The unbound brain-to-plasma concentration ratio (K
p,uu,brain
) is a parameter that indicates the extent of central nervous system penetration. Pharmaceutical companies build prediction models ...because many experiments are required to obtain K
p,uu,brain
. However, the lack of data hinders the design of an accurate prediction model. To construct a quantitative structure-activity relationship (QSAR) model with a small dataset of K
p,uu,brain
, we investigated whether the prediction accuracy could be improved by incorporating software-predicted brain penetration-related parameters (BPrPs) as explanatory variables for pharmacokinetic parameter prediction. We collected 88 compounds with experimental K
p,uu,brain
from various official publications. Random forest was used as the machine learning model. First, we developed prediction models using only structural descriptors. Second, we verified the predictive accuracy of each model with the predicted values of BPrPs incorporated in various combinations. Third, the K
p,uu,brain
of the in-house compounds was predicted and compared with the experimental values. The prediction accuracy was improved using five-fold cross-validation (RMSE = 0.455, r
2
= 0.726) by incorporating BPrPs. Additionally, this model was verified using an external in-house dataset. The result suggested that using BPrPs as explanatory variables improve the prediction accuracy of the K
p,uu,brain
QSAR model when the available number of datasets is small.
Development consists of growth and differentiation, which can be partially decoupled and can be affected by environmental factors to different extents. In amphibians, variation in the larval ...environment influences development and causes changes in post-metamorphic shape. We examined post-metamorphic consequences, both morphological and locomotory, of alterations in growth and development. We reared tadpoles of two phylogenetically and ecologically distant frog species (the red-eyed treefrog Agalychnis callidryas and the African clawed frog Xenopus laevis) under different temperatures with ad libitum food supply and under different food levels at a constant temperature. Low temperature and low food levels both resulted in similarly extended larval periods. However, low temperature yielded relatively long-legged frogs with a lower degree of ossification than warm temperature, whereas low food yielded relatively short-legged frogs with a higher degree of ossification than high food levels. Such allometric differences had no effect on locomotor performance of juveniles. Our results provide a basis for understanding the relationship between growth, differentiation and post-metamorphic shape in anurans and help explain many of the discrepancies reported in previous studies.
Abstract
The disk-loaded structures (DLS) in the muon LINAC are under development for the J-PARC muon g–2/EDM experiment. Four DLSs with an accelerating gradient of 20 MV/m take charge of muon ...acceleration from 40 MeV to 212 MeV, which corresponds to 70% to 94% of the speed of light. The quasi-constant gradient type TM01-2π/3 mode DLSs with gradually varying disk spacing was designed and it was confirmed that the cumulative phase slip due to the mismatch between muon and phase velocity can be suppressed to less than 2 degrees at the frequency of 2592 MHz. In addition, the optimum synchronous phase and the lattice were investigated to satisfy the requirements of the total emittance less than 1.5π mm mrad and the momentum spread less than 0.1% in RMS.
We present the first ever comprehensive statistical study of the spatiotemporal characteristics of field-aligned currents in the terrestrial magnetosphere-ionosphere system using multi point ...measurements. We determine how the FAC density, variability and scale size are coupled. The three ST 5 satellites were in a pearls-on-a-string formation making measurements of the magnetic field with variable inter-spacecraft separations ranging from a few seconds to about 10 min. More than 4700 sets of satellite passes are analyzed using a robust correlation analysis aimed at determining the variability of the FAC system as a function of scale size and satellite spacing. We find significant differences between the FAC characteristics on the dayside and on the nightside in terms of dynamics of the current systems. On the dayside the FAC characteristics are found to be independent of IMF Bz and geomagnetic activity while the nightside indicates increased variability during disturbed conditions. The boundary separating highly and poorly correlated FACs can be fitted by a linear line for satellite separations shorter than 60 s (dayside) and 160 s (nightside). We interpret this as the dayside and nightside magnetospheric reconfiguration times respectively. For times exceeding this the FAC characteristics are suggested to be controlled by the solar wind (dayside) and plasma sheet (nightside) dynamics. Finally, the characteristics of FAC system with scale sizes larger than ~200 km (at ionospheric altitude) appear to be stable and repeatable on time scales of the order of a minute (i.e. comparable to the low-altitude orbiting satellite's traverse time across the auroral belt). In this sense, our results effectively validate the Iijima and Potemra (1978) assumption that on average the large-scale currents with scale sizes of the Region1 and Region2 are quasi-persistently significant in the transport of energy and momentum between the magnetosphere and the ionosphere.
Although the promotional effects on osteoblasts of pulsed electromagnetic fields have been well-demonstrated, the effects of static magnetic fields (SMF) remain unclear; nevertheless, magnets have ...been clinically used as a ’force source’ in various orthodontic treatments. We undertook the present investigation to study the effects of SMF on osteoblastic differentiation, proliferation, and bone nodule formation using a rat calvaria cell culture. During a 20-day culture, the values of the total area and the number and average size of bone nodules showed high levels in the presence of SMF. In the matrix development and mineralization stages, the calcium content in the matrix and two markers of osteoblastic phenotype (alkaline phosphatase and osteocalcin) also showed a significant increase. Accordingly, these findings suggest that SMF stimulates bone formation by promoting osteoblastic differentiation and/or activation.
A divertor simulation experimental module (D-module) in the tandem mirror GAMMA 10/PDX was used for the study of plasma detachment. In previous studies, it was difficult to measure far-upstream ...plasma parameters in the D-module, and only electrostatic probes on the target plate were used to perform electron temperature and density measurements. To study the detached plasma structure, a Thomson scattering (TS) system and a microwave interferometer system have been installed to measure the inside plasma parameters of the D-module, and a movable electrostatic probe has been placed at the inlet of the D-module to measure the inlet plasma density and temperature. The TS system in the central cell observed the electron temperature and density of the core plasma simultaneously. These measurements revealed the entire density and temperature structure from the core plasma to the divertor plate. The line average electron density measured by the microwave interferometer showed a rollover behavior during detachment. The results indicated that the ionization region was located around the center of the D-module, and it appears to move upstream along the axis.
Early-time optical observations of supernova (SN) 2005cs in the Whirlpool Galaxy (M51) are reported. Photometric data suggest that SN 2005cs is a moderately underluminous Type II plateau SN (SN IIP). ...The SN was unusually blue at early epochs (U−B≈−0.9 about three days after explosion) which indicates very high continuum temperatures. The spectra show relatively narrow P Cygni features, suggesting ejecta velocities lower than observed in more typical SNe IIP. The earliest spectra show weak absorption features in the blue wing of the He i 5876-Å absorption component and, less clearly, of Hβ and Hα. Based on spectral modelling, two different interpretations can be proposed: these features may either be due to high-velocity H and He i components, or (more likely) be produced by different ions (N ii, Si ii). Analogies with the low-luminosity, 56Ni-poor, low-velocity SNe IIP are also discussed. While a more extended spectral coverage is necessary in order to determine accurately the properties of the progenitor star, published estimates of the progenitor mass seem not to be consistent with stellar evolution models.
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•Friction welding of Ti–6Al–4V and low carbon steel (LCS) were investigated.•The joining phenomena at friction pressure of 30MPa were similar to that of 120MPa.•The joint with low ...friction pressure had the IMC interlayer at the weld interface.•The fracture of LCS side was obtained at high friction and forge pressures.•The joint should be made with the whole weld interface temperature below 1350K.
Dissimilar metal joints (dissimilar joints) have such several advantages as high functionalities for the industrial usage. However, the dissimilar joints have severe problems such as generating the intermediate layer consisting of a brittle intermetallic compound (IMC interlayer) during welding process. Friction welding is very useful for making of dissimilar joint. This paper described the joining phenomena and the tensile strength of friction welded joint between titanium alloy (Ti–6Al–4V) and low carbon steel (LCS). The joining phenomena during the friction process such as joining behavior, friction torque, and temperature changes at the weld interface were measured. The effects of friction pressure, friction time and forge pressure on the joint strength were also investigated, and the metallurgical characteristics of joints were observed and analyzed. Then, the joint, which had 100% joint efficiency, the fracture on the LCS base metal with no crack at the weld interface, and no IMC interlayer on the weld interface, could be successfully achieved. It was suggested that the joint should be made with high friction pressure, opportune friction time to prevent generating of the IMC interlayer, and with high forge pressure in order to achieve completely joining of the weld interface.
A buncher cavity has been developed for the muons accelerated by a radio-frequency quadrupole linac (RFQ). The buncher cavity is designed for β=v∕c=0.04 at an operational frequency of 324 MHz. It ...employs a double-gap structure operated in the TEM mode for the required effective voltage with compact dimensions, in order to account for the limited space of the experiment. The measured resonant frequency and unloaded quality factor are 323.95 MHz and 3.06×103, respectively. The buncher cavity was successfully operated for longitudinal bunch size measurement of the muons accelerated by the RFQ.
Microrobots are promising tools for the treatment of biological cells because of their lack of skill dependence, high throughput, and high repeatability. Integration of a microfluidic chip and ...robotics based on microelectromechanical systems technology is a key challenge for biomedical innovations. In addition to the advantage of environmental control by a microfluidic chip, robots enable physical operations on the cell with high throughput. This paper presents high-speed microrobotic actuation driven by permanent magnets in a microfluidic chip. The developed microrobot has a milli-Newton-level output force from a permanent magnet, micrometer-level positioning accuracy, and drive speed of over 280 mm/s. The riblet surface, which is a regularly arrayed V-groove, reduces fluid friction and enables high-speed actuation. Ni and Si composite fabrication was employed to form the optimum riblet shape on the microrobot's surface by wet and dry etching. The evaluation experiments show that the microrobot can be actuated at a rate of up to 90 Hz, which is more than ten times higher than that of the microrobot without a riblet. Two distinguish applications of the developed microrobots were demonstrated in a microfluidic chip.
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