Development of a stochastic biokinetic method and its application to internal dose estimation for insoluble cesium-bearing particles

ABSTRACT

Spherical cesium-bearing particles were found around the Fukushima Daiichi Nuclear Power Plant after its accident. These particles are insoluble with high specific activities. If such a particle is incorporated into the body, it is expected that the radioactive cesium contained in the particle will move as a single particulate material without being distributed throughout the body. Consequently, internal doses vary depending on the pathway of the particle in the body. Therefore, general deterministic methods for dose estimation are not applicable to the intake of small number of cesium-bearing particles. In this study, a Monte Carlo method was developed to evaluate a probability density function of internal doses for inhalation of a particulate material. In addition, a biokinetic model was constructed to consider the insolubility of the particles. Probability density functions of committed equivalent and effective doses were estimated using the constructed biokinetic model with the developed computation method. As a result, the uncertainty of the doses was very large for single particle inhalation. However, it was observed that this uncertainty decreased with increasing number of simultaneously inhaled particles. On the other hand, the consideration about the insolubility made the doses somewhat higher than those based on the general cesium model.     

Neuroprotective actions of FK506 in experimental stroke: in vivo evidence against an antiexcitotoxic mechanism

The cellular mechanisms underlying the neuroprotective action of the immunosuppressant FK506 in experimental stroke remain uncertain, although in vitro studies have implicated an antiexcitotoxic action involving nitric oxide and calcineurin. The present in vivo study demonstrates that intraperitoneal pretreatment with 1 and 10 mg/kg FK506, doses that reduced the volume of ischemic cortical damage by 56-58%, did not decrease excitotoxic damage induced by quinolinate, NMDA, and AMPA. Similarly, intravenous FK506 did not reduce the volume of striatal quinolinate lesions at a dose (1 mg/kg) that decreased ischemic cortical damage by 63%. The temporal window for FK506 neuroprotection was defined in studies demonstrating efficacy using intravenous administration at 120 min, but not 180 min, after middle cerebral artery occlusion. The noncompetitive NMDA receptor antagonist MK801 reduced both ischemic and excitotoxic damage. Histopathological data concerning striatal quinolinate lesions were replicated in neurochemical experiments. MK801, but not FK506, attenuated the loss of glutamate decarboxylase and choline acetyltransferase activity induced by intrastriatal injection of quinolinate. The contrasting efficacy of FK506 in ischemic and excitotoxic lesion models cannot be explained by drug pharmacokinetics, because brain FK506 content rose rapidly using both treatment protocols and was sustained at a neuroprotective level for 3 d. Although these data indicate that an antiexcitotoxic mechanism is unlikely to mediate the neuroprotective action of FK506 in focal cerebral ischemia, the finding that intravenous cyclosporin A (20 mg/kg) reduced ischemic cortical damage is consistent with the proposed role of calcineurin.     

Chemical modification and site-directed mutagenesis of Tyr36 of 3-isopropylmalate dehydrogenase from Thermits thermophUus HB8

3-Isopropylmalate dehydrogenase from an extreme thermo-phile,Thermus thermophUus HB8, was chemically modified with tetranitromethanewhich nitrated 1.5-2.0 Tyr residues per subunit. The nitrationwas biphask and parallel to the loss of activity. The modifiedresidue in the first phase was identified to be Tyr36, whichis distantly located from the active site of the enzyme. Thefunction of Tyr36 was investigated by site-specific replacementwith Phe. The Michaelis constant for the substrate or co-enzymewas not altered by the replacement, whereas the catalytic constantdecreased down to -5%. X-ray analysis of the mutant enzyme revealedthat Arg94 moved the largest distance among the active siteresidues, that is, the NH1 and NH2 of the guanidino group moved1.11 and 1.32 Å respectively. The results suggest thatArg94 is responsible for the enzyme catalysis     

A Glutathione‐Responsive Short Sequence of Metal–Organic Complex Array

A short metal–organic complex array (MOCA) containing a sequence of RPtRRu ( 1_Cl ) was found to exhibit unique responses to a major biothiol, glutathione (GSH). Upon binding of GSH to 1_Cl , the resultant 1:1 complex ( 1_GS ) formed nanofibrous assemblies that suggested supramolecular polymerization through the double‐salt‐bridge structure formation. The binding behavior of this MOCA sequence to calf thymus DNA was also dependent on GSH; a larger conformational change of DNA was observed upon binding with 1_GS , relative to that with 1_Cl .     

Indene Compounds Synthetically Derived from Vitamin D Have Selective Antibacterial Action on Helicobacter pylori

Helicobacter pylori infects the human stomach and is closely linked with the development of gastric cancer. When detected, this pathogen can be eradicated from the human stomach using wide‐spectrum antibiotics. However, year by year, H. pylori strains resistant to the antibacterial action of antibiotics have been increasing. The development of new antibacterial substances effective against drug‐resistant H. pylori is urgently required. Our group has recently identified extremely selective bactericidal effects against H. pylori in (1R,3aR,7aR)‐1‐[(1R)‐1,5‐dimethylhexyl]octahydro‐7a‐methyl‐4H‐inden‐4‐one (VDP1) (otherwise known as Grundmann's ketone), an indene compound derived from the decomposition of vitamin D₃ and proposed the antibacterial mechanism whereby VDP1 induces the bacteriolysis by interacting at least with PtdEtn (dimyristoyl‐phosphatidylethanolamine [di‐14:0 PtdEtn]) retaining two 14:0 fatty acids of the membrane lipid constituents. In this study, we synthesized new indene compounds ((1R,3aR,7aR)‐1‐((2R,E)‐5,6‐dimethylhept‐3‐en‐2‐yl)‐7a‐methyloctahydro‐4H‐inden‐4‐one [VD2‐1], (1R,3aR,7aR)‐1‐((S)‐1‐hydroxypropan‐2‐yl)‐7a‐methyloctahydro‐1H‐inden‐4‐ol [VD2‐2], and (1R,3aR,7aR)‐7a‐methyl‐1‐((R)‐6‐methylheptan‐2‐yl)octahydro‐1H‐inden‐4‐ol [VD3‐1]) using either vitamin D₂ or vitamin D₃ as materials. VD2‐1 and VD3‐1 selectively disrupted the di‐14:0 PtdEtn vesicles without destructing the vesicles of PtdEtn (dipalmitoyl‐phosphatidylethanolamine) retaining two 16:0 fatty acids. In contrast, VD2‐2, an indene compound lacking an alkyl group, had no influence on the structural stability of both PtdEtn vesicles. In addition, VD2‐1 and VD3‐1 exerted extremely selective bactericidal action against H. pylori without affecting the viability of commonplace bacteria. Meanwhile, VD2‐2 almost forfeited the bactericidal effects on H. pylori. These results suggest that the alkyl group of the indene compounds has a crucial conformation to interact with di‐14:0 PtdEtn of H. pylori membrane lipid constituents whereby the bacteriolysis is ultimately induced.     

Rapidly Solidified Thick Nickel Base Alloy Deposit with Carbide Particles Produced by Plasma Spraying

Ni-1.5 wt.% C, Ni-1.5 wt.%C-14 wt.%Cr, and Ni-1.5 wt.%C-29 wt.%Cr alloy powders were low-pressure plasma sprayed to produce nickel-base composite deposits with dispersed carbide particles. The constituent of the as-sprayed deposit formed on a water-cooled substrate from the Ni-1.5 wt.%C alloy powder is a nickel phase that is supersaturated with carbon. The deposit heat-treated at 673 K in vacuum consists of a nickel phase, nickel carbide, and graphite. In the case of the Ni-1.5 wt.%C-14 wt.%Cr alloy powder, the as-sprayed deposit produced on a water-cooled substrate is made up of a nickel phase that is supersaturated with chromium and carbon, and subsequent heat-treatment of the deposit leads to the formation of chromium carbide and graphite. When the non-cooled substrate is used, the as-sprayed deposit consists of a nickel phase, chromium carbide, and graphite. The as-sprayed deposit formed on a non-cooled substrate from the Ni-1.5 wt.%C-29 wt.%Cr alloy powder is composed of a nickel phase, chromium carbide, and graphite.     

Rhombic‐Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs

DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency‐modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic‐shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one‐third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3‐turn crossover design rhombic‐shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force‐controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties.     

Shape and topology optimization based on the convected level set method

The aim of this research is to construct a shape optimization method based on the convected level set method, in which the level set function is defined as a truncated smooth function obtained by using a sinus filter based on a hyperbolic tangent function. The local property of the hyperbolic tangent function dramatically reduces the generation of red the error between the specified profile of the hyperbolic tangent function and the level set function that is updated using a time evolution equation. In addition, the small size of the error facilitates the use of convective reinitialization, whose basic idea is that the reinitialization is embedded in the time evolution equation, whereas such treatment is typically conducted in a separate calculation in conventional level set methods. The convected level set method can completely avoid the need for additional calculations when performing reinitialization. The validity and effectiveness of our presented method are tested with a mean compliance minimization problem and a problem for the design of a compliant mechanism.     

Histological features of the vomeronasal organ in the giraffe,Giraffa camelopardalis

The vomeronasal organ (VNO) that preferentially detects species‐specific substances is diverse among animal species, and its morphological properties seem to reflect the ecological features of animals. This histological study of two female reticulated giraffes (Giraffa camelopardalis reticulata) found that the VNO is developed in giraffes. The lateral and medial regions of the vomeronasal lumen were covered with sensory and nonsensory epithelia, respectively. The vomeronasal glands were positive for periodic acid‐Schiff and alcian blue (pH 2.5) stains. The VNO comprises several large veins like others in the order Cetartiodactyla, suggesting that these veins function in a pumping mechanism in this order. In addition, numerous thin‐walled vessels located immediately beneath the epithelia covering the lumen entirely surrounded the vomeronasal lumen. This sponge‐like structure might function as a specific secondary pump in giraffes.