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Polyene macrolides, such as nystatin A1, amphotericin B, and NPP A1, belong to a large family of valuable antifungal polyketide compounds that are typically produced by soil actinomycetes. Previously, NPP B1, a novel NPP A1 derivative harboring a heptaene core structure, was generated by introducing two amino acid substitutions in the putative NADPH-binding motif of the enoyl reductase domain in module 5 of the NPP A1 polyketide synthase in Pseudonocardia autotrophica. This derivative showed superior antifungal activity to NPP A1. In this study, another novel derivative called NPP B2 was developed, which lacks a hydroxyl group at the C10 position by site-specific gene disruption of the P450 hydroxylase NppL. To stimulate the extremely low expression of the NPP B2 biosynthetic pathway genes, the 32-kb NPP-specific regulatory gene cluster was overexpressed via site-specific chromosomal integration. The extra copy of the six NPP-specific regulatory genes led to a significant increase in the NPP B2 yield from 0.19 to 7.67 mg/L, which is the highest level of NPP B2 production ever achieved by the P. autotrophica strain. Subsequent in vitro antifungal activity and toxicity studies indicated that NPP B2 exhibited similar antifungal activity but significantly lower hemolytic toxicity than NPP B1. These results suggest that an NPP biosynthetic pathway refactoring and overexpression of its pathway-specific regulatory genes is an efficient approach to stimulating the production of an extremely low-level metabolite, such as NPP B2 in a pathway-engineered rare actinomycete strain.

Atmospheric dispersion simulations can provide crucial information to assess radioactive plumes in the environment for nuclear emergency preparedness. However, it is a difficult and time-consuming task to make simulations assuming many possible scenarios and to derive data from a vast number of results. Therefore, an interface was developed to assist users in conveying telltale characteristics of plumes from a large database of simulation results by WSPEEDI-II. Evaluation of the effectiveness of the interface was conducted, which made use of WSPEEDI-II simulations that are in time segments of 1-hour for the first 20-days of radioactive release from the Fukushima Daiichi Nuclear Power Plant (1F). As a result, 480 case scenarios are generated. To simplify and highlight the important data, the user interface displays essential quantitative data to the user. In addition, the user may conduct sensitivity analysis with the help of the interface by changing the input of time and type of radionuclide to generate many different case scenarios.

Pseudonocardia autotrophica was previously identified to produce a toxicity-reduced and solubility-improved disaccharide-containing anti-fungal compound belonging to the tetraene-family, Nystatin-like Pseudonocardia Polyene A1 (NPP A1). Subsequently NPP B1, a novel derivative harboring a heptaene core structure, was produced by a pathway-engineered Pseudonocardia strain through inactivation of the specific enoly reductase gene domain in the NPP biosynthetic gene cluster. Although in vitro and in vivo efficacy and toxicity studies indicate that NPP B1 is a promising lead antifungal compound, further improvement is required to increase the extremely low production yield in the pathway-engineered strain. To overcome this challenge, we performed the N-methyl-N′-nitro-N-nitrosoguanidine (NTG) iterative random mutagenesis, followed by zone-of-inhibition agar plug assay. After three rounds of the mutagenesis-and-screening protocol, the production yield of NPP B1 increased to 6.25 mg/L, which is more than an eightfold increase compared to the parental strain. The qRT-PCR analysis revealed that transcripts of the NPP B1 biosynthetic genes were increased in the mutant strain. Interestingly, an endogenous 125-kb plasmid was found to be eliminated through this mutagenesis. To further improve the NPP B1 production yield, the 32-kb NPP-specific regulatory gene cluster was cloned and overexpressed in the mutant strain. The chromosomal integration of the extra copy of the six NPP-specific regulatory genes led to an additional increase of NPP B1 yield to 31.6 mg/L, which is the highest production level of NPP B1 ever achieved by P. autotrophica strains. These results suggest that a synergistic combination of both the traditional and genetic strain improvement approaches is a very efficient strategy to stimulate the production of an extremely low-level metabolite (such as NPP B1) in a pathway-engineered rare actinomycetes strain.

Polyene macrolides such as nystatin A1 and amphotericin B belong to a large family of very valuable antifungal polyketide compounds typically produced by soil actinomycetes. Recently, nystatin-like Pseudonocardia polyene (NPP) A1 has been identified as a unique disaccharide-containing tetraene antifungal macrolide produced by Pseudonocardia autotrophica. Despite its significantly increased water solubility and decreased hemolytic activity, its antifungal activity remains limited compared with that of nystatin A1. In this study, we developed NPP B1, a novel NPP A1 derivative harboring a heptaene core structure, by introducing two amino acid substitutions in the putative NADPH-binding motif of the enoyl reductase domain in module 5 of the NPP A1 polyketide synthase NppC. The low level NPP B1 production yield was successfully improved by eliminating the native plasmid encoding a polyketide biosynthetic gene cluster present in P. autotrophica. In vitro and in vivo antifungal activity and toxicity studies indicated that NPP B1 exhibited comparable antifungal activity against Candida albicans and was less toxic than the most potent heptaene antifungal, amphotericin B. Moreover, NPP B1 showed improved pharmacokinetic parameters compared to those of amphotericin B, suggesting that NPP B1 could be a promising candidate for development into a pharmacokinetically improved and less-toxic polyene antifungal antibiotic.

A comparative study was performed with different designs of the fast breeder reactor (FBR) blanket to evaluate the performance of plutonium breeding accompanied with denaturing, and trans-uranium (TRU) transmutation for enhancement of the proliferation resistance and actinide management in the future fuel cycle. Four designs of the FBR blanket fuel were intercompared, conventional depleted uranium (DU) oxide fuels, DU with TRU oxide fuels, DU with TRU oxide fuels with homogeneous/heterogeneous moderators. As results, with heterogeneous moderator in the axial and the radial blanket fuels, the greatest TRU transmutation and plutonium denaturing performance were attained without deteriorating fuel breeding. Design optimization was performed as for ZrH 1.65 moderator rod/pellet arrangement in the axial and the radial blanket fuel assemblies. The optimum number of moderator rods per assembly was 25 (11% of the number of total rods) with proper mutual interval (2–3 cm) and symmetrical arrangement in the radial blanket, and insertion of 1 cm thick ZrH 1.65 moderator pellets to 4 and 10 cm from the top and the bottom planes of the active core was the optimum design in the axial blanket, in order to achieve the highest TRU transmutation ratio and plutonium denaturing performance without deteriorating fuel breeding. From the non-proliferation aspect, material attractiveness of plutonium were evaluated comparing with the criterion based on decay heat, and required TRU doping ratio in DU with TRU oxide fuel were proved to be as 1.6–2.5 wt.% with heterogeneous moderator, 2.1–3.0 wt.% with homogeneous moderator, and 4.1–5.0 wt.% without moderator. The heterogeneous loading of moderation showed the great advantages in fuel treatment in clear the heat generation limit criterion, as well as mass requirement to the initial and multi-cycle phase.

The present paper is focused on the feasibility of reduced-moderation water reactor (RMWR) which could simultaneously achieve the extension of core life-time, and highly protected plutonium (Pu) breeding performance with short compound system doubling time (CSDT) by neptunium-237 (237Np) or americium-241 (241Am) doping of the inner blanket of the RMWR. As a preliminary analysis of the RMWR, a simplified fuel pin configuration was analyzed. In case of 60% doping of 237Np and 241Am in the inner blanket, the maximum available effective full power days (EFPDs) were much longer and were about 15,100 and 14,200 EFPDs, respectively. For the proliferation resistance of Pu produced in the blanket, the total Pu in the inner and lower/upper blanket was below the practically unusable criterion for an explosive device proposed by Pellaud, and was technically unfeasible for high-technology hypothetical nuclear explosive devices (HNEDs) proposed by Kessler and Kimura. The protected Pu breeding performance was analyzed and in case of 60% doping of 237Np and 241Am, CSDT was short by approximately 40 and 50 years. Therefore, the feasibility of RMWR was shown which could simultaneously achieve the extension of core life-time and have highly protected Pu breeding performance with short CSDT by doping the inner blanket with minor actinides (MAs). The objective of this study was thus to evaluate the performance of the concept with respect to the core life-time, proliferation resistance of Pu and CSDT. The technological feasibility of such core concept will have to be evaluated by further dedicated analyses.

The design consideration of depleted U and Am (DU-Am) oxide fuel pin was performed for Pu denaturing in the framework of the protected plutonium production based on the irradiation analyses of the DU samples irradiated in the environment of broad range of neutron energy in the experimental fast reactor Joyo. From the results of irradiation analyses of DU, it was confirmed that there is a strong dependence of transmutation behavior of DU on the ratio of neutron flux in the resonance region to the total neutron flux, namely resonance neutron ratio, even in a fast reactor. Also, it was confirmed that there is a strong effect of sample material form and shape on generated Pu nuclide inventory especially near the reflector area (>20% resonance neutron ratio), because of the intensive self-shielding of 238 U, though less is expected for 241 Am. Sensitivity study of hypothetical DU-Am oxide fuel pellet irradiation on neutron energy and burn-up was performed to evaluate significant gradient of radial 238 Pu isotopic composition profile (e.g., from 12% to 18% distribution in 3% Am doping, in 30% resonance neutron ratio and in the neutron fluence of 4.0 × 10 22 n/cm 2 inside a large pellet with softened neutron spectrum), and vulnerability of the fuel pellet surface in terms of Pu denaturing was revealed. Design consideration of radial zoning of 241 Am content was introduced to flatten the radial distribution of isotopic composition of Pu. The results of radial zoning of 241 Am (4% and 3% Am in the outer and inner zone of DU-Am oxide fuel pellet) in hypothetical irradiation neutronics analysis showed the radial profile of produced Pu is over 15 at.% of 238 Pu isotopic composition in any zone and meets the criterion of Kimura et al. based on decay heat of Pu to impede utilization to fission explosive devices.

The proliferation resistance of plutonium can be enhanced by isotopic denaturing and one of the features of Pu isotopic denaturing is increasing of the spontaneous fission neutron emission rate. A high spontaneous fission neutron emission rate causes “predetonation” in a nuclear explosive device, and it makes the designing and building of a nuclear explosive device more complicated. In this paper, the enhancement of Pu proliferation resistance by isotopic denaturing was evaluated based on spontaneous fission neutron emission rate using a simple nuclear explosive device model. The feature of spontaneous fission neutron was evaluated with probabilistic approach, and a new Pu categorization which makes enable to categorize plutonium by its isotopic compositions was proposed based on the evaluation results. The Pu categorization was applied to an evaluation of the proliferation resistance of plutonium produced in LWRs and FBRs using the evaluation function, “Attractiveness” for two types of plutonium; plutonium produced in typical LWRs and FBRs, and denatured plutonium produced by transmutation of MAs.

A feasibility study on simultaneous approaches to the extension of core life-time and the high protected plutonium (Pu) breeding by introducing the axial inner blanket and doping minor actinides (MAs) in a large-scale sodium-cooling fast breeder reactor (FBR) has been performed for mix-oxide (MOX) and metallic fuel. The maximum available effective full power days (EFPDs) in MOX-fueled FBR with introducing the axial inner blanket and MA was extended from 1700 to 2900 compared with the conventional MOX-fueled FBR. The maximum available EFPDs in the case of metallic-fueled FBR with introducing the axial inner blanket and MA was extended to 5900. Conventional Attractiveness ( ATTR ) to evaluate the proliferation resistance of Pu based on isotopic material barriers such as decay heat (DH) and spontaneous fission neutron rate (SN) was modified by taking into account bare critical mass (BCM) as Attractiveness mod ( ATTR mod ), which was applied to evaluate the proliferation resistance of Pu generated in the axial inner blanket and axial/radial outer blankets. It was found that if only a small amount (4–5 wt.%) of MA are doped into the axial inner blanket and axial/radial outer blanket in both MOX and metallic fuel, the proliferation resistance of Pu was increased to satisfy the criteria of “practically unusable for an explosive device” proposed by Pellaud and “technically unfeasible for a high-technology hypothetical nuclear explosive devices (HNEDs)” proposed by Kessler and Kimura. The fissionable Pu inventory ratio ( FPIR ), defined as the ratio of inventory of 238 Pu, 239 Pu and 241 Pu at the beginning of cycle (BOC) to that at the given irradiation time, was introduced to survey the breeding characteristics of FBR. FPIR at the end of cycle (EOC) in MOX-fueled FBR with doping MA into the axial inner blanket and axial/radial outer blankets was increased from 1.008 to 1.168 compare with the conventional MOX-fueled FBR. In addition, FPIR at EOC in metallic-fueled FBR with doping MA into the axial inner blanket and axial/radial outer blankets was increased to 1.263. In the present study, the feasibility of simultaneous approaches to the extension of core life-time and the high protected Pu breeding has been confirmed by the introduction of the axial inner blanket and MA doping.

This paper describes loss of coolant accident (LOCA) analyses of the Supercritical-pressure Water-Cooled Fast Reactor (Super Fast Reactor). The features of the Super Fast Reactor are high power density and downward flow cooled fuel channels for the improvement of the economic potential of the Super Fast Reactor with high outlet steam temperature. The LOCA induces large pressure and coolant density change in the core. This change influences the flow distribution among the downward flow parallel channels. It will affect the safety of the Super Fast Reactor. LOCA analysis of Super Fast Reactor is important to understand the safety features of the Super Fast Reactor. Keeping the flow rate in the core is important for the safety of the Super Fast Reactor. In LOCA, it is difficult to maintain an adequate flow rate due to the once-through coolant cycle and the downward flow cooled fuel assemblies. Therefore, the early actuation of the Automatic Depressurization System (ADS) and reduction of the maximum linear he...

The practical feasibility of 126Sn transmutation in spallation targets of accelerator-driven systems was evaluated from the viewpoints of accumulation of radioactive spallation products and neutron production as well as transmutation amount of 126Sn. A cylindrical liquid 126Sn target whose length depends on proton beam energy was described, based on a Pb-Bi target design of accelerator-driven system being developed in JAEA. A proton beam of 1.5 GeV-20mA was estimated to give the transmutation rate of 126Sn 6.4 kg/yr, which corresponds to the amount of 126Sn annually discharged in 27 LWRs of 1GWt and 33 GWd/THM. The equilibrium radioactivity of spallation products would reach 9% of that of 126Sn transmuted in the spallation target, and the equilibrium toxicity would be just 3%. Some parametric analyses showed that the effective half-life of 126Sn could be reduced through a proper reduction of the target size. The 126Sn target was calculated to produce 40 neutrons per proton of 1.5 GeV and give a neutron sp...

The 3-D extension C5G7 MOX benchmark, which is a follow-up benchmark of the C5G7 MOX on deterministic 2-D/3-D MOX fuel assembly transport calculations without spatial homogenization, aims at providing a more challenging test of the abilities of currently available 3-D methods to handle the spatial heterogeneities of reactor core. The geometry configuration was modified with some significant changes including control rod insertion in order to check real 3-D effects with the previous benchmark. In this work, THREEDANT code within DANTSYS code package, which solves the multi-group discrete ordinates form of the Boltzmann transport equation in x–y–z and r–z–theta geometries, was employed to perform the benchmark calculations with the spatial approximation to a square shape of the circular fuel pin and the angular approximation to S8. The calculation results from THREEDANT indicate that the power decrements due to control rod insertion are larger than those in the reference solution and are also more sensitive. In addition, a sensitivity study on mesh refinement was performed to produce a higher quality solution. In the results, it is found that the 4 × 4 grid per pin cell in the THREEDANT calculation is sufficiently refined so that very little benefit is obtained by increasing the mesh size.

The C5G7 MOX benchmark was proposed to test the ability of commercial transport codes to treat reactor core problems without spatial homogenization. The benchmark requires solutions in the form of normalized pin powers as well as the eigenvalue. In the work, the two-dimensional benchmark calculation using the TWODANT code within the DANTSYS code package has been performed with proper spatial and angular approximations. The TWODANT code solves the multigroup discrete ordinates form of the Boltzmann transport equation in two-dimensional geometry. The calculation results show a good agreement in comparison with the reference solution obtained from a seven-group MCNP calculation. In addition, sensitivity studies on mesh and angular refinements have been performed to produce a higher quality solution. In the results, it is found that in the TWODANT calculation the spatial approximation in a staircase form of the circular fuel pin with relatively high quadrature order of S N is a viable method for solving the2-D C5G7 benchmark.

The beam shaping assembly design has been investigated in order to improve the epithermal neutron beam for accelerator-based boron neutron capture therapy in intensity and quality, and dosimetric evaluation for the beams has been performed using both mathematical and voxel head phantoms with MCNP runs. The neutron source was assumed to be produced from a conventional 2.5 MeV proton accelerator with a thick (7)Li target. The results indicate that it is possible to enhance epithermal neutron flux remarkably as well as to embody a good spectrum shaping to epithermal neutrons only with the proper combination of moderator and reflector. It is also found that a larger number of thermal neutrons can reach deeply into the brain and, therefore, can reduce considerably the treatment time for brain tumours. Consequently, the epithermal neutron beams designed in this study can treat more effectively deep-seated brain tumours.

Currently, two systems for TRU (transuranics) transmutation, the critical and the subcritical reactor systems, are being investigated by many research groups. Both systems have their own advantages and disadvantages. In this study, the comparative analyses of nuclear characteristics between both systems were performed. The fuel loaded into a TRU transmutation reactor includes few fertile nuclides, which contribute to stability and safety of the nuclear reactor. Thus, this study was focused on the intrinsic difference in the dynamic parameters between both systems. At the same time, the neutronic effects of the external source and the neutron absorber on the nuclear characteristics were also analyzed for the subcritical and the critical systems, respectively. Neutron flux spectrum, fuel temperature coefficient, coolant temperature coefficient, delayed neutron fraction, and neutron generation time were considered for comparative analyses. Based on the obtained results, some conclusions and proposals...

Summary form only given, as follows. For a pulsed neutron generation, a low energy Mather-type plasma focus device has been designed and experimented. The stored energy and discharge peak current are 2.2 kJ (capacitor bank; /spl mu/F /spl times/ 8) and 147 kA respectively. To optimize in this plasma focus device, different geometry (shape and length), dielectric insulator and capacitance of the capacitor have been tried. A new plasma focusing with increased capacitance ( 8 /spl mu/F /spl rarr/ 32 /spl mu/F) has been obtained, and focusing condition will be explained.

A subcritical reactor for TRU (Transuranics) transmutation, HYPER (HYbrid Power Extraction Reactor), is under development at KAERI (Korea Atomic Energy Research Institute). For the HYPER system, a pyrochemical process is being considered for fuel reprocessing, due to its own characteristics of nuclear proliferation resistance. Separated from the partitioning process, the fuel contains not only TRU but also the considerable percentages of impurities such as uranium and lanthanides. In our previous studies, the eigen mode calculation had been performed without the external source effects, for the purpose of analyzing the fuel composition effects on the HYPER core characteristics. And the results had shown that the dynamic behavior of the HYPER system becomes unstable as the amount of impurities increases. In this paper, the external source neutron effects on the core characteristics sensitivity to the fuel composition were investigated. Assuming various recovery factors of uranium and lanthanides, some dyna...

The optimum focusing conditions of the Hanyang University Plasma Focus (HUPF) device have been obtained by determining maximum power input to the focusing plasma while changing pressure at one fixed electrode, which leads to the maximum neutron generation. Six electrodes of different lengths have been used according to the snow-plow model to determine the conditions for the maximum neutron production of the HUPF device, namely 1.6×108 (n/shot) with 17 cm electrode length and a 3.4 Torr pressure.