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1.
Biol Pharm Bull ; 37(3): 439-46, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24583862

RESUMO

The stereoselective transport of methotrexate (L-amethopterin, L-MTX) and its antipode (D-amethopterin, D-MTX) by human reduced folate carrier (hRFC) has been examined in HEK293 cells expressing H27-hRFC and R27-hRFC. The uptake of both L-MTX and D-MTX increased as the extracellular pH increased from 6.0 to 7.4. The initial uptake rate of L-MTX into the H27- and R27-hRFCs of the HEK293 cells followed Michaelis-Menten kinetics with Km values of approximately 0.24 and 0.47 µM, respectively. Dixon plots revealed that the [(3)H]-L-MTX uptake mediated by the H27- and R27-hRFCs was inhibited competitively by unlabeled L-MTX with Ki values of approximately 0.1 and 0.5 µM, respectively. D-MTX also competitively inhibited the H27- and R27-hRFC mediated uptake of [(3)H]-L-MTX with Ki values of approximately 3.4 and 3.2 µM, respectively. The RFC-mediated uptake clearance of L-MTX was approximately 15-fold greater than that of D-MTX in the H27-hRFC-HEK293 cells, and was more than 30-fold greater than that of D-MTX in the R27-hRFC-HEK293 cells. The results of the current study have revealed that the enantiomers of MTX enantiomers can be transported in a stereoselective manner by the H27- and R27-hRFCs because of significant differences in the affinities of the enantiomers to the hRFC.


Assuntos
Antagonistas do Ácido Fólico/metabolismo , Metotrexato/metabolismo , Proteína Carregadora de Folato Reduzido/genética , Adulto , Transporte Biológico/genética , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Cinética , Masculino , Proteína Carregadora de Folato Reduzido/metabolismo , Estereoisomerismo , Transfecção , Adulto Jovem
2.
Sci Rep ; 13(1): 10918, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37407602

RESUMO

Huge coastal boulders are useful to reconstruct the size of past extreme waves such as those associated with tsunamis and storms using inverse-type or forward-type boulder transport models. These models fundamentally require the precise shape of boulders. Traditionally, they have often been assumed to be rectangular or ellipsoidal with three axes measured in the field. However, if the boulder's shape is complex, this method is unable to represent the actual shape accurately. Therefore, it prevents estimation of the tsunami or storm size reasonably using models. For this reason, boulders have recently been surveyed using 3D scanning techniques such as LiDAR. However, coastal boulders now on land in tropical and subtropical areas such as Japan and Tonga are often covered by deep vegetation, which makes 3D surveys difficult. This report presents new methods to ascertain boulder shapes when they are obscured by vegetation. First, using UAV-type and mobile-type LiDAR, we scanned well-known tsunami boulders in southwestern Japan that had been covered with deep vegetation. Then, we developed a new method to extract only boulders and filter out vegetation from a point cloud. Thereby, we created 3D models of the boulders. We improved the boulder transport model further to assume the 3D boulder model accurately. In addition to coastal boulders, this filtering method is expected to be useful for unveiling any object, such as an archaeological structure, that is hidden in deep vegetation.

3.
Sci Rep ; 8(1): 13620, 2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206405

RESUMO

The giant 1771 Yaeyama tsunami occurred in the southwestern part of the Ryukyu Arc, a region on an obliquely subducting plate boundary, which shows no direct evidence of inter-plate coupling. Studies of tsunami boulders and deposits suggest that the recurrence interval of comparably giant tsunamis is roughly 500 to 1000 years. Tsunami source models, which include either slip on a shallow plate boundary or active faulting plus a landslide on the overriding plate, are controversial because of inconsistencies in the geophysical and geological data. We discovered a seafloor depression that is approximately 30 km wide and 80 km long extending in the ESE-WNW direction. This depression is accompanied by a seaward bulge on the accretionary prism along the Ryukyu Trench, which is based on detailed bathymetric data and interpreted to be the result of accretionary prism collapse and seaward displacement by rotational slide. A simple tsunami simulation shows that the slide is a plausible source of the 1771 tsunami. We propose a collapse model, in which the accretionary prism remained over-steepened as strike-slip faulting removed the prism toe. Our model indicates that some oblique subduction zones are capable of generating giant tsunamis regardless of weak or strong coupling.

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