drop accident. Tests at Savannah River National Laboratory (SRNL) are being performed to characterize the properties of fuel clad relative to a mechanical accident condition such as a container drop. Unirradiated ZIRLO tubing samples have been charged with a range of hydride levels to simulate actual fuel rod levels. Samples of the hydrogen charged tubes were exposed to a radial hydride growth treatment (RHGT) consisting of heating to 400°C, applying initial hoop stresses of 90 to 170 MPa with controlled cooling and producing hydride precipitates. Initial samples have been tested using both a) ring compression test (RCT) which is shown to be sensitive to radial hydride and b) three-point bend tests which are less sensitive to radial hydride effects. Hydrides are generated in Zirconium based fuel cladding as a result of coolant (water) oxidation of the clad, hydrogen release, and a portion of the released (nascent) hydrogen absorbed into the clad and eventually exceeding the hydrogen solubility limit. The orientation of the hydrides relative to the subsequent normal and accident strains has a significant impact on the failure susceptability. In this study the impacts of stress, temperature and hydrogen levels are evaluated in reference to the propensity for hydride reorientation from the circumferential to the radial orientation. In addition the effects of radial hydrides on the Quasi Ductile Brittle Transition Temperature (DBTT) were measured. The results suggest that a) the severity of the radial hydride impact is related to the hydrogen level-peak temperature combination (for example at a peak drying temperature of 400°C; 800 PPM hydrogen has less of an impact/ less radial hydride fraction than 200 PPM hydrogen for the same thermal

Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.

Science.gov (United States)

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-05-05

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic type III neuregulin1-ErbB signaling targets alpha7 nicotinic acetylcholine receptors to axons.

Science.gov (United States)

Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W; Talmage, David A

2008-06-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

Science.gov (United States)

Hancock, Melissa L.; Canetta, Sarah E.; Role, Lorna W.; Talmage, David A.

2008-01-01

Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of α7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface α7 nAChRs, which results from a redistribution of preexisting intracellular pools of α7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting α7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function. PMID:18458158

In vivo type 2 cannabinoid receptor-targeted tumor optical imaging using a near infrared fluorescent probe.

Science.gov (United States)

Zhang, Shaojuan; Shao, Pin; Bai, Mingfeng

2013-11-20

The type 2 cannabinoid receptor (CB2R) plays a vital role in carcinogenesis and progression and is emerging as a therapeutic target for cancers. However, the exact role of CB2R in cancer progression and therapy remains unclear. This has driven the increasing efforts to study CB2R and cancers using molecular imaging tools. In addition, many types of cancers overexpress CB2R, and the expression levels of CB2R appear to be associated with tumor aggressiveness. Such upregulation of the receptor in cancer cells provides opportunities for CB2R-targeted imaging with high contrast and for therapy with low side effects. In the present study, we report the first in vivo tumor-targeted optical imaging using a novel CB2R-targeted near-infrared probe. In vitro cell fluorescent imaging and a competitive binding assay indicated specific binding of NIR760-mbc94 to CB2R in CB2-mid delayed brain tumor (DBT) cells. NIR760-mbc94 also preferentially labeled CB2-mid DBT tumors in vivo, with a 3.7-fold tumor-to-normal contrast enhancement at 72 h postinjection, whereas the fluorescence signal from the tumors of the mice treated with NIR760 free dye was nearly at the background level at the same time point. SR144528, a CB2R competitor, significantly inhibited tumor uptake of NIR760-mbc94, indicating that NIR760-mbc94 binds to CB2R specifically. In summary, NIR760-mbc94 specifically binds to CB2R in vitro and in vivo and appears to be a promising molecular tool that may have great potential for use in diagnostic imaging of CB2R-positive cancers and therapeutic monitoring as well as in elucidating the role of CB2R in cancer progression and therapy.

Radition-induced genetic damage in plutella xylostella

International Nuclear Information System (INIS)

Ismail bin Bahari; Mahani binti Mohamad

1993-01-01

Radiation-induced chromosomal aberrations in progenies of irradiated Plutella xylostella was determined in a F1 sterility study. A total of 4 types of crosses (irradiated males against unirradiated females, irradiated females against unirradiated males, both parents irradiated and normal) were made following gamma irradiation at the pupal stage. Testes squash preparations made from F1 male larvae revealed 3 main types of chromosomal abberations induced by doses of 100, 150 and 200 Gy. Results obtained indicate the possibility of using chromosome translocations as the genetic marker

FUNCTIONAL GENOMICS IDENTIFIES TIS21-DEPENDENT MECHANISMS AND PUTATIVE CANCER DRUG TARGETS UNDERLYING MEDULLOBLASTOMA SHH-TYPE DEVELOPMENT

Directory of Open Access Journals (Sweden)

Giulia Gentile

2016-11-01

Full Text Available We have recently generated a novel medulloblastoma (MB mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1+-Tis21KO.ts main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs. By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced. Here, we further analyzed the genes deregulated in a Tis21-dependent manner (Patched1+-is21 wild-type versus Ptch1+-Tis21 knockout, among which are a number of down-regulated tumor inhibitors and up-regulated tumor facilitators, focusing on pathways potentially involved in the tumorigenesis and on putative new drug targets.The data analysis using bioinformatic tools revealed: i a link between the Shh signaling and the Tis21-dependent impairment of the GCPs migration, through a Shh-dependent deregulation of the clathrin-mediated chemotaxis operating in the primary cilium through the Cxcl3-Cxcr2 axis; ii a possible lineage shift of Shh-type GCPs toward retinal precursor phenotype the neural cell type involved in group 3 MB; iii the identification of a subset of putative drug targets for MB, involved, among the others, in the regulation of Hippo signaling and centrosome assembly. Finally, our findings define also the role of Tis21 in the regulation of gene expression, through epigenetic and RNA processing mechanisms, influencing the fate of the GCPs.

Surface modifications caused by a swift heavy ion irradiation on crystalline p-type gallium antimonide

Science.gov (United States)

Jadhav, Vidya

2015-09-01

Surface modifications caused by a swift heavy ion irradiation on crystalline p-type gallium antimonide crystal have been reported. Single crystal, 1 0 0> orientations and ∼500 μm thick p-type GaSb samples with carrier concentration of 3.30 × 1017 cm-3 were irradiated at 100 MeV Fe7+ ions. We have used 15UD Pelletron facilities at IUAC with varying fluences of 5 × 1010-1 × 1014 ions cm-2. The effects of irradiation on these samples have been investigated using, spectroscopic ellipsometry, atomic force microscopy and ultraviolet-visible-NIR spectroscopy techniques. Ellipsometry parameters, psi (Ψ) and delta (Δ) for the unirradiated sample and samples irradiated with different fluences were recorded. The data were fit to a three phase model to determine the refractive index and extinction coefficient. The refractive index and extinction coefficient for various fluences in ultraviolet, visible, and infrared, regimes were evaluated. Atomic force microscopy has been used to study these surface modifications. In order to have more statistical information about the surface, we have plotted the height structure histogram for all the samples. For unirradiated sample, we observed the Gaussian fitting. This result indicates the more ordered height structure symmetry. Whereas for the sample irradiated with the fluence of 1 × 1013, 5 × 1013 and 1 × 1014 ions cm-2, we observed the scattered data. The width of the histogram for samples irradiated up to the fluence of 1 × 1013 ion cm-2 was found to be almost same however it decreased at higher fluence. UV reflectance spectra of the sample irradiated with increasing fluences exhibit three peaks at 292, 500 and 617 nm represent the high energy GaSb; E1, E1 + Δ and E2 band gaps in all irradiated samples.

Targeting TGF-β Signaling by Antisense Oligonucleotide-mediated Knockdown of TGF-β Type I Receptor

Directory of Open Access Journals (Sweden)

Dwi U Kemaladewi

2014-01-01

Full Text Available Duchenne muscular dystrophy (DMD is caused by lack of functional dystrophin and results in progressive myofiber damage and degeneration. In addition, impaired muscle regeneration and fibrosis contribute to the progressive pathology of DMD. Importantly, transforming growth factor-β (TGF-β is implicated in DMD pathology and is known to stimulate fibrosis and inhibit muscle regeneration. In this study, we present a new strategy to target TGF-β signaling cascades by specifically inhibiting the expression of TGF-β type I receptor TGFBR1 (ALK5. Antisense oligonucleotides (AONs were designed to specifically induce exon skipping of mouse ALK5 transcripts. AON-induced exon skipping of ALK5 resulted in specific downregulation of full-length receptor transcripts in vitro in different cell types, repression of TGF-β activity, and enhanced C2C12 myoblast differentiation. To determine the effect of these AONs in dystrophic muscles, we performed intramuscular injections of ALK5 AONs in mdx mice, which resulted in a decrease in expression of fibrosis-related genes and upregulation of Myog expression compared to control AON-injected muscles. In summary, our study presents a novel method to target TGF-β signaling cascades with potential beneficial effects for DMD.

The Effect of E-Selen Antioxidant on the Fatty Acids Content of the Homogenate of Unirradiated and Irradiated Pupae of Ceratitis Capitata

International Nuclear Information System (INIS)

Zaghloul, Y.S.; Abbassy, S.A.; Elakhdar, E.A.H.; Elakhdar, E.A.H.

2011-01-01

As antioxidant E-selen was added to the larval artificial diets of the Mediterranean fruit fly, Ceratitis capitata. The produced full grown pupae were exposed to gamma rays at dose rate of 90 Gy. The fatty acid contents of the normal and irradiated insects were analyzed to test to what extent, the uptake of the antioxidant will ameliorate the physiological damage induced to the medfly pupae, as a result of their exposure to irradiation. The results obtained by using Gas-liquid chromatography of fatty acid methyl esters, showed the palmitic and oleic acids to be the most predominant fatty acids in all pupal homogenates in both normal and irradiated pupae, either by the uptake of doses of the E-selen or without. The uptake of E-Selen with a dose of 0.3 mg led to a complete absence of the lauric and myristic acids in the homogenates of the unirradiated pupae of the medfly. This absence of lauric and myristic acids was accompanied by a decrease in the concentrations of the palmitic and linoleic acids reaching 25.17% and 32.98%, respectively as compared to pupae without the uptake of antioxidant. The concentrations of both the stearic and oleic acids showed an obvious increment reaching 199.22% and 58.94%, respectively, relative to those reared on the defined media and no added E.Selen. Exposure of the pupae to a dose of 90 Gy, resulted in an increment in the concentrations of the saturated lauric and myristic acid reaching 96.77% and 34.07%, respectively, relative to the untreated ones. While, at the same dose level, there were decrements in the concentrations of the palmitic, stearic, oleic and linoleic acids with percentages reaching 6.4, 9.22, 3.65 and 1.15%, respectively as compared to unirradiated controls. Irradiation of the pupae with sterilizing dose (90 Gy) after up taking the E-Selen in their larval diets, led to the increase of the concentrations of lauric, oleic and linoleic acids by ratios of 16.82, 8.84 and 29.26%, respectively as compared to their

A combination of process of care and clinical target among type 2 diabetes mellitus patients in general medical clinics and specialist diabetes clinics at hospital levels.

Science.gov (United States)

Sieng, Sokha; Hurst, Cameron

2017-08-07

This study compares a combination of processes of care and clinical targets among patients with type 2 diabetes mellitus (T2DM) between specialist diabetes clinics (SDCs) and general medical clinics (GMCs), and how differences between these two types of clinics differ with hospital type (community, provincial and regional). Type 2 diabetes mellitus patient medical records were collected from 595 hospitals (499 community, 70 provincial, 26 regional) in Thailand between April 1 to June 30, 2012 resulting in a cross-sectional sample of 26,860 patients. Generalized linear mixed modeling was conducted to examine associations between clinic type and quality of care. The outcome variables of interest were split into clinical targets and process of care. A subsequent subgroup analysis was conducted to examine if the nature of clinical target and process of care differences between GMCs and SDCs varied with hospital type (regional, provincial, community). Regardless of the types of hospitals (regional, provincial, or community) patients attending SDCs were considerably more likely to have eye and foot exam. In terms of larger hospitals (regional and provincial) patients attending SDCs were more likely to achieve HbA1c exam, All FACE exam, BP target, and the Num7Q. Interestingly, SDCs performed better than GMCs at only provincial hospitals for LDL-C target and the All7Q. Finally, patients with T2DM who attended community hospital-GMCs had a better chance of achieving the blood pressure target than patients who attended community hospital-SDCs. Specialized diabetes clinics outperform general medical clinics for both regional and provincial hospitals for all quality of care indicators and the number of quality of care indicators achieved was never lower. However, this better performance of SDC was not observed in community hospital. Indeed, GMCs outperformed SDCs for some quality of care indicators in the community level setting.

Bystander effects of radiation

International Nuclear Information System (INIS)

Umar, Neethu Fathima; Daniel, Nittu

2013-01-01

The Radiation-Induced Bystander Effect is the phenomenon in which unirradiated cells show irradiated effects due to the signals received from nearby irradiated cells. Evidence suggests that targeted cytoplasmic irradiation results in mutation in the nucleus of the hit cells. Cells that are not directly hit by an alpha particle, but are in the vicinity of one that is hit, also contribute to the genotoxic response of the cell population. When cells are irradiated, and the medium is transferred to unirradiated cells, these unirradiated cells show bystander responses when assayed for clonogenic survival and oncogenic transformation. The demonstration of a bystander effect in human tissues and, more recently, in whole organisms have clear implication of the potential relevance of the non-targeted response to human health. This effect may also contribute to the final biological consequences of exposure to low doses of radiation. The radiation-induced bystander effect represents a paradigm shift in our understanding of the radiobiological effects of ionizing radiation, in that extranuclear and extracellular events may also contribute to the final biological consequences of exposure to low doses of radiation. Multiple pathways are involved in the bystander phenomenon, and different cell types respond differently to bystander signalling. Using cDNA microarrays, a number of cellular signalling genes, including cyclooxygenase-2 (CQX-2), have been shown to be casually linked to the bystander phenomenon. The observation that inhibition of the phosphorylation of extracellular signal-related kinase (ERK) suppressed the bystander response further confirmed the important role of the mitogen-activated protein kinase (MAPK) signalling cascade in the bystander process. The cells deficient in mitochondrial DNA showed a significantly reduced response to bystander signalling, suggesting a functional role of mitochondria in the signalling process. (author)

Gas target neutron generator studies

International Nuclear Information System (INIS)

Chatoorgoon, V.

1978-01-01

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

Insulin-sparing and fungible effects of E4orf1 combined with an adipocyte-targeting sequence in mouse models of type 1 and type 2 diabetes.

Science.gov (United States)

Yoon, I-S; Park, S; Kim, R-H; Ko, H L; Nam, J-H

2017-10-01

Obesity impairs glycemic control and causes insulin resistance and type 2 diabetes. Adenovirus 36 (Ad36) infection can increase the uptake of excess glucose from blood into adipocytes by increasing GLUT4 translocation through the Ras-Akt signaling pathway, which bypasses PI3K-Akt-mediated insulin receptor signaling. E4orf1, a viral gene expressed early during Ad36 infection, is responsible for this insulin-sparing effect and may be an alternative target for improving insulin resistance. To deliver the gene to adipocytes only, we connected the adipocyte-targeting sequence (ATS) to the 5' end of E4orf1 (ATS-E4orf1). In vitro transfection of ATS-E4orf1 into preadipocytes activated factors for GLUT4 translocation and adipogenesis to the same extent as did Hemagglutinin (HA)-E4orf1 transfection as positive reference. Moreover, the Transwell migration assay also showed that ATS-E4orf1 secreted by liver cells activated Akt in preadipocytes. We used a hydrodynamic gene delivery technique to deliver ATS-E4orf1 into high-fat diet-fed and streptozotocin-injected mice (disease models of type 2 and type 1 diabetes, respectively). ATS-E4orf1 improved the ability to eliminate excess glucose from the blood and ameliorated liver function in both disease models. These findings suggest that ATS-E4orf1 has insulin-sparing and fungible effects in type 2 and 1 diabetes independent of the presence of insulin.

Application effect of TEM sounding survey on prospecting and target area selection of sandstone-type uranium deposits

International Nuclear Information System (INIS)

He Jianguo; Liang Shanming; Zhao Cuiping

2006-01-01

Based on the results of transient electromagnetic (TEM) sounding survey during recent years regional geological reconnaissance with drilling (1:250000), the application effect of TEM sounding survey during regional reconnaissance is summarized in this paper. It is suggested that the data of TEM sounding are useful in judging hydrodynamic conditions of groundwater and determining favorable areas for uranium ore-formation; TEM sounding in large areas may be proper for prospecting in gobi-desert areas and be beneficial for regional reconnaissance and target area selection, and may reduce the target area and provide basis for further drilling program. It is of popularized significance in the prospecting for sandstone-type uranium deposits. (authors)

Photochemical Targeting Of Phagocytic Trabecular Meshwork Cells Using Chlorin E6 Coupled Microspheres

Science.gov (United States)

Latina, M. A.; Kobsa, P. H.; Rakestraw, S. L.; Crean, E. A.; Hasan, T.; Yarmush, M. L.

1989-03-01

We have investigated a novel and efficient delivery system utilizing photosensitizer-coupled-latex microspheres to photochemically target and kill phagocytic trabecular meshwork (TM) cells. TM cells are the most actively phagocytic cells within the anterior chamber of the eye and are located within an optically accessible discrete band. This delivery system, along with the property of cell photocytosis, will achieve double selectivity by combining preferential localization of the photosensitizer to the target cells with spatial localization of illumination on the target cells. All experiments were performed with preconfluent bovine TM cells, 3rd to 4th passage, plated in 15 mm wells. Chlorin e6 monoethylene diamine monoamide was conjugated to the surface of 1.0 Am MX Duke Scientific fluorescent latex microspheres. Spectroscopic analysis revealed an average of 1.3 x 10 -17 moles of chlorin e6 per microsphere. TM cells were incubated for 18 hours with 5 x 10 7 microspheres/ml in MEM with 10% FCS, washed with MEM, and irradiated through fresh media using an argon-pumped dye laser emitting .2 W at 660 nm. A dose-survival study indicated that energy doses of 10 J/cm2 or greater resulted in greater than 95% cell death as determined by ethidium bromide exclusion. Cell death could be demonstrated as early as 4 hours post-irradiation. TM cells incubated with a solution of chlorin e6 at a concentration equal to that conjugated to the microspheres showed no cell death. Unirradiated controls also showed no cell death.

Blood pressure targets in type 2 diabetes. Evidence against or in favour of an aggressive approach.

Science.gov (United States)

Mancia, Giuseppe; Grassi, Guido

2018-03-01

When associated with high blood pressure, type 2 diabetes mellitus is characterised by a high risk of adverse cardiovascular (CV) and renal outcomes. However, both can be effectively reduced by antihypertensive treatment. Current guidelines on the treatment of hypertension emphasize the need to effectively treat high blood pressure in diabetic individuals, but their recommendations differ in terms of the optimal target blood pressure value to aim for in order to maximise CV and renal protection. In some guidelines the recommended target blood pressure values are blood pressure values close or even less than 130/80 mmHg are recommended. This paper will discuss the evidence for and against a conservative or more aggressive blood pressure target for treated diabetic hypertensive individuals based on the evidence provided by randomised trials, trial meta-analyses and large observational studies. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90 mmHg, and that values approaching 130/80 mmHg should be recommended. However, evidence in favour of even lower systolic values, i.e. <130 mmHg, is limited and is definitively against a reduction to <120 mmHg.

Water flow experiment using the PIV technique and the thermal hydraulic analysis on the cross-flow type mercury target model

International Nuclear Information System (INIS)

Haga, Katsuhiro; Terada, Atsuhiko; Kaminaga, Masanori; Hino, Ryutaro

2001-01-01

In this study the effectiveness of the cross-flow type mercury target structure was evaluated experimentally and analytically. The average water flow velocity field in the target mock-up model, which was fabricated with plexiglass, was measured at room temperature using the PIV (Particle Image Velocimetry) technique. The water flow analyses were conducted and the analytical results were compared with the experimental results. The experimental results showed that the cross-flow could be realized in the former part of the proton beam path where the heat load by the spallation reaction is large, and the analytical result of the water flow velocity field showed good correspondence to the experimental result in the case of the Reynolds number of more than 4.83 x 10 5 at the model inlet. With these results, the effectiveness of the cross-flow type mercury target structure and the present analysis code system was demonstrated. Then the mercury flow field and the temperature distribution in the target container were analyzed assuming the proton beam energy and power of 3 GeV and 5 MW. The analytical result showed that the cross-flow field of mercury, which is similar to the water flow field, could also be attained. (author)

A modified R-type bacteriocin specifically targeting Clostridium difficile prevents colonization of mice without affecting gut microbiota diversity.

Science.gov (United States)

Gebhart, Dana; Lok, Stephen; Clare, Simon; Tomas, Myreen; Stares, Mark; Scholl, Dean; Donskey, Curtis J; Lawley, Trevor D; Govoni, Gregory R

2015-03-24

Clostridium difficile is a leading cause of nosocomial infections worldwide and has become an urgent public health threat requiring immediate attention. Epidemic lineages of the BI/NAP1/027 strain type have emerged and spread through health care systems across the globe over the past decade. Limiting person-to-person transmission and eradicating C. difficile, especially the BI/NAP1/027 strain type, from health care facilities are difficult due to the abundant shedding of spores that are impervious to most interventions. Effective prophylaxis for C. difficile infection (CDI) is lacking. We have genetically modified a contractile R-type bacteriocin ("diffocin") from C. difficile strain CD4 to kill BI/NAP1/027-type strains for this purpose. The natural receptor binding protein (RBP) responsible for diffocin targeting was replaced with a newly discovered RBP identified within a prophage of a BI/NAP1/027-type target strain by genome mining. The resulting modified diffocins (a.k.a. Avidocin-CDs), Av-CD291.1 and Av-CD291.2, were stable and killed all 16 tested BI/NAP1/027-type strains. Av-CD291.2 administered in drinking water survived passage through the mouse gastrointestinal (GI) tract, did not detectably alter the mouse gut microbiota or disrupt natural colonization resistance to C. difficile or the vancomycin-resistant Enterococcus faecium (VREF), and prevented antibiotic-induced colonization of mice inoculated with BI/NAP1/027-type spores. Given the high incidence and virulence of the pathogen, preventing colonization by BI/NAP1/027-type strains and limiting their transmission could significantly reduce the occurrence of the most severe CDIs. This modified diffocin represents a prototype of an Avidocin-CD platform capable of producing targetable, precision anti-C. difficile agents that can prevent and potentially treat CDIs without disrupting protective indigenous microbiota. Treatment and prevention strategies for bacterial diseases rely heavily on traditional

Ethnic food perspective of North Dakota Common Emmer Wheat and relevance for health benefits targeting type 2 diabetes

Directory of Open Access Journals (Sweden)

Ashish Christopher

2018-03-01

Full Text Available Background: Ancient grains with ethnic food origins are gaining renewed interest in contemporary food design due to its balanced nutritional profiles and health benefits. The “North Dakota Common Emmer Wheat” (Triticum dicoccum, a tetraploid species, had ethnic origins with German immigrants from Russia migrating to North Dakota in late 19th century. Targeting such grains with ethnic origins that are rich in fibers, amino acids, minerals, and other bioactive compounds has significant merit for advancing health benefits against emerging diet-linked chronic diseases. Based on this rationale, phenolic-linked antioxidant and antihyperglycemic properties of North Dakota Common Emmer Wheat was compared with those of other commercial wheat cultivars in order to integrate it into a health-targeted food design based on past ethnic food insights. Methods: Aqueous extracts of the North Dakota Common Emmer Wheat (with and without hull and two other commercial wheat varieties, Barlow and Coteau, were analyzed before and after milling. The total soluble phenolic content, phenolic acid profile, protein content, antioxidant activity, type 2 diabetes relevant α-amylase, and α-glucosidase enzyme inhibitory activities were determined using in vitro assay models. Results: North Dakota Common Emmer Wheat with hull had highest total soluble phenolic content and associated antioxidant and antihyperglycemic properties (before and after milling when compared to the other commercial wheat cultivars. Conclusion: Results indicated that North Dakota Common Emmer Wheat with hull can be integrated into a health-targeted contemporary food design as a part of dietary support against chronic hyperglycemia and oxidative stress associated with early stages type 2 diabetes. Keywords: Antioxidant, Enzyme inhibitors, Ethnic wheat, North Dakota Common Emmer, Phenolics, Type 2 diabetes

Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice

International Nuclear Information System (INIS)

Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.

1988-01-01

Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes and platelets, and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) reponse to schistosomular antigens. However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity nor serum anti-schistosomulum extract antibody levels were affected. The pattern of 125 I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential. (author)

Target and ion source developments for a helium-jet type ISOL at the Kyoto university reactor

International Nuclear Information System (INIS)

Kawase, Yoichi; Okano, Kotoyuki; Funakoshi, Yoshihiro

1985-01-01

A target system and ion sources for a He-jet type ISOL have been successfully constructed and the characteristics have been studied. The beam intensities of short-lived fission products have been much improved by increasing the He gas pressure owing to a range effect of fission products in the He gas and a short transport time effect of aerosols in a target chamber and a capillary. An oscillating electron ion source has been coupled with the He-jet system and ten kinds of elements have been ionized with efficiencies of 0.4-2.4%. A high temperature thermal ion source has been studied to ionize the alkali, alkaline-earth and rare-earth elements. The effects of the He-jet on the ion source have been discussed. (orig.)

Visceral adipose tissue macrophage-targeted TACE silencing to treat obesity-induced type 2 diabetes.

Science.gov (United States)

Yong, Seok-Beom; Song, Yoonsung; Kim, Yong-Hee

2017-12-01

Obesity is an increasingly prevalent global health problem. Due to its close relations with metabolic diseases and cancer, new therapeutic approaches for treating obesity and obesity-induced metabolic diseases are required. Visceral white adipose tissue (WAT) has been closely associated with obesity-induced inflammation and adipose tissue macrophages (ATMs) are responsible for obesity-induced inflammation by releasing inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6. TNF-α converting enzyme (TACE) is a transmembrane enzyme that induces the enzymatic cleavage and release of inflammatory cytokines. In this study, we developed a nonviral gene delivery system consisting of an oligopeptide (ATS-9R) that can selectively target visceral ATMs. In here we shows visceral adipose tissue-dominant inflammatory gene over-expressions in obese mouse and our strategy enabled the preferential delivery of therapeutic genes to visceral ATMs and successfully achieved ATM-targeted gene silencing. Finally, ATS-9R-mediated TACE gene silencing in visceral ATMs alleviated visceral fat inflammation and improved type 2 diabetes by reducing whole body inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Repair and mutagenesis of herpes simplex virus in UV-irradiated monkey cells

International Nuclear Information System (INIS)

Lytle, C.D.; Goddard, J.G.; Lin, C.H.

1980-01-01

Mutagenic repair in mammalian cells was investigated by determining the mutagenesis of UV-irradiated or unirradiated herpes simplex virus in UV-irradiated CV-1 monkey kidney cells. These results were compared with the results for UV-enhanced virus reactivation (UVER) in the same experimental situation. High and low multiplicities of infection were used to determine the effects of multiplicity reactivation (MR). UVER and MR were readily demonstrable and were approximately equal in amount in an infectious center assay. For this study, a forward-mutation assay was developed to detect virus mutants resistant to iododeoxycytidine (ICdR), probably an indication of the mutant virus being defective at its thymidine kinase locus. ICdR-resistant mutants did not have a growth advantage over wild-type virus in irradiated or unirradiated cells. Thus, higher fractions of mutant virus indicated greater mutagenesis during virus repair and/or replication. The data showed that: (1) unirradiated virus was mutated in unirradiated cells, providing a background level of mutagenesis; (2) unirradiated virus was mutated about 40% more in irradiated cells, indicating that virus replication (DNA synthesis) became more mutagenic as a result of cell irradiation; (3) irradiated virus was mutated much more (about 6-fold) than unirradiated virus, even in unirradiated cells; (4) cell irradiation did not change the mutagenesis of irradiated virus except at high multiplicity of infection. High multiplicity of infection did not demonstrate UVER or MR alone to be either error-free or error-prone. When the two processes were present simultaneously, they were mutagenic. (orig.)

Study of Irradiation Effects on the Fracture Properties of A533-Series Ferritic Steels

International Nuclear Information System (INIS)

Lee, Yong Bok; Lee, Gyeong Geun; Kwon, Jun Hyun

2011-01-01

Since the Kori nuclear power plant unit 3 (Kori-3) was founded in 1986, the surveillance tests have been conducted five times. One of the primary objectives of the surveillance test is to determine the effects of irradiation on reactor pressure vessel (RPV) steel embrittlement. The RPV is made out of ferritic steels such as SA533 type B class 1, which were used for early nuclear power plants industry including Kori-2, 3, 4 and Yonggwang-1, 2 units in Korea. The Westinghouse supplied Kori-3 with the RPV steels ASTM A533 grade B class 1, which is equivalent to SA533 type B class 1. The irradiation effects on tensile properties in ASTM A533 grade B class 1 steel had been studied by Steichen and Williams. They experimentally determined the effect of strain rate and temperature on the tensile properties of unirradiated and irradiated A533 grade B steel 1. The effects of neutron irradiation on ferritic steels could be determined from tensile properties, as well as the fracture strength and toughness measurements. Hunter and Williams have reported that the strength and ductility for unirradiated material at a low strain rate increase with decreasing test temperature. Also, neutron irradiation increases strength and decreases ductility. Crosley and Ripling revealed that the yield strength of unirradiated material rapidly increases with the strain rate. Therefore, yield strength for unirradiated and irradiated materials should be determined by test parameters along with strain rate and temperature. In this study we compare ASTM A533 grad B class 1 steel obtained from several papers with SA533 type B class 1 steel taken from the surveillance data of Kori-3 unit, whose mechanical property of unirradiated and irradiated materials was correlated with the rate-temperature parameter

CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

Directory of Open Access Journals (Sweden)

Olusiji A. Akinrinmade

2017-09-01

Full Text Available To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64 have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia

Directory of Open Access Journals (Sweden)

Eduardo Laborda

2017-10-01

Full Text Available The treatment of patients with acute myeloid leukemia (AML with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR-engineered T-cells (CAR-T-cells, a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression. C-type lectin-like molecule-1 (CLL1 or CLEC12A is a myeloid lineage antigen that is expressed by malignant cells in more than 90% of AML patients. CLL1 is not expressed by healthy Hematopoietic Stem Cells (HSCs, and is therefore a promising target for CAR-T-cell therapy. Here, we describe the development and optimization of an anti-CLL1 CAR-T-cell with potent activity on both AML cell lines and primary patient-derived AML blasts in vitro while sparing healthy HSCs. Furthermore, in a disseminated mouse xenograft model using the CLL1-positive HL60 cell line, these CAR-T-cells completely eradicated tumor, thus supporting CLL1 as a promising target for CAR-T-cells to treat AML while limiting myelosuppressive toxicity.

Repair of gamma radiation damage in wild type and a radiation sensitive mutant of Deinococcus radiodurans

International Nuclear Information System (INIS)

Mizuma, Nagayo

1989-01-01

In an effort to examine production and repair of radiation-induced single and double strand breaks in the DNA, a repair-deficient wild type and a repair-deficient mutant, UV17, of Deinococcus radiodurans were subjected to Co-60 gamma irradiation at a dose rate of 6.3 kGy/hr for wild type and 3.9 kGy/hr for UV17 mutant. The shoulder of the curve of UV17 mutant was narrow but existed with the intercept of 0.7 kGy and the corresponding value of the wild type was 4.2 kGy. Mutant cells exhibited about 6 fold increases in sensitivity for the shoulder relative to the wild type. The D 37 doses in the wild type and the mutant were 0.57 kGy and 0.25 kGy, respectively. From the survival curves, difference in the sensitivity between two strains was mainly due to difference of repair capacity than the number of radiation sensitive target. Sedimentation rate of the main component in the irradiated cells of UV17 mutant increased almost to the level of unirradiated control by the postincubation at 30deg C for 3 hrs. The results indicated that this sensitive mutant also exhibited an ability to restore single strand breaks after exposure to a sublethal dose of 0.6 kGy. When restitution of double strand breaks was analyzed by sedimentation in a neutral sucrose gradient, the wild type showed restitution to DNA-membrane complex from large part of the breaks. For UV17 mutant, the apparent increase in DNA-membrane complex formation was seen after 3 hours incubation. Large part of the decrease in the activities of peak 2 was recovered in the peak 1 for the wild type. For the mutant, there was little restitution to peak 1. Almost free DNA component in UV17 mutant, therefore, was merely degraded into shorter pieces. Restoration of DNA-membrane complex from free DNA derived from gamma-ray induced double strand scission involved closely in the repair of gamma-induced damage and survival. (N.K.)

Perceptions of similarity and response to selected comparison targets in type 2 diabetes.

Science.gov (United States)

Arigo, Danielle; Smyth, Joshua M; Suls, Jerry M

2015-01-01

Social comparisons (i.e. self-evaluations relative to others) may affect motivation for diabetes self-care behaviours. Comparisons can have either positive or negative effects, but it is not clear what differentiates these responses. This study tested the effect of a patient's perceived similarity to a comparison target on motivation for self-care. Individuals with type 2 diabetes (n = 180, MA1c = 7.59%) selected to read one of four brief descriptions of a patient with diabetes. Participants rated their motivation for self-care behaviours prior and subsequent to reading and reported the extent to which they focused on similarities between the self and the selected patient while reading. Perceived similarity moderated the effect of selection on motivation for self-care (p = .01, η2 = .06). Increased motivation was observed if participants focused on similarities with patients 'doing better' (i.e. high coping effectiveness/low symptom severity) and decreased motivation if they focused on similarities with patients 'doing worse' (low coping effectiveness/high symptom severity). Providing social comparison information in diabetes management (and perhaps other chronic diseases) may improve motivation for self-care among some patients. A subset of patients, however, may benefit from guidance to focus on similarities with certain targets.

Dissolution of unirradiated UO2 fuel in synthetic groundwater. Final report (1996-1998)

International Nuclear Information System (INIS)

Ollila, K.

1999-05-01

This study was a part of the EU R and D programme 1994-1998: Nuclear Fission Safety, entitled 'Source term for performance assessment of spent fuel as a waste form'. The research carried out at VTT Chemical Technology was focused on the effects of granitic groundwater composition and redox conditions on UO 2 solubility and dissolution mechanisms. The synthetic groundwater compositions simulated deep granitic fresh and saline groundwaters, and the effects of the near-field material, bentonite, on very saline groundwater. Additionally, the Spanish granite/bentonite water was used. The redox conditions (Eh), which are obviously the most important factors that influence on UO 2 solubility under the disposal conditions of spent fuel, varied from strongly oxidising (air-saturated), anaerobic (N 2 , O 2 2 , low Eh). The objective of the air-saturated dissolution experiments was to yield the maximum solution concentrations of U, and information on the formation of secondary phases that control the concentrations, with different groundwater compositions. The static batch solubility experiments of long duration (up to 1-2 years) were performed using unirradiated UO 2 pellets and powder. Under anaerobic and reducing conditions, the solubilities were also approached from oversaturation. The results of the oxic, air-saturated dissolution experiments with UO 2 powder showed that the increase in the salinity ( -5 M, were at the level of the theoretical solubility of schoepite or another uranyl oxide hydrate, e.g. becquerelite (possibly Na-polyuranate). The higher alkalinity of the fresh (Allard) composition increased the aqueous U concentration. Only some kind of oxidised U-phase (U 3 O 8 -UO 3 ) was identified with XRD when studying possible secondary phases after the contact time of one year with all groundwater compositions. Longer contact times are needed to identify secondary phases predicted by modelling (EQ3/6). In the anoxic dissolution experiments with UO 2 pellets, the

Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

Energy Technology Data Exchange (ETDEWEB)

Ohkawa, Mayumi [Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Ohno, Yoshiya [Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-shi, Hyogo 650-8530 (Japan); Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan); Tanaka, Toshiyuki [Laboratory of Immunobiology, Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe-shi, Hyogo 650-8530 (Japan); Saya, Hideyuki [Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8502 (Japan); Seki, Masayuki; Enomoto, Takemi [Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Aoba-ku, Sendai 980-8578 (Japan); Yagi, Hideki [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan); Hashimoto, Yoshiyuki [Tohoku University, Sendai (Japan); Masuko, Takashi, E-mail: masuko@phar.kindai.ac.jp [Cell Biology Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University, 4-1 Kowakae 3-chome, Higashiosaka-shi, Osaka 577-8502 (Japan)

2011-03-25

Highlights: {yields} We established LAT1 amino-acid transporter-disrupted DT40 cells. {yields} LAT1-disrupted cells showed slow growth and lost the oncogenicity. {yields} siRNA and mAb inhibited human tumor growth in vitro and in vivo. {yields} LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1{sup -/-}) cell clones, derived from a heterozygous LAT1{sup +/-} clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1{sup -/-} DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1{sup -/-} cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1{sup -/-} DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1{sup -/-} DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1{sup +/-} DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.

Oncogenicity of L-type amino-acid transporter 1 (LAT1) revealed by targeted gene disruption in chicken DT40 cells: LAT1 is a promising molecular target for human cancer therapy

International Nuclear Information System (INIS)

Ohkawa, Mayumi; Ohno, Yoshiya; Masuko, Kazue; Takeuchi, Akiko; Suda, Kentaro; Kubo, Akihiro; Kawahara, Rieko; Okazaki, Shogo; Tanaka, Toshiyuki; Saya, Hideyuki; Seki, Masayuki; Enomoto, Takemi; Yagi, Hideki; Hashimoto, Yoshiyuki; Masuko, Takashi

2011-01-01

Highlights: → We established LAT1 amino-acid transporter-disrupted DT40 cells. → LAT1-disrupted cells showed slow growth and lost the oncogenicity. → siRNA and mAb inhibited human tumor growth in vitro and in vivo. → LAT1 is a promising target molecule for cancer therapy. -- Abstract: L-type amino-acid transporter 1 (LAT1) is the first identified light chain of CD98 molecule, disulfide-linked to a heavy chain of CD98. Following cDNA cloning of chicken full-length LAT1, we have constructed targeting vectors for the disruption of chicken LAT1 gene from genomic DNA of chicken LAT1 consisting of 5.4 kb. We established five homozygous LAT1-disrupted (LAT1 -/- ) cell clones, derived from a heterozygous LAT1 +/- clone of DT40 chicken B cell line. Reactivity of anti-chicken CD98hc monoclonal antibody (mAb) with LAT1 -/- DT40 cells was markedly decreased compared with that of wild-type DT40 cells. All LAT1 -/- cells were deficient in L-type amino-acid transporting activity, although alternative-splice variant but not full-length mRNA of LAT1 was detected in these cells. LAT1 -/- DT40 clones showed outstandingly slow growth in liquid culture and decreased colony-formation capacity in soft agar compared with wild-type DT40 cells. Cell-cycle analyses indicated that LAT1 -/- DT40 clones have prolonged cell-cycle phases compared with wild-type or LAT1 +/- DT40 cells. Knockdown of human LAT1 by small interfering RNAs resulted in marked in vitro cell-growth inhibition of human cancer cells, and in vivo tumor growth of HeLa cells in athymic mice was significantly inhibited by anti-human LAT1 mAb. All these results indicate essential roles of LAT1 in the cell proliferation and occurrence of malignant phenotypes and that LAT1 is a promising candidate as a molecular target of human cancer therapy.

Radioimmunodetection of membrane type-1 matrix metalloproteinase relevant to tumor malignancy with a pre-targeting method

International Nuclear Information System (INIS)

Sano, Kohei; Temma, Takashi; Kuge, Yuji; Kudo, Takashi; Kamihashi, Junko; Saji, Hideo; Zhao, Songji

2010-01-01

Since membrane type-1 matrix metalloproteinase (MT1-MMP) is exclusively expressed in tumors and is closely associated with metastasis and invasion, MT1-MMP is a potential target of radiotracers for the evaluation of tumor malignancy. In this study, we planned to visualize MT1-MMP in vivo by a two-step pre-targeting strategy using a streptavidin (SAv)-biotin system combined with anti-MT1-MMP monoclonal immunoglobulin (IgG) (anti-MT1-MMP monoclonal antibody (mAb)). Streptavidinylated anti-MT1-MMP mAb was synthesized by reacting biotinylated anti-MT1-MMP mAb with SAv. In the pre-targeting study, FM3A mouse breast carcinoma-implanted mice were injected with anti-MT1-MMP mAb-SAv, followed 72 h later with radioiodinated biotin, (3-[ 123/125 I]iodobenzoyl)norbiotinamide( 123/125 I-IBB). Biodistribution and imaging (single photon emission computed tomography (SPECT)/CT) data were collected at several time points in the 24 h period following introduction of the tracer. The comparison groups were injected with 125 I-IBB alone or with 125 I-IBB pre-targeted with negative control IgG-SAv. In the pre-targeting study for MT1-MMP, within 1 h of tracer injection, rapid tumor uptake and abrupt clearance from the blood of radioactivity (2.22, 0.87% injected dose/g at 1 h) were observed. The tumor to blood (T/B) radioactivity ratios were significantly higher than those from mice dosed with the pre-targeting negative control (p 125 I-IBB alone did not accumulate in tumors. SPECT/CT image analysis of FM3A bearing mice showed high-contrast tumor images after 3 h with minimal blood-pool activity. The present study that uses a pre-targeting method showed high T/B radioactivity ratios and clear tumor images of MT1-MMP. This imaging method may be useful for the clinical diagnosis of malignant tumors. (author)

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

OpenAIRE

Guan, Jing; Wang, Wanying; Sun, Baolin

2017-01-01

ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show...

Development of fission Mo production technology

International Nuclear Information System (INIS)

Kim, B. K.; Park, K. B.; Jun, B. J.; Park, J. H.; Choung, W. M.; Lee, K. I.; Woo, M. S.; Whang, D. S.; Kim, Y. K.; Yoo, J. H.; Sohn, D. S.; Lee, Y. W.; Na, S. H.; Koo, Y. H.; Hwang, D. H.; Joo, P. K.

1997-08-01

The feasibility study is accomplished in this project for the development of fission moly production. The KAERI process proposed for development in KAERI is discussed together with those of the American Cintichem and Russian IPPE, each of which would be plausible for introduction whenever the indigenous development is not much feasible. For the conceptual design of the KAERI irradiation target, analysis method is set up and some preliminary analysis is performed accordingly for the candidate design. To establish chemical process concepts for the afore-mentioned three processes, characteristics, operation conditions, and the management of the generated wastes are investigated. Basic requirements of hotcell facilities for chemical processing and a possible way of utilizing the existing hotcells are discussed in parallel with the counter-measures for the construction of new hotcell facilities. Various conditions of target irradiation for fission moly production in Hanaro are analyzed. Plan for introduction of the relevant technology introduction and for procurement of highly enriched uranium are considered. On the basis of assuming some conditions, the economic feasibility study for fission moly production is also overviewed. (author). 22 refs., 28 tabs., 24 figs

Opinions of patients with type 2 diabetes about responsibility, setting targets and willingness to take medication: a cross-sectional survey.

NARCIS (Netherlands)

Gorter, K.J.; Tuytel, G.J.; Leeuw, R.R. de; Bensing, J.M.; Rutten, G.E.H.M.

2011-01-01

OBJECTIVE: To assess opinions and their determinants of patients with type 2 diabetes about responsibility for managing their diabetes, setting treatment targets and willingness taking medication. METHODS: Questionnaire survey carried out in general practices and outpatient clinics across the

Polarized targets in high energy physics

Energy Technology Data Exchange (ETDEWEB)

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

1994-12-01

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

Polarized targets in high energy physics

International Nuclear Information System (INIS)

Cates, G.D. Jr.

1994-01-01

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

Discovery of antimicrobial compounds targeting bacterial type FAD synthetases.

Science.gov (United States)

Sebastián, María; Anoz-Carbonell, Ernesto; Gracia, Begoña; Cossio, Pilar; Aínsa, José Antonio; Lans, Isaías; Medina, Milagros

2018-12-01

The increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme. Bacterial FADSs are potential antibacterial targets because of differences to mammalian enzymes, particularly at the FAD producing site. We have optimised an activity-based high throughput screening assay targeting Corynebacterium ammoniagenes FADS (CaFADS) that identifies inhibitors of its different activities. We selected the three best high-performing inhibitors of the FMN:adenylyltransferase activity (FMNAT) and studied their inhibition mechanisms and binding properties. The specificity of the CaFADS hits was evaluated by studying also their effect on the Streptococcus pneumoniae FADS activities, envisaging differences that can be used to discover species-specific antibacterial drugs. The antimicrobial effect of these compounds was also evaluated on C. ammoniagenes, S. pneumoniae, and Mycobacterium tuberculosis cultures, finding hits with favourable antimicrobial properties.

Hypertension in patients with type 2 diabetes mellitus: Targets and management.

Science.gov (United States)

Pavlou, Dimitra I; Paschou, Stavroula Α; Anagnostis, Panagiotis; Spartalis, Michael; Spartalis, Eleftherios; Vryonidou, Andromachi; Tentolouris, Nicholas; Siasos, Gerasimos

2018-06-01

Two-thirds of patients with type 2 diabetes mellitus (T2DM) have arterial hypertension. Hypertension increases the incidence of both micro- and macrovascular complications in these patients, while the co-existence of these two major risk factors leads to a four-fold increased risk for cardiovascular disease (CVD) compared with normotensive non-diabetic controls. The aim of this article is to comprehensively review the literature and present updated information on targets for blood pressure (BP) and on the management of hypertension in patients with T2DM. A BP target of <140/90 mmHg applies to most patients, but individualization is always important. All classes of antihypertensive drugs can be used in the management of hypertension in patients with T2DM, as long as they are effective and safe and after taking co-morbidities into account. Angiotensin-converting-enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are the ideal choice for initial or early treatment of hypertension in patients with T2DM and albuminuria. Combination of two or more drugs seems to be inevitable as most of these patients demonstrate resistant hypertension. The combination of ACE inhibitors with ARBs should be avoided. Thiazide and thiazide-like diuretics might be beneficial, alone or in a fixed-dose combination with ACE inhibitors or ARBs. Calcium channel blockers (CCBs) constitute an ideal option as a second- or third-line agent. Beta-blockers are not considered as first-line antihypertensive agents, except for those patients with heart failure or previous myocardial infarction. The addition of mineralocorticoid receptor antagonists to a triple-drug therapy seems the next ideal step. Gender-specific characteristics regarding BP, T2DM and CVD should be taken into consideration, even if different recommendations do not exist yet. Copyright © 2018. Published by Elsevier B.V.

The target effect: visual memory for unnamed search targets.

Science.gov (United States)

Thomas, Mark D; Williams, Carrick C

2014-01-01

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

Surface modifications caused by a swift heavy ion irradiation on crystalline p-type gallium antimonide

Energy Technology Data Exchange (ETDEWEB)

Jadhav, Vidya, E-mail: vj1510@yahoo.com

2015-09-01

Surface modifications caused by a swift heavy ion irradiation on crystalline p-type gallium antimonide crystal have been reported. Single crystal, 1 0 0〉 orientations and ∼500 μm thick p-type GaSb samples with carrier concentration of 3.30 × 10{sup 17} cm{sup −3} were irradiated at 100 MeV Fe{sup 7+} ions. We have used 15UD Pelletron facilities at IUAC with varying fluences of 5 × 10{sup 10}–1 × 10{sup 14} ions cm{sup −2}. The effects of irradiation on these samples have been investigated using, spectroscopic ellipsometry, atomic force microscopy and ultraviolet–visible–NIR spectroscopy techniques. Ellipsometry parameters, psi (Ψ) and delta (Δ) for the unirradiated sample and samples irradiated with different fluences were recorded. The data were fit to a three phase model to determine the refractive index and extinction coefficient. The refractive index and extinction coefficient for various fluences in ultraviolet, visible, and infrared, regimes were evaluated. Atomic force microscopy has been used to study these surface modifications. In order to have more statistical information about the surface, we have plotted the height structure histogram for all the samples. For unirradiated sample, we observed the Gaussian fitting. This result indicates the more ordered height structure symmetry. Whereas for the sample irradiated with the fluence of 1 × 10{sup 13}, 5 × 10{sup 13} and 1 × 10{sup 14} ions cm{sup −2}, we observed the scattered data. The width of the histogram for samples irradiated up to the fluence of 1 × 10{sup 13} ion cm{sup −2} was found to be almost same however it decreased at higher fluence. UV reflectance spectra of the sample irradiated with increasing fluences exhibit three peaks at 292, 500 and 617 nm represent the high energy GaSb; E{sub 1}, E{sub 1} + Δ and E{sub 2} band gaps in all irradiated samples.

Surface modifications caused by a swift heavy ion irradiation on crystalline p-type gallium antimonide

International Nuclear Information System (INIS)

Jadhav, Vidya

2015-01-01

Surface modifications caused by a swift heavy ion irradiation on crystalline p-type gallium antimonide crystal have been reported. Single crystal, 1 0 0〉 orientations and ∼500 μm thick p-type GaSb samples with carrier concentration of 3.30 × 10 17 cm −3 were irradiated at 100 MeV Fe 7+ ions. We have used 15UD Pelletron facilities at IUAC with varying fluences of 5 × 10 10 –1 × 10 14 ions cm −2 . The effects of irradiation on these samples have been investigated using, spectroscopic ellipsometry, atomic force microscopy and ultraviolet–visible–NIR spectroscopy techniques. Ellipsometry parameters, psi (Ψ) and delta (Δ) for the unirradiated sample and samples irradiated with different fluences were recorded. The data were fit to a three phase model to determine the refractive index and extinction coefficient. The refractive index and extinction coefficient for various fluences in ultraviolet, visible, and infrared, regimes were evaluated. Atomic force microscopy has been used to study these surface modifications. In order to have more statistical information about the surface, we have plotted the height structure histogram for all the samples. For unirradiated sample, we observed the Gaussian fitting. This result indicates the more ordered height structure symmetry. Whereas for the sample irradiated with the fluence of 1 × 10 13 , 5 × 10 13 and 1 × 10 14 ions cm −2 , we observed the scattered data. The width of the histogram for samples irradiated up to the fluence of 1 × 10 13 ion cm −2 was found to be almost same however it decreased at higher fluence. UV reflectance spectra of the sample irradiated with increasing fluences exhibit three peaks at 292, 500 and 617 nm represent the high energy GaSb; E 1 , E 1 + Δ and E 2 band gaps in all irradiated samples

Targeting the autolysis loop of urokinase-type plasminogen activator with conformation-specific monoclonal antibodies.

Science.gov (United States)

Botkjaer, Kenneth A; Fogh, Sarah; Bekes, Erin C; Chen, Zhuo; Blouse, Grant E; Jensen, Janni M; Mortensen, Kim K; Huang, Mingdong; Deryugina, Elena; Quigley, James P; Declerck, Paul J; Andreasen, Peter A

2011-08-15

Tight regulation of serine proteases is essential for their physiological function, and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of uPA (urokinase-type plasminogen activator) in different human cancer types, with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA's activity. In the present study we characterize the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found to harbour the epitopes for three conformation-specific monoclonal antibodies, two with a preference for the zymogen form pro-uPA, and one with a preference for active uPA. All three antibodies were shown to have overlapping epitopes, with three common residues being crucial for all three antibodies, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active uPA-specific antibody by shielding the access of plasminogen to the active site. Furthermore, using immunofluorescence, the conformation-specific antibodies mAb-112 and mAb-12E6B10 enabled us to selectively stain pro-uPA or active uPA on the surface of cultured cells. Moreover, in various independent model systems, the antibodies inhibited tumour cell invasion and dissemination, providing evidence for the feasibility of pharmaceutical intervention with serine protease activity by targeting surface loops that undergo conformational changes during zymogen activation. © The Authors Journal compilation © 2011 Biochemical Society

Characterization of the omega-conotoxin target. Evidence for tissue-specific heterogeneity in calcium channel types

International Nuclear Information System (INIS)

Cruz, L.J.; Johnson, D.S.; Olivera, B.M.

1987-01-01

Omega-Conotoxin GVIA (omega-CgTx-VIA) is a 27 amino acid peptide from the venom of the fish-hunting snail, Conus geographus, that blocks voltage-activated Ca channels. The characterization of a biologically active, homogeneous 125 I-labeled monoiodinated Tyr 22 derivative of omega-conotoxin GVIA and its use in binding and cross-linking studies are described. The 125 I-labeled toxin is specifically cross-linked to a receptor protein with an apparent M/sub r/ of 135,000. The stoichiometry between omega-conotoxin and nitrendipine binding sites in different chick tissues was determined. Skeletal muscle has a high concentration of [ 3 H]nitrendipine binding sites but no detectable omega-conotoxin sites. Brain microsomes have both binding sites, but omega-conotoxin targets are in excess. These results, combined with recent electrophysiological studies define four types of Ca channels in chick tissues, N, T, L/sub n/ (omega sensitive), and L/sub m/ (omega insensitive), and are consistent with the hypothesis that the α-subunits of certain neuronal Ca 2+ channels (L/sub n/, N) are the molecular targets of omega-conotoxin GVIA

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.

High-velocity Penetration of Concrete Targets with Three Types of Projectiles: Experiments and Analysis

Directory of Open Access Journals (Sweden)

Shuang Zhang

Full Text Available Abstract This study conducted high-velocity penetration experiments using conventional ogive-nose, double-ogive-nose, and grooved-tapered projectiles of approximately 2.5 kg and initial velocities between 1000 and 1360 m/s to penetrate or perforate concrete targets with unconfined compressive strengths of nominally 40MPa. The penetration performance data of these three types of projectiles with two different types of materials (i.e., AerMet100 and DT300 were obtained. The crater depth model considering both the projectile mass and the initial velocity was proposed based on the test results and a theoretical analysis. The penetration ability and the trajectory stability of these three projectile types were compared and analyzed accordingly. The results showed that, under these experimental conditions, the effects of these two different kinds of projectile materials on the penetration depth and mass erosion rate of projectile were not obvious. The existing models could not reflect the crater depths for projectiles of greater weights or higher velocities, whereas the new model established in this study was reliable. The double-ogive-nose has a certain effect of drag reduction. Thus, the double-ogive-nose projectile has a higher penetration ability than the conventional ogive-nose projectile. Meanwhile, the grooved-tapered projectile has a better trajectory stability, because the convex parts of tapered shank generated the restoring moment to stabilize the trajectory.

Dissolution rates of unirradiated UO2, UO2 doped with 233U, and spent fuel under normal atmospheric conditions and under reducing conditions using an isotope dilution method

International Nuclear Information System (INIS)

Ollila, Kaija; Albinsson, Yngve; Oversby, Virginia; Cowper, Mark

2003-10-01

The experimental results given in this report allow us to draw the following conclusions. 1) Tests using unirradiated fuel pellet materials from two different manufacturers gave very different dissolution rates under air atmosphere testing. Tests for fragments of pellets from different pellets made by the same manufacturer gave good agreement. This indicates that details of the manufacturing process have a large effect on the behavior of unirradiated UO 2 in dissolution experiments. Care must be taken in interpreting differences in results obtained in different laboratories because the results may be affected by manufacturing effects. 2) Long-term tests under air atmosphere have begun to show the effects of precipitation. Further testing will be needed before the samples reach steady state. 3) Testing of unirradiated UO 2 in systems containing an iron strip to produce reducing conditions gave [U] less than detection limits ( 235 U added as spike was recovered, indicating that 90% of the spike had precipitated onto the solid sample or the iron strip. 9) Tests of UO 2 pellet materials containing 233 U to provide an alpha decay activity similar to that expected for spent fuel 3000 and 10,000 years after disposal showed that the pellet materials behaved as expected under air atmosphere conditions, showing that the manufacturing method was successful. 10) Early testing of the 233 U-doped materials under reducing conditions showed relatively rapid (30 minute) dissolution of small amounts of U at the start of the puff test procedure. Results of analyses of an acidified fraction of the same solutions after 1 or 2 weeks holding indicate that the solutions were inhomogeneous, indicating the presence of colloidal material or small grains of solid. 11) Samples from the 233 U-doped tests initially indicated dissolution of solid during the first week of testing, with some indication of more rapid dissolution of the material with the higher doping. 12) The second cycle of testing

miRNA and Degradome Sequencing Reveal miRNA and Their Target Genes That May Mediate Shoot Growth in Spur Type Mutant “Yanfu 6”

Science.gov (United States)

Song, Chunhui; Zhang, Dong; Zheng, Liwei; Zhang, Jie; Zhang, Baojuan; Luo, Wenwen; Li, Youmei; Li, Guangfang; Ma, Juanjuan; Han, Mingyu

2017-01-01

The spur-type growth habit in apple trees is characterized by short internodes, increased number of fruiting spurs, and compact growth that promotes flowering and facilitates management practices, such as pruning. The molecular mechanisms responsible for regulating spur-type growth have not been elucidated. In the present study, miRNAs and the expression of their potential target genes were evaluated in shoot tips of “Nagafu 2” (CF) and spur-type bud mutation “Yanfu 6” (YF). A total of 700 mature miRNAs were identified, including 202 known apple miRNAs and 498 potential novel miRNA candidates. A comparison of miRNA expression in CF and YF revealed 135 differentially expressed genes, most of which were downregulated in YF. YF also had lower levels of GA, ZR, IAA, and ABA hormones, relative to CF. Exogenous applications of GA promoted YF shoot growth. Based on the obtained results, a regulatory network involving plant hormones, miRNA, and their potential target genes is proposed for the molecular mechanism regulating the growth of YF. miRNA164, miRNA166, miRNA171, and their potential targets, and associated plant hormones, appear to regulate shoot apical meristem (SAM) growth. miRNA159, miRNA167, miRNA396, and their potential targets, and associated plant hormones appear to regulate cell division and internode length. This study provides a foundation for further studies designed to elucidate the mechanism underlying spur-type apple architecture. PMID:28424721

Antiproton Target

CERN Multimedia

1980-01-01

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

Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

Directory of Open Access Journals (Sweden)

Linn S Strandberg

Full Text Available Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB.We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells.Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

THE KFIB EXPERIMENT

Energy Technology Data Exchange (ETDEWEB)

Youngblood, Gerald E.; Senor, David J.; Jones, Russell H.; Kowbel, W.; Kohyama, A.

2000-06-30

Several rod-shaped specimens with uniaxially packed fibers (Hi-Nicalon™, Hi-Nicalon™ Type S, Tyranno™ SA and Amoco K1100™ types) in a pre-ceramic polymer matrix were fabricated. By using appropriate analytic models, the bare fiber thermal conductivity (Kf) will be determined as a function of temperature up to 1000°C before and after irradiation for samples cut from these rods. Preliminary thermal conductivity data for unirradiated fibers (Hi-Nicalon™ and Tyranno™ SA-B SiC and K1100™ graphite) and for three types of unirradiated composites made from these fibers (2D-Nicalon S/SiC multilayer/CVI-SiC, 3D-Nicalon S/PIP-SiC, and 2D-8HS Tyrannohex™ HP) are presented.

Evidence for induction of DNA double strand breaks in the bystander response to targeted soft X-rays in repair deficient CHO cells

International Nuclear Information System (INIS)

Kashino, Genro; Suzuki, Keiji; Prise, K.M.

2005-01-01

Evidence is accumulating that irradiated cells produce some signals which interact with non-exposed cells in the same population. Here, we analysed the mechanism of such a bystander effect from targeted cells to non-targeted cells. Firstly, in order to investigate the bystander effect in Chinese hamster ovary (CHO) cell lines we irradiated a single cell within a population and scored the formation of micronuclei. When a single nucleus in the population, of double strand break repair deficient xrs5 cells, was targeted with 1 Gy of Al-K soft X-rays, elevated numbers of micronuclei were induced in the neighbouring unirradiated cells. The induction of micronuclei was also observed when conditioned medium was transferred from irradiated to non-irradiated xrs5 cells. These results suggest that DNA double strand breaks are caused by factors secreted in the medium from irradiated cells. To clarify the involvements of radical species in the bystander response, cells were treated with 0.5%DMSO 1 hour before irradiation and then bystander effects were estimated in xrs5 cells. The results showed clearly that DMSO treatment during X-irradiation suppress the induction of micronuclei in bystander xrs5 cells, when conditioned medium was transferred from irradiated xrs5 cells. Therefore, it is suggested that radical species induced by ionizing radiation are important for producing bystander signals. (author)

Targets and tactics

DEFF Research Database (Denmark)

Woo, V; Shestakova, M V; Ørskov, C

2008-01-01

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

An archaeal CRISPR type III-B system exhibiting distinctive RNA targeting features and mediating dual RNA and DNA interference

DEFF Research Database (Denmark)

Peng, Wenfang; Feng, Mingxia; Feng, Xu

2015-01-01

CRISPR-Cas systems provide a small RNA-based mechanism to defend against invasive genetic elements in archaea and bacteria. To investigate the in vivo mechanism of RNA interference by two type III-B systems (Cmr-α and Cmr-β) in Sulfolobus islandicus, a genetic assay was developed using plasmids...... carrying an artificial mini-CRISPR (AC) locus with a single spacer. After pAC plasmids were introduced into different strains, Northern analyses confirmed that mature crRNAs were produced from the plasmid-borne CRISPR loci, which then guided gene silencing to target gene expression. Spacer mutagenesis....... islandicus Cmr-α mediated transcription-dependent DNA interference, the Cmr-α constitutes the first CRISPR system exhibiting dual targeting of RNA and DNA....

Target cells in internal dosimetry

Energy Technology Data Exchange (ETDEWEB)

Goessner, W

2003-07-01

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

Target cells in internal dosimetry

International Nuclear Information System (INIS)

Goessner, W.

2003-01-01

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

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

Science.gov (United States)

Spiers, Gary D.

2001-01-01

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

Discrimination of source reactor type by multivariate statistical analysis of uranium and plutonium isotopic concentrations in unknown irradiated nuclear fuel material.

Science.gov (United States)

Robel, Martin; Kristo, Michael J

2008-11-01

The problem of identifying the provenance of unknown nuclear material in the environment by multivariate statistical analysis of its uranium and/or plutonium isotopic composition is considered. Such material can be introduced into the environment as a result of nuclear accidents, inadvertent processing losses, illegal dumping of waste, or deliberate trafficking in nuclear materials. Various combinations of reactor type and fuel composition were analyzed using Principal Components Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLSDA) of the concentrations of nine U and Pu isotopes in fuel as a function of burnup. Real-world variation in the concentrations of (234)U and (236)U in the fresh (unirradiated) fuel was incorporated. The U and Pu were also analyzed separately, with results that suggest that, even after reprocessing or environmental fractionation, Pu isotopes can be used to determine both the source reactor type and the initial fuel composition with good discrimination.

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

Science.gov (United States)

Jin, Shouheng; Tian, Shuo; Luo, Man; Xie, Weihong; Liu, Tao; Duan, Tianhao; Wu, Yaoxing; Cui, Jun

2017-10-19

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

Science.gov (United States)

Desprez, Pierre-Yves; Campisi, Judith

2014-08-19

A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

Low cycle fatigue properties of neutron irradiated solid HIP 316L(N). ITER Task T214, NET deliverable GB6 ECN-5

International Nuclear Information System (INIS)

Rensman, J.; Van Osch, E.V.; Tjoa, G.L.; Boskeljon, J.; Van Hoepen, J.

1998-05-01

The Low Cycle Fatigue (LCF) properties of neutron irradiated Hot Isostatically Pressed (HIP) joints of type 316L(N) stainless steel (heat PM-130) have been measured, as well as the LCF properties of reference 316L(N)-ERHII. Cylindrical LCF test specimens of 3 mm diameter were irradiated in the High Flux Reactor (HFR) in Petten, The Netherlands, simulating the first wall conditions of future fusion reactors by a combination of high displacement damage with proportional amounts of helium. The solid HIP specimens were irradiated up to a target dose level of 5 dpa at a temperature of 550K. The damage levels realised range from 3.0 to 4.4 dpa, with helium contents up to 41 appm. Testing temperature was equal to the irradiation temperature: 550K. The report contains the experimental conditions and summarises the results, which are given in terms of first cycle stress, the peak stress, the number of cycles where the peak stress is reached, the stress at half life and the plastic strain at half life, and the total number of cycles to failure, N f . The main conclusions are that the unirradiated solid-HIP materials has the same LCF properties as unirradiated 316L(N)-ERHII plate material. The neutron irradiation induces both hardening and reduction of fatigue life. The bond does not seem to have any effect on the fatigue properties for the unirradiated solid HIP 316L(N), whereas a combined effect of irradiation and the bond cannot be established. No failures related to debonding of the joint were observed for the tests. 7 refs

Structural impact of armor monoblock dimensions on the failure behavior of ITER-type divertor target components: Size matters

Energy Technology Data Exchange (ETDEWEB)

Li, Muyuan; You, Jeong-Ha, E-mail: you@ipp.mpg.de

2016-12-15

Highlights: • Quantitative assessment of size effects was conducted numerically for W monoblock. • Decreasing the width of W monoblock leads to a lower risk of failure. • The Cu interlayer was not affected significantly by varying armor thickness. • The predicted trends were in line with the experimental observations. - Abstract: Plenty of high-heat-flux tests conducted on tungsten monoblock type divertor target mock-ups showed that the threshold heat flux density for cracking and fracture of tungsten armor seems to be related to the dimension of the monoblocks. Thus, quantitative assessment of such size effects is of practical importance for divertor target design. In this paper, a computational study about the thermal and structural impact of monoblock size on the plastic fatigue and fracture behavior of an ITER-type tungsten divertor target is reported. As dimensional parameters, the width and thickness of monoblock, the thickness of sacrificial armor, and the inner diameter of cooling tube were varied. Plastic fatigue lifetime was estimated for the loading surface of tungsten armor and the copper interlayer by use of a cyclic-plastic constitutive model. The driving force of brittle crack growth through the tungsten armor was assessed in terms of J-integral at the crack tip. Decrease of the monoblock width effectively reduced accumulation of plastic strain at the armor surface and the driving force of brittle cracking. Decrease of sacrificial armor thickness led to decrease of plastic deformation at the loading surface due to lower surface temperature, but the thermal and mechanical response of the copper interlayer was not affected by the variation of armor thickness. Monoblock with a smaller tube diameter but with the same armor thickness and shoulder thickness experienced lower fatigue load. The predicted trends were in line with the experimental observations.

Effect of gene-targeted mutation in TNF receptor (p55) on contact hypersensitivity and ultraviolet B-induced immunosuppression

Energy Technology Data Exchange (ETDEWEB)

Kondo, Seiji; Wang, Binghe; Fujisawa, Hiroshi [Univ. of Toronto, Ontario (Canada)] [and others

1995-10-15

Tumor necrosis factor {alpha} (TNF-{alpha}) is a pleiotropic proinflammatory cytokine. TNF-{alpha} has been implicated in the pathogenesis of delayed-type hypersensitivity reactions such as allergic contact hypersensitivity and has been suggested as a mediator of ultraviolet B (UVB)-induced immunosuppression. Conflicting reports, however, exist concerning the effects of TNF-{alpha} on contact hypersensitivity (CHS). To determine the role of TNF-{alpha} in the generation and regulation of CHS, gene-targeted mutant mice lacking TNF-receptor (p55) gene (TNF-R1(-) mice) were treated with dinitrofluorobenzene (DNFB) to induce CHS. TNF-R1(-) mice showed significant hyperresponsiveness in CHS (152.8 {+-} 20.9%, p < 0.025) compared with normal syngeneic mice (C57BL/6) assessed by ear swelling. To determine whether UVB can induce suppression in TNF-R1(-) mice, mice were irradiated on the shaved abdomen with 96 ml/cm{sup 2} UVB and 3 days later they were painted with 0.5% DNFB (sensitization dose), followed 5 days later with 0.2% DNFB to the left ear (challenge dose). Significant suppression of CHS was observed both locally (sensitization on irradiated site) and systemically (sensitization on unirradiated site) in UVB-irradiated TNF-R1(-) mice as well as in normal mice. To rule out possible signaling through p75 TNF-R, the mice were treated with anti-TNF-{alpha} Ab (V1q), which can neutralize any TNF effects through either receptor. V1q had no effect on these phenomena observed in TNF-R1(-) mice. These results suggest that TNF-{alpha} plays a regulatory role in CHS but is not required to induce UVB-mediated immunosuppression. 45 refs., 5 figs.

Target for production of X-rays

Energy Technology Data Exchange (ETDEWEB)

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

2004-10-01

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

Target for production of X-rays

International Nuclear Information System (INIS)

Korenev, S.A.

2004-01-01

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

Target for production of X-rays

Science.gov (United States)

Korenev, S. A.

2004-09-01

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

Targeted overexpression of endothelial nitric oxide synthase in endothelial cells improves cerebrovascular reactivity in Ins2Akita-type-1 diabetic mice.

Science.gov (United States)

Chandra, Saurav B; Mohan, Sumathy; Ford, Bridget M; Huang, Lei; Janardhanan, Preethi; Deo, Kaiwalya S; Cong, Linlin; Muir, Eric R; Duong, Timothy Q

2016-06-01

Reduced bioavailability of nitric oxide due to impaired endothelial nitric oxide synthase (eNOS) activity is a leading cause of endothelial dysfunction in diabetes. Enhancing eNOS activity in diabetes is a potential therapeutic target. This study investigated basal cerebral blood flow and cerebrovascular reactivity in wild-type mice, diabetic mice (Ins2(Akita+/-)), nondiabetic eNOS-overexpressing mice (TgeNOS), and the cross of two transgenic mice (TgeNOS-Ins2(Akita+/-)) at six months of age. The cross was aimed at improving eNOS expression in diabetic mice. The major findings were: (i) Body weights of Ins2(Akita+/-) and TgeNOS-Ins2(Akita+/-) were significantly different from wild-type and TgeNOS mice. Blood pressure of TgeNOS mice was lower than wild-type. (ii) Basal cerebral blood flow of the TgeNOS group was significantly higher than cerebral blood flow of the other three groups. (iii) The cerebrovascular reactivity in the Ins2(Akita+/-) mice was significantly lower compared with wild-type, whereas that in the TgeNOS-Ins2(Akita+/-) was significantly higher compared with the Ins2(Akita+/-) and TgeNOS groups. Overexpression of eNOS rescued cerebrovascular dysfunction in diabetic animals, resulting in improved cerebrovascular reactivity. These results underscore the possible role of eNOS in vascular dysfunction in the brain of diabetic mice and support the notion that enhancing eNOS activity in diabetes is a potential therapeutic target. © The Author(s) 2015.

The influence of low dose irradiation on the creep properties of type 316 welds

International Nuclear Information System (INIS)

Marshall, P.; Steeds, J.W.; Lin, Y.P.; Finlan, G.T.

1987-01-01

Fully instrumented creep and stress rupture tests have been performed at 873K for times up to 20,000h on a series of type 316 steel/17Cr 8Ni 2Mo weld metal specimens in the unirradiated and thermal neutron irradiated conditions. The specimens tested included all weld metal longitudinal and transverse composites in the as-welded condition and following a stress relief heat treatment of 10h at 1075K. Simulated heat affected zone (HAZ) specimens were also tested. Analysis of the creep results combined with metallography, autoradiography and TEM established that the decrease in properties of irradiated samples is caused by an increasing secondary strain rate due to enhanced helium induced grain boundary fracture of the simulated HAZ and enhanced interdendritic fracture in the weld metal. Implications of strength reductions on the design of welded structures subjected to thermal irradiation are briefly assessed. (author)

Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I.

Science.gov (United States)

Brockhoff, Marielle; Rion, Nathalie; Chojnowska, Kathrin; Wiktorowicz, Tatiana; Eickhorst, Christopher; Erne, Beat; Frank, Stephan; Angelini, Corrado; Furling, Denis; Rüegg, Markus A; Sinnreich, Michael; Castets, Perrine

2017-02-01

Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease. In a well-characterized mouse model for DM1 (HSALR mice), activation of AMPK signaling in muscle was impaired under starved conditions, while mTORC1 signaling remained active. In parallel, autophagic flux was perturbed in HSALR muscle and in cultured human DM1 myotubes. Pharmacological approaches targeting AMPK/mTORC1 signaling greatly ameliorated muscle function in HSALR mice. AICAR, an AMPK activator, led to a strong reduction of myotonia, which was accompanied by partial correction of misregulated alternative splicing. Rapamycin, an mTORC1 inhibitor, improved muscle relaxation and increased muscle force in HSALR mice without affecting splicing. These findings highlight the involvement of AMPK/mTORC1 deregulation in DM1 muscle pathophysiology and may open potential avenues for the treatment of this disease.

Radiation-induced base substitution mutagenesis in single-stranded DNA phage M13

International Nuclear Information System (INIS)

Brandenburger, A.; Godson, G.N.; Glickman, B.W.; Sluis, C.A. van

1981-01-01

To elucidate the relative contributions of targeted and untargeted mutations to γ and UV radiation mutagenesis, the DNA sequences of 174 M13 revertant phages isolated from stocks of irradiated or unirradiated amber mutants grown in irradiated (SOS-induced) or unirradiated (non-induced) host bacteria, have been determined. Differences in the spectra of base change mutations induced in the various conditions were apparent, but no obvious specificity of mutagenesis was detected. In particular, under the present conditions, pyrimidine dimers did not seem to be the principal sites of UV-induced base substitution mutagenesis, suggesting that such mutagenesis occurs at the sites of lesions other than pyrimidine dimers, or is untargeted. (U.K.)

Literature evidence in open targets - a target validation platform.

Science.gov (United States)

Kafkas, Şenay; Dunham, Ian; McEntyre, Johanna

2017-06-06

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

Dissolution of unirradiated UO{sub 2} fuel in synthetic groundwater. Final report (1996-1998)

Energy Technology Data Exchange (ETDEWEB)

Ollila, K. [VTT Chemical Technology, Espoo (Finland)

1999-05-01

This study was a part of the EU R and D programme 1994-1998: Nuclear Fission Safety, entitled `Source term for performance assessment of spent fuel as a waste form`. The research carried out at VTT Chemical Technology was focused on the effects of granitic groundwater composition and redox conditions on UO{sub 2} solubility and dissolution mechanisms. The synthetic groundwater compositions simulated deep granitic fresh and saline groundwaters, and the effects of the near-field material, bentonite, on very saline groundwater. Additionally, the Spanish granite/bentonite water was used. The redox conditions (Eh), which are obviously the most important factors that influence on UO{sub 2} solubility under the disposal conditions of spent fuel, varied from strongly oxidising (air-saturated), anaerobic (N{sub 2}, O{sub 2} < l ppm) to reducing (N{sub 2}, low Eh). The objective of the air-saturated dissolution experiments was to yield the maximum solution concentrations of U, and information on the formation of secondary phases that control the concentrations, with different groundwater compositions. The static batch solubility experiments of long duration (up to 1-2 years) were performed using unirradiated UO{sub 2} pellets and powder. Under anaerobic and reducing conditions, the solubilities were also approached from oversaturation. The results of the oxic, air-saturated dissolution experiments with UO{sub 2} powder showed that the increase in the salinity (< 1.7 M) had a minor effect on the measured steady-state concentrations of U. The concentrations, (1.2 ...2.5) x 10{sup -5} M, were at the level of the theoretical solubility of schoepite or another uranyl oxide hydrate, e.g. becquerelite (possibly Na-polyuranate). The higher alkalinity of the fresh (Allard) composition increased the aqueous U concentration. Only some kind of oxidised U-phase (U{sub 3}O{sub 8}-UO{sub 3}) was identified with XRD when studying possible secondary phases after the contact time of one year

Herpes simplex virus produces larger plaques when assayed on ultraviolet irradiated CV1 cells

International Nuclear Information System (INIS)

Coohill, T.P.; Babich, M.A.; Taylor, W.D.; Snipes, W.

1980-01-01

Plaque development for either untreated or UV treated irradiated Herpes simplex virus Type 1 was faster when assayed on UV irradiated CV1 cells. This Large Plaque Effect only occurred if a minimum delay of 12h between cell irradiation and viral inoculation was allowed. Shorter delays gave plaques that were smaller than controls (unirradiated virus-unirradiated cells). The effect was maximal for a 48-h delay and remained unchanged for delays as long as 84h. The effect was greatest for cell exposures of 10Jm -2 . (author)

Targeting trichothecene biosynthetic genes

NARCIS (Netherlands)

Wei, Songhong; Lee, van der Theo; Verstappen, Els; Gent, van Marga; Waalwijk, Cees

2017-01-01

Biosynthesis of trichothecenes requires the involvement of at least 15 genes, most of which have been targeted for PCR. Qualitative PCRs are used to assign chemotypes to individual isolates, e.g., the capacity to produce type A and/or type B trichothecenes. Many regions in the core cluster

Diabetes-related symptoms and negative mood in participants of a targeted population-screening program for type 2 diabetes: the Hoorn screening study

NARCIS (Netherlands)

Adriaanse, M.C.; Dekker, J.M.; Spijkerman, A.M.W.; Twisk, J.W.R.; Nijpels, M.G.A.A.M.; van der Ploeg, H.M.; Heine, R.J.; Snoek, F.J.

2005-01-01

Objective: To determine the level of diabetes-related symptom distress and its association with negative mood in subjects participating in a targeted population-screening program, comparing those identified as having type 2 diabetes vs. those who did not. Research design and methods: This study was

Effectiveness of treat-to-target strategy for LDL-cholesterol control in type 2 diabetes: post-hoc analysis of data from the MIND.IT study.

Science.gov (United States)

Ardigò, Diego; Vaccaro, Olga; Cavalot, Franco; Rivellese, Albarosa Angela; Franzini, Laura; Miccoli, Roberto; Patti, Lidia; Boemi, Massimo; Trovati, Mariella; Zavaroni, Ivana

2014-04-01

The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study. MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach. Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p < 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction <0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p < 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target. The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

Tensile properties of neutron irradiated solid HIP 316L(N). ITER Task T214, NET deliverable GB6 ECN-5

International Nuclear Information System (INIS)

Van Osch, E.V.; Tjoa, G.L.; Boskeljon, J.; Van Hoepen, J.

1998-05-01

The tensile properties of neutron irradiated Hot Isostatically Pressed (HIP) joints of type 316L(N) stainless steel (heat PM-130) have been measured. Cylindrical tensile test specimens of 4 mm diameter were irradiated in the High Flux Reactor (HFR) in Petten, The Netherlands, simulating the first wall conditions by a combination of high displacement damage with proportional amounts of helium. The solid HIP specimens were irradiated up to a target dose level of 5 dpa at a temperature of 550K. The damage levels realized range from 3.0 to 4.1 dpa, with helium contents up to 38 appm. Post irradiation testing temperatures ranged from 300 to 700K. The report contains the experimental conditions and summarises the results, which are given in terms of engineering stresses and strains and reduction of area. The main conclusions are that the unirradiated solid-HIP material is very soft, assumingly due to the relatively large grain size. Neutron irradiation induces both hardening and reduction of ductility, similar to the behaviour of 316L(N) plate. No failures related to debonding were observed for the tests of the unirradiated samples, however one of eight tested irradiated specimens fractured in the HIP joint, showing a flat fracture surface and a low reduction of area. 6 refs

Who breaches the four-hour emergency department wait time target? A retrospective analysis of 374,000 emergency department attendances between 2008 and 2013 at a type 1 emergency department in England.

Science.gov (United States)

Bobrovitz, Niklas; Lasserson, Daniel S; Briggs, Adam D M

2017-11-02

The four-hour target is a key hospital emergency department performance indicator in England and one that drives the physical and organisational design of the ED. Some studies have identified time of presentation as a key factor affecting waiting times. Few studies have investigated other determinants of breaching the four-hour target. Therefore, our objective was to describe patterns of emergency department breaches of the four-hour wait time target and identify patients at highest risk of breaching. This was a retrospective cohort study of a large type 1 Emergency department at an NHS teaching hospital in Oxford, England. We analysed anonymised individual level patient data for 378,873 emergency department attendances, representing all attendances between April 2008 and April 2013. We examined patient characteristics and emergency department presentation circumstances associated with the highest likelihood of breaching the four-hour wait time target. We used 374,459 complete cases for analysis. In total, 8.3% of all patients breached the four-hour wait time target. The main determinants of patients breaching the four-hour wait time target were hour of arrival to the ED, day of the week, patient age, ED referral source, and the types of investigations patients receive (p target were older, presented at night, presented on Monday, received multiple types of investigation in the emergency department, and were not self-referred (p target including patient age, ED referral source, the types of investigations patients receive, as well as the hour, day, and month of arrival to the ED. Efforts to reduce the number of breaches could explore late-evening/overnight staffing, access to diagnostic tests, rapid discharge facilities, and early assessment and input on diagnostic and management strategies from a senior practitioner.

TARGET Research Goals

Science.gov (United States)

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

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.

Influence of specimen size/type on the fracture toughness of five irradiated RPV materials

International Nuclear Information System (INIS)

Sokolov, Mikhail A; Lucon, Enrico

2015-01-01

The Heavy-Section Steel Irradiation (HSSI) Program had previously irradiated five reactor pressure vessel (RPV) steels/welds at fast neutron fluxes of about 4 to 8 x 10 11 n/cm 2 /s (>1 MeV) to fluences from 0.5 to 3.4 10 19 n/cm 2 and at 288 °C. The unirradiated fracture toughness tests were performed by Oak Ridge National Laboratory with 12.7-mm and 25.4-mm thick (0.5T and 1T) compact specimens, while the HSSI Program provided tensile and 5 x 10-mm three-point bend specimens to SCK-CEN for irradiation in the in-pile section of the Belgian Reactor BR2 at fluxes > 10 13 n/cm 2 /s and subsequent testing by SCK-CEN. The BR2 irradiations were conducted at about 2 and 4 x 10 13 n/cm 2 /s with irradiation temperature between 295 °C and 300 °C (water temperature), and to fluences between 6 and 10 x 10 19 n/cm 2 . The irradiation-induced shifts of the Master Curve reference temperatures, ΔT 0 , for most of the materials deviated from the embrittlement correlations much more than expected, motivating the testing of 5 x 10-mm three-point bend specimens of all five materials in the unirradiated condition to eliminate specimen size and geometry as a variable. Tests of the unirradiated small bend specimens resulted in Master Curve reference temperatures, ΔT 0 , 25 °C to 53 °C lower than those from the larger compact specimens, meaning that the irradiation-induced reference temperature shifts, ΔT 0 , were larger than the initial measurements, resulting in much improved agreement between the measured and predicted fracture toughness shifts.

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

NARCIS (Netherlands)

DENIJS, G; HOEKSTRA, R; MORGENSTERN, R

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

A blow-in windowless gas target

International Nuclear Information System (INIS)

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

1996-01-01

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

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

Directory of Open Access Journals (Sweden)

Yi-An Chen

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

Observation of Rayleigh-Taylor-like structures in a laser-accelerated foil

International Nuclear Information System (INIS)

Whitlock, R.R.; Emery, M.H.; Stamper, J.A.; McLean, E.A.; Obenschain, S.P.; Peckerar, M.C.

1984-01-01

Laser-accelerated targets have been predicted to be subject to the Rayleigh-Taylor hydrodynamic instability. The development of the instability was studied by introducing mass thickness variations in foil targets and observing the development of the target nonuniformities by side-on flash x radiography. Observations were made of target structures and mass redistribution effects which resemble Rayleigh-Taylor bubbles and spikes, including not only advanced broadening of the spike tips on the laser-irradiated side of the foil but also projections of mass on the unirradiated side. The observations compare well with numerical simulations

Hybrid value foraging: How the value of targets shapes human foraging behavior.

Science.gov (United States)

Wolfe, Jeremy M; Cain, Matthew S; Alaoui-Soce, Abla

2018-04-01

In hybrid foraging, observers search visual displays for multiple instances of multiple target types. In previous hybrid foraging experiments, although there were multiple types of target, all instances of all targets had the same value. Under such conditions, behavior was well described by the marginal value theorem (MVT). Foragers left the current "patch" for the next patch when the instantaneous rate of collection dropped below their average rate of collection. An observer's specific target selections were shaped by previous target selections. Observers were biased toward picking another instance of the same target. In the present work, observers forage for instances of four target types whose value and prevalence can vary. If value is kept constant and prevalence manipulated, participants consistently show a preference for the most common targets. Patch-leaving behavior follows MVT. When value is manipulated, observers favor more valuable targets, though individual foraging strategies become more diverse, with some observers favoring the most valuable target types very strongly, sometimes moving to the next patch without collecting any of the less valuable targets.

Beam splitting to improve target life in neutron generators

International Nuclear Information System (INIS)

Farrell, J.P.

1976-01-01

In a neutron generator in which a tritium-titanium target is bombarded by a deuterium ion beam, the target half-life is increased by separating the beam with a weak magnetic field to provide three separate beams of atomic, diatomic, and triatomic deuterium ions which all strike the target at different adjacent locations. Beam separation in this manner eliminates the problem of one type ion impairing the neutron generating efficiency of other type ions, thereby effecting more efficient utilization of the target material

Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin

International Nuclear Information System (INIS)

Chua, Melvin Lee Kiang; Somaiah, Navita; Bourne, Sara; Daley, Frances; A'Hern, Roger; Nuta, Otilia; Davies, Sue; Herskind, Carsten; Pearson, Ann; Warrington, Jim; Helyer, Sarah; Owen, Roger; Yarnold, John; Rothkamm, Kai

2011-01-01

Purpose: The aim of this study was to compare inter-individual and inter-cell type variation in DNA double-strand break (DSB) repair following in vivo irradiation of human skin. Materials and methods: Duplicate 4 mm core biopsies of irradiated and unirradiated skin were collected from 35 patients 24 h after 4 Gy exposure using 6 MeV electrons. Residual DSB were quantified by scoring 53BP1 foci in dermal fibroblasts, endothelial cells, superficial keratinocytes and basal epidermal cells. Results: Coefficients of inter-individual variation for levels of residual foci 24 h after in vivo irradiation of skin were 39.9% in dermal fibroblasts, 44.3% in endothelial cells, 32.9% in superficial keratinocytes and 46.4% in basal epidermal cells (p < 0.001, ANOVA). In contrast, the coefficient of inter-cell type variation for residual foci levels was only 11.3% in human skin between the different epidermal and dermal cells (p = 0.034, ANOVA). Foci levels between the different skin cell types were correlated (Pearson's R = 0.855-0.955, p < 0.001). Conclusions: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin.

Characterizations of power loads on divertor targets for type-I, compound and small ELMs in the EAST superconducting tokamak

DEFF Research Database (Denmark)

Wang, L.; Xu, G.S.; Guo, H.Y.

2013-01-01

-III ELMy H-modes. The energy loss and divertor power load are systematically characterized for these different ELMy H-modes to provide a physics basis for the next-step high-power long-pulse operations in EAST. Both type-I and compound ELMs exhibit good confinement (H98(y,2) ∼ 1). A significant loss......The Experimental Advanced Superconducting Tokamak (EAST) has recently achieved a variety of H-mode regimes with different edge-localized mode (ELM) dynamics, including type-I ELMs, compound ELMs, which are manifested by the onset of a large spike followed by a sequence of small spikes on Dα......-III ELMs. It is remarkable that the new very small ELMy H-modes exhibit even lower target power deposition than type-III ELMs, with the peak heat flux generally below 1 MW m−2. These very small ELMs are usually accompanied by broadband fluctuations with frequencies ranging from 20 to 50 kHz, which may...

X-ray tube target

International Nuclear Information System (INIS)

Weber, R.G.

1980-01-01

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

Combinatorial microRNA target predictions

DEFF Research Database (Denmark)

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

2005-01-01

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

Toxin production of non-proteolytic Cl. botulinum type B in radurized fish. Part of a coordinated programme on the wholesomeness of the process of food irradiation

International Nuclear Information System (INIS)

Suhadi, F.

1981-02-01

Toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in radurized raw fish and in radurized Pindang fish was investigated. In radurized Pindang fish samples, inoculation was done either before or after cooking. Radurization process with 2 and 3 kGy caused the extension of storage life of Rastrelliger sp., Euthynnus sp., and Scomberomorus sp. by factors of 2 and 2.5 at storage temperatures between 5 and 10 0 C. In general at 10.5 +- 0.3 0 C, no toxin was formed before the samples were spoiled both in irradiated and unirradiated samples. At 5.6 +- 0.5 0 C no toxin was formed until after the samples were spoiled. The earliest toxin formation in unirradiated Pindang samples stored at ambient temperature was detected after the samples were spoiled. In irradiated Pindang samples inoculated with C. botulinum spores after cooking and stored at ambient temperature the toxin formation was detected before the samples were spoiled. However, if the inoculation was done before the fish was processed into Pindang, the toxin was always detected after the samples were spoiled regardless of the irradiation dose, strain and inoculation level. As fish may be contaminated - if at all - with spores of C. botulinum in its raw state, processing of fish into Pindang and irradiation would not contribute to the health hazard concerning botulism even if the samples are stored at ambient temperature

Microstructure and mechanical properties of unirradiated low activation ferritic steel

International Nuclear Information System (INIS)

Hsu, C.Y.; Lechtenberg, T.A.

1986-01-01

Transmission electron micrographs of normalized and tempered 9Cr-2.5W-0.3V-0.15C low activation ferritic steel showed tempered lath-type martensite with precipitation of rod and plate-like carbides at lath and grain boundaries. X-ray diffraction analysis of the extracted replicas revealed nearly 100% M 23 C 6 carbides (a=1.064 nm), with no indication of Fe 2 W-type Laves phase even after thermal aging at 600 0 C/1000 h. Thermal aging increased the number density of rod-like M 23 C 6 along prior austenite grain boundaries and martensite lath boundaries. The elevated-temperature tensile strengths of this steel are about 10% higher than the average strengths of commercial heats of 9Cr-1Mo and modified 9Cr-1Mo steels up to 650 0 C, with equivalent uniform elongation and ∝50% decrease in total elongation. The DBTT was determined to be -25 0 C which is similar to other 9Cr-1Mo steels. Fractographic examination of tensile tested specimens shows a mixed mode of equiaxed and elongated dimples at test temperatures above 400 0 C. Modification of the Ga3X alloy composition for opimization of materials properties is discussed. However, the proposed low activation ferritic steel shows the promise of improved mechanical properties over 9Cr-1Mo steels. (orig.)

Targeted next generation sequencing identified a novel mutation in MYO7A causing Usher syndrome type 1 in an Iranian consanguineous pedigree.

Science.gov (United States)

Kooshavar, Daniz; Razipour, Masoumeh; Movasat, Morteza; Keramatipour, Mohammad

2018-01-01

Usher syndrome (USH) is characterized by congenital hearing loss and retinitis pigmentosa (RP) with a later onset. It is an autosomal recessive trait with clinical and genetic heterogeneity which makes the molecular diagnosis much difficult. In this study, we introduce a pedigree with two affected members with USH type 1 and represent a cost and time effective approach for genetic diagnosis of USH as a genetically heterogeneous disorder. Target region capture in the genes of interest, followed by next generation sequencing (NGS) was used to determine the causative mutations in one of the probands. Then segregation analysis in the pedigree was conducted using PCR-Sanger sequencing. Targeted NGS detected a novel homozygous nonsense variant c.4513G > T (p.Glu1505Ter) in MYO7A. The variant is segregating in the pedigree with an autosomal recessive pattern. In this study, a novel stop gained variant c.4513G > T (p.Glu1505Ter) in MYO7A was found in an Iranian pedigree with two affected members with USH type 1. Bioinformatic as well as pedigree segregation analyses were in line with pathogenic nature of this variant. Targeted NGS panel was showed to be an efficient method for mutation detection in hereditary disorders with locus heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of the optical scattering characteristics of different types of space targets

International Nuclear Information System (INIS)

Han, Yi; Sun, Huayan; Feng, Jianguang; Li, Liang

2014-01-01

This paper mainly focused on the measurement, evaluation and potential identification methods of the unresolved space target's photometric characteristics. The bidirectional reflectance distribution function (BRDF) measurement system was introduced first, and then the measurement error of BRDF and its influence on target's optical cross section (OCS) and magnitude were analyzed. Then, different space targets’ OCS and magnitude changing with different factors, such as surface materials and shapes, flying conditions and working states, were analyzed respectively, and some general inclusions of variation laws were deduced. This research can provide references for future studies on space target classification and identification based on the photometric measurement data. (paper)

Preliminary investigation of solid target geometry

Energy Technology Data Exchange (ETDEWEB)

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

1997-11-01

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

Block Ignition Inertial Confinement Fusion (ICF) with Condensed Matter Cluster Type Targets for p-B11 Powered Space Propulsion

International Nuclear Information System (INIS)

Miley, George H.; Hora, H.; Badziak, J.; Wolowski, J.; Sheng Zhengming; Zhang Jie; Osman, F.; Zhang Weiyan; Tuhe Xia

2009-01-01

The use of laser-driven Inertial Confinement Fusion (ICF) for space propulsion has been the subject of several earlier conceptual design studies, (see: Orth, 1998; and other references therein). However, these studies were based on older ICF technology using either 'direct' or 'in-direct x-ray driven' type target irradiation. Important new directions have opened for laser ICF in recent years following the development of 'chirped' lasers capable of ultra short pulses with powers of TW up to few PW which leads to the concept of 'fast ignition (FI)' to achieve higher energy gains from target implosions. In a recent publication the authors showed that use of a modified type of FI, termed 'block ignition' (Miley et al., 2008), could meet many of the requirements anticipated (but not then available) by the designs of the Vehicle for Interplanetary Space Transport Applications (VISTA) ICF fusion propulsion ship (Orth, 2008) for deep space missions. Subsequently the first author devised and presented concepts for imbedding high density condensed matter 'clusters' of deuterium into the target to obtain ultra high local fusion reaction rates (Miley, 2008). Such rates are possible due to the high density of the clusters (over an order of magnitude above cryogenic deuterium). Once compressed by the implosion, the yet higher density gives an ultra high reaction rate over the cluster volume since the fusion rate is proportional to the square of the fuel density. Most recently, a new discovery discussed here indicates that the target matrix could be composed of B 11 with proton clusters imbedded. This then makes p-B 11 fusion practical, assuming all of the physics issues such as stability of the clusters during compression are resolved. Indeed, p-B 11 power is ideal for fusion propulsion since it has a minimum of unwanted side products while giving most of the reaction energy to energetic alpha particles which can be directed into an exhaust (propulsion) nozzle. Power plants

Block Ignition Inertial Confinement Fusion (ICF) with Condensed Matter Cluster Type Targets for p-B11 Powered Space Propulsion

Science.gov (United States)

Miley, George H.; Hora, H.; Badziak, J.; Wolowski, J.; Sheng, Zheng-Ming; Zhang, Jie; Osman, F.; Zhang, Weiyan; tu He, Xia

2009-03-01

The use of laser-driven Inertial Confinement Fusion (ICF) for space propulsion has been the subject of several earlier conceptual design studies, (see: Orth, 1998; and other references therein). However, these studies were based on older ICF technology using either "direct "or "in-direct x-ray driven" type target irradiation. Important new directions have opened for laser ICF in recent years following the development of "chirped" lasers capable of ultra short pulses with powers of TW up to few PW which leads to the concept of "fast ignition (FI)" to achieve higher energy gains from target implosions. In a recent publication the authors showed that use of a modified type of FI, termed "block ignition" (Miley et al., 2008), could meet many of the requirements anticipated (but not then available) by the designs of the Vehicle for Interplanetary Space Transport Applications (VISTA) ICF fusion propulsion ship (Orth, 2008) for deep space missions. Subsequently the first author devised and presented concepts for imbedding high density condensed matter "clusters" of deuterium into the target to obtain ultra high local fusion reaction rates (Miley, 2008). Such rates are possible due to the high density of the clusters (over an order of magnitude above cryogenic deuterium). Once compressed by the implosion, the yet higher density gives an ultra high reaction rate over the cluster volume since the fusion rate is proportional to the square of the fuel density. Most recently, a new discovery discussed here indicates that the target matrix could be composed of B11 with proton clusters imbedded. This then makes p-B11 fusion practical, assuming all of the physics issues such as stability of the clusters during compression are resolved. Indeed, p-B11 power is ideal for fusion propulsion since it has a minimum of unwanted side products while giving most of the reaction energy to energetic alpha particles which can be directed into an exhaust (propulsion) nozzle. Power plants using p

DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens

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Dolores L. Guzmán-Herrador

2017-08-01

Full Text Available We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

Shiva target irradiation facility

International Nuclear Information System (INIS)

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

1977-01-01

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

Testing of LWR fuel rods to support criticality safety analysis of transport accident conditions

Energy Technology Data Exchange (ETDEWEB)

Purcell, P.C. [BNFL International Transport, Spent Fuel Services (United Kingdom); Dallongeville, M. [COGEMA Logistics (AREVA Group) (France)

2004-07-01

For the transport of low enriched materials, criticality safety may be demonstrated by applying pessimistic modelling assumptions that bound any realistic case. Where Light Water Reactor (LWR) fuel is being transported, enrichment levels are usually too high to permit this approach and more realistic data is needed. This requires a method by which the response of LWR fuel under impact accident conditions can be approximated or bounded. In 2000, BNFL and COGEMA LOGISTICS jointly commenced the Fuel Integrity Project (FIP) whose objective was to develop such methods. COGEMA LOGISTICS were well advanced with a method for determining the impact response of unirradiated fuel, but required further test data before acceptance by the Transport Regulators. The joint project team extensively discussed the required inputs to the FIP, from which it was agreed that BNFL would organise new tests on both unirradiated and irradiated fuel samples and COGEMA LOGISTICS would take major responsibility for evaluating the test results. Tests on unirradiated fuel rod samples involved both dynamic and quasi-static loading on fuel samples. PWR fuel rods loaded with uranium pellets were dropped vertically from 9m onto a rigid target and this was repeated on BWR fuel rods, similar tests on empty fuel rods were also conducted. Quasi-static tests were conducted on 530 mm long PWR and BWR fuel specimens under axial loading. Tests on irradiated fuel samples were conducted on high burn-up fuel rods of both PWR and BWR types. These were believed original to the FIP project and involved applying bending loads to simply supported pressurised rod specimens. In one test the fuel rod was heated to nearly 500oC during loading, all specimens were subject to axial impact before testing. Considerable experience of fuel rod testing and new data was gained from this test programme.

Testing of LWR fuel rods to support criticality safety analysis of transport accident conditions

International Nuclear Information System (INIS)

Purcell, P.C.; Dallongeville, M.

2004-01-01

For the transport of low enriched materials, criticality safety may be demonstrated by applying pessimistic modelling assumptions that bound any realistic case. Where Light Water Reactor (LWR) fuel is being transported, enrichment levels are usually too high to permit this approach and more realistic data is needed. This requires a method by which the response of LWR fuel under impact accident conditions can be approximated or bounded. In 2000, BNFL and COGEMA LOGISTICS jointly commenced the Fuel Integrity Project (FIP) whose objective was to develop such methods. COGEMA LOGISTICS were well advanced with a method for determining the impact response of unirradiated fuel, but required further test data before acceptance by the Transport Regulators. The joint project team extensively discussed the required inputs to the FIP, from which it was agreed that BNFL would organise new tests on both unirradiated and irradiated fuel samples and COGEMA LOGISTICS would take major responsibility for evaluating the test results. Tests on unirradiated fuel rod samples involved both dynamic and quasi-static loading on fuel samples. PWR fuel rods loaded with uranium pellets were dropped vertically from 9m onto a rigid target and this was repeated on BWR fuel rods, similar tests on empty fuel rods were also conducted. Quasi-static tests were conducted on 530 mm long PWR and BWR fuel specimens under axial loading. Tests on irradiated fuel samples were conducted on high burn-up fuel rods of both PWR and BWR types. These were believed original to the FIP project and involved applying bending loads to simply supported pressurised rod specimens. In one test the fuel rod was heated to nearly 500oC during loading, all specimens were subject to axial impact before testing. Considerable experience of fuel rod testing and new data was gained from this test programme

Radiation-enhanced precipitation in a V-10 wt % Ti alloy

International Nuclear Information System (INIS)

Agarwal, S.C.; Taylor, A.

1976-01-01

A V-10 wt % Ti alloy was irradiated with 2.7 MeV 51 V + at 650 0 C to doses of 2 to 60 dpa. No void swelling was observed at any dose. The irradiation resulted in an enhancement of a precipitation process similar to that observed in unirradiated materials. The precipitates in irradiated specimens were found to have the NaCl-type cubic crystal structure with a lattice parameter of TiO. The orientation relationship between the matrix and the precipitates was the same as that observed under thermal equilibrium conditions in unirradiated materials

Yersinia pestis targets neutrophils via complement receptor 3

Science.gov (United States)

Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

2015-01-01

Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

Unirradiated characteristics of U-Si alloys as dispersed-phase fuels

International Nuclear Information System (INIS)

Domagala, R.F.; Wiencek, T.C.

1987-06-01

To satisfy the power demands of many research reactors, a new LEU fuel with a high density and U content was needed. Any fuel must be compatible with Al and its alloys so that it may be fabricable as a dispersed-phase in Al alloy and Al matrix plate-type elements following, as nearly as possible, established commercial manufacturing techniques. U-Si and U-Si-Al alloys at or near the composition of U 3 Si were immediately attractive because of work documented by the Canadians. 8 refs., 2 figs

Predicting drug-target interactions using restricted Boltzmann machines.

Science.gov (United States)

Wang, Yuhao; Zeng, Jianyang

2013-07-01

In silico prediction of drug-target interactions plays an important role toward identifying and developing new uses of existing or abandoned drugs. Network-based approaches have recently become a popular tool for discovering new drug-target interactions (DTIs). Unfortunately, most of these network-based approaches can only predict binary interactions between drugs and targets, and information about different types of interactions has not been well exploited for DTI prediction in previous studies. On the other hand, incorporating additional information about drug-target relationships or drug modes of action can improve prediction of DTIs. Furthermore, the predicted types of DTIs can broaden our understanding about the molecular basis of drug action. We propose a first machine learning approach to integrate multiple types of DTIs and predict unknown drug-target relationships or drug modes of action. We cast the new DTI prediction problem into a two-layer graphical model, called restricted Boltzmann machine, and apply a practical learning algorithm to train our model and make predictions. Tests on two public databases show that our restricted Boltzmann machine model can effectively capture the latent features of a DTI network and achieve excellent performance on predicting different types of DTIs, with the area under precision-recall curve up to 89.6. In addition, we demonstrate that integrating multiple types of DTIs can significantly outperform other predictions either by simply mixing multiple types of interactions without distinction or using only a single interaction type. Further tests show that our approach can infer a high fraction of novel DTIs that has been validated by known experiments in the literature or other databases. These results indicate that our approach can have highly practical relevance to DTI prediction and drug repositioning, and hence advance the drug discovery process. Software and datasets are available on request. Supplementary data are

Physical protection of export/import and transportation of nuclear material in the Slovak Republic

International Nuclear Information System (INIS)

Vaclav, J

2002-01-01

Full text: The paper contains short overview about average amount of nuclear materials transported on the territory of the Slovak Republic in a year, and the physical protection of these nuclear materials. There are several types of transportation and export/import of nuclear materials in the SR: fresh fuel import; import of other unirradiated nuclear materials (e.g. depleted uranium, natural uranium); export of unirradiated nuclear materials (e.g. natural uranium); internal transportation of fresh fuel; internal transportation of other unirradiated nuclear materials; internal transportation of spent fuel. The main objective of the nuclear regulatory authority SR is to supervise observation of the national legislation as follows: the act no. 130 / 1998 on peaceful use of nuclear energy; UJD SR's regulation no. 186/1999 which details the physical protection of the nuclear facilities, nuclear materials, and radioactive waste (following requirements of INFCIRC 225 / Rev. 4); UJD SR's regulation no. 284 / 1999 which details conditions of nuclear material and radioactive wastes transportation. (author)

ATTAINMENT OF TREATMENT TARGETS AMONG TYPE 2 DIABETIC PATIENTS FIRST ATTENDING A TERTIARY CARE SETTING IN SUBURBAN KERALA

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Sajeeth Kumar

2016-03-01

Full Text Available BACKGROUND Type 2 diabetes is growing in epidemic proportions worldwide, particularly in Asian subcontinent and especially in India. The disease takes a toll on the health system of a country, especially the developing nations. AIMS AND OBJECTIVES To study the attainment of metabolic and anthropometric goals of individuals with type 2 diabetes attending a tertiary care centre. MATERIALS AND METHODS i Informed consents were obtained. ii The study subjects were subjected to a detailed clinical, anthropometrical and biochemical evaluation at baseline by a dedicated diabetologist. iii These data were collected using a structured questionnaire and were analysed using EPI INFO (Ver 3.4.1. RESULTS A total of 350 cases were studied. Overall, 76.3% of patients could not achieve ADA A1c goal and 36.3% had very poor glycaemic control as evidenced by A1c >9%. CONCLUSIONS Despite the increasing awareness of type 2 diabetes both among attending physicians and patients, attainment of treatment targets still is a challenge even at a tertiary care setting. The lifestyle and dietary habits may be a main contributing factor for this situation. More focus needs to be given to nutritional aspects and physical exercise in not only in patients with type 2 diabetes mellitus, but also in apparently healthy individuals of the productive age group so that the disease can be delayed if not prevented.

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

radiolabelled regulatory peptides and their metabolically stabilised analogues. Antigen epitopes: Antibodies, as unlabelled biological drugs, are becoming of increasing interest. They exert an antibody-dependent cellular cytotoxicity which leads to lysis of tumour cells. Radiolabelled versions of these (and other) antibodies are being developed worldwide. The disadvantage of the long circulating time of antibodies can be solved by engineering fragments such as diabodies, bivalent single chain variable fragments (scFv), minibodies or by pretargeting approaches. Transmembrane transporters: Other interesting targets are transporters for radiolabelled amino acids and nutrients. Cancer cells require an increased supply of many such nutrients and obtain these by increased expression of some types of amino-acid transporter. A more detailed analysis of the relationship between amino-acid uptake and transporter expression in normal and malignant cells would be very valuable in identifying the clinical therapeutic potential of this class of tracer. Tumour blood supply: Tumours require an efficient blood supply to grow and metastatise and active angiogenesis of new blood vessels is a feature of many tumours. Specific receptors expressed during this process represent a novel class of targets for TRT. Extra-cellular matrix: Recently, another relevant class of target antigens has raised interest. Lectins, or carbohydrate binding proteins, recognize specific oligosaccharide structures on glycoproteins and glycolipids. It is well known that protein and lipid glycosylation are consistently altered in cancer cells for the aberrant activity of specific glycosyltransferase and glycosydases. Experimental evidence demonstrated that tumor growth and progression may depend, at least in part, on the presence of altered glycoproteins on the cell surface, which can mediate aberrant receptor-ligand interactions. (author)

Implications of publicly available genomic data resources in searching for therapeutic targets of obesity and type 2 diabetes.

Science.gov (United States)

Jung, Sungwon

2018-04-20

Obesity and type 2 diabetes (T2D) are two major conditions that are related to metabolic disorders and affect a large population. Although there have been significant efforts to identify their therapeutic targets, few benefits have come from comprehensive molecular profiling. This limited availability of comprehensive molecular profiling of obesity and T2D may be due to multiple challenges, as these conditions involve multiple organs and collecting tissue samples from subjects is more difficult in obesity and T2D than in other diseases, where surgical treatments are popular choices. While there is no repository of comprehensive molecular profiling data for obesity and T2D, multiple existing data resources can be utilized to cover various aspects of these conditions. This review presents studies with available genomic data resources for obesity and T2D and discusses genome-wide association studies (GWAS), a knockout (KO)-based phenotyping study, and gene expression profiles. These studies, based on their assessed coverage and characteristics, can provide insights into how such data can be utilized to identify therapeutic targets for obesity and T2D.

An integrated tool to study MHC region: accurate SNV detection and HLA genes typing in human MHC region using targeted high-throughput sequencing.

Directory of Open Access Journals (Sweden)

Hongzhi Cao

Full Text Available The major histocompatibility complex (MHC is one of the most variable and gene-dense regions of the human genome. Most studies of the MHC, and associated regions, focus on minor variants and HLA typing, many of which have been demonstrated to be associated with human disease susceptibility and metabolic pathways. However, the detection of variants in the MHC region, and diagnostic HLA typing, still lacks a coherent, standardized, cost effective and high coverage protocol of clinical quality and reliability. In this paper, we presented such a method for the accurate detection of minor variants and HLA types in the human MHC region, using high-throughput, high-coverage sequencing of target regions. A probe set was designed to template upon the 8 annotated human MHC haplotypes, and to encompass the 5 megabases (Mb of the extended MHC region. We deployed our probes upon three, genetically diverse human samples for probe set evaluation, and sequencing data show that ∼97% of the MHC region, and over 99% of the genes in MHC region, are covered with sufficient depth and good evenness. 98% of genotypes called by this capture sequencing prove consistent with established HapMap genotypes. We have concurrently developed a one-step pipeline for calling any HLA type referenced in the IMGT/HLA database from this target capture sequencing data, which shows over 96% typing accuracy when deployed at 4 digital resolution. This cost-effective and highly accurate approach for variant detection and HLA typing in the MHC region may lend further insight into immune-mediated diseases studies, and may find clinical utility in transplantation medicine research. This one-step pipeline is released for general evaluation and use by the scientific community.

Global Analysis of a Model of Viral Infection with Latent Stage and Two Types of Target Cells

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Shuo Liu

2013-01-01

Full Text Available By introducing the probability function describing latency of infected cells, we unify some models of viral infection with latent stage. For the case that the probability function is a step function, which implies that the latency period of the infected cells is constant, the corresponding model is a delay differential system. The model with delay of latency and two types of target cells is investigated, and the obtained results show that when the basic reproduction number is less than or equal to unity, the infection-free equilibrium is globally stable, that is, the in-host free virus will be cleared out finally; when the basic reproduction number is greater than unity, the infection equilibrium is globally stable, that is, the viral infection will be chronic and persist in-host. And by comparing the basic reproduction numbers of ordinary differential system and the associated delayed differential system, we think that it is necessary to elect an appropriate type of probability function for predicting the final outcome of viral infection in-host.

Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus

Energy Technology Data Exchange (ETDEWEB)

Shan, Qun, E-mail: shanp@jsnu.edu.cn; Zheng, Guihong, E-mail: ghzhengsd@jsnu.edu.cn; Zhu, Aihua, E-mail: ahzhu@jsnu.edu.cn; Cao, Li, E-mail: 948113717@qq.com; Lu, Jun, E-mail: lu-jun75@163.com; Wu, Dongmei, E-mail: wdm8610@jsnu.edu.cn; Zhang, ZiFeng, E-mail: zhangzifengsuper@jsnu.edu.cn; Fan, Shaohua, E-mail: fshfly@126.com; Sun, Chunhui, E-mail: 306484866@qq.com; Hu, Bin, E-mail: hubin@jsnu.edu.cn; Zheng, Yuanlin, E-mail: ylzheng@jsnu.edu.cn

2016-09-01

Emerging evidence has shown that microRNA-mediated gene expression modulation plays a crucial role in the pathogenesis of type 2 diabetes mellitus, but the novel miRNAs involved in type 2 diabetes and its functional regulatory mechanisms still need to be determined. In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35 mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as a target of miR-10a in vitro and in vivo. CREB1 and its downstream fibronectin (FN, extracellular matrix) were increased in HFD/STZ-treated mice, which was reversed by kidney miR-10a overexpression. The content of CREB1 and FN was increased by miR-10a knockdown in kidney of naïve mice. Furthermore, histone deacetylase 3 (HDAC3) was revealed to be increased in kidney of HFD/STZ mice, accompanied with the augmentation of ACR ratio and FN level. Knockdown of HDAC3 with siRNA significantly caused the increase of miR-10a, resulting in the decrease in CREB1 and FN expression in kidney of HFD/STZ mice. Contrarily, HDAC3 overexpression mediated by lentivirus decreased miR-10a content, and enhanced ACR value, CREB1 and FN formation in naïve mice. Collectively, these results elucidate that HDAC3/miR-10a/CREB1 serves as a new mechanism underlying kidney injury, providing potential therapeutic targets in type 2 diabetes. - Highlights: • Diabetes induces the decrease of miR-10a level in the kidney. • MiR-10a overexpression improves kidney damage of diabetes. • MiR-10a targeting CREB1/FN

Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus

International Nuclear Information System (INIS)

Shan, Qun; Zheng, Guihong; Zhu, Aihua; Cao, Li; Lu, Jun; Wu, Dongmei; Zhang, ZiFeng; Fan, Shaohua; Sun, Chunhui; Hu, Bin; Zheng, Yuanlin

2016-01-01

Emerging evidence has shown that microRNA-mediated gene expression modulation plays a crucial role in the pathogenesis of type 2 diabetes mellitus, but the novel miRNAs involved in type 2 diabetes and its functional regulatory mechanisms still need to be determined. In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35 mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as a target of miR-10a in vitro and in vivo. CREB1 and its downstream fibronectin (FN, extracellular matrix) were increased in HFD/STZ-treated mice, which was reversed by kidney miR-10a overexpression. The content of CREB1 and FN was increased by miR-10a knockdown in kidney of naïve mice. Furthermore, histone deacetylase 3 (HDAC3) was revealed to be increased in kidney of HFD/STZ mice, accompanied with the augmentation of ACR ratio and FN level. Knockdown of HDAC3 with siRNA significantly caused the increase of miR-10a, resulting in the decrease in CREB1 and FN expression in kidney of HFD/STZ mice. Contrarily, HDAC3 overexpression mediated by lentivirus decreased miR-10a content, and enhanced ACR value, CREB1 and FN formation in naïve mice. Collectively, these results elucidate that HDAC3/miR-10a/CREB1 serves as a new mechanism underlying kidney injury, providing potential therapeutic targets in type 2 diabetes. - Highlights: • Diabetes induces the decrease of miR-10a level in the kidney. • MiR-10a overexpression improves kidney damage of diabetes. • MiR-10a targeting CREB1/FN

Uncertainties in thick-target PIXE analysis

International Nuclear Information System (INIS)

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

1983-01-01

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

High-efficiency target-ion sources for RIB generation

International Nuclear Information System (INIS)

Alton, G.D.

1993-01-01

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

Combining Cell Type-Restricted Adenoviral Targeting with Immunostaining and Flow Cytometry to Identify Cells-of-Origin of Lung Cancer.

Science.gov (United States)

Best, Sarah A; Kersbergen, Ariena; Asselin-Labat, Marie-Liesse; Sutherland, Kate D

2018-01-01

Lung cancers display considerable intertumoral heterogeneity, leading to the classification of distinct tumor subtypes. Our understanding of the genetic aberrations that underlie tumor subtypes has been greatly enhanced by recent genomic sequencing studies and state-of-the-art gene targeting technologies, highlighting evidence that distinct lung cancer subtypes may be derived from different "cells-of-origin". Here, we describe the intra-tracheal delivery of cell type-restricted Ad5-Cre viruses into the lungs of adult mice, combined with immunohistochemical and flow cytometry strategies for the detection of lung cancer-initiating cells in vivo.

Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types

Directory of Open Access Journals (Sweden)

Kristina M. Ilieva

2018-01-01

Full Text Available Overexpression of the chondroitin sulfate proteoglycan 4 (CSPG4 has been associated with the pathology of multiple types of such as melanoma, breast cancer, squamous cell carcinoma, mesothelioma, neuroblastoma, adult and pediatric sarcomas, and some hematological cancers. CSPG4 has been reported to exhibit a role in the growth and survival as well as in the spreading and metastasis of tumor cells. CSPG4 is overexpressed in several malignant diseases, while it is thought to have restricted and low expression in normal tissues. Thus, CSPG4 has become the target of numerous anticancer treatment approaches, including monoclonal antibody-based therapies. This study reviews key potential anti-CSPG4 antibody and immune-based therapies and examines their direct antiproliferative/metastatic and immune activating mechanisms of action.

Implosion of the small cavity and large cavity cannonball targets

International Nuclear Information System (INIS)

Nishihara, Katsunobu; Yamanaka, Chiyoe.

1984-01-01

Recent results of cannonball target implosion research are briefly reviewed with theoretical predictions for GEKKO XII experiments. The cannonball targets are classified into two types according to the cavity size ; small cavity and large cavity. The compression mechanisms of the two types are discussed. (author)

Influence of specimen size/type on the fracture toughness of five irradiated RPV materials

Energy Technology Data Exchange (ETDEWEB)

Sokolov, Mikhail A [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lucon, Enrico [National Inst. of Standards and Technology (NIST), Boulder, CO (United States)

2015-01-01

The Heavy-Section Steel Irradiation (HSSI) Program had previously irradiated five reactor pressure vessel (RPV) steels/welds at fast neutron fluxes of about 4 to 8 x 10¹¹ n/cm²/s (>1 MeV) to fluences from 0.5 to 3.4 10¹⁹ n/cm² and at 288 °C. The unirradiated fracture toughness tests were performed by Oak Ridge National Laboratory with 12.7-mm and 25.4-mm thick (0.5T and 1T) compact specimens, while the HSSI Program provided tensile and 5 x 10-mm three-point bend specimens to SCK-CEN for irradiation in the in-pile section of the Belgian Reactor BR2 at fluxes > 10¹³ n/cm²/s and subsequent testing by SCK-CEN. The BR2 irradiations were conducted at about 2 and 4 x 10¹³ n/cm²/s with irradiation temperature between 295 °C and 300 °C (water temperature), and to fluences between 6 and 10 x 10¹⁹n/cm². The irradiation-induced shifts of the Master Curve reference temperatures, ΔT₀, for most of the materials deviated from the embrittlement correlations much more than expected, motivating the testing of 5 x 10-mm three-point bend specimens of all five materials in the unirradiated condition to eliminate specimen size and geometry as a variable. Tests of the unirradiated small bend specimens resulted in Master Curve reference temperatures, T₀, 25 °C to 53 °C lower than those from the larger compact specimens, meaning that the irradiation-induced reference temperature shifts, ΔT₀, were larger than the initial measurements, resulting in much improved agreement between the measured and predicted fracture toughness shifts.

Facts about Type 2

Medline Plus

Full Text Available ... or insulin to help you meet your target blood glucose levels. Type 2 usually gets worse over time – even if ... About Type 2 Recently Diagnosed Treatment and Care Blood Glucose ... Living With Type 2 Diabetes Program donate en -- A Future Without ...

Change detection in urban and rural driving scenes: Effects of target type and safety relevance on change blindness.

Science.gov (United States)

Beanland, Vanessa; Filtness, Ashleigh J; Jeans, Rhiannon

2017-03-01

The ability to detect changes is crucial for safe driving. Previous research has demonstrated that drivers often experience change blindness, which refers to failed or delayed change detection. The current study explored how susceptibility to change blindness varies as a function of the driving environment, type of object changed, and safety relevance of the change. Twenty-six fully-licenced drivers completed a driving-related change detection task. Changes occurred to seven target objects (road signs, cars, motorcycles, traffic lights, pedestrians, animals, or roadside trees) across two environments (urban or rural). The contextual safety relevance of the change was systematically manipulated within each object category, ranging from high safety relevance (i.e., requiring a response by the driver) to low safety relevance (i.e., requiring no response). When viewing rural scenes, compared with urban scenes, participants were significantly faster and more accurate at detecting changes, and were less susceptible to "looked-but-failed-to-see" errors. Interestingly, safety relevance of the change differentially affected performance in urban and rural environments. In urban scenes, participants were more efficient at detecting changes with higher safety relevance, whereas in rural scenes the effect of safety relevance has marginal to no effect on change detection. Finally, even after accounting for safety relevance, change blindness varied significantly between target types. Overall the results suggest that drivers are less susceptible to change blindness for objects that are likely to change or move (e.g., traffic lights vs. road signs), and for moving objects that pose greater danger (e.g., wild animals vs. pedestrians). Copyright © 2017 Elsevier Ltd. All rights reserved.

Accelerator and neutron targets: a survey

International Nuclear Information System (INIS)

Kobisk, E.H.

1974-01-01

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

Performance tests for integral reactor nuclear fuel

Energy Technology Data Exchange (ETDEWEB)

Sohn, Dong-Seong; Yim, Jeong-Sik; Lee, Chong-Tak; Kim, Han-Soo; Koo, Yang-Hyun; Lee, Byung-Ho; Cheon, Jin-Sik; Oh, Je-Yong

2006-02-15

An integral type reactor SMART plans to utilize metallic Zr-U fuel which is Zr-based alloy with 34{approx}38 wt% U. In order to verify the technologies for the design and manufacturing of the fuel and get a license, performance tests were carried out. Experimental Fuel Assembly (EFA) manufactured in KAERI is being successfully irradiated in the MIR reactor of RIAR from September 4 2004, and it has achieved burnup of 0.21 g/cc as of January 25 2006. Thermal properties of irradiated Zr-U fuel were measured. Up to the phase transformation temperature, thermal diffusivity increased linearly in proportion to temperature. However its dependence on the burnup was not significant. RIA tests with 4 unirradiated Zr-U fuel rods were performed in Kurchatov Institute to establish a safety criterion. In the case of the un-irradiated Zr-U fuel, the energy deposition during the control rod ejection accident should be less than 172 cal/g to prevent the failure accompanying fuel fragmentation and dispersal. Finally the irradiation tests of fuel rods have been performed at HANARO. The HITE-2 test was successfully completed up to a burnup of 0.31 g/cc. The HITE-3 test began in February 2004 and will be continued up to a target burnup of 0.6 g/cc.

Toxin formation by Clostridium botulinum type B in radurized fish

International Nuclear Information System (INIS)

Suhadi, F.; Thayib, S.S.

1981-01-01

The relation between maximum storage life and earliest toxin formation by proteolytic and nonproteolytic strains of C. botulinum type B in irradiated and unirradiated raw fish was determinated. The fish species used were Rastrelliger sp., Euthynnus sp. and Scomberomorus sp. Uninoculated fish samples held under the same treatment conditions were evaluated for the estimation of storage life by untrained panelist. The results showed that a storage temperature at or lower than 5.6 0 C is recommended in order to avoid botulism hazard caused by nonproteolytic type B. When the samples were inoculated with spores of proteolytic strains, no toxic samples were found during the storage life in all treatments with storage temperatures at or lower than 10.2 0 C. Toxin formation by proteolytic strains of C. botulinum type B in boiled (''Pindang'') chub mackerel (Rastrelliger sp.) under storage at ambient temperatures (27-31 0 C) was also determinated. The results showed that in the samples which were inoculated before the process of ''Pindang'', the earliest toxin formations were detected after the samples were spoiled regardless of the irradiation dose, strain and inoculum level; while in control unsalted samples, toxin was detected before or after the samples were spoiled, depending on the strain and inoculum level. Salt content in ordinary ''Pindang'' fish plays a major role both in extension of the storage life and the delay in toxin formation. When the samples were inoculated after the process of ''Pindang'', toxin was detected before or after the samples were spoiled, depending on the strain, salt content, irradiation dose and inoculum level. Irradiation does not prevent the toxin formation in ''Pindang'' fish if the samples are heavily contaminated with proteolytic strains of C. botulinum type B after cooking. (author)

Targeted presurgical decompensation in patients with yaw-dependent facial asymmetry.

Science.gov (United States)

Kim, Kyung-A; Lee, Ji-Won; Park, Jeong-Ho; Kim, Byoung-Ho; Ahn, Hyo-Won; Kim, Su-Jung

2017-05-01

Facial asymmetry can be classified into the rolling-dominant type (R-type), translation-dominant type (T-type), yawing-dominant type (Y-type), and atypical type (A-type) based on the distorted skeletal components that cause canting, translation, and yawing of the maxilla and/or mandible. Each facial asymmetry type represents dentoalveolar compensations in three dimensions that correspond to the main skeletal discrepancies. To obtain sufficient surgical correction, it is necessary to analyze the main skeletal discrepancies contributing to the facial asymmetry and then the skeletal-dental relationships in the maxilla and mandible separately. Particularly in cases of facial asymmetry accompanied by mandibular yawing, it is not simple to establish pre-surgical goals of tooth movement since chin deviation and posterior gonial prominence can be either aggravated or compromised according to the direction of mandibular yawing. Thus, strategic dentoalveolar decompensations targeting the real basal skeletal discrepancies should be performed during presurgical orthodontic treatment to allow for sufficient skeletal correction with stability. In this report, we document targeted decompensation of two asymmetry patients focusing on more complicated yaw-dependent types than others: Y-type and A-type. This may suggest a clinical guideline on the targeted decompensation in patient with different types of facial asymmetries.

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

Science.gov (United States)

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

2013-02-01

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

Contributed Review: The novel gas puff targets for laser-matter interaction experiments

Energy Technology Data Exchange (ETDEWEB)

Wachulak, Przemyslaw W., E-mail: wachulak@gmail.com [Institute of Optoelectronics, Military University of Technology, Ul. Gen. S. Kaliskiego 2, 00-908 Warsaw (Poland)

2016-09-15

Various types of targetry are used nowadays in laser matter interaction experiments. Such targets are characterized using different methods capable of acquiring information about the targets such as density, spatial distribution, and temporal behavior. In this mini-review paper, a particular type of target will be presented. The targets under consideration are gas puff targets of various and novel geometries. Those targets were investigated using extreme ultraviolet (EUV) and soft X-ray (SXR) imaging techniques, such as shadowgraphy, tomography, and pinhole camera imaging. Details about characterization of those targets in the EUV and SXR spectral regions will be presented.

Thermal-hydraulic design of cross-flow type mercury target for JAERI/KEK joint project

International Nuclear Information System (INIS)

Kaminaga, Masanori; Terada, Atsuhiko; Haga, Katsuhiro; Kinoshita, Hidetaka; Hino, Ryutaro

2001-01-01

The Japan Atomic Energy Research Institute (JAERI) and the High Energy Accelerator Research Organization (KEK) are promoting a plan to construct a neutron scattering facility. In the facility, 1 MW pulsed proton beam from a high-intensity proton accelerator will be injected into a mercury target in order to produce high-intensity neutrons for use in the fields of life and material sciences. In the spallation mercury target system design, an integrated structure of target vessel with a safety hull was proposed to ensure the safety and to collect mercury in case of mercury leakage caused by the target beam window failure. The inner structure arrangement of the mercury target vessel was determined based on the thermal hydraulic analytical results of 3 GeV, 1 MW proton beam injection. The safety hull consists of vessels for helium and heavy water. The vessels for mercury target, helium and heavy water will be connected each other by reinforcement ribs mounted on the surface of each vessel. From the structural analyses, the structural integrity of the safety hull would be maintained under the static pressure of 0.5 MPa. (author)

The Opportunistic Pathogen Serratia marcescens Utilizes Type VI Secretion To Target Bacterial Competitors ▿†

Science.gov (United States)

Murdoch, Sarah L.; Trunk, Katharina; English, Grant; Fritsch, Maximilian J.; Pourkarimi, Ehsan; Coulthurst, Sarah J.

2011-01-01

The type VI secretion system (T6SS) is the most recently described and least understood of the protein secretion systems of Gram-negative bacteria. It is widely distributed and has been implicated in the virulence of various pathogens, but its mechanism and exact mode of action remain to be defined. Additionally there have been several very recent reports that some T6SSs can target bacteria rather than eukaryotic cells. Serratia marcescens is an opportunistic enteric pathogen, a class of bacteria responsible for a significant proportion of hospital-acquired infections. We describe the identification of a functional T6SS in S. marcescens strain Db10, the first report of type VI secretion by an opportunist enteric bacterium. The T6SS of S. marcescens Db10 is active, with secretion of Hcp to the culture medium readily detected, and is expressed constitutively under normal growth conditions from a large transcriptional unit. Expression of the T6SS genes did not appear to be dependent on the integrity of the T6SS. The S. marcescens Db10 T6SS is not required for virulence in three nonmammalian virulence models. It does, however, exhibit dramatic antibacterial killing activity against several other bacterial species and is required for S. marcescens to persist in a mixed culture with another opportunist pathogen, Enterobacter cloacae. Importantly, this antibacterial killing activity is highly strain specific, with the S. marcescens Db10 T6SS being highly effective against another strain of S. marcescens with a very similar and active T6SS. We conclude that type VI secretion plays a crucial role in the competitiveness, and thus indirectly the virulence, of S. marcescens and other opportunistic bacterial pathogens. PMID:21890705

Visualizing Energy on Target: Molecular Dynamics Simulations

Science.gov (United States)

2017-12-01

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

Facts about Type 2

Medline Plus

Full Text Available ... or insulin to help you meet your target blood glucose levels. Type 2 usually gets worse over time – even if ... About Type 2 Recently Diagnosed Treatment and Care Blood Glucose ... the Living With Type 2 Diabetes Program donate en -- A Future Without ...

Classical realizability in the CPS target language

DEFF Research Database (Denmark)

Frey, Jonas

2016-01-01

Motivated by considerations about Krivine's classical realizability, we introduce a term calculus for an intuitionistic logic with record types, which we call the CPS target language. We give a reformulation of the constructions of classical realizability in this language, using the categorical...... techniques of realizability triposes and toposes. We argue that the presentation of classical realizability in the CPS target language simplifies calculations in realizability toposes, in particular it admits a nice presentation of conjunction as intersection type which is inspired by Girard's ludics....

Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

Directory of Open Access Journals (Sweden)

Rust Steven

2013-02-01

using the anti-CD73 antibody, which bound other ‘triple negative’ breast cancer cell lines and produced significant tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Conclusions This study has demonstrated that multiple methods are required to successfully analyse the membranome of a desired cell type. It has also successfully demonstrated that phenotypic antibody screening provides a mechanism for rapidly discovering and evaluating antibody tractable targets, which can significantly accelerate the therapeutic discovery process.

Targeting BRCAness in Gastric Cancer

Science.gov (United States)

2017-10-01

Award Number: W81XWH-16-1-0470 TITLE: Targeting BRCAness in Gastric Cancer PRINCIPAL INVESTIGATOR: Yelena Janjigian CONTRACTING ORGANIZATION...Sloan-Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: October 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical...Targeting BRCAness in Gastric Cancer 5b. GRANT NUMBER W81XWH-16-1-0473 (Ashworth) 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Eric Collisson, David

SU-G-JeP2-04: Comparison Between Fricke-Type 3D Radiochromic Dosimeters for Real-Time Dose Distribution Measurements in MR-Guided Radiation Therapy

International Nuclear Information System (INIS)

Lee, H; Alqathami, M; Wang, J; Ibbott, G; Kadbi, M; Blencowe, A

2016-01-01

Purpose: To assess MR signal contrast for different ferrous ion compounds used in Fricke-type gel dosimeters for real-time dose measurements for MR-guided radiation therapy applications. Methods: Fricke-type gel dosimeters were prepared in 4% w/w gelatin prior to irradiation in an integrated 1.5 T MRI and 7 MV linear accelerator system (MR-Linac). 4 different ferrous ion (Fe2?) compounds (referred to as A, B, C, and D) were investigated for this study. Dosimeter D consisted of ferrous ammonium sulfate (FAS), which is conventionally used for Fricke dosimeters. Approximately half of each cylindrical dosimeter (45 mm diameter, 80 mm length) was irradiated to ∼17 Gy. MR imaging during irradiation was performed with the MR-Linac using a balanced-FFE sequence of TR/TE = 5/2.4 ms. An approximate uncertainty of 5% in our dose delivery was anticipated since the MR-Linac had not yet been fully commissioned. Results: The signal intensities (SI) increased between the un-irradiated and irradiated regions by approximately 8.6%, 4.4%, 3.2%, and 4.3% after delivery of ∼2.8 Gy for dosimeters A, B, C, and D, respectively. After delivery of ∼17 Gy, the SI had increased by 24.4%, 21.0%, 3.1%, and 22.2% compared to the un-irradiated regions. The increase in SI with respect to dose was linear for dosimeters A, B, and D with slopes of 0.0164, 0.0251, and 0.0236 Gy"−"1 (R"2 = 0.92, 0.97, and 0.96), respectively. Visually, dosimeter A had the greatest optical contrast from yellow to purple in the irradiated region. Conclusion: This study demonstrated the feasibility of using Fricke-type dosimeters for real-time dose measurements with the greatest optical and MR contrast for dosimeter A. We also demonstrated the need to investigate Fe"2"+ compounds beyond the conventionally utilized FAS compound in order to improve the MR signal contrast in 3D dosimeters used for MR-guided radiation therapy. This material is based upon work supported by the National Science Foundation Graduate

SU-G-JeP2-04: Comparison Between Fricke-Type 3D Radiochromic Dosimeters for Real-Time Dose Distribution Measurements in MR-Guided Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Lee, H; Alqathami, M; Wang, J; Ibbott, G [UT MD Anderson Cancer Center, Houston, TX (United States); Kadbi, M [MR Therapy, Philips healthTech, Cleveland, OH (United States); Blencowe, A [The University of South Australia, South Australia, SA (Australia)

2016-06-15

Purpose: To assess MR signal contrast for different ferrous ion compounds used in Fricke-type gel dosimeters for real-time dose measurements for MR-guided radiation therapy applications. Methods: Fricke-type gel dosimeters were prepared in 4% w/w gelatin prior to irradiation in an integrated 1.5 T MRI and 7 MV linear accelerator system (MR-Linac). 4 different ferrous ion (Fe2?) compounds (referred to as A, B, C, and D) were investigated for this study. Dosimeter D consisted of ferrous ammonium sulfate (FAS), which is conventionally used for Fricke dosimeters. Approximately half of each cylindrical dosimeter (45 mm diameter, 80 mm length) was irradiated to ∼17 Gy. MR imaging during irradiation was performed with the MR-Linac using a balanced-FFE sequence of TR/TE = 5/2.4 ms. An approximate uncertainty of 5% in our dose delivery was anticipated since the MR-Linac had not yet been fully commissioned. Results: The signal intensities (SI) increased between the un-irradiated and irradiated regions by approximately 8.6%, 4.4%, 3.2%, and 4.3% after delivery of ∼2.8 Gy for dosimeters A, B, C, and D, respectively. After delivery of ∼17 Gy, the SI had increased by 24.4%, 21.0%, 3.1%, and 22.2% compared to the un-irradiated regions. The increase in SI with respect to dose was linear for dosimeters A, B, and D with slopes of 0.0164, 0.0251, and 0.0236 Gy{sup −1} (R{sup 2} = 0.92, 0.97, and 0.96), respectively. Visually, dosimeter A had the greatest optical contrast from yellow to purple in the irradiated region. Conclusion: This study demonstrated the feasibility of using Fricke-type dosimeters for real-time dose measurements with the greatest optical and MR contrast for dosimeter A. We also demonstrated the need to investigate Fe{sup 2+} compounds beyond the conventionally utilized FAS compound in order to improve the MR signal contrast in 3D dosimeters used for MR-guided radiation therapy. This material is based upon work supported by the National Science Foundation

Target Detection, Identification, and Marksmanship Under Various Types of Physiological Strain

National Research Council Canada - National Science Library

Tikuisis, Peter

2006-01-01

.... Using a small arms trainer (SAT), target detection, identification, and engagement were tested under a variety of conditions including heat and cold exposure, fatiguing exercise, and sleep deprivation, with caffeine intervention...

Drug-targeting methodologies with applications: A review

Science.gov (United States)

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

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

THERMAL CONDUCTIVITY OF SIC AND C FIBERS

Energy Technology Data Exchange (ETDEWEB)

Youngblood, Gerald E.; Senor, David J.; Kowbel, W.; Webb, J.; Kohyama, Akira

2000-09-01

Several rod-shaped specimens with uniaxially packed fibers (Hi-Nicalon, Hi-Nicalon Type S, Tyranno SA and Amoco K1100 types) and a pre-ceramic polymer matrix have been fabricated. By using appropriate analytic models, the bare fiber thermal conductivity (Kf) and the interface thermal conductance (h) will be determined as a function of temperature up to 1000?C before and after irradiation for samples cut from these rods. Initial results are: (1) for unirradiated Hi-Nicalon SiC fiber, Kf varied from 4.3 up to 5.9 W/mK for the 27-1000?C range, (2) for unirradiated K1100 graphite fiber, Kf varied from 576 down to 242 W/mK for the 27-1000?C range, and (3) h = 43 W/cm2K at 27?C as a typical fiber/matrix interface conductance.

Foraging through multiple target categories reveals the flexibility of visual working memory.

Science.gov (United States)

Kristjánsson, Tómas; Kristjánsson, Árni

2018-02-01

A key assumption in the literature on visual attention is that templates, actively maintained in visual working memory (VWM), guide visual attention. An important question therefore involves the nature and capacity of VWM. According to load theories, more than one search template can be active at the same time and capacity is determined by the total load rather than a precise number of templates. By an alternative account only one search template can be active within visual working memory at any given time, while other templates are in an accessory state - but do not affect visual selection. We addressed this question by varying the number of targets and distractors in a visual foraging task for 40 targets among 40 distractors in two ways: 1) Fixed-distractor-number, involving two distractor types while target categories varied from one to four. 2) Fixed-color-number (7), so that if the target types were two, distractors types were five, while if target number increased to three, distractor types were four (etc.). The two accounts make differing predictions. Under the single-template account, we should expect large switch costs as target types increase to two, but switch-costs should not increase much as target types increase beyond two. Load accounts predict an approximately linear increase in switch costs with increased target type number. The results were that switch costs increased roughly linearly in both conditions, in line with load accounts. The results are discussed in light of recent proposals that working memory reflects lingering neural activity at various sites that operate on the stimuli in each case and findings showing neurally silent working memory representations. Copyright © 2017 Elsevier B.V. All rights reserved.

Innate-Type and Acquired-Type Allergy Regulated by IL-33

Directory of Open Access Journals (Sweden)

Tomohiro Yoshimoto

2014-01-01

Full Text Available We propose two types of allergic response: IgE-dependent and IgE-independent, and designate these as 'acquired-type allergy' and 'innate-type allergy', respectively. IL-33 stimulates both innate (basophils, mast cells, or group 2 innate lymphoid cells and acquired (Th2 cells allergy-related cells to induce and/or augment Th2 cytokine production, which leads to eosinophilic inflammation in vivo. Thus, IL-33 is an essential regulator for both 'innate-type allergy' and 'acquired-type allergy', and might be an attractive therapeutic target for allergic diseases.

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

Directory of Open Access Journals (Sweden)

Shihua Zhang

2018-02-01

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

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

Science.gov (United States)

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

2018-01-01

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

Comparative measurements of exodeviations in the three types of intermittent exotropia

Directory of Open Access Journals (Sweden)

Hong Wang

2014-12-01

Full Text Available AIM: To compare the results of 4 methods for measuring angle of exodeviation in the three types of intermittent exotropia, including when looking at indoor distance target of 6m, looking at indoor distance target of 30m, looking at outdoor far distance target, after 1h diagnostic occlusion test. METHODS: Prospective case series study. Sixty-five patients with intermittent exotropia between June 2013 and June 2014 were enrolled in the Department of Ophthalmology, Affiliated Hospital to Qingdao University, included 37 males and 28 females with average age(12.5±6.2years. All the patients were measured when looking at indoor distance target of 6m, looking at indoor distance target of 30m, looking at outdoor far distance target, after 1h diagnostic occlusion test. Intermittent exotropia was divided into basic type, convergence insufficiency type and divergence excess type, which was based on the different result of between the distance and near measurements. The One-way test was applied to analyze the four methods of measuring angle of exodeviation in the three types of intermittent exotropia. LSD-t test was applied to compare the differences between each two methods in each type.RESULTS: The distance exodeviations tested with looking at indoor distance target of 6m, looking at indoor distance target of 30m, looking at outdoor far distance target, after 1h diagnostic occlusion test were basic type(45.4±21.0, 55.0±15.0, 64.68±17.7, 68.75±16.6PD, convergence insufficiency type(33.3±14.0, 44.9±12.9, 43.6±11.8, 54.6±11.2PD, divergence excess type(55.6±17.4, 66.3±18.8, 76.9±16.4, 78.1±15.6PD. There were obviously differences between each two methods in each type(basic type F=9.649, P=0.00; convergence insufficiency type F=6.886, P=0.001; divergence excess type F=7.989, P=0.00. Compared with looking at indoor distance target of 30m, looking at outdoor far distance target(basic type P=0.044, divergence excess type P=0.048and after 1h diagnostic

Decay of paramagnetic centers in polyacetylene

International Nuclear Information System (INIS)

Hola, O.

1994-01-01

The time dependences of the relative concentration of spins in irradiated and unirradiated samples of polyacetylene have been studied. Similar courses of the decay of paramagnetic centers were observed in both types of samples. (author) 6 refs.; 1 fig

Method for mounting laser fusion targets for irradiation

Science.gov (United States)

Fries, R. Jay; Farnum, Eugene H.; McCall, Gene H.

1977-07-26

Methods for preparing laser fusion targets of the ball-and-disk type are disclosed. Such targets are suitable for irradiation with one or two laser beams to produce the requisite uniform compression of the fuel material.

MAGNETIC ACTIVITY ANALYSIS FOR A SAMPLE OF G-TYPE MAIN SEQUENCE KEPLER TARGETS

Energy Technology Data Exchange (ETDEWEB)

Mehrabi, Ahmad [Department of Physics, Bu Ali Sina University, 65178, 016016, Hamedan (Iran, Islamic Republic of); He, Han [National Astronomical Observatories, Chinese Academy of Sciences, Beijing (China); Khosroshahi, Habib, E-mail: mehrabi@basu.ac.ir [School of Astronomy, Institute for Research in Fundamental Sciences (IPM), 19395-5531, Tehran (Iran, Islamic Republic of)

2017-01-10

The variation of a stellar light curve owing to rotational modulation by magnetic features (starspots and faculae) on the star’s surface can be used to investigate the magnetic properties of the host star. In this paper, we use the periodicity and magnitude of the light-curve variation as two proxies to study the stellar magnetic properties for a large sample of G-type main sequence Kepler targets, for which the rotation periods were recently determined. By analyzing the correlation between the two magnetic proxies, it is found that: (1) the two proxies are positively correlated for most of the stars in our sample, and the percentages of negative, zero, and positive correlations are 4.27%, 6.81%, and 88.91%, respectively; (2) negative correlation stars cannot have a large magnitude of light-curve variation; and (3) with the increase of rotation period, the relative number of positive correlation stars decreases and the negative correlation one increases. These results indicate that stars with shorter rotation period tend to have positive correlation between the two proxies, and a good portion of the positive correlation stars have a larger magnitude of light-curve variation (and hence more intense magnetic activities) than negative correlation stars.

Behaviour of rock-like oxide fuels under reactivity-initiated accident conditions

International Nuclear Information System (INIS)

Kazuyuki, Kusagaya; Takehiko, Nakamura; Makio, Yoshinaga; Hiroshi, Akie; Toshiyuki, Yamashita; Hiroshi, Uetsuka

2002-01-01

Pulse irradiation tests of three types of un-irradiated rock-like oxide (ROX) fuel - yttria-stabilised zirconia (YSZ) single phase, YSZ and spinel (MgAl 2 O 4 ) homogeneous mixture and particle-dispersed YSZ/spinel - were conducted in the Nuclear Safety Research Reactor to investigate the fuel behaviour under reactivity-initiated accident conditions. The ROX fuels failed at fuel volumetric enthalpies above 10 GJ/m 3 , which was comparable to that of un-irradiated UO 2 fuel. The failure mode of the ROX fuels, however, was quite different from that of the UO 2 fuel. The ROX fuels failed with fuel pellet melting and a part of the molten fuel was released out to the surrounding coolant water. In spite of the release, no significant mechanical energy generation due to fuel/coolant thermal interaction was observed in the tested enthalpy range below∼12 GJ/m 3 . The YSZ type and homogenous YSZ/spinel type ROX fuels failed by cladding burst when their temperatures peaked, while the particle-dispersed YSZ/spinel type ROX fuel seemed to have failed by cladding local melting. (author)

Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus.

Science.gov (United States)

Shan, Qun; Zheng, Guihong; Zhu, Aihua; Cao, Li; Lu, Jun; Wu, Dongmei; Zhang, ZiFeng; Fan, Shaohua; Sun, Chunhui; Hu, Bin; Zheng, Yuanlin

2016-09-01

Emerging evidence has shown that microRNA-mediated gene expression modulation plays a crucial role in the pathogenesis of type 2 diabetes mellitus, but the novel miRNAs involved in type 2 diabetes and its functional regulatory mechanisms still need to be determined. In this study, we assessed the role of miR-10a in extracellular matrix accumulation in the kidney of diabetic mellitus induced by combining administration of chronic high fat diet (HFD) and low dosage of streptozotocin (STZ, 35mg/kg). Here, we found that HFD/STZ administration decreased the level of microRNA (miR-10a) expression in ICR strain mice. Overexpression of miR-10a alleviated the increased ratio of urine albumin-to-creatinine (ACR) ratio of HFD/STZ mice. In contrast, knockdown of miR-10a increased the ratio of kidney ACR in naïve mice. Furthermore, cAMP response element binding protein 1 (CREB1) was validated as a target of miR-10a in vitro and in vivo. CREB1 and its downstream fibronectin (FN, extracellular matrix) were increased in HFD/STZ-treated mice, which was reversed by kidney miR-10a overexpression. The content of CREB1 and FN was increased by miR-10a knockdown in kidney of naïve mice. Furthermore, histone deacetylase 3 (HDAC3) was revealed to be increased in kidney of HFD/STZ mice, accompanied with the augmentation of ACR ratio and FN level. Knockdown of HDAC3 with siRNA significantly caused the increase of miR-10a, resulting in the decrease in CREB1 and FN expression in kidney of HFD/STZ mice. Contrarily, HDAC3 overexpression mediated by lentivirus decreased miR-10a content, and enhanced ACR value, CREB1 and FN formation in naïve mice. Collectively, these results elucidate that HDAC3/miR-10a/CREB1 serves as a new mechanism underlying kidney injury, providing potential therapeutic targets in type 2 diabetes. Copyright © 2016. Published by Elsevier Inc.

Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

Science.gov (United States)

Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

2017-12-12

Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

Rescue of HIV-1 release by targeting widely divergent NEDD4-type ubiquitin ligases and isolated catalytic HECT domains to Gag.

Directory of Open Access Journals (Sweden)

Eric R Weiss

2010-09-01

Full Text Available Retroviruses engage the ESCRT pathway through late assembly (L domains in Gag to promote virus release. HIV-1 uses a PTAP motif as its primary L domain, which interacts with the ESCRT-I component Tsg101. In contrast, certain other retroviruses primarily use PPxY-type L domains, which constitute ligands for NEDD4-type ubiquitin ligases. Surprisingly, although HIV-1 Gag lacks PPxY motifs, the release of HIV-1 L domain mutants is potently enhanced by ectopic NEDD4-2s, a native isoform with a naturally truncated C2 domain that appears to account for the residual titer of L domain-defective HIV-1. The reason for the unique potency of the NEDD4-2s isoform has remained unclear. We now show that the naturally truncated C2 domain of NEDD4-2s functions as an autonomous Gag-targeting module that can be functionally replaced by the unrelated Gag-binding protein cyclophilin A (CypA. The residual C2 domain of NEDD4-2s was sufficient to transfer the ability to stimulate HIV-1 budding to other NEDD4 family members, including the yeast homologue Rsp5, and even to isolated catalytic HECT domains. The isolated catalytic domain of NEDD4-2s also efficiently promoted HIV-1 budding when targeted to Gag via CypA. We conclude that the regions typically required for substrate recognition by HECT ubiquitin ligases are all dispensable to stimulate HIV-1 release, implying that the relevant target for ubiquitination is Gag itself or can be recognized by divergent isolated HECT domains. However, the mere ability to ubiquitinate Gag was not sufficient to stimulate HIV-1 budding. Rather, our results indicate that the synthesis of K63-linked ubiquitin chains is critical for ubiquitin ligase-mediated virus release.

Emotional effects of shooting activities : 'real' versus 'virtual' actions and targets

NARCIS (Netherlands)

Rauterberg, G.W.M.; Marinelli, D.

2003-01-01

The results of an empirical study are presented to investigate the relationship between different action types (real versus virtual shooting) and different target types (real versus virtual targets) on the actual emotional state (wellbeing)of the player. The results show significantly that virtual

Advances in targeted delivery of small interfering RNA using simple bioconjugates

DEFF Research Database (Denmark)

Nielsen, Christoffer; Kjems, Jørgen; Sorensen, Kristine Rothaus

2014-01-01

with a targeting moiety, in a simple bioconjugate construct. We discuss the use of different types of targeting moieties, as well as the different conjugation strategies employed for preparing these bioconjugate constructs that deliver the siRNA to target cells. We focus especially on the in-built or passive......Introduction: Development of drugs based on RNA interference by small interfering RNA (siRNA) has been progressing slowly due to a number of challenges associated with the in vivo behavior of siRNA. A central problem is controlling siRNA delivery to specific cell types. Here, we review existing...... literature on one type of strategy for solving the issue of cell-specific delivery of siRNA, namely delivering the siRNA as part of simple bioconjugate constructs. Areas covered: This review presents current experience from strategies aimed at targeting siRNA to specific cell types, by associating the siRNA...

In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA

Science.gov (United States)

Landau, Dustin J; Brooks, Elizabeth Drake; Perez-Pinera, Pablo; Amarasekara, Hiruni; Mefferd, Adam; Li, Songtao; Bird, Andrew; Gersbach, Charles A; Koeberl, Dwight D

2016-01-01

Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P Ia, as compared with normal littermates, at 8 months following vector administration (P Ia. PMID:26865405

Target identification using Zernike moments and neural networks

Science.gov (United States)

Azimi-Sadjadi, Mahmood R.; Jamshidi, Arta A.; Nevis, Andrew J.

2001-10-01

The development of an underwater target identification algorithm capable of identifying various types of underwater targets, such as mines, under different environmental conditions pose many technical problems. Some of the contributing factors are: targets have diverse sizes, shapes and reflectivity properties. Target emplacement environment is variable; targets may be proud or partially buried. Environmental properties vary significantly from one location to another. Bottom features such as sand, rocks, corals, and vegetation can conceal a target whether it is partially buried or proud. Competing clutter with responses that closely resemble those of the targets may lead to false positives. All the problems mentioned above contribute to overly difficult and challenging conditions that could lead to unreliable algorithm performance with existing methods. In this paper, we developed and tested a shape-dependent feature extraction scheme that provides features invariant to rotation, size scaling and translation; properties that are extremely useful for any target classification problem. The developed schemes were tested on an electro-optical imagery data set collected under different environmental conditions with variable background, range and target types. The electro-optic data set was collected using a Laser Line Scan (LLS) sensor by the Coastal Systems Station (CSS), located in Panama City, Florida. The performance of the developed scheme and its robustness to distortion, rotation, scaling and translation was also studied.

Targeting innate immunity to downmodulate adaptive immunity and reverse type 1 diabetes

Directory of Open Access Journals (Sweden)

Itoh A

2017-05-01

antigen-presenting cells (APCs that mediate decreased adaptive T-cell responses. Here, we review our current knowledge and suggest future prospects for targeting innate immunity in T1D immunotherapy. Keywords: type 1 diabetes, antigen-specific therapy, innate immunity, Toll-like receptors

Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians.

Science.gov (United States)

Qaseem, Amir; Wilt, Timothy J; Kansagara, Devan; Horwitch, Carrie; Barry, Michael J; Forciea, Mary Ann

2018-04-17

The American College of Physicians developed this guidance statement to guide clinicians in selecting targets for pharmacologic treatment of type 2 diabetes. The National Guideline Clearinghouse and the Guidelines International Network library were searched (May 2017) for national guidelines, published in English, that addressed hemoglobin A1c (HbA1c) targets for treating type 2 diabetes in nonpregnant outpatient adults. The authors identified guidelines from the National Institute for Health and Care Excellence and the Institute for Clinical Systems Improvement. In addition, 4 commonly used guidelines were reviewed, from the American Association of Clinical Endocrinologists and American College of Endocrinology, the American Diabetes Association, the Scottish Intercollegiate Guidelines Network, and the U.S. Department of Veterans Affairs and Department of Defense. The AGREE II (Appraisal of Guidelines for Research and Evaluation II) instrument was used to evaluate the guidelines. Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of benefits and harms of pharmacotherapy, patients' preferences, patients' general health and life expectancy, treatment burden, and costs of care. Clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes. Clinicians should consider deintensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%. Clinicians should treat patients with type 2 diabetes to minimize symptoms related to hyperglycemia and avoid targeting an HbA1c level in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population.

Tensile properties of unirradiated PCA from room temperature to 7000C

International Nuclear Information System (INIS)

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

1983-01-01

The tensile properties of Prime Candidate Alloy (PCA) austenitic stainless steel after three different thermomechanical treatments were determined from room temperature to 700 0 C. The solution-annealed PCA had the lowest strength and highest ductility, while the reverse was true for the 25%-cold-worked material. The PCA containing titanium-rich MC particles fell between the other two heats. The cold-worked PCA had nearly the same tensile properties as cold-worked type 316 stainless steel. Both alloys showed ductility minima at 300 0 C

Student Target Marketing Strategies for Universities

Science.gov (United States)

Lewison, Dale M.; Hawes, Jon M.

2007-01-01

As colleges and universities adopt marketing orientations to an ever-increasing extent, the relative merits of mass marketing and target marketing must also be explored. Researchers identify buyer types as potential students focused on quality, value or economy. On the other axis, learner types are described as those who focus on career,…

Chief Executive Officer Power Message Types as a Function of Organizational Target Types.

Science.gov (United States)

Freiberg, Kevin L.; Hellweg, Susan A.

To explore the specific types of power that emerge in the communication messages chief executive officers (CEOs) use when interacting with others--particularly superiors, peers, and subordinates--15 CEOs were asked to respond to three hypothetical situations. During 60-minute tape-recorded interviews, they were asked what they would say to…

Processes and effects of targeted online advertising among children

OpenAIRE

Reijmersdal, E.A. van; Rozendaal, E.; Smink, N.; Noort, G. van; Buijzen, M.A.

2017-01-01

Increasingly, information from children's profile pages on social network sites is being used to target online advertising, a phenomenon known as profile targeting. This practice has raised concerns in society and academia; however, its effects among children remain unstudied. Therefore, we investigated the effects of profile targeting on children's brand responses (i.e., brand attitude and purchase intention). We examined two types of targeting: targeting of product and of form (i.e., color)...

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

Science.gov (United States)

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

2016-12-01

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

Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus

DEFF Research Database (Denmark)

Hemmingsen, Bianca; Lund, Søren; Gluud, Christian Nyfeldt

2011-01-01

Patients with type 2 diabetes mellitus (T2D) exhibit an increased risk of cardiovascular disease and mortality compared to the background population. Observational studies report a relationship between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients...... with T2D....

Extrapolation of vertical target motion through a brief visual occlusion.

Science.gov (United States)

Zago, Myrka; Iosa, Marco; Maffei, Vincenzo; Lacquaniti, Francesco

2010-03-01

It is known that arbitrary target accelerations along the horizontal generally are extrapolated much less accurately than target speed through a visual occlusion. The extent to which vertical accelerations can be extrapolated through an occlusion is much less understood. Here, we presented a virtual target rapidly descending on a blank screen with different motion laws. The target accelerated under gravity (1g), decelerated under reversed gravity (-1g), or moved at constant speed (0g). Probability of each type of acceleration differed across experiments: one acceleration at a time, or two to three different accelerations randomly intermingled could be presented. After a given viewing period, the target disappeared for a brief, variable period until arrival (occluded trials) or it remained visible throughout (visible trials). Subjects were asked to press a button when the target arrived at destination. We found that, in visible trials, the average performance with 1g targets could be better or worse than that with 0g targets depending on the acceleration probability, and both were always superior to the performance with -1g targets. By contrast, the average performance with 1g targets was always superior to that with 0g and -1g targets in occluded trials. Moreover, the response times of 1g trials tended to approach the ideal value with practice in occluded protocols. To gain insight into the mechanisms of extrapolation, we modeled the response timing based on different types of threshold models. We found that occlusion was accompanied by an adaptation of model parameters (threshold time and central processing time) in a direction that suggests a strategy oriented to the interception of 1g targets at the expense of the interception of the other types of tested targets. We argue that the prediction of occluded vertical motion may incorporate an expectation of gravity effects.

Post irradiation examination of type 316 stainless steels for in-pile Oarai water loop No.2 (OWL-2)

International Nuclear Information System (INIS)

Shibata, Akira; Kimura, Tadashi; Nagata, Hiroshi; Aoyama, Masashi; Kanno, Masaru; Ohmi, Masao

2010-11-01

The Oarai water loop No.2 (OWL-2) was installed in JMTR in 1972 for the purpose of irradiation experiments of fuel element and component material for light water reactors. Type 316 stainless steels (SSs) were used for tube material of OWL-2 in the reactor. But data of mechanical properties of highly irradiated Type 316 SSs has been insufficient since OWL-2 was installed. Therefore surveillance tests of type 316 SSs which were irradiated up to 3.4x10 25 n/m 2 in fast neutron fluence (>1 MeV) were performed. Meanwhile type 316 stainless steel (SS) is widely used in JMTR such as other irradiation apparatus and irradiation capsule, and additional data of type 316 SSs irradiated higher is required. Therefore post irradiation examinations of surveillance specimens made of type 316 SSs which were irradiated up to 1.0x10 26 n/m 2 in fast neutron fluence were performed and reported in this paper. In this result of surveillance tests of type 316 SSs irradiated up to 1.0x10 26 n/m 2 , tensile strength increase with increase of Neutron fluence and total elongation decreased with increase of Neutron fluence compared to unirradiated specimens and specimens irradiated up to 3.4x10 25 n/m 2 . This tendency has good agreement with results of 10 24 - 10 25 n/m 2 in fast neutron fluence. More than 37% in total elongation was confirmed in all test conditions. It was confirmed that type 316 SS irradiated up to 1.0x10 26 n/m 2 in fast neutron fluence has enough ductility as structure material. (author)

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice

Directory of Open Access Journals (Sweden)

Dominic Jauvin

2017-06-01

Full Text Available Myotonic dystrophy type 1 (DM1, a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTGn trinucleotide repeat in the 3′ UTR of the human dystrophia myotonica protein kinase (DMPK gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2′-4′-constrained, ethyl-modified (ISIS 486178 antisense oligonucleotide (ASO targeted to the 3′ UTR of the DMPK gene, which led to a 70% reduction in CUGexp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUGexp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs.

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice.

Science.gov (United States)

Jauvin, Dominic; Chrétien, Jessina; Pandey, Sanjay K; Martineau, Laurie; Revillod, Lucille; Bassez, Guillaume; Lachon, Aline; MacLeod, A Robert; Gourdon, Geneviève; Wheeler, Thurman M; Thornton, Charles A; Bennett, C Frank; Puymirat, Jack

2017-06-16

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG) n trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUG exp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUG exp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.

Science.gov (United States)

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C; Fire, Andrew Z; Sánchez-Amat, Antonio

2017-08-17

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea . One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.

Drug-target interaction prediction via class imbalance-aware ensemble learning.

Science.gov (United States)

Ezzat, Ali; Wu, Min; Li, Xiao-Li; Kwoh, Chee-Keong

2016-12-22

Multiple computational methods for predicting drug-target interactions have been developed to facilitate the drug discovery process. These methods use available data on known drug-target interactions to train classifiers with the purpose of predicting new undiscovered interactions. However, a key challenge regarding this data that has not yet been addressed by these methods, namely class imbalance, is potentially degrading the prediction performance. Class imbalance can be divided into two sub-problems. Firstly, the number of known interacting drug-target pairs is much smaller than that of non-interacting drug-target pairs. This imbalance ratio between interacting and non-interacting drug-target pairs is referred to as the between-class imbalance. Between-class imbalance degrades prediction performance due to the bias in prediction results towards the majority class (i.e. the non-interacting pairs), leading to more prediction errors in the minority class (i.e. the interacting pairs). Secondly, there are multiple types of drug-target interactions in the data with some types having relatively fewer members (or are less represented) than others. This variation in representation of the different interaction types leads to another kind of imbalance referred to as the within-class imbalance. In within-class imbalance, prediction results are biased towards the better represented interaction types, leading to more prediction errors in the less represented interaction types. We propose an ensemble learning method that incorporates techniques to address the issues of between-class imbalance and within-class imbalance. Experiments show that the proposed method improves results over 4 state-of-the-art methods. In addition, we simulated cases for new drugs and targets to see how our method would perform in predicting their interactions. New drugs and targets are those for which no prior interactions are known. Our method displayed satisfactory prediction performance and was

Preparation of FMD type A87/IRN inactivated vaccine by gamma irradiation and the immune response on guinea pig

International Nuclear Information System (INIS)

Sedeh, Farahnaz Motamedi; Shafaee, Kamal; Fatolahi, Hadi; Arbabi, Kourosh; Khorasani, Akbar

2008-01-01

FMD is one of the most economically damaging diseases that affect livestock animals. In this study FMD Virus type A87/IRN was multiplied on BHK21 cells. The virus was titrated by TCID50 method, it was 10 7.5 /ml. The FMD virus samples were inactivated by gamma ray from 60 Co source at -20 deg C. Safety test was done by IBRS2 monolayer cell culture method, also antigenicity of irradiated and un-irradiated virus samples were studied by Complement Fixation Test. The dose/survival curve for irradiated FMD Virus was drawn, the optimum dose range for inactivation of FMDV type A87/IRN and unaltered antigenicity was obtained 40-44 kGy. The inactivated virus samples by irradiation and ethyleneimine (EI) were formulated respectively as vaccine with Al(OH) 3 gel and other substances. The vaccines were inoculated to Guinea pigs and the results of Serum Neutralization Test for the normal vaccine and radio-vaccine showed protective titer after 8 months. The potency test of the inactivated vaccines was done, PD50 Value of the vaccines were calculated 7.06 and 5.6 for inactivated vaccine by EI and gamma irradiation respectively. (author)

Hexon and fiber of adenovirus type 14 and 55 are major targets of neutralizing antibody but only fiber-specific antibody contributes to cross-neutralizing activity.

Science.gov (United States)

Feng, Ying; Sun, Xikui; Ye, Xianmiao; Feng, Yupeng; Wang, Jinlin; Zheng, Xuehua; Liu, Xinglong; Yi, Changhua; Hao, Mingli; Wang, Qian; Li, Feng; Xu, Wei; Li, Liang; Li, Chufang; Zhou, Rong; Chen, Ling; Feng, Liqiang

2018-05-01

Re-emerging human adenoviruses type 14 (HAdV14) and 55 (HAdV55) represent two highly virulent adenoviruses. The neutralizing antibody (nAb) responses elicited by infection or immunization remain largely unknown. Herein, we generated hexon-chimeric HAdV14 viruses harboring each single or entire hexon hyper-variable-regions (HVR) from HAdV55, and determined the neutralizing epitopes of human and mouse nAbs. In human sera, hexon-targeting nAbs are type-specific and mainly recognize HVR2, 5, and 7. Fiber-targeting nAbs are only detectable in sera cross-neutralizing HAdV14 and HAdV55 and contribute substantially to cross-neutralization. Penton-binding antibodies, however, show no significant neutralizing activities. In mice immunized with HAdV14 or HAdV55, a single immunization mainly elicited hexon-specific nAbs, which recognized HAdV14 HVR1, 2, and 7 and HAdV55 HVR1 and 2, respectively. After a booster immunization, cross-neutralizing fiber-specific nAbs became detectable. These results indicated that hexon elicits type-specific nAbs whereas fiber induces cross-neutralizing nAbs to HAdV14 and HAdV55, which are of significance in vaccine development. Copyright © 2018 Elsevier Inc. All rights reserved.

Oxidative dissolution of unirradiated Mimas MOX fuel (U/Pu oxides) in carbonated water under oxic and anoxic conditions

Energy Technology Data Exchange (ETDEWEB)

Odorowski, Mélina [CEA/DEN/DTCD/SECM/LMPA, BP 17171, 30207 Bagnols-sur-Cèze Cedex (France); MINES ParisTech, PSL Research University, Centre de Géosciences, 35 rue St Honoré, 77305 Fontainebleau (France); Jégou, Christophe, E-mail: christophe.jegou@cea.fr [CEA/DEN/DTCD/SECM/LMPA, BP 17171, 30207 Bagnols-sur-Cèze Cedex (France); De Windt, Laurent [MINES ParisTech, PSL Research University, Centre de Géosciences, 35 rue St Honoré, 77305 Fontainebleau (France); Broudic, Véronique; Peuget, Sylvain; Magnin, Magali; Tribet, Magaly [CEA/DEN/DTCD/SECM/LMPA, BP 17171, 30207 Bagnols-sur-Cèze Cedex (France); Martin, Christelle [Agence nationale pour la gestion des déchets radioactifs (Andra), DRD/CM, 1-7 rue Jean-Monnet, 92298 Châtenay-Malabry Cedex (France)

2016-01-15

Few studies exist concerning the alteration of Mimas Mixed-OXide (MOX) fuel, a mixed plutonium and uranium oxide, and data is needed to better understand its behavior under leaching, especially for radioactive waste disposal. In this study, two leaching experiments were conducted on unirradiated MOX fuel with a strong alpha activity (1.3 × 10{sup 9} Bq.g{sub MOX}{sup −1} reproducing the alpha activity of spent MOX fuel with a burnup of 47 GWd·t{sub HM}{sup −1} after 60 years of decay), one under air (oxic conditions) for 5 months and the other under argon (anoxic conditions with [O{sub 2}] < 1 ppm) for one year in carbonated water (10{sup −2} mol L{sup −1}). For each experiment, solution samples were taken over time and Eh and pH were monitored. The uranium in solution was assayed using a kinetic phosphorescence analyzer (KPA), plutonium and americium were analyzed by a radiochemical route, and H{sub 2}O{sub 2} generated by the water radiolysis was quantified by chemiluminescence. Surface characterizations were performed before and after leaching using Scanning Electron Microscopy (SEM), Electron Probe Microanalyzer (EPMA) and Raman spectroscopy. Solubility diagrams were calculated to support data discussion. The uranium releases from MOX pellets under both oxic and anoxic conditions were similar, demonstrating the predominant effect of alpha radiolysis on the oxidative dissolution of the pellets. The uranium released was found to be mostly in solution as carbonate species according to modeling, whereas the Am and Pu released were significantly sorbed or precipitated onto the TiO{sub 2} reactor. An intermediate fraction of Am (12%) was also present as colloids. SEM and EPMA results indicated a preferential dissolution of the UO{sub 2} matrix compared to the Pu-enriched agglomerates, and Raman spectroscopy showed the Pu-enriched agglomerates were slightly oxidized during leaching. Unlike Pu-enriched zones, the UO{sub 2} grains were much more

International Nuclear Target Development Society workshop 1983: proceedings

International Nuclear Information System (INIS)

Thomas, G.

1983-01-01

Separate abstracts were prepared for 11 of the 19 papers presented. Eight papers were previously included in the data base. Discussion group session papers on carbon stripper foils, problems in producing heavy-ion targets, and problems in producing general type targets are included

Quantitative analysis of wild-type and V600E mutant BRAF proteins in colorectal carcinoma using immunoenrichment and targeted mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Chen, Hang [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122 (China); Hsiao, Yung-Chin [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Chiang, Sum-Fu [Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Wu, Chia-Chun; Lin, Yu-Tsun [Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Liu, Hsuan [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Zhao, Hong [Experimental Center of Functional Subjects, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122 (China); Chen, Jinn-Shiun [Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Chang, Yu-Sun [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Department of Otolaryngology, Chang Gung Memorial Hospital, Linkou, Taiwan (China); and others

2016-08-24

The BRAF V600E mutation is one of the most common mutations implicated in the development of several types of cancer including colorectal cancer (CRC), where it is associated with aggressive disease phenotypes and poor outcomes. The status of the BRAF V600E mutation is frequently determined by direct DNA sequencing. However, no previous study has sought to quantify the BRAF V600E protein in cancer specimens. Here, we evaluated immunoenrichment coupled with two MS-based quantitative techniques, namely multiple reaction monitoring (MRM) and single ion monitoring conjugated accurate inclusion mass screening (SIM-AIMS), to detect and precisely quantify wild-type (WT) and V600E mutant BRAF proteins in DNA sequence-confirmed CRC tissue specimens. WT and V600E BRAF proteins were immunoprecipitated from a CRC cell line (HT-29), and their representative peptides ({sup 592}IGDFGLATVK{sup 601} and {sup 592}IGDFGLATEK{sup 601}, respectively) were confirmed by LC-MS/MS analysis and then quantified by MRM or SIM-AIMS with spiked stable isotope-labeled peptide standards. Both assays worked well for measuring WT BRAF from different amounts of HT-29 cell lysates, but the MRM assay was more sensitive than SIM-AIMS assay for quantifying lower levels of V600E BRAF. In protein extracts (2 mg) from 11 CRC tissue specimens, the MRM assay could measure WT BRAF in all 11 cases (0.32–1.66 ng) and the V600E BRAF in two cases (0.1–0.13 ng; mutant-to-WT ratio, 0.16–0.17). The SIM-AIMS assay could also detect WT and V600E BRAF in CRC specimens, but the measured levels of both targets were lower than those determined by MRM assay. Collectively, this study provides an effective method to precisely quantify WT and V600E BRAF proteins in complex biological samples using immunoenrichment-coupled targeted MS. Since the V600E BRAF protein has emerged as an important therapeutic target for cancer, the developed assay should facilitate future BRAF-related basic and clinical studies

Tracking considerations for fixed target B experiments at SSC and LHC

International Nuclear Information System (INIS)

McManus, A.P.; Conetti, S.; Corti, G.; Cox, B.; Dukes, E.C.; Lawry, T.; Nelson, K.; Tzamouranis, I.

1993-01-01

Fixed target beauty (B) experiments proposed at the SSC or LHC come in two basic types. Extracted beam experiments use a bent crystal of silicon or some other method to extract a beam of protons parasitically from the circulating beam as the collider experiments are taking data. The two chief extracted beam experiments are the LHB collaboration at the LHC and the SFT collaboration at the SSC. The second type of fixed target experiment places the detector around the circulating beam using a gas jet or thin wire(s) as a target. The (GAJET) experiment proposed at CERN for LHC and the Hera-B experiment at DESY are of this type

Predicting ground contact events for a continuum of gait types: An application of targeted machine learning using principal component analysis.

Science.gov (United States)

Osis, Sean T; Hettinga, Blayne A; Ferber, Reed

2016-05-01

An ongoing challenge in the application of gait analysis to clinical settings is the standardized detection of temporal events, with unobtrusive and cost-effective equipment, for a wide range of gait types. The purpose of the current study was to investigate a targeted machine learning approach for the prediction of timing for foot strike (or initial contact) and toe-off, using only kinematics for walking, forefoot running, and heel-toe running. Data were categorized by gait type and split into a training set (∼30%) and a validation set (∼70%). A principal component analysis was performed, and separate linear models were trained and validated for foot strike and toe-off, using ground reaction force data as a gold-standard for event timing. Results indicate the model predicted both foot strike and toe-off timing to within 20ms of the gold-standard for more than 95% of cases in walking and running gaits. The machine learning approach continues to provide robust timing predictions for clinical use, and may offer a flexible methodology to handle new events and gait types. Copyright © 2016 Elsevier B.V. All rights reserved.

TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

Energy Technology Data Exchange (ETDEWEB)

Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I [Henry Ford Health System, Detroit, MI (United States); Sethi, S [Karmanos Cancer Center, Detroit, MI (United States); Klein, M [Children' s Hospital of Michigan, Detroit, MI (United States)

2014-06-15

Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

TH-E-BRF-07: Raman Spectroscopy for Radiation Treatment Response Assessment in a Lung Metastases Mouse Model

International Nuclear Information System (INIS)

Devpura, S; Barton, K; Brown, S; Siddiqui, F; Chetty, I; Sethi, S; Klein, M

2014-01-01

Purpose: Raman spectroscopy is an optical spectroscopic method used to probe chemical information about a target tissue. Our goal was to investigate whether Raman spectroscopy is able to distinguish lung tumors from normal lung tissue and whether this technique can identify the molecular changes induced by radiation. Methods: 4T1 mouse breast cancer cells were implanted subcutaneously into the flanks of 6 Balb/C female mice. Four additional mice were used as “normal lung” controls. After 14 days, 3 mice bearing tumors received 6Gy to the left lung with 6MV photons and the other three were treated as “unirradiated tumor” controls. At a 24-hour time point, lungs were excised and the specimens were sectioned using a cryostat; alternating sections were either stained with hematoxylin and eosin (H and E) for evaluation by a pathologist or unstained for Raman measurements. 240 total Raman spectra were collected; 84 from normal lung controls; 63 from unirradiated tumors and 64 from tumors irradiated with 6Gy in a single fraction. Raman spectra were also collected from normal lung tissues of mice with unirradiated tumors. Principal component analysis (PCA) and discriminant function analysis (DFA) were performed to analyze the data. Results: Raman bands assignable to DNA/RNA showed prominent contributions in tumor tissues while Raman bands associated with hemoglobin showed strong contributions in normal lung tissue. PCA/DFA analysis identified normal lung tissue and tumor with 100% and 98.4% accuracy, respectively, relative to pathologic scoring. Additionally, normal lung tissues from unirradiated mice bearing tumors were classified as normal with 100% accuracy. In a model consisting of unirradiated and irradiated tumors identification accuracy was 79.4% and 93.8% respectively, relative to pathologic assessment. Conclusion: Initial results demonstrate the promise for Raman spectroscopy in the diagnosis normal vs. lung metastases as well as the assessment of

Structural integrity of heavy liquid-metal target installed in spallation neutron facility. Part 4: Consideration by fracture mechanics of target container window

International Nuclear Information System (INIS)

Ishikura, Syuichi; Kogawa, Hiroyuki; Futakawa, Masatoshi; Kikuchi, Kenji; Haga, Katsuhiro; Kaminaga, Masanori; Hino, Ryutaro

2004-01-01

Developments of the neutron scattering facility is carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (mercury) target used as a spallation neutron source in a MW-class neutron scattering facility, static and dynamic stress (including pressure wave in mercury) behaviors due to the incident of 1MW-pulsed proton beam (Maximum heat density is 461W/cc) were analyzed. In the analyses, two type target containers with semi-cylindrical type and flat-type beam windows were used as analytical models. As a result, it is confirmed that the stress generated by the pressure wave becomes the largest at the center of the beam window, and the flat-type beam window is more advantageous from the structural viewpoint than the semi-cylindrical type beam window. It has been understood that the stress generated in the beam window by the pressure wave can be treated as the secondary stress. Then, it has been understood that the stress and the stress range generated in the target window were bellow the allowable stress level defined by the standard of JIS on the maximum stress and fatigue strength. It has been experimentally confirmed that a cavitation was generated by generating the negative pressure in mercury near the target beam window and a collapse of cavitation damaged to the target container material, as pits. Then, the fracture mechanical analyses were carried out on the pit and a crack on pit tip. Consequently, it was clarified that the crack would not propagate because the inner surface of the beam window was become the compressive stress field due to the steady state thermal stress. Moreover, the evaluation technique of the cavitation which would be needed in the future was summarized. (author)

International Nuclear Target Development Society workshop 1983: proceedings

Energy Technology Data Exchange (ETDEWEB)

Thomas, G. (ed.)

1983-01-01

Separate abstracts were prepared for 11 of the 19 papers presented. Eight papers were previously included in the data base. Discussion group session papers on carbon stripper foils, problems in producing heavy-ion targets, and problems in producing general type targets are included. (WHK)

Plasmonic nanodiamonds: targeted core-shell type nanoparticles for cancer cell thermoablation.

Science.gov (United States)

Rehor, Ivan; Lee, Karin L; Chen, Kevin; Hajek, Miroslav; Havlik, Jan; Lokajova, Jana; Masat, Milan; Slegerova, Jitka; Shukla, Sourabh; Heidari, Hamed; Bals, Sara; Steinmetz, Nicole F; Cigler, Petr

2015-02-18

Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell are designed and synthesized. The architecture of particles is analyzed and confirmed in detail using electron tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor are demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Materials design data for reduced activation martensitic steel type EUROFER

Energy Technology Data Exchange (ETDEWEB)

Tavassoli, A.-A.F. E-mail: tavassoli@cea.fr; Alamo, A.; Bedel, L.; Forest, L.; Gentzbittel, J.-M.; Rensman, J.-W.; Diegele, E.; Lindau, R.; Schirra, M.; Schmitt, R.; Schneider, H.C.; Petersen, C.; Lancha, A.-M.; Fernandez, P.; Filacchioni, G.; Maday, M.F.; Mergia, K.; Boukos, N.; Baluc,; Spaetig, P.; Alves, E.; Lucon, E

2004-08-01

Materials design limits derived so far from the data generated in Europe for the reduced activation ferritic/martensitic (RAFM) steel type Eurofer are presented. These data address the short-term needs of the ITER Test Blanket Modules and a DEMOnstration fusion reactor. Products tested include plates, bars, tubes, TIG and EB welds, as well as powder consolidated blocks and solid-solid HIP joints. Effects of thermal ageing and low dose neutron irradiation are also included. Results are sorted and screened according to design code requirements before being introduced in reference databases. From the physical properties databases, variations of magnetic properties, modulus of elasticity, density, thermal conductivity, thermal diffusivity, specific heat, mean and instantaneous linear coefficients of thermal expansion versus temperature are derived. From the tensile and creep properties databases design allowable stresses are derived. From the instrumented Charpy impact and fracture toughness databases, ductile to brittle transition temperature, toughness and behavior of materials in different fracture modes are evaluated. From the fatigue database, total strain range versus number of cycles to failure curves are plotted and used to derive fatigue design curves. Cyclic curves are also derived and compared with monotonic hardening curves. Finally, irradiated and aged materials data are compared to ensure that the safety margins incorporated in unirradiated design limits are not exceeded.

Striatal activity is modulated by target probability.

Science.gov (United States)

Hon, Nicholas

2017-06-14

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

The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

Directory of Open Access Journals (Sweden)

Baca Chan

2017-05-01

Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

Family with sequence similarity 83, member B is a predictor of poor prognosis and a potential therapeutic target for lung adenocarcinoma expressing wild-type epidermal growth factor receptor.

Science.gov (United States)

Yamaura, Takumi; Ezaki, Junji; Okabe, Naoyuki; Takagi, Hironori; Ozaki, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Fukuhara, Mitsuro; Muto, Satoshi; Matsumura, Yuki; Hasegawa, Takeo; Hoshino, Mika; Osugi, Jun; Shio, Yutaka; Waguri, Satoshi; Tamura, Hirosumi; Imai, Jun-Ichi; Ito, Emi; Yanagisawa, Yuka; Honma, Reiko; Watanabe, Shinya; Suzuki, Hiroyuki

2018-02-01

Lung adenocarcinoma (ADC) patients with tumors that harbor no targetable driver gene mutation, such as epidermal growth factor receptor ( EGFR ) gene mutations, have unfavorable prognosis, and thus, novel therapeutic targets are required. Family with sequence similarity 83, member B ( FAM83B ) is a biomarker for squamous cell lung cancer. FAM83B has also recently been shown to serve an important role in the EGFR signaling pathway. In the present study, the molecular and clinical impact of FAM83B in lung ADC was investigated. Matched tumor and adjacent normal tissue samples were obtained from 216 patients who underwent complete lung resection for primary lung ADC and were examined for FAM83B expression using cDNA microarray analysis. The associations between FAM83B expression and clinicopathological parameters, including patient survival, were examined. FAM83B was highly expressed in tumors from males, smokers and in tumors with wild-type EGFR . Multivariate analyses further confirmed that wild-type EGFR tumors were significantly positively associated with FAM83B expression. In survival analysis, FAM83B expression was associated with poor outcomes in disease-free survival and overall survival, particularly when stratified against tumors with wild-type EGFR . Furthermore, FAM83B knockdown was performed to investigate its phenotypic effect on lung ADC cell lines. Gene silencing by FAM83B RNA interference induced growth suppression in the HLC-1 and H1975 lung ADC cell lines. FAM83B may be involved in lung ADC tumor proliferation and can be a predictor of poor survival. FAM83B is also a potential novel therapeutic target for ADC with wild-type EGFR .

Research and development on materials for the SPES target

Directory of Open Access Journals (Sweden)

Corradetti Stefano

2014-03-01

Full Text Available The SPES project at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro is focused on the production of radioactive ion beams. The core of the SPES facility is constituted by the target, which will be irradiated with a 40 MeV, 200 µA proton beam in order to produce radioactive species. In order to efficiently produce and release isotopes, the material constituting the target should be able to work under extreme conditions (high vacuum and temperatures up to 2000 °C. Both neutron-rich and proton-rich isotopes will be produced; in the first case, carbon dispersed uranium carbide (UCx will be used as a target, whereas to produce p-rich isotopes, several types of targets will have to be irradiated. The synthesis and characterization of different types of material will be reported. Moreover, the results of irradiation and isotopes release tests on different uranium carbide target prototypes will be discussed.

JAERI/KEK target material program overview

International Nuclear Information System (INIS)

Kikuchi, Kenji; Kogawa, Hiroyuki; Sasa, Toshinobu

2001-01-01

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

Thermal shock analysis of liquid-mercury spallation target

CERN Document Server

Ishikura, S; Futakawa, M; Hino, R; Date, H

2002-01-01

The developments of the neutron scattering facilities are carried out under the high-intensity proton accelerator project promoted by JAERI and KEK. To estimate the structural integrity of the heavy liquid-metal (Hg) target used as a spallation neutron source in a MW-class neutron scattering facility, dynamic stress behavior due to the incident of a 1 MW-pulsed proton beam was analyzed by using FEM code. Two-type target containers with semi-cylindrical type and flat-plate type window were used as models for analyses. As a result, it is confirmed that the stress (pressure wave) generated by dynamic thermal shock becomes the largest at the center of window, and the flat-plate type window is more advantageous from the structural viewpoint than the semi-cylindrical type window. It has been understood that the stress generated in the window by the pressure wave can be treated as the secondary stress. (author)

New Conotoxin SO-3 Targeting N-type Voltage-Sensitive Calcium Channels

Directory of Open Access Journals (Sweden)

Lei Wen

2006-04-01

Full Text Available Selective blockers of the N-type voltage-sensitive calcium (CaV channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to ω-conotoxin MVIIA (MVIIA, a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.

Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells.

Science.gov (United States)

Li, Q S; Meng, F Y; Zhao, Y H; Jin, C L; Tian, J; Yi, X J

2017-08-01

This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p. Plasma miR-214-5p was highly expressed in patients with bone fracture compared with HCs after fracture (p extracellular matrix (ECM) formation of osteoblastic MC3T3-E1 cells by targeting COL4A1. Cite this article: Q. S. Li, F. Y. Meng, Y. H. Zhao, C. L. Jin, J. Tian, X. J. Yi. Inhibition of microRNA-214-5p promotes cell survival and extracellular matrix formation by targeting collagen type IV alpha 1 in osteoblastic MC3T3-E1 cells. Bone Joint Res 2017;6:464-471. DOI: 10.1302/2046-3758.68.BJR-2016-0208.R2. © 2017 Yi et al.

Positron annihilation and Moessbauer studies of neutron irradiated reactor pressure vessel steels

International Nuclear Information System (INIS)

Brauer, G.; Matz, W.; Liszkay, L.; Molnar, B.

1990-11-01

Positron annihilation (lifetime, Doppler broadening) and Moessbauer studies on unirradiated, neutron irradiated and neutron irradiated plus annealed reactor pressure vessel steels (Soviet type 15Kh2NMFA) are presented. The role of microstructural properties and the formation of irradiation-induced precipitates is discussed. (orig.) [de

Facts about Type 2

Medline Plus

Full Text Available ... to help you meet your target blood glucose levels. Type 2 usually gets worse over time – even if you don’t need medications at first, you may need to later on. Some groups have a higher risk for developing type 2 diabetes than ...

Facts about Type 2

Medline Plus

Full Text Available ... or insulin to help you meet your target blood glucose levels. Type 2 usually gets worse over time – even if you don’t need medications at first, you may need to later on. Some groups have a higher risk for developing type 2 ...

CdSe/ZnS Quantum Dots-Labeled Mesenchymal Stem Cells for Targeted Fluorescence Imaging of Pancreas Tissues and Therapy of Type 1 Diabetic Rats.

Science.gov (United States)

Liu, Haoqi; Tang, Wei; Li, Chao; Lv, Pinlei; Wang, Zheng; Liu, Yanlei; Zhang, Cunlei; Bao, Yi; Chen, Haiyan; Meng, Xiangying; Song, Yan; Xia, Xiaoling; Pan, Fei; Cui, Daxiang; Shi, Yongquan

2015-12-01

Mesenchymal stem cells (MSCs) have been used for therapy of type 1 diabetes mellitus. However, the in vivo distribution and therapeutic effects of transplanted MSCs are not clarified well. Herein, we reported that CdSe/ZnS quantum dots-labeled MSCs were prepared for targeted fluorescence imaging and therapy of pancreas tissues in rat models with type 1 diabetes. CdSe/ZnS quantum dots were synthesized, their biocompatibility was evaluated, and then, the appropriate concentration of quantum dots was selected to label MSCs. CdSe/ZnS quantum dots-labeled MSCs were injected into mouse models with type 1 diabetes via tail vessel and then were observed by using the Bruker In-Vivo F PRO system, and the blood glucose levels were monitored for 8 weeks. Results showed that prepared CdSe/ZnS quantum dots owned good biocompatibility. Significant differences existed in distribution of quantum dots-labeled MSCs between normal control rats and diabetic rats (p quantum dots-labeled MSC injection. Statistical differences existed between the blood glucose levels of the diabetic rat control group and MSC-injected diabetic rat group (p < 0.01), and the MSC-injected diabetic rat group displayed lower blood glucose levels. In conclusion, CdSe/ZnS-labeled MSCs can target in vivo pancreas tissues in diabetic rats, and significantly reduce the blood glucose levels in diabetic rats, and own potential application in therapy of diabetic patients in the near future.

Synthetic Genetic Targeting of Genome Instability in Cancer

International Nuclear Information System (INIS)

Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.

2013-01-01

Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets

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.

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

Comparison of toxin production by clostridium botulinum type E in irradiated vacuum-packed trout (Salmo gairdneri)

International Nuclear Information System (INIS)

Hussain, A.M.; Ehlermann, D.; Diehl, J.F.

1977-01-01

Trouts obtained from a nearby Fish farm were slaughtered, gutted, cut into 100 g samples and inoculated with 10 1 , 10 3 and 10 5 spores per g of Clostridium botulinum type E. The vacuum-packed samples were stored under melting ice (0 0 C) and at temperatures of 5 0 and 10 0 C for periods of up to 8 weeks. At weekly intervals, occurrence of spoilage and toxin production were determined. Only at 10 0 C storage, the irradiated samples showed toxin production before spoilage was observed. When the fishes were stored at 5 0 C, no toxicity occurred before spoilage was observed even in samples treated with doses as high as 200 krad. Samples stored under melting ice, irradiated or unirradiated, never showed toxin production. It is concluded that the radurization of fish at doses of about 100 or 200 krad and at storage temperatures of melting ice or up to 5 0 C is safe with regard to a possible botulism risk. (orig.) [de

Natural products to target inflammation

NARCIS (Netherlands)

Allijn, Iris Eva

2016-01-01

Chapter 1 Most Western lifestyle diseases such as type 2 diabetes mellitus, cardiovascular disease and cancer have a chronic inflammatory process at its base. Therefore, inflammation is an important therapeutic target. Due to their potency, steroidal drugs dominate the current treatment of

Laser fusion target fabrication. Status report, 30 April 1974

International Nuclear Information System (INIS)

Fries, R.J.; Farnum, E.H.

1974-11-01

The laser fusion target fabrication effort at Los Alamos Scientific Laboratory has been successful in producing targets of the general design requested by, and with a range of parameters acceptable to, the theoretical designers and to the laser/target interaction physics experimentalists. Many novel techniques for handling and measuring the properties of various types of hollow microballoons were developed. (U.S.)

Targeting Signaling Pathways in Epithelial Ovarian Cancer

Directory of Open Access Journals (Sweden)

Johannes Haybaeck

2013-05-01

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

Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

Science.gov (United States)

Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

2013-01-01

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

Beyond typing and grading: target analysis in individualized therapy as a new challenge for tumour pathology.

Science.gov (United States)

Kreipe, Hans H; von Wasielewski, Reinhard

2007-01-01

In order to bring about its beneficial effects in oncology, targeted therapy depends on accurate target analysis. Whether cells of a tumour will be sensitive to a specific treatment is predicted by the detection of appropriate targets in cancer tissue by immunohistochemistry or molecular methods. In most instances this is performed by histopathologists. Reliability and reproducibility of tissue-based target analysis in histopathology require novel measures of quality assurance by internal and external controls. As a model for external quality assurance in targeted therapy an annual inter-laboratory trial has been set up in Germany applying tissue arrays with up to 60 mammary cancer samples which are tested by participants for expression of HER2/neu and steroid hormone receptors.

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

Tumor-targeted nanomedicines for cancer theranostics

Science.gov (United States)

Lammers, Twan; Shi, Yang

2017-01-01

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

Fixed target physics at high energies

International Nuclear Information System (INIS)

Kirk, T.B.

1984-01-01

The number and type of fixed target experiments that can be pursued at a proton synchrotron are very large. The advent of the Fermilab superconducting accelerator, the Tevatron, will extend and improve the results which are given here from recent CERN and Fermilab experiments. The sample of experiments given in this paper is neither meant to be inclusive nor intensive. Hopefully, it will give the flavor of contemporary fixed target physics to a predominantly cosmic ray oriented audience. (author)

Knowledge-based identification of the ERK2/STAT3 signal pathway as a therapeutic target for type 2 diabetes and drug discovery.

Science.gov (United States)

Kinoshita, Takayoshi; Doi, Kentaro; Sugiyama, Hajime; Kinoshita, Shuhei; Wada, Mutsuyo; Naruto, Shuji; Tomonaga, Atsushi

2011-09-01

Many existing agents for diabetes therapy are unable to restore or maintain normal glucose homeostasis or prevent the eventual emergence of hyperglycemia-related complication. Therefore, agents based on novel mechanisms are sought to complement and extend the current therapeutic approaches. Based on the initial paper research, we focused on active STAT3 as an attractive pharmacological target for type 2 diabetes. The subsequent text mining with a unique query to identify suppressors but not activators of STAT3 revealed the ERK2/STAT3 pathway as a novel diabetes target. The description of ERK2 inhibitors as diabetes target had not been found in our text mining research at present. The mechanism-based peptide inhibitor for ERK2 was identified using the knowledge of the KIM sequence, which has an important role in the recognition of cognate kinases, phosphatases, scaffold proteins, and substrates. The peptide inhibitor was confirmed to exert effects in vitro and in vivo. The peptide inhibitor conferred a significant decrease in HOMA-IR levels on Day 28 compared with that in the vehicle group. Besides lowering the fasting blood glucose level, the peptide inhibitor also attenuated the blood glucose increment in the fed state, as compared with the vehicle group. © 2011 John Wiley & Sons A/S.

Preservation of ethnic food dodol combination of irradiation and atmosphere modified packaging

International Nuclear Information System (INIS)

Tanhindarto, Rindy P

1998-01-01

An investigation was conducted to determine the suitable types of modified atmosphere treatment combined with irradiation to extend the storage life of dodol at room temperature. The samples were obtained from the manufacture and the production date was known. The sample were vacuum-packed, vacuum-packed with N 2 , and vacuum-packed with CO 2 in polyethylene laminated nylon pouches. A part of the samples were unirradiated, and the irradiated ones received total doses of 2,5 and 5 kGy. The quality of the samples were determined by chemical, microbiological, and organoleptic test. The results showed that the three types of packaging combined with irradiation were not significant. The storage life of irradiation treatment with the doses of 2,5 and 5 kGy combined with modified atmosphere treatment dodol could be extended up to 10 and 12 months, respectively. For Unirradiated dodol, the storage life could be extended up to 8 months. (authors)

NCI-MATCH Trial Links Targeted Drugs to Mutations

Science.gov (United States)

Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced that the trial will seek to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.

The Vasopressin Type-2 Receptor and Prostaglandin Receptors EP2 and EP4 can Increase Aquaporin-2 Plasma Membrane Targeting Through a cAMP Independent Pathway

DEFF Research Database (Denmark)

Olesen, Emma Tina Bisgaard; Moeller, Hanne Bjerregaard; Assentoft, Mette

2016-01-01

Apical membrane targeting of the collecting duct water channel aquaporin-2 (AQP2) is essential for body water balance. As this event is regulated by Gs coupled 7-transmembrane receptors such as the vasopressin type 2 receptor (V2R) and the prostanoid receptors EP2 and EP4, it is believed to be c...

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

Science.gov (United States)

Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

2017-02-01

To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Revising ecological assumptions about Human papillomavirus interactions and type replacement.

Science.gov (United States)

Murall, Carmen Lía; McCann, Kevin S; Bauch, Chris T

2014-06-07

The controversy over whether vaccine-targeted HPV types will be replaced by other oncogenic, non-vaccine-targeted types remains unresolved. This is in part because little is known about the ecology of HPV types. Patient data has been interpreted to suggest independence or facilitative interactions between types and therefore replacement is believed to be unlikely. With a novel mathematical model, we investigated which HPV type interactions and their immune responses gave qualitatively similar patterns frequently observed in patients. To assess the possibility of type replacement, vaccination was added to see if non-vaccine-targeted types increased their 'niche'. Our model predicts that independence and facilitation are not necessary for the coexistence of types inside hosts, especially given the patchy nature of HPV infection. In fact, independence and facilitation inadequately represented co-infected patients. We found that some form of competition is likely in natural co-infections. Hence, non-vaccine-targeted types that are not cross-reactive with the vaccine could spread to more patches and can increase their viral load in vaccinated hosts. The degree to which this happens will depend on replication and patch colonization rates. Our results suggest that independence between types could be a fallacy, and so without conclusively untangling HPV within-host ecology, type replacement remains theoretically viable. More ecological thinking is needed in future studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

High thermal conductivity SiC/SiC composites for fusion applications -- 2

International Nuclear Information System (INIS)

Kowbel, W.; Tsou, K.T.; Withers, J.C.; Youngblood, G.E.

1998-01-01

This report covers material presented at the IEA/Jupiter Joint International Workshop on SiC/SiC Composites for Fusion Structural Applications held in conjunction with ICFRM-8, Sendai, Japan, Oct. 23--24, 1997. An unirradiated SiC/SiC composite made with MER-developed CVR SiC fiber and a hybrid PIP/CVI SiC matrix exhibited room temperature transverse thermal conductivity of 45 W/mK. An unirradiated SiC/SiC composite made from C/C composite totally CVR-converted to a SiC/SiC composite exhibited transverse thermal conductivity values of 75 and 35 W/mK at 25 and 1000 C, respectively. Both types of SiC/SiC composites exhibited non-brittle failure in flexure testing

A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis.

Science.gov (United States)

Sun, Hui; Kamanova, Jana; Lara-Tejero, Maria; Galán, Jorge E

2016-03-01

Microbial infections usually lead to host innate immune responses and inflammation. These responses most often limit pathogen replication although they can also result in host-tissue damage. The enteropathogenic bacteria Salmonella Typhimurium utilizes a type III secretion system to induce intestinal inflammation by delivering specific effector proteins that stimulate signal transduction pathways resulting in the production of pro-inflammatory cytokines. We show here that a family of related Salmonella Typhimurium effector proteins PipA, GogA and GtgA redundantly target components of the NF-κB signaling pathway to inhibit transcriptional responses leading to inflammation. We show that these effector proteins are proteases that cleave both the RelA (p65) and RelB transcription factors but do not target p100 (NF-κB2) or p105 (NF-κB1). A Salmonella Typhimurium strain lacking these effectors showed increased ability to stimulate NF-κB and increased virulence in an animal model of infection. These results indicate that bacterial pathogens can evolve determinants to preserve host homeostasis and that those determinants can reduce the pathogen's virulence.

Preliminary Beam Irradiation Test for RI Production Targets at KOMAC

Energy Technology Data Exchange (ETDEWEB)

Yoon, Sang Pil; Kwon, Hyeok Jung; Kim, Han Sung; Cho, Yong Sub; Seol, Kyung Tae; Song, Young Gi; Kim, Dae Il; Jung, Myung Hwan; Kim, Kye Ryung; Min, Yi Sub [KAERI, Daejeon (Korea, Republic of)

2016-05-15

The new beamline and target irradiation facility has been constructed for the production of therapeutic radio-isotope. Sr-82 and Cu-67 were selected as the target isotope in this facility, they are promising isotope for the PET imaging and cancer therapy. For the facility commissioning, the irradiation test for the prototype-target was conducted to confirm the feasibility of radio-isotope production, the proto-type targets are made of RbCl pellet and the natural Zn metal for Sr-82 and Cu-67 production respectively, In this paper, an introduction to the RI production targetry system and the results of the preliminary beam irradiation test are discussed. the low-flux beam irradiation tests for proto-type RI target have been conducted. As a result of the beam irradiation tests, we could obtain the evidence of Sr-82 and Cu-67 production, have confirmed the feasibility of Sr-82 and Cu-67 production at KOMAC RI production facility.

Preliminary Beam Irradiation Test for RI Production Targets at KOMAC

International Nuclear Information System (INIS)

Yoon, Sang Pil; Kwon, Hyeok Jung; Kim, Han Sung; Cho, Yong Sub; Seol, Kyung Tae; Song, Young Gi; Kim, Dae Il; Jung, Myung Hwan; Kim, Kye Ryung; Min, Yi Sub

2016-01-01

The new beamline and target irradiation facility has been constructed for the production of therapeutic radio-isotope. Sr-82 and Cu-67 were selected as the target isotope in this facility, they are promising isotope for the PET imaging and cancer therapy. For the facility commissioning, the irradiation test for the prototype-target was conducted to confirm the feasibility of radio-isotope production, the proto-type targets are made of RbCl pellet and the natural Zn metal for Sr-82 and Cu-67 production respectively, In this paper, an introduction to the RI production targetry system and the results of the preliminary beam irradiation test are discussed. the low-flux beam irradiation tests for proto-type RI target have been conducted. As a result of the beam irradiation tests, we could obtain the evidence of Sr-82 and Cu-67 production, have confirmed the feasibility of Sr-82 and Cu-67 production at KOMAC RI production facility

Modeling the effects of fast-neutron irradiation on the subsequent mechanical behaviour of type 316 stainless steel

International Nuclear Information System (INIS)

Dimelfi, R.J.; Kramer, J.M.

1980-01-01

A model describing the subsequent mechanical behaviour of type 316 stainless steel exposed to a fast reactor environment is presented. A constitutive law for the flow stress, based on the Voce equation, is introduced. The strain-rate and temperature-dependence of the flow stress is formulated in this equation; and it is assumed that all contributions to changes in the flow stress, at a given temperature and strain-rate, are manifested in a single hardness parameter. Physically-based models for work hardening, irradition hardening, and irradiation softening are presented. By combining the constitutive law with the relations describing the hardness, a system of equations is presented which describes the mechanical response of the material after specified neutron irradiation and thermal exposure. When the model is used to analyze flow stress data on unirradiated material as well as material irradiated over a wide range of fluence and temperature, agreement between predicted and observed behaviour is shown, supporting the assumption of a single flow law incorporating a single hardness parameter. (orig.)

The Stricter the Better? The Relationship between Targeted HbA1c Values and Metabolic Control of Pediatric Type 1 Diabetes Mellitus.

Science.gov (United States)

Braun, Marcin; Tomasik, Bartlomiej; Wrona, Ewa; Fendler, Wojciech; Jarosz-Chobot, Przemyslawa; Szadkowska, Agnieszka; Zmysłowska, Agnieszka; Wilson, Jayne; Mlynarski, Wojciech

2016-01-01

It remains unclear how HbA1c recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus. To evaluate this we compared reported HbA1c with guideline thresholds. We searched systematically MEDLINE and EMBASE for studies reporting on HbA1c in children with T1DM and grouped them according to targeted HbA1c obtained from regional guidelines. We assessed the discrepancies in the metabolic control between these groups by comparing mean HbA1c extracted from each study and the differences between actual and targeted HbA1c. We included 105 from 1365 searched studies. The median (IQR) HbA1c for the study population was 8.30% (8.00%-8.70%) and was lower in "6.5%" than in "7.5%" as targeted HbA1c level (8.20% (7.85%-8.57%) versus 8.40% (8.20%-8.80%); p = 0.028). Median difference between actual and targeted HbA1c was 1.20% (0.80%-1.70%) and was higher in "6.5%" than in "7.5%" (1.70% (1.30%-2.07%) versus 0.90% (0.70%-1.30%), resp.; p HbA1c levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the "6.5%" group. A meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further.

Interim guidance for the safe transport of reprocessed uranium

International Nuclear Information System (INIS)

1994-06-01

Increasingly reprocessed uranium is being used for the fabrication of nuclear fuel elements. Different intermediate reprocessing steps are carried out at different locations. Therefore, transportation of uranium material is necessary. Due to the difference in isotope composition of reprocessed uranium then unirradiated uranium a doubt is casted on the presumption that packages used for the transport of unirradiated uranium are automatically suitable for reprocessed uranium compounds. The Standing Advisory Group on the Safe Transport of Radioactive Material (SAGSTRAM) recommended that the issue be reviewed by consultants and that a document be developed that would give guidance to users of the Regulations. This TECDOC is the result of the endeavors of the experts convened at two Consultants Services meetings. It contains guidance on the provisions in the current Regulations as well as proposals for changes to the new Revised Edition whose publication is planned for 1996. This document demonstrates that under the present Transport Regulations it is possible in most cases to ship reprocessed uranium compounds in the same packages as unirradiated uranium compounds. In few cases a more stringent package type is required. 8 refs, 22 figs, 19 tabs

Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus

DEFF Research Database (Denmark)

Hemmingsen, Bianca; Lund, Søren; Gluud, Christian

2013-01-01

Patients with type 2 diabetes mellitus (T2D) have an increased risk of cardiovascular disease and mortality compared to the background population. Observational studies report an association between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients...... with T2D. Our previous systematic review of intensive glycaemic control versus conventional glycaemic control was based on 20 randomised clinical trials that randomised 29 ,986 participants with T2D. We now report our updated review....

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

International Nuclear Information System (INIS)

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

1989-01-01

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

Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease.

Science.gov (United States)

Mostafa, S A; Coleman, R L; Agbaje, O F; Gray, A M; Holman, R R; Bethel, M A

2018-01-01

Glucose-lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA 1c reductions might reduce risk is unclear. Participant-level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with established cardiovascular disease were used in a Type 2 diabetes-specific simulation model to quantify the likely impact of different HbA 1c decrements on complication rates. Ten-year micro- and macrovascular rates were estimated with HbA 1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA 1c decrement. Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean (sd) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL-cholesterol 2.3 (0.9) mmol/l, HDL-cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1-15.6) years. Ten-year cumulative relative risk reductions for modelled HbA 1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetes-related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single-eye blindness. These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA 1c reductions in Type 2 diabetes. © 2017 Diabetes UK.

New method to calculate the mechanical properties of unirradiated fuel cladding from ring tensile tests

Energy Technology Data Exchange (ETDEWEB)

Martin-Rengel, M.A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren s/n, E-28040 Madrid (Spain); Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain); Gomez, F.J.; Ruiz-Hervias, J.; Caballero, L.; Valiente, A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren s/n, E-28040 Madrid (Spain)

2009-06-15

displacement of the loading piece and another one between the equivalent stress in the same point and the nominal applied stress. In the first iteration a calculation is performed with an approximate plastic stress-strain law, and the two above-mentioned relationships are used to determine a new law from the experimental results. In the second iteration the calculation takes into account the new plastic stress-strain law and determines two new relationships. After a few iterations an excellent fit is obtained. This method is an improvement of the original method by Arsene and Bai [3] and allows obtaining the plastic stress-strain curve in the hoop direction in a consistent way. The experimental data used in this work to check the validity of the procedure have been obtained on unirradiated Zirlo cladding, with the standard alloy composition and geometry (outer diameter of the cladding 9.5 mm and a wall thickness of 0.56 mm). References: [1]. Arsene, S.; Bai, J.B. A new approach to measuring transverse properties of structural tubing by a ring test, Journal of Testing and Evaluation, 24: 386-391 (1996) [2]. Arsene, S.; Bai, J. 'A new approach to measuring transverse properties of structural tubing by a ring test-experimental investigation', Journal of Testing and Evaluation, 26: 26-30 (1998) [3]. Arsene, S.; Bai, J.B.; 'Hydride embrittlement and irradiation effects on the hoop mechanical properties of pressurized water reactor (PWR) and boiling-water reactor (BWR) zircaloy cladding tubes: Part I. Hydride embrittlement in stress-relieved, annealed, and recrystallized zircaloys at 20 deg. C and 300 deg. C', Metallurgical and materials and transactions A, 34A: 553-566 (2003) [4]. Chang-Sun Seok, Bong-Kook, K.Linga, 'The properties of the ring and burst creep of zirlo claddings', Engineering Failure Analysis, 13: 389-397 (2006). (authors)

Design a 10 kJ IS Mather Type Plasma Focus for Solid Target Activation to Produce Short-Lived Radioisotopes 12C(d,n)13N

Science.gov (United States)

Sadat Kiai, S. M.; Adlparvar, S.; Sheibani, S.; Elahi, M.; Safarien, A.; Farhangi, S.; Zirak, A. R.; Alhooie, S.; Mortazavi, B. N.; Khalaj, M. M.; Khanchi, A. R.; Dabirzadeh, A. A.; Kashani, A.; Zahedi, F.

2010-10-01

A 10 kJ (15 kV, 88 μF) IS (Iranian Sun) Mather type plasma focus device has been studied to determine the activity of a compound exogenous carbon solid target through 12C(d,n)13N nuclear reaction. The produced 13N is a short-lived radioisotope with a half-life of 9.97 min and threshold energy of 0.28 MeV. The results indicate that energetic deuterons impinging on the solid target can produce yield of = 6.7 × 10-5 with an activity of A = 6.8 × 104 Bq for one plasma focus shut and A ν = 4 × 105 Bq for 6 shut per mint when the projectile maximum deuterons energy is E max = 3 MeV.

Projectile rapidity dependence in target fragmentation

International Nuclear Information System (INIS)

Haustein, P.E.; Cumming, J.B.; Hseuh, H.C.

1979-01-01

The thick-target, thick-catcher technique was used to determine mean kinetic properties of selected products of the fragmentation of Cu by 1 H, 4 He, and 12 C ions (180 to 28,000 MeV/amu). Momentum transfer, as inferred from F/B ratios, is ovserved to occur most efficiently for the lower velocity projectiles. Recoil properties of target fragments vary strongly with product mass, but show only a weak dependence on projectile type. The projectile's rapidity is shown to be a useful variable for quantitative intercomparison of different reactions. These results indicate that E/sub proj//A/sub proj/ is the dominant parameter which governs the mean recoil behavior of target fragments. 20 references

Neutron performance analysis for ESS target proposal

International Nuclear Information System (INIS)

Magán, M.; Terrón, S.; Thomsen, K.; Sordo, F.; Perlado, J.M.; Bermejo, F.J.

2012-01-01

In the course of discussing different target types for their suitability in the European Spallation Source (ESS) one main focus was on neutronics' performance. Diverse concepts have been assessed baselining some preliminary engineering and geometrical details and including some optimization. With the restrictions and resulting uncertainty imposed by the lack of detailed designs optimizations at the time of compiling this paper, the conclusion drawn is basically that there is a little difference in the neutronic yield of the investigated targets. Other criteria like safety, environmental compatibility, reliability and cost will thus dominate the choice of an ESS target.

Effects of degradation on third phase formation in the extraction of Th(NO3)4 by trialkyl phosphates

International Nuclear Information System (INIS)

Benadict Rakesh, K.; Suresh, A.; Vasudeva Rao, P.R.

2014-01-01

It is well known that solvents undergo chemical and radiolytic degradation during processing and in general the degradation products affect organic-aqueous phase separation, extraction and stripping behaviour, density, viscosity etc. In the present study, an attempt has been made to understand the effects of irradiation (100 MRad with 60 Co- γ-source) on third phase formation in the extraction of Th(IV) from nitric acid media by 1.1 M solutions of tri-n-butyl phosphate (TBP) and tri-iso-amyl phosphate (TiAP) in n-dodecane (n-DD). Two types of irradiated solvents, namely Type 1 solvents containing only primary degradation products (formed by the degradation of TBP molecules) and Type 2 solvents containing primary as well as secondary degradation products (surfactant type molecules formed by the reaction between the degradation products of extractant and diluent) were prepared by dissolving required amount of irradiated extractant in unirradiated n-DD and irradiating 1.1 M solutions of extractant in n-DD, respectively. These solvents with and without washing with 5 M NaOH solution have been investigated for third phase formation. The variations of limiting organic concentration (LOC) for third phase formation as a function of equilibrium aqueous phase acidity are shown. LOC values for third phase formation by unirradiated solvents reported in our earlier work are also shown. These figures depict that LOC values for Type 1 solvents are lower than the corresponding unirradiated solvents and can be attributed to the decrease in the extractant concentration by degradation. Estimation of extractant in Type 1 solvents by nitric acid equilibration method after the removal of primary degradation products by washing with 5 M NaOH solution revealed that extractant concentrations have been reduced to 1.03 M and 1.05 M for TBP and TiAP, respectively. Estimation of extractant in Type 2 solvents revealed 1.07 M extractant concentration in TBP and TiAP solvents. However, data

Preliminary microstructural characterization by transmission electron microscopy of 14 MeV neutron irradiated type 316 stainless steel

International Nuclear Information System (INIS)

Echer, C.J.

1977-01-01

Substantial changes in the mechanical properties of 316 stainless steel were observed after neutron irradiation (phi/sub t/ = 2.3 x 10 21 n/m 2 and E = 14 MeV) at 25 0 C. Comparison of microstructures of the unirradiated and neutron irradiated materials were evaluated using transmission electron microscopy. Evidence of small defect clusters in the irradiated material was found. These findings are consistent with other investigators also evaluating low dose irradiations

Plasmonic Nanodiamonds – Targeted Core-shell Type Nanoparticles for Cancer Cell Thermoablation

Science.gov (United States)

Rehor, Ivan; Lee, Karin L.; Chen, Kevin; Hajek, Miroslav; Havlik, Jan; Lokajova, Jana; Masat, Milan; Slegerova, Jitka; Shukla, Sourabh; Heidari, Hamed; Bals, Sara

2015-01-01

Targeted biocompatible nanostructures with controlled plasmonic and morphological parameters are promising materials for cancer treatment based on selective thermal ablation of cells. Here, core-shell plasmonic nanodiamonds consisting of a silica-encapsulated diamond nanocrystal coated in a gold shell is designed and synthesized. The architecture of particles is analyzed and confirmed in detail using 3-dimensional transmission electron microscope tomography. The particles are biocompatibilized using a PEG polymer terminated with bioorthogonally reactive alkyne groups. Azide-modified transferrin is attached to these particles, and their high colloidal stability and successful targeting to cancer cells overexpressing the transferrin receptor is demonstrated. The particles are nontoxic to the cells and they are readily internalized upon binding to the transferrin receptor. The high plasmonic cross section of the particles in the near-infrared region is utilized to quantitatively ablate the cancer cells with a short, one-minute irradiation by a pulse 750-nm laser. PMID:25336437

Alternative splicing affects the targeting sequence of peroxisome proteins in Arabidopsis.

Science.gov (United States)

An, Chuanjing; Gao, Yuefang; Li, Jinyu; Liu, Xiaomin; Gao, Fuli; Gao, Hongbo

2017-07-01

A systematic analysis of the Arabidopsis genome in combination with localization experiments indicates that alternative splicing affects the peroxisomal targeting sequence of at least 71 genes in Arabidopsis. Peroxisomes are ubiquitous eukaryotic cellular organelles that play a key role in diverse metabolic functions. All peroxisome proteins are encoded by nuclear genes and target to peroxisomes mainly through two types of targeting signals: peroxisomal targeting signal type 1 (PTS1) and PTS2. Alternative splicing (AS) is a process occurring in all eukaryotes by which a single pre-mRNA can generate multiple mRNA variants, often encoding proteins with functional differences. However, the effects of AS on the PTS1 or PTS2 and the targeting of the protein were rarely studied, especially in plants. Here, we systematically analyzed the genome of Arabidopsis, and found that the C-terminal targeting sequence PTS1 of 66 genes and the N-terminal targeting sequence PTS2 of 5 genes are affected by AS. Experimental determination of the targeting of selected protein isoforms further demonstrated that AS at both the 5' and 3' region of a gene can affect the inclusion of PTS2 and PTS1, respectively. This work underscores the importance of AS on the global regulation of peroxisome protein targeting.

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

Science.gov (United States)

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

2011-02-10

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

An investigation of bystander effects in Schizosaccharomyces pombe

International Nuclear Information System (INIS)

DeVeaux, L.C.; Wells, D.P.; Durtschi, L.S.; Reda, M.; Frujinoiu, C.; Harmon, F.

2003-01-01

Full text: 'Bystander' effects have been documented in various mammalian cell types and appear to act by two distinct mechanisms. One response requires a functional gap-junction. A non gap-junction-mediated response has also been observed in human cell lines, indicating release of a signaling factor. No analogous response has been investigated in unicellular organisms. Given that DNA damage signaling pathways are present in simple eukaryotes, we investigated bystander signaling effects using a single-celled organism, the fission yeast Schizosaccharomyces pombe. This organism may provide a much simpler model system than higher eukaryotic cells for studying these effects. We measured survival and mutation rate in an unirradiated culture after exposure to an irradiated culture. These two cultures were mixed immediately after irradiation, and any signaling factor that was produced had direct and continuous access to the unirradiated cells during subsequent cell divisions. The irradiated culture was from a multiply auxotrophic strain, whereas the unirradiated culture was from a prototrophic strain. Surviving colonies of the unirradiated culture were thus easily distinguished from those arising from irradiated cells. Mutation rates were measured as forward mutation to 2-deoxyglucose resistance. We have investigated bystander effects with electron and gamma dose from 6 to 20 MeV electron linacs. We varied electron beam energies, dose rates and temporal distributions of dose. The importance of this research stems from the fundamental evolutionary significance of cell signaling of any kind in unicellular systems, representing a major step toward the evolution of multi-cellular states

PAX3-FOXO1: Zooming in on an "undruggable" target.

Science.gov (United States)

Wachtel, Marco; Schäfer, Beat W

2018-06-01

Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets. In this review, we will discuss the current knowledge regarding potential therapeutic targets that might contribute to indirect interference with PAX3-FOXO1 activity in alveolar rhabdomyosarcoma at the different molecular levels and extrapolate these findings to fusion transcription factors in general. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Preparation of graphite targets for radiocarbon dating by tandem accelerator mass spectrometer (TAMS)

International Nuclear Information System (INIS)

Lowe, D.C.

1984-01-01

The introduction of TAMS has exciting implications for radiocarbon dating but improved sample preparation methods are needed. This paper describes a promising method for the conversion of a few milligrams of wood or charcoal into graphite targets for use in a caesium sputter ion source. Targets containing a large proportion of G-type graphite produced large C - currents, but those containing a high proportion of turbostatic Tn graphite were unsatisfactory; the type of graphite in the target is clearly of significance. (author)

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.

Membranes as sensitive targets in thymocyte apoptosis

International Nuclear Information System (INIS)

Ramakrishnan, N.; McClain, D.E.; Catravas, G.N.

1993-01-01

The role of cellular membranes in thymocyte apoptosis has been examined. Trolox, a water soluble analogue of vitamin E and inhibitor of membrane damage, inhibits DNA fragmentation in thymocytes exposed to γ-radiation, and is most effective in inhibiting DNA fragmentation when added to cells within 30 min post-irradiation. Exposure to trolox only during irradiation did not prevent DNA fragmentation. Incubation of the irradiated cell suspension with trolox for 2h post-irradiation was sufficient to prevent DNA fragmentation measured at 24 h in irradiated cells, suggesting that trolox irreversibly inhibits a cellular lesion required for apoptosis. The induction of DNA fragmentation appears to be related to a concurrent, pronounced flow of Ca 2+ into the cell. At 3 h post-irradiation the amount of Ca 2+ in irradiated thymocytes was more than twice that of unirradiated thymocytes. Trolox treatment completely blocked the radiation-induced influx of Ca 2+ into the thymocytes. These results suggest that membrane damage is a critical lesion involved in DNA fragmentation in thymocyte apoptosis. (author)

Does Angling Technique Selectively Target Fishes Based on Their Behavioural Type?

Directory of Open Access Journals (Sweden)

Alexander D M Wilson

Full Text Available Recently, there has been growing recognition that fish harvesting practices can have important impacts on the phenotypic distributions and diversity of natural populations through a phenomenon known as fisheries-induced evolution. Here we experimentally show that two common recreational angling techniques (active crank baits versus passive soft plastics differentially target wild largemouth bass (Micropterus salmoides and rock bass (Ambloplites rupestris based on variation in their behavioural tendencies. Fish were first angled in the wild using both techniques and then brought back to the laboratory and tested for individual-level differences in common estimates of personality (refuge emergence, flight-initiation-distance, latency-to-recapture and with a net, and general activity in an in-lake experimental arena. We found that different angling techniques appear to selectively target these species based on their boldness (as characterized by refuge emergence, a standard measure of boldness in fishes but not other assays of personality. We also observed that body size was independently a significant predictor of personality in both species, though this varied between traits and species. Our results suggest a context-dependency for vulnerability to capture relative to behaviour in these fish species. Ascertaining the selective pressures angling practices exert on natural populations is an important area of fisheries research with significant implications for ecology, evolution, and resource management.

A horizontal dilution refrigerator for polarized target

International Nuclear Information System (INIS)

Isagawa, S.; Ishimoto, S.; Masaike, A.; Morimoto, K.

1978-01-01

A horizontal dilution refrigerator was constructed with a view to the spin frozen target and the deuteron polarized target. High cooling power at high temperature such as 3.7 mW at 400 mK serves for overcoming a heat load of microwave to polarize the nuclear spins in the target material. The cooling power at 50 mK was 50 μW, which is sufficient to hold the high nuclear polarization for long time. The lowest temperature reached was 26 mK. The refrigerator has rather simple heat exchangers, a long stainless steel double tube heat exchanger and two coaxial type heat exchangers with sintered copper. The mixing chamber is made of polytetrafluoroethylene (TFE) and demountable so that the target material can be easily put into it. (Auth.)

Characterization of genetically targeted neuron types in the zebrafish optic tectum

Directory of Open Access Journals (Sweden)

Estuardo eRobles

2011-02-01

Full Text Available The optically transparent larval zebrafish is ideally suited for in vivo analyses of neural circuitry controlling visually guided behaviors. However, there is a lack of information regarding specific cell types in the major retinorecipient brain region of the fish, the optic tectum. Here we report the characterization of three previously unidentified tectal cell types that are specifically labeled by dlx5/6 enhancer elements. In vivo laser scanning microscopy in conjunction with ex vivo array tomography revealed that these neurons differ in their morphologies, synaptic connectivity, and neurotransmitter phenotypes. The first type is an excitatory bistratified periventricular interneuron (bsPVIN that forms a dendritic arbor in the retinorecipient stratum fibrosum griseum et superficiale (SFGS and an axonal arbor in the stratum griseum centrale (SGC. The second type, a GABAergic nonstratified periventricular interneuron (nsPVIN, extends a bushy arbor containing both dendrites and axons into the SGC and the deepest sublayers of the SFGS. The third type is a GABAergic periventricular projection neuron (PVPN that extends a dendritic arbor into the SGC and a long axon to the torus semicircularis, medulla oblongata, and anterior hindbrain. Interestingly, the same axons form en passant synapses within the deepest neuropil layer of the tectum, the stratum album centrale. This approach revealed several novel aspects of tectal circuitry, including: (1 a glutamatergic mode of transmission from the superficial, retinorecipient neuropil layers to the deeper, output layers, (2 the presence of interneurons with mixed dendrite/axon arbors likely involved in local processing, and (3 a heretofore unknown GABAergic tectofugal projection to midbrain and hindbrain. These observations establish a framework for studying the morphological and functional differentiation of neural circuits in the zebrafish visual system.

Alzheimer’s Disease, Brain Injury, and C.N.S. Nanotherapy in Humans: Sonoporation Augmenting Drug Targeting

Directory of Open Access Journals (Sweden)

Joseph S. D’Arrigo

2017-11-01

Full Text Available Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion are available. Versatile small-molecule drug(s targeting multiple pathways of Alzheimer’s disease pathogenesis are known. By incorporating such drug(s into the targeted lipid-coated microbubble/nanoparticle-derived (LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly scavenger receptor class B type I (SR-BI, making it possible for various Alzheimer’s-related cell types to be simultaneously sought for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s include a characteristic lipid-coated microbubble (LCM subpopulation (i.e., a stable LCM suspension; such LCM substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer’s patient.

Do We Need a Patient-Centered Target for Systolic Blood Pressure in Hypertensive Patients With Type 2 Diabetes Mellitus?

Science.gov (United States)

Wan, Eric Yuk Fai; Yu, Esther Yee Tak; Fung, Colman Siu Cheung; Chin, Weng Yee; Fong, Daniel Yee Tak; Chan, Anca Ka Chun; Lam, Cindy Lo Kuen

2017-12-01

The current trend on diabetes mellitus management advocates replacing the paradigm from a uniform to an individualized patient-centered systolic blood pressure (SBP), but there is no consensus on the achieved treatment goals of SBP level. The study aimed at evaluating the association between SBP and the risk of cardiovascular diseases (CVD) and all-cause mortality for diabetic patients to identify patient-centered treatment targets. A retrospective study was conducted on 95 086 Chinese adult primary care patients with type 2 diabetes mellitus and hypertension. Using the average of the annual SBP records (updated SBP) over a median follow-up of 5.9 years, the risks of overall CVD, all-cause mortality, and their composite associated with SBP were evaluated using Cox proportional hazards regression. Subgroup analysis was performed on the incidence of CVD by stratifying patient's baseline characteristics. The SBP range for the lowest risk of CVD and all-cause mortality was 130 to 134 mm Hg among type 2 diabetes mellitus population. A J-shaped curvilinear relationship was identified between SBP and risk of CVD and all-cause mortality, irrespective of patients' characteristics. The findings showed that all patients with SBP diabetic management. © 2017 American Heart Association, Inc.

Dissolution rates of unirradiated UO{sub 2}, UO{sub 2} doped with {sup 233}U, and spent fuel under normal atmospheric conditions and under reducing conditions using an isotope dilution method

Energy Technology Data Exchange (ETDEWEB)

Ollila, Kaija [VTT Processes, Helsinki (Finland); Albinsson, Yngve [Chalmers Univ. of Technology, Goeteborg (Sweden); Oversby, Virginia [VMO Konsult, Stockholm (Sweden); Cowper, Mark [AEA Technology, Harwell (United Kingdom)

2003-10-01

The experimental results given in this report allow us to draw the following conclusions. 1) Tests using unirradiated fuel pellet materials from two different manufacturers gave very different dissolution rates under air atmosphere testing. Tests for fragments of pellets from different pellets made by the same manufacturer gave good agreement. This indicates that details of the manufacturing process have a large effect on the behavior of unirradiated UO{sub 2} in dissolution experiments. Care must be taken in interpreting differences in results obtained in different laboratories because the results may be affected by manufacturing effects. 2) Long-term tests under air atmosphere have begun to show the effects of precipitation. Further testing will be needed before the samples reach steady state. 3) Testing of unirradiated UO{sub 2} in systems containing an iron strip to produce reducing conditions gave [U] less than detection limits (<0.02 ppb) after a few days to a few weeks of testing. Uranium recovered from the rinsing of reaction vessels and from acid stripping of vessels was shown to be from dissolution of grains of solid dislodged when the samples were handled after the tests were terminated. 4) Batch tests conducted under reducing conditions showed evidence of colloidal material in the early solution samples. 5) In the batch tests, measurements taken at day 3 and day 5 show that precipitation occurs from day 3 to day 5 without any further dissolution of the solid. 6) At termination of the batch tests, all but one sample had [U] in solution less than detection limits (< 0.02 ppb). Materials recovered in test termination samples showed evidence for recovery of small amounts - amounts corresponding to that expected from a few grains of 5 to 10 {mu}m size - in the acidified solution samples. These are interpreted to have been dislodged during sample handling operations. 7) Batch test data show that increasing test duration beyond 2 weeks does not provide

MicroRNA-194 promotes the growth, migration, and invasion of ovarian carcinoma cells by targeting protein tyrosine phosphatase nonreceptor type 12

Directory of Open Access Journals (Sweden)

Liang T

2016-07-01

Full Text Available Tian Liang, Liru Li, Yan Cheng, Chengcheng Ren, Guangmei Zhang Department of Gynecology and Obstetrics, The first Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Hei Longjiang, People’s Republic of China Abstract: Ovarian carcinoma is the most lethal gynecologic malignancy among women. Ovarian cancer metastasis is the main reason for poor prognosis. MicroRNAs (miRNAs have been shown to play an important role in tumorigenesis and metastasis in various cancers by affecting the expression of their targets. In this study, we explored the role of miR-194 in ovarian cancer. Real-time polymerase chain reaction assays showed that miR-194 was significantly upregulated in ovarian cancer tissues. Overexpression of miR-194 in ovarian cancer cells promotes cell proliferation, migration, and invasion; in contrast, inhibition of the expression of miR-194 has the opposite effects. Meanwhile, bioinformatics tools were used to identify protein tyrosine phosphatase nonreceptor type 12 (PTPN12 as a potential target of miR-194. The luciferase assay showed that miR-194 directly binds to the 3'-untranslated region of PTPN12. Western blot analysis and quantitative real-time polymerase chain reaction assay revealed that PTPN12 expression was negatively associated with miR-194 expression in both ovarian cancer tissues and cells. Thus, we conclude that miR-194 targets PTPN12 and functions as an oncogene in ovarian cancer cells. This novel pathway may provide a new insight to explain ovarian cancer development and metastasis. Keywords: miR-194, ovarian cancer, PTPN12, metastasis

Calculating the energy spectrum of neutrons from tritium target of the NG-150 type generator

International Nuclear Information System (INIS)

Bortash, A.I.; Kuznetsov, V.S.

1987-01-01

Calculation procedure of neutron spectra yielding from the NG-150 generator target chamber with regard to deutron moderation is suggested. Using the suggested procedure, neutron spectra for different escape angles formed in the tritium target are calculated. The spectrum of neutrons scattered in cooling water is calculated. The mean energy of neutrons escaping at the angle of 0 deg equalling 14.5 MeV is obtained

Targeting the CACNA1A IRES as a Treatment for Spinocerebellar Ataxia Type 6.

Science.gov (United States)

Pastor, Parviz Daniel Hejazi; Du, Xiaofei; Fazal, Sarah; Davies, Andre N; Gomez, Christopher M

2018-02-01

We have discovered that the P/Q-type voltage-gated Ca 2+ channel (VGCC) gene, CACNA1A, encodes both the α1A (Cav2.1) subunit and a newly recognized transcription factor, α1ACT, by means of a novel internal ribosomal entry site (IRES) within the α1A C-terminal coding region. α1ACT, when mutated with an expansion of the polyglutamine tract in the C-terminus, gives rise to spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A gene would result in the loss of the essential Cav2.1 channel, the IRES controlling α1ACT expression is an excellent target for selective silencing of α1ACT as a therapeutic intervention for SCA6. We performed a high-throughput screen of FDA-approved small molecules using a dual luciferase reporter system and identified ten hits able to selectively inhibit the IRES. We identified four main candidates that showed selective suppression of α1ACT relative to α1A in HEK cells expressing a native CACNA1A vector. We previously pursued another avenue of molecular intervention through miRNA silencing. We studied three human miRNAs (miRNA-711, -3191-5p, -4786) that would potentially bind to sequences within the CACNA1A IRES region, based on an miRNA prediction program. Only miRNA-3191-5p was found to selectively inhibit the translation of α1ACT in cells. We developed a hyperacute model of SCA6 in mice by injecting a pathogenic form of the IRES-mediated α1ACT (AAV9-α1ACTQ33). Finally, we tested the effectiveness of the miRNA therapy by co-expressing either control miRNA or miRNA-3191-5p and found that miRNA-3191-5p decreased the levels of α1ACTQ33 and prevented the hyperacute disease in mice. These studies provide the proof of principle that a therapy directed at selectively preventing α1ACT expression could be used to treat SCA6.

Benchmarking CRISPR on-target sgRNA design.

Science.gov (United States)

Yan, Jifang; Chuai, Guohui; Zhou, Chi; Zhu, Chenyu; Yang, Jing; Zhang, Chao; Gu, Feng; Xu, Han; Wei, Jia; Liu, Qi

2017-02-15

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based gene editing has been widely implemented in various cell types and organisms. A major challenge in the effective application of the CRISPR system is the need to design highly efficient single-guide RNA (sgRNA) with minimal off-target cleavage. Several tools are available for sgRNA design, while limited tools were compared. In our opinion, benchmarking the performance of the available tools and indicating their applicable scenarios are important issues. Moreover, whether the reported sgRNA design rules are reproducible across different sgRNA libraries, cell types and organisms remains unclear. In our study, a systematic and unbiased benchmark of the sgRNA predicting efficacy was performed on nine representative on-target design tools, based on six benchmark data sets covering five different cell types. The benchmark study presented here provides novel quantitative insights into the available CRISPR tools. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Targeting Malignant Brain Tumors with Antibodies

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Rok Razpotnik

2017-09-01

Full Text Available Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood–brain barrier (BBB makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs, and cell-based approaches. We have already shown the successful delivery of single-chain fragment variable (scFv with CPP as a linker between two variable domains in the brain. Antibodies normally face poor penetration through the BBB, with some variants sufficiently passing the barrier on their own. A “Trojan horse” method allows passage of biomolecules, such as antibodies, through the BBB by receptor-mediated transcytosis (RMT. Such examples of therapeutic antibodies are the bispecific antibodies where one binding specificity recognizes and binds a BBB receptor, enabling RMT and where a second binding specificity recognizes an antigen as a therapeutic target. On the other hand, cell-based systems such as stem cells (SCs are a promising delivery system because of their tumor tropism and ability to cross the BBB. Genetically engineered SCs can be used in gene therapy, where they express anti-tumor drugs, including antibodies. Different types and sources of SCs have been studied for the delivery of therapeutics to the brain; both mesenchymal stem cells (MSCs and neural stem cells (NSCs show great potential. Following the success in treatment of leukemias and lymphomas, the adoptive T-cell therapies, especially the chimeric antigen receptor-T cells (CAR-Ts, are making their way into glioma treatment as another type of cell

75 FR 73987 - Target Date Disclosure

Science.gov (United States)

2010-11-30

... principal strategies (including a general description of the types of assets held by the investment), and... information about TDFs that apply age or target retirement-based asset allocations, described in paragraph (e..., the description must satisfy three requirements. The first is an explanation of the asset allocation...

Chemotherapeutic targets in parasites: contemporary strategies

National Research Council Canada - National Science Library

Mansour, Tag E; Mansour, Joan MacKinnon

2002-01-01

... identify effective antiparasitic agents. An introduction to the early development of parasite chemotherapy is followed by an overview of biophysical techniques and genomic and proteomic analyses. Several chapters are devoted to specific types of chemotherapeutic agents and their targets in malaria, trypanosomes, leishmania, and amitochondrial...

Intensive integrated therapy of type 2 diabetes

DEFF Research Database (Denmark)

Gaede, Peter; Pedersen, Oluf

2004-01-01

The macro- and microvascular burden of type 2 diabetes is well established. A number of recent single risk factor intervention trials targeting hyperglycemia, dyslipidemia, hypertension, procoagulation, microalbumuria, and existing cardiovascular disorders have, however, shown major beneficial...... effects on long-term outcome. The results from these studies are anticipated to change the future management of type 2 diabetes, and most of the updated national guidelines for the treatment of type 2 diabetes recommend a multipronged approach driven by ambitious treatment targets. The outcome...... of this intensive integrated therapy has, however, only been investigated in a few studies of patients with type 2 diabetes. One of these trials, the Steno-2 Study, showed that intensive intervention for an average of 7.8 years cuts cardiovascular events as well as nephropathy, retinopathy, and autonomic neuropathy...

AMPK activation: a therapeutic target for type 2 diabetes?

OpenAIRE

Saha, Asish; Coughlan,Kimberly; Valentine,Rudy; Ruderman,Neil

2014-01-01

Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a...

Fixed target facility at the SSC

Energy Technology Data Exchange (ETDEWEB)

Loken, S.C.; Morfin, J.G.

1985-01-01

The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group led by E. Colton whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required. 13 references, 5 figures.

Fixed target facility at the SSC

International Nuclear Information System (INIS)

Loken, S.C.; Morfin, J.G.

1985-01-01

The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group led by E. Colton whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required. 13 references, 5 figures

Neutronic and thermal-hydraulic analysis of devices for irradiation of LEU targets type of UALx-Al and U-Ni to production of 99Mo in reactor IEA-R1 and RMB

International Nuclear Information System (INIS)

Domingos, Douglas Borges

2014-01-01

In this work neutronic and thermal-hydraulic analyses were made to compare three types of targets (UAl 2 -Al, U-Ni cylindrical and U-Ni plate) used for the production of 99 Mo by fission of 235 U. Some experiments were conducted to validate the neutronic and thermal-hydraulics methodologies used in this work. For the neutronic calculations the computational programs NJOY99.0, AMPX-II and HAMMERTECHNION were used to generate the cross sections. SCALE 6.0 and CITATION computational programs were used for three-dimensional calculations of the reactor cores, fuel burning and the production of 99 Mo. The computational programs MTRCR-IEAR1 and ANSYS CFX were used to calculate the thermal and hydraulic parameters of the irradiation devices and for comparing them to limits and design criteria. First were performed neutronic and thermal-hydraulic analyzes for the reactor IEA-R1 with the targets of UAl 2 -Al (10 mini plates). Analyses have shown that the total activity obtained for 99 Mo on the mini plates does not meet the demand of Brazilian hospitals (450 Ci/week) and that no limit of thermo-hydraulic design is overtaken. Next, the same calculations were performed for the three target types in Multipurpose Brazilian Reactor (MBR). The neutronic analyzes demonstrated that the three targets meet the demand of Brazilian hospitals. The thermal hydraulic analysis shows that a minimum speed of 7 m/s for the target UAl 2 -Al, 8 m/s for the cylindrical target U-Ni and 9 m/s for the target U-Ni plate will be necessary in the irradiation device to not exceed the design limits. Were performed experiments using a test bench for validate the methodologies for the thermal-hydraulic calculation. The experiments performed to validate the neutronic calculations were made in the reactor IPEN/MB-01. All experiments were simulated with the methodologies described above and the results compared. The simulations results showed good agreement with experimental results. (author)

Targeting composite treatment of type 2 diabetes in middle-income ...

African Journals Online (AJOL)

The management of type 2 diabetes mellitus (T2DM) has improved over the ... The epidemic of new cases of T2DM over the past two decades, particularly among ... of clinical strategies to lower hyperglycaemia and reduce costly morbidity and ...

Genetically Targeted Dipeptidyl Peptidase-4 Inhibitor Use in a Patient with a Novel Mutation of MODY type 4

Directory of Open Access Journals (Sweden)

Christian Mangrum

2015-01-01

Full Text Available Maturity onset diabetes of the young (MODY is a rare form of diabetes mellitus typically seen in young adults that results from pancreatic beta-cell dysfunction. MODY4 is a rare subtype caused by a PDX1 mutation. In this case, we present a nonobese 26-year-old male with polyuria and polydipsia. Lab work showed a blood glucose of 511 mg/dL, no ketones or antibodies (insulin, islet cell, and glutamic acid decarboxylase [GAD], C-peptide of 1.6 ng/mL, and A1c 9.3%. Genetic analysis revealed a novel nonsense mutation in the PDX1 gene, consistent with MODY type 4. Given this patient's particular genetic mutation affecting the incretin pathway, sitagliptin was substituted for glyburide, which led to significant improvement in glycemic control. Our case report identifies a unique mutation in a rare form of MODY and outlines management of ensuing diabetes through targeting its inherent genetic mutation.

Power and the objectification of social targets.

Science.gov (United States)

Gruenfeld, Deborah H; Inesi, M Ena; Magee, Joe C; Galinsky, Adam D

2008-07-01

Objectification has been defined historically as a process of subjugation whereby people, like objects, are treated as means to an end. The authors hypothesized that objectification is a response to social power that involves approaching useful social targets regardless of the value of their other human qualities. Six studies found that under conditions of power, approach toward a social target was driven more by the target's usefulness, defined in terms of the perceiver's goals, than in low-power and baseline conditions. This instrumental response to power, which was linked to the presence of an active goal, was observed using multiple instantiations of power, different measures of approach, a variety of goals, and several types of instrumental and noninstrumental target attributes. Implications for research on the psychology of power, automatic goal pursuit, and self-objectification theory are discussed.

Electron spin resonance (ESR) studies on irradiated cocoa beans and niger seeds

International Nuclear Information System (INIS)

Mangaonkar, S.R.; Natarajan, V.; Sastry, M.D.; Desai, S.R.P.; Kulkarni, P.R.

1997-01-01

Electron spin resonance (ESR) spectra of irradiated (10kGy) and unirradiated cocoa beans and niger seeds have been compared. Unirradiated cocoa beans failed to give any ESR signal, whereas after irradiation (10kGy) an ESR signal at g = 2.0042 was observed. However, ESR signals are given by both irradiated and unirradiated niger seeds. The intensity of signal was found to be dose-dependent up to 10kGy for both seeds. The signals were stable up to 180 days in both cases. The results indicate the possibility of using ESR for distinguishing between irradiated and unirradiated cocoa beans but not for niger seeds

Jet target intense neutron source

International Nuclear Information System (INIS)

Meier, K.L.

1977-01-01

A jet target Intense Neutron Source (INS) is being built by the Los Alamos Scientific Laboratory with DOE/MFE funding in order to perform radiation damage experiments on materials to be used in fusion power reactors. The jet target can be either a supersonic or a subsonic jet. Each type has its particular advantages and disadvantages, and either of the jets can be placed inside the spherical blanket converter which will be used to simulate a fusion reactor neutron environment. Preliminary mock-up experiments with a 16-mA, 115 keV, H + ion beam on a nitrogen gas supersonic jet show no serious problems in the beam formation, transport, or jet interaction

Facts about Type 2

Medline Plus

Full Text Available ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... medications or insulin to help you meet your target blood glucose levels. Type 2 usually gets worse ...

Physics with polarized electrons and targets

International Nuclear Information System (INIS)

Donnelly, T.W.

1984-01-01

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

High-Throughput Characterization of Cascade type I-E CRISPR Guide Efficacy Reveals Unexpected PAM Diversity and Target Sequence Preferences.

Science.gov (United States)

Fu, Becky Xu Hua; Wainberg, Michael; Kundaje, Anshul; Fire, Andrew Z

2017-08-01

Interactions between Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs and CRISPR-associated (Cas) proteins form an RNA-guided adaptive immune system in prokaryotes. The adaptive immune system utilizes segments of the genetic material of invasive foreign elements in the CRISPR locus. The loci are transcribed and processed to produce small CRISPR RNAs (crRNAs), with degradation of invading genetic material directed by a combination of complementarity between RNA and DNA and in some cases recognition of adjacent motifs called PAMs (Protospacer Adjacent Motifs). Here we describe a general, high-throughput procedure to test the efficacy of thousands of targets, applying this to the Escherichia coli type I-E Cascade (CRISPR-associated complex for antiviral defense) system. These studies were followed with reciprocal experiments in which the consequence of CRISPR activity was survival in the presence of a lytic phage. From the combined analysis of the Cascade system, we found that (i) type I-E Cascade PAM recognition is more expansive than previously reported, with at least 22 distinct PAMs, with many of the noncanonical PAMs having CRISPR-interference abilities similar to the canonical PAMs; (ii) PAM positioning appears precise, with no evidence for tolerance to PAM slippage in interference; and (iii) while increased guanine-cytosine (GC) content in the spacer is associated with higher CRISPR-interference efficiency, high GC content (>62.5%) decreases CRISPR-interference efficiency. Our findings provide a comprehensive functional profile of Cascade type I-E interference requirements and a method to assay spacer efficacy that can be applied to other CRISPR-Cas systems. Copyright © 2017 by the Genetics Society of America.

Four-Week Strategy-Based Training to Enhance Prospective Memory in Older Adults: Targeting Intention Retention Is More Beneficial than Targeting Intention Formation.

Science.gov (United States)

Ihle, Andreas; Albiński, Rafal; Gurynowicz, Kamila; Kliegel, Matthias

2018-01-01

So far, training of prospective memory (PM) focused on very short instances (single sessions) and targeted the intention-formation phase only. We aimed to compare the effectiveness of 2 different 4-week strategy-based PM training types, namely imagery training (targeting the encoding of the PM intention in the intention-formation phase) versus rehearsal training (targeting the maintenance of the PM intention in the intention-retention phase) in older adults. We used a 4-week training protocol (8 sessions in total, 2 sessions per week). From the 44 participants, 21 were randomly assigned to the imagery training (vividly imagining a mental picture to memorize the connection between the PM cue words and related actions during intention formation) and 23 to the rehearsal training (rehearsing the PM cue words during intention retention). The criterion PM task was assessed before and after the training. Comparing the effectiveness of both training types, we found a significant time by training type interaction on PM accuracy in terms of PM cue detection, F(1, 42) = 6.07, p = 0.018, η2p = 0.13. Subsequent analyses revealed that the rehearsal training was more effective in enhancing PM accuracy in terms of PM cue detection than the imagery training. Strategy-based PM training in older adults targeting the maintenance of the PM intention in the intention-retention phase may be more effective in enhancing PM accuracy in terms of PM cue detection than the strategy targeting the encoding of the PM intention in the intention-formation phase. This suggests that for successful prospective remembering, older adults may need more support to keep the PM cues active in memory while working on the ongoing task than to initially encode the PM intention. © 2018 S. Karger AG, Basel.

Impact of targeted education on managing warning and error signals by children and adolescents with type 1 diabetes using the Accu-Chek Combo Insulin Pump System

Directory of Open Access Journals (Sweden)

Asma Deeb

2017-09-01

Full Text Available Purpose Insulin pumps are widely used in diabetes. They are equipped with safety alarms to alert users. Pump manuals contain alarm codes and how to troubleshoot them. However, these manuals are lengthy and difficult to use, particularly in emergencies. We aim to assess the impact of targeted education on warnings and errors in improving competency to troubleshoot the alarms. Methods Twenty-one patients, with a median age of 13, were recruited over a 5-month period. Each patient had 2 study visits. The frequencies and types of alarms were recorded, and patients were given a summary sheet that outlined common alarms encountered and troubleshooting tips. In visit 2, the frequencies and types of alarms were compared to those of visit 1. The patients were asked to fill a questionnaire and to rate the education session given in visit 1, their level of competency in decrypting alarm codes, and their promptness in responding to alarms. Results Low cartridge (W1, low battery (W2, and bolus cancelled (W8 were the commonest warnings. The most noted errors were occlusion (E4, power interruption (E8, empty battery (E2, set not primed (E11, and cartridge empty (E1. The numbers of warning and error signals markedly decreased after targeted education (P<0.05. The ability in decrypting warning signals significantly improved (P=0.02, and the frequency of response to pump alarms significantly increased (P=0.001. Conclusions Certain warnings and errors are more common than others in insulin pumps. Targeted education is useful in improving competency and response of patients in managing pump alarms.

Angiogenesis and vascular targeting: Relevance for hyperthermia

DEFF Research Database (Denmark)

Horsman, Michael R

2008-01-01

The creation of a functional blood supply from the normal tissue vasculature via the process of angiogenesis is critical for the continued growth and development of solid tumours. This importance has led to the concept of targeting the tumour vasculature as a therapeutic strategy, and two major...... types of vascular targeting agents (VTAs) have developed; those that inhibit the angiogenic process-angiogenesis inhibiting agents (AIAs)-and those that specifically damage the already established neovasculature-vascular disrupting agents (VDAs). The tumour vasculature also plays a critical role...

Is ultraviolet enhanced reactivation of mammalian virus mutagenic

International Nuclear Information System (INIS)

Bockstahler, L.E.; Hellman, K.B.; Cantwell, J.M.; Strickland, A.

1981-01-01

Ultraviolet enhanced reactivation consists of an increase in the survival of certain uv-irradiated mammalian viruses when assayed for infectivity in uv-irradiated host mammalian cells, as compared with unirradiated cells. In this report ultraviolet enhanced reactivation is described, and a review is presented of investigations from this and other laboratories to establish whether or not this process is mutagenic. The answer to this question may help establish if error-prone DNA repair is induced in irradiated mammalian cells. We approached the mutagenesis question by examining the phenotypic reversion of a uv-irradiated temperature sensitive mutant of Herpes simplex virus to wild type growth in uv-irradiated monkey kidney cells. Apparent reversion was observed in both irradiated and unirradiated cells. No correlation could be found between the extent of reversion and uv exposure to the cells. The conclusions from studies reported by other investigators using various mammalian virus mutagenesis systems are conflicting. It was generally agreed that viral mutagenesis occurs when irradiated virus is passaged through either irradiated or unexposed cells. However, in some studies it was found that the frequency of mutagenesis in irradiated cells was greater than that in unirradiated cells, while in other studies increased mutagenesis in irradiated cells was not observed

Target injection methods for inertial fusion energy

International Nuclear Information System (INIS)

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

1994-06-01

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

Preliminary analysis of a target factory for laser fusion

International Nuclear Information System (INIS)

Sherohman, J.W.; Hendricks, C.D.

1980-01-01

An analysis of a target factory leading to the determination of production expressions has provided for the basis of a parametric study. Parameters involving the input and output rate of a process system, processing yield factors, and multiple processing steps and production lines have been used to develop an understanding of their dependence on the rate of target injection for laser fusion. Preliminary results have indicated that a parametric study of this type will be important in the selection of processing methods to be used in the final production scheme of a target factory

Word form Encoding in Chinese Word Naming and Word Typing

Science.gov (United States)

Chen, Jenn-Yeu; Li, Cheng-Yi

2011-01-01

The process of word form encoding was investigated in primed word naming and word typing with Chinese monosyllabic words. The target words shared or did not share the onset consonants with the prime words. The stimulus onset asynchrony (SOA) was 100 ms or 300 ms. Typing required the participants to enter the phonetic letters of the target word,…

Lenses matching of compound eye for target positioning

Science.gov (United States)

Guo, Fang; Zheng, Yan Pei; Wang, Keyi

2012-10-01

Compound eye, as a new imaging method with multi-lens for a large field of view, could complete target positioning and detection fastly, especially at close range. Therefore it could be applicated in the fields of military and medical treatment and aviation with vast market potential and development prospect. Yet the compound eye imaging method designed use three layer construction of multiple lens array arranged in a curved surface and refractive lens and imaging sensor of CMOS. In order to simplify process structure and increase the imaging area of every sub-eye, the imaging area of every eye is coved with the whole CMOS. Therefore, for several imaging point of one target, the corresponding lens of every imaging point is unkonown, and thus to identify. So an algorithm was put forward. Firstly, according to the Regular Geometry relationship of several adjacent lenses, data organization of seven lenses with a main lens was built. Subsequently, by the data organization, when one target was caught by several unknown lenses, we search every combined type of the received lenses. And for every combined type, two lenses were selected to combine and were used to calculate one three-dimensional (3D) coordinate of the target. If the 3D coordinates are same to the some combine type of the lenses numbers, in theory, the lenses and the imaging points are matched. So according to error of the 3D coordinates is calculated by the different seven lenses numbers combines, the unknown lenses could be distinguished. The experimental results show that the presented algorithm is feasible and can complete matching task for imaging points and corresponding lenses.

The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities.

Science.gov (United States)

Brunkwall, Louise; Orho-Melander, Marju

2017-06-01

The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatric surgery). We go on to review some potential future gut-based glucose-lowering approaches involving microbiota, including the development of personalised nutrition and probiotic approaches, identification of therapeutic components of probiotics, targeted delivery of propionate in the proximal colon, targeted delivery of metformin in the lower gut, faecal microbiota transplantation, and the incorporation of genetically modified bacteria that express therapeutic factors into microbiota. Finally, future avenues and challenges for understanding the interplay between human nutrition, genetics

DGAT: novel therapeutic target for obesity and type 2 diabetes mellitus.

Science.gov (United States)

Subauste, Angela; Burant, Charles F

2003-12-01

Obesity is currently an exceptionally common problem in humans. The last several years have produced a significant number of breakthroughs in obesity related areas of investigation. Triglycerides are considered the main form of storage of excess calories in fat. A key enzyme in the synthesis of triglycerides is acylCoA: diacylglycerol acyltransferase (DGAT). Recent studies have shown that mice deficient in this enzyme are resistant to diet induced obesity and have increased insulin and leptin sensitivity. These effects suggest that inhibition of DGAT in vivo may be a novel therapeutic target not only for obesity but also for diabetes.

Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information.

Science.gov (United States)

Vogel, Ulrich; Szczepanowski, Rafael; Claus, Heike; Jünemann, Sebastian; Prior, Karola; Harmsen, Dag

2012-06-01

Neisseria meningitidis causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.

Design of a tripartite network for the prediction of drug targets

Science.gov (United States)

Kunimoto, Ryo; Bajorath, Jürgen

2018-02-01

Drug-target networks have aided in many target prediction studies aiming at drug repurposing or the analysis of side effects. Conventional drug-target networks are bipartite. They contain two different types of nodes representing drugs and targets, respectively, and edges indicating pairwise drug-target interactions. In this work, we introduce a tripartite network consisting of drugs, other bioactive compounds, and targets from different sources. On the basis of analog relationships captured in the network and so-called neighbor targets of drugs, new drug targets can be inferred. The tripartite network was found to have a stable structure and simulated network growth was accompanied by a steady increase in assortativity, reflecting increasing correlation between degrees of connected nodes leading to even network connectivity. Local drug environments in the tripartite network typically contained neighbor targets and revealed interesting drug-compound-target relationships for further analysis. Candidate targets were prioritized. The tripartite network design extends standard drug-target networks and provides additional opportunities for drug target prediction.

A fixed target facility at the SSC

International Nuclear Information System (INIS)

Loken, S.; Morfin, J.G.

1984-01-01

The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required

Identification of food preserved by ionizing radiation; Preliminary tests in strawberries using thermoluminescent (TL)

International Nuclear Information System (INIS)

Rubio, T.; Sillano, O.; Espinoza, J.; Roman, A.; Deza, A.

1992-01-01

TL measurements, of irradiated and unirradiated strawberries were carried out, using peel, seeds (achenes), leaves and sediment. The four types of samples presented a different thermoluminescence response. The best results were obtained with sediment removed from the soil of the fruit surface. It is concluded that TL is a promising technique for detecting irradiated strawberries using sediment samples. (author)

Realization of a liquid hydrogen target

International Nuclear Information System (INIS)

Libin, J.F.; Gangnant, F.

1997-01-01

Experiments by the SPEG facility at GANIL need liquid hydrogen targets of some cm 3 . To achieve such targets, temperatures lower than 20 K must be obtained while their thin windows must withstand to pressures higher than 1000 m bars at these temperatures. Havar windows of 4.4 μm thickness met these requirements. A RW5 type Leybold cryo-generator was used as well as a system of ohmic heaters allowing regaining the initial state in a time equivalent with time elapsed for cooling. The working regime was chosen to be constant volume - variable pressure. The various components of this equipment (cryogenic head, buffer volume, hydrogen reservoir and vacuum pump) were coupled through 'aeroquip' allowing by dismantling and changes to keep the hydrogen isolated from the ambient atmosphere. The tests confirmed the accuracy of estimations done for the buffer volume and pressure. The only uncertainty is related to the window deformations. The time of cooling and reheating of target is around one hour. This allows during an experiment to aerate the chamber as the target was accessible to any necessary intervention

Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

Science.gov (United States)

Narayanan, Ramesh; Dalton, James T.

2016-01-01

Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER) and human epidermal growth factor receptor (HER2) are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR) is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease. Ironically, both nonsteroidal agonists and antagonists for the AR are undergoing clinical trials, making AR a complicated target to understand in breast cancer. This review provides a detailed account of AR’s therapeutic role in breast cancer. PMID:27918430

Thin film production of ceramic high-Tc-superconductors (targets)

International Nuclear Information System (INIS)

1992-01-01

Presently high-quality thin superconducting films having high T c 's may prepared by the sputtering technique. However, a large-area coating is required for an industrial application. One requirement is the availability of sputter targets with controlled and reproducible properties. By means of basic experiments with respect to powder processing, shaping and the densification process superconducting targets up to 200 mm in diameter were prepared in the Y-Ba-Cu-O- system. Additionally, targets from other systems with different geometries (e.g. ring targets) were prepared. These targets were submitted to the project partners as well as to other institutes and companies. During the course of this project the foundations for an industrial-type coating of large-area substrates were elaborated. (orig.). 9 refs., 5 tabs., 15 figs [de

Androgen Receptor: A Complex Therapeutic Target for Breast Cancer

Directory of Open Access Journals (Sweden)

Ramesh Narayanan

2016-12-01

Full Text Available Molecular and histopathological profiling have classified breast cancer into multiple sub-types empowering precision treatment. Although estrogen receptor (ER and human epidermal growth factor receptor (HER2 are the mainstay therapeutic targets in breast cancer, the androgen receptor (AR is evolving as a molecular target for cancers that have developed resistance to conventional treatments. The high expression of AR in breast cancer and recent discovery and development of new nonsteroidal drugs targeting the AR provide a strong rationale for exploring it again as a therapeutic target in this disease. Ironically, both nonsteroidal agonists and antagonists for the AR are undergoing clinical trials, making AR a complicated target to understand in breast cancer. This review provides a detailed account of AR’s therapeutic role in breast cancer.

Effects of grafts of single anterior pituitary glands on the incidence and type of mammary neoplasm in neutron- or γ-irradiated Fischer female rats

International Nuclear Information System (INIS)

Clifton, K.H.; Douple, E.B.; Sridharan, B.N.

1976-01-01

Three batches comprised of 48 young adult Fischer female rats each were subjected to total-body irradiation with 50 rads modified fission neutrons, or were given 600 rads 137 Cs γ-rays, or served as unirradiated controls. On the day following exposure, one-half of each batch was grafted with a single anterior pituitary gland beneath the left kidney capsule. The animals were observed for mammary neoplasia and all those that died during the experiment were autopsied. The experiment was terminated 538 +- 13 days after irradiation when all neutron-irradiated, pituitary-grafted animals had one or more mammary tumors. Only 2 of the 23 untreated rats that survived until termination of the experiment developed mammary fibroadenomas, and none had mammary carcinomas. The incidence of fibroadenomas was increased, and a single carcinoma was found in unirradiated rats with pituitary grafts. Irradiation alone caused an increase in the incidence of mammary fibroadenomas and the appearance of carcinomas. Fibroadenomas were markedly increased by the addition of pituitary grafts to irradiation. Carcinoma incidence was less markedly affected. The neutron dose of 50 rads was slightly more effective in inducing mammary neoplasms than the 600-rad dose of γ-rays

Truck accident involving unirradiated nuclear fuel

International Nuclear Information System (INIS)

Carlson, R.W.; Fischer, L.E.

1992-07-01

In the early morning of Dec. 16, 1991, a severe accident occurred when a passenger vehicle traveling in the wrong direction collided with a tractor trailer carrying 24 nuclear fuel assemblies in 12 containers on Interstate 1-91 in Springfield, Massachusetts. This paper documents the mechanical circumstances of the accident and the physical environment to which the containers were exposed and the response of the containers and their contents. The accident involved four impacts where the truck was struck by the car, impacted on the center guardrail, impacted on the outer concrete barrier and came to rest against the center guardrail. The impacts were followed by a fire that began in the engine compartment, spread to the.tractor and cab, and eventually spread to the trailer and payload. The fire lasted for about three hours and the packages were involved in the fire for about two hours. As a result of the fire, the tractor-trailer was completely destroyed and the packages were exposed to flames with temperatures between 1300 degrees F and 1800 degrees F. The fuel assemblies remained intact during the accident and there was no release of any radioactive material during the accident. This was a very severe accident; however, the injuries were minor and at no time was the public health and safety at risk

Characterization of phosphorus segregation in neutron-irradiated Russian pressure vessel steel weld

International Nuclear Information System (INIS)

Miller, M.K.; Jayaram, R.; Russell, K.F.

1995-01-01

An atom probe field ion microscopy characterization of three Russian pressure vessel steels has been performed. Field ion micrographs of several lath boundaries have indicated that they are decorated with a semicontinuous film of discrete brightly-imaging precipitates that were identified as molybdenum carbonitrides. In addition, extremely high phosphorus levels were measured at the lath boundaries. The phosphorus was found to be confined to an extremely narrow region indicative of monolayer type segregation. The phosphorus coverage determined from the atom probe results of the unirradiated materials agree with predictions based on McLean's equilibrium model of grain boundary segregation. The boundary phosphorus coverage of a neutron-irradiated weld material was significantly higher than in the unirradiated material. Ultrafine darkly-imaging copper- and phosphorus-enriched precipitates were also observed in the matrix of the neutron-irradiated material. (orig.)

Separate effects of irradiation and of graft-versus-host reaction on rat mucosal mast cells

International Nuclear Information System (INIS)

Cummins, A.G.; Munro, G.H.; Huntley, J.F.; Miller, H.R.P.; Ferguson, A.

1989-01-01

T cell mediated immune responses in the gut can produce enteropathy and malabsorption. The authors investigated the relevance of mucosal mast cells (MMC) to the mechanisms of this enteropathy by using graft-versus-host reaction (GvHR) in the rat as a model of mucosal delayed type hypersensitivity. x-irradiation, with or without GvHR, led to the virtual disappearance of jejunal MMC, undetectable jejunal rat mast cell protease (RMCPII) and very low levels of RMCPII in serum (all p<0.01 when compared with unirradiated controls). These experiments show that there is a modest expansion in jejunal MMC in unirradiated rats with semiallogeneic GvHR, whereas irradiation, alone or associated with GvHR, profoundly depletes MMC for at least two weeks. The enteropathy of GvHR can evolve in the virtual absence of MMC. (author)

Post-pulse detail metallographic examinations of low-enriched uranium silicide plate-type miniature fuel

International Nuclear Information System (INIS)

Yanagisawa, Kazuaki

1991-10-01

Pulse irradiation at Nuclear Safety Research Reactor (NSRR) was performed using low-enriched (19.89 w% 235 U) unirradiated silicide plate-type miniature fuel which had a density of 4.8 gU/cm 3 . Experimental aims are to understand the dimensional stability and to clarify the failure threshold of the silicide plate-type miniature fuel under power transient conditions through post-pulse detail metallographic examinations. A silicide plate-type miniature fuel was loaded into an irradiation capsule and irradiated by a single pulse. Deposited energies given in the experiments were 62, 77, 116 and 154 cal/g·fuel, which lead to corresponding peak fuel plate temperatures, 201 ± 28degC, 187 ± 10degC, 418 ± 74degC and 871 ± 74degC, respectively. Below 400degC, reliability and dimensional stability of the silicide plate fuel was sustained, and the silicide plate fuel was intact. Up to 540degC, wall-through intergranular crackings occurred in the Al-3%Mg alloy cladding. With the increase of the temperature, the melting of the aluminum cladding followed by recrystallization, the denudation of fuel core and the plate-through intergranular cracking were observed. With the increase of the temperature beyond 400degC, the bowing of fuel plate became significant. Above the temperature of 640degC molten aluminum partially reacted with the fuel core, partially flowed downward under the influence of surface tension and gravity, and partially formed agglomerations. Judging from these experimental observations, the fuel-plate above 400degC tends to reduce its dimensional stability. Despite of the apparent silicide fuel-plate failure, neither generation of pressure pulse nor that of mechanical energy occurred at all. (J.P.N.)

Preliminary investigation on the extension of shelf-life of boiled Chub mackerel by irradiation

Energy Technology Data Exchange (ETDEWEB)

Loaharanu, P; Prombubesara, C; Songprasertchai, S

1971-12-31

The influence of irradiation on the extension of shelf-life of boiled Chub mackerel stored at room temperature (25-30{sup 0}C) was investigated. It was found that boiled Chub mackerel irradiated at 0.1, 0.2, or 0.3 Mrad could be kept with good organoleptic properties at room temperature for 5, 8, and 11 days respectively; while the unirradiated sample could be kept for only 2 days. Boiled Chub mackerel used in this study was found to be heavily contaminated with microorganisms. Irradiation at doses mentioned caused reduction of more than 99% of bacteria. Bacillus and Acinetobacter were found to predominate in the irradiated boiled mackerel. The predominant flora in unirradiated boiled mackerel included Micrococcus, Staphylococcus, Bacillus, Acinetobacter, and Proteus. E. coli was always detected in unirradiated samples and was occasionally detected only in samples irradiated at 0.1 Mrad. Trimethylamine nitrogen (TMA-N) content, total volatile basic nitrogen (TVB-N) content, and total bacterial count (TBC) were used as indices of decomposition of both irradiated and unirradiated samples. TMA-N and TBC were found to be good indices of quality of only unirradiated boiled Chub mackerel, whereas TVB-N was found to be a good index of quality of both irradiated and unirradiated samples.

Dynamic effects of interaction of composite projectiles with targets

Energy Technology Data Exchange (ETDEWEB)

Zakharov, V. M. [Scientific Research Institute of Applied Mathematics and Mechanics of Tomsk State University, 36, Lenin Avenue, Tomsk, 634050 (Russian Federation)

2016-01-15

The process of high-speed impact of projectiles against targets of finite thickness is experimentally investigated. Medium-hard steel plates are used as targets. The objective of this research is to carry out a comparative analysis of dynamic effects of interaction of various types of projectiles with targets, such as characteristics of destruction of the target, the state of the projectile behind the target, and particularities of the after-penetration stream of fragments after the target has been pierced. The projectiles are made of composites on the basis of tungsten carbide obtained by caking and the SHS-technology. To compare effectiveness of composite projectiles steel projectiles are used. Their effectiveness was estimated in terms of the ballistic limit. High density projectiles obtained by means of the SHS-technology are shown to produce results comparable in terms of the ballistic limit with high-strength projectiles that contain tungsten received by caking.