In-air experimental achievement of high-voltage DC power supply to be installed in a tandem electrostatic accelerator system for boron neutron capture therapy application.

The boron neutron capture therapy (BNCT) system developed by the Korea Institute of Radiological and Medical Sciences is a compact neutron source that can be installed at medical institutes. The target energy was accelerated to a maximum of 2.4 MeV-20 mA by introducing a gas stripping device that converts negative hydrogen ions into positive ions. By using the tandem-type accelerator in this way, a high-voltage DC power supply was designed with 1.2 MV-45 mA as the maximum capability. The design was improved to reduce the number of stages of a Cockcroft-Walton voltage multiplier. Hence, the ripple risk of the DC flat top resulting from unwanted stray capacitance was lowered. The overall height and volume of the Cockcroft-Walton voltage multiplier were reduced to less than half those of the existing design method, making miniaturization possible. After such advanced design and manufacturing, performance tests were performed at 750 kV-45 mA under 23 stages of the Cockcroft-Walton voltage multiplier, which is the highest level that can perform at its maximum under in-air conditions. It demonstrated stable performance under in-air conditions without breakdown for 2 h, even at 620 kV-35 mA. To reach the final target of 1.2 MV-45 mA, the groundwork is laid for achieving experimental performance while satisfying the optimal requirements in SF6 gas.

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin.

BACKGROUND: Dimeric human erythropoietin (dHuEPO) peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg) mice expressing dHuEPO and to investigate the characteristics of these mice. METHODS: A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile), was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. RESULTS: A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47) of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11). We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females) were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764). Reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) were used for validating the results of the microarray analysis of mRNA expression. CONCLUSIONS: In conclusion, dHuEPO tg mice caused excessive erythrocytosis that led to abnormal blood composition, short lifespan, and abnormal splenomegaly. Further, we identified 2,672 genes associated with splenomegaly by microarray analysis. These results could be useful in the development of dHuEPO-producing tg animals.

Optimal design of high-voltage DC power supply of 1.2 MV/45 mA applied to boron neutron capture therapy system.

To build a proton beam accelerator that can be applied to a boron neutron capture therapy system based on an electrostatic accelerator, a high-voltage direct-current (DC) power supply system equivalent to the generation of neutrons should be provided. The symmetrical Cockcroft-Walton voltage multiplier method is suitable for stable acceleration of the proton beam in the tandem electrostatic accelerator in this system. Before the second step-up with the Cockcroft-Walton circuit, the design of the inverter is prioritized by preponderantly considering the first voltage and resonance frequency. Moreover, the optimized stacking number is determined with consideration of the ripple voltage, voltage drop, average output voltage, and fundamental harmonics, and a design is performed to set related parameter values to be stable in the flat-top region of the voltage. A high-voltage DC power supply system of 1.2 MV/45 mA is needed for a stable terminal energy of 2.4 MeV/20 mA. Such a design can be optimized by securing reliable data using a simulation tool on the basis of theoretical calculations. This will become a formidable touchstone in manufacturing technology based on acquiring practical know-how for setting up a tandem electrostatic accelerator-based boron neutron capture therapy system in the future.

Molecular characterization of bovine placental and ovarian 20α-hydroxysteroid dehydrogenase.

The enzyme 20α-hydroxysteroid dehydrogenase (20α-HSD) catalyzes the conversion of progesterone to its inactive form, 20α-hydroxyprogesterone. This enzyme plays a critical role in the regulation of luteal function in female mammals. In this study, we conducted the characterization and functional analyses of bovine 20α-HSD from placental and ovarian tissues. The nucleotide sequence of bovine 20α-HSD showed significant homology to that of goats (96%), humans (84%), rabbits (83%), and mice (81%). The mRNA levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. Northern blot analysis revealed a 1.2  kb mRNA in the bovine placental and ovarian tissues. An antibody specific to bovine 20α-HSD was generated in a rabbit immunized with the purified, recombinant protein. Recombinant 20α-HSD protein produced in mammalian cells had a molecular weight of ∼37  kDa. Bacterially expressed bovine 20α-HSD protein showed enzymatic activity. The expression pattern of the 20α-HSD protein in the pre-parturition placenta and the CL1 stage of the estrous cycle was similar to the level of 20α-HSD mRNA expression. Immunohistochemical analysis also revealed that bovine 20α-HSD protein was intensively localized in the large luteal cells during the late estrous cycle.

Expression of aldo-keto reductase family 1 member C1 (AKR1C1) gene in porcine ovary and uterine endometrium during the estrous cycle and pregnancy.

BACKGROUND: The aldo-keto reductase family 1 member C1 (AKR1C1) belongs to a superfamily of NADPH-dependent reductases that convert a wide range of substrates, including carbohydrates, steroid hormones, and endogenous prostaglandins. The 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) is a member of AKR family. The aims of this study were to determine its expression in the ovary and uterus endometrium during the estrous cycle and pregnancy. METHODS: Rapid amplification of cDNA ends (RACE) experiments were performed to obtain the 5' and 3' ends of the porcine 20 alpha-HSD cDNA. Reverse-transcriptase-PCR (RT-PCR), real-time PCR, northern blot analysis, and western blot analysis were performed to examine the expression of porcine 20 alpha-HSD. Immunohistochemical analysis was also performed to determine the localization in the ovary. RESULTS: The porcine 20 alpha-HSD cDNA is 957 bp in length and encodes a protein of 319 amino acids. The cloned cDNA was virtually the same as the porcine AKR1C1 gene (337 amino acids) reported recently, and only differed in the C-terminal region (the AKR1C1 gene has a longer C-terminal region than our sequence). The 20 alpha-HSD gene (from now on referred to as AKR1C1) cloned in this paper encodes a deletion of 4 amino acids, compared with the C-terminal region of AKR1C1 genes from other animals. Porcine AKR1C1 mRNA was expressed on day 5, 10, 12, 15 of the cycle and 0-60 of pregnancy in the ovary. The mRNA was also specifically detected in the uterine endometrium on day 30 of pregnancy. Western blot analysis indicated that the pattern of AKR1C1 protein in the ovary during the estrous cycle and uterus during early pregnancy was similar to that of AKR1C1 mRNA expression. The recombinant protein produced in CHO cells was detected at approximately 37 kDa. Immunohistochemical analysis also revealed that pig AKR1C1 protein was localized in the large luteal cells in the early stages of the estrous cycle and before parturition. CONCLUSIONS: Our study demonstrated that AKR1C1 mRNA and protein are coordinately expressed in the luteal cell of ovary throughout the estrous cycle and in the uterus on day 30 of pregnancy. Thus, the porcine AKR1C1 gene might control important mechanisms during the estrous cycle.

Experimental study of an initially pressurized water target irradiated by a proton beam.

This experimental visualization study was conducted to investigate and define the phenomena of an initially pressurized liquid water target that can prevent the boiling of water when the target is irradiated with a 30-MeV proton beam produced using the MC-50 Cyclotron at Korea Institute of Radiological and Medical Sciences. At various initial pressures and proton beam currents, the behavior of the target water was investigated using a complementary metal-oxide-semiconductor camera. We confirmed that an appropriate initial pressure could indeed prevent local bulk boiling, and be determined by solving Rayleigh's equation and the Clausius-Clapeyron equation for homogeneous bubble growth using the measured bubble size generated at the Bragg-peak region. The saturation temperature of the initial pressure must be higher than the calculated local water temperature at the Bragg-peak region. The final pressure of the water target increased proportionally with the initial pressure and proton beam current. The penetration depth of the beam varied with beam current and slightly with the final pressure, as evidenced by the emission of blue light in all experimental cases.

Performance of an impedance-variable pulsed high-power electron-beam accelerator based on energy efficient transmission.

Versatile high-power pulsed electron-beam accelerators that meet the requirements of pulsed high-power specifications are needed for appropriate applications in medical industry, defense, and other industries. The pulsed electron beam accelerator comprising a Marx generator and Blumlein pulse forming line (PFL) is designed to accelerate the electron beams at the level of 1 MeV when electrostatically discharging. The performance specifications of Marx generators consisting of a 100 kV DC power supply, R-L-C circuit, and high voltage switch are at a maximum 800 kV. At this time, by using the capacitance mismatching principle between the Marx generator and the Blumlein PFL under the law of preserving the amount of charge, it is possible to generate a high voltage in the form of a square pulse up to about 1.1 MV, as much as 1.37 times the charged voltage of the Marx generator. As a result, energy transmission from the Marx generator with a high efficiency of about 85% to the Blumlein PFL is possible. The aim of this study is that the pulsed high-power electron-beam accelerator can be used to change the diode impedance, and the energy of the accelerated electron beam reaches a level of 1 MeV with the square pulse width of about 100 ns at the flat-top in the range of relativistic electron beam generation. Performance tests were securely carried out by installing a dummy load based on CuSO4 solution varying the diode impedance to deter damage to the circuit by preventing reflected waves from being generated in the load.