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Male animals exhibit positive and negative infant-directed behaviors, yet the underlying neural mechanisms remain unknown. The amygdalohippocampal area (AHi) regulates social behavior through neural projections to multiple brain regions. Although AHi neurons that project to the medial preoptic area (MPOA) were reported to promote infanticide in male mice, MPOA-projecting AHi neurons are activated by both parenting and infanticide, suggesting heterogeneity within these neurons. Here using a newly developed, virus-mediated projection-specific and activity-dependent cell labeling method (vPAL), we uncovered two distinct functional, electrophysiological, and transcriptional populations in MPOA-projecting AHi neurons, designated infanticide-related and parenting-related neurons. Furthermore, activation of serotonin receptor 7, which is highly expressed in parenting neurons, selectively suppressed infanticide while promoting parenting in virgin male mice. This study provides a better understanding of the neuronal populations, functions, and properties that previous labeling methods masked.

Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear. Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histologic analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory monosynapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a presynaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression.SIGNIFICANCE STATEMENTThe medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated not only by oxytocin but also by neural input from several regions.

The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood. Here, using a mouse model of neuropathic pain, we demonstrated neuronal plasticity in the bed nucleus of the stria terminalis (BNST), which plays a critical role in chronic pain–induced maladaptive anxiety. Electrophysiology demonstrated that chronic pain increased inhibitory inputs to lateral hypothalamus (LH)–projecting BNST neurons. Chemogenetic manipulation revealed that sustained suppression of LH-projecting BNST neurons played a crucial role in chronic pain–induced anxiety. Furthermore, using a molecular genetic approach, we demonstrated that chronic pain elevated the excitability of a specific subpopulation of BNST neurons, which express cocaine- and amphetamine-regulated transcript (CART). The elevated excitability of CART-positive neurons caused the increased inhibitory inputs to LH-projecting BNST neurons, thereby inducing anxiety-like behavior. These findings shed light on how chronic pain induces psychiatric disorders, characterized by maladaptive anxiety.

Smart monitoring, particularly at intersections, is a promising service that is being considered for the concept of smart cities. A network of light detection and ranging (LIDAR) sensors, which generates point cloud data in real time, can be used to detect people's mobility in smart monitoring. Due to the sheer volume of point cloud data, data transmission requires a significant amount of communication resources. In order to monitor people's mobility in real time, it is necessary to reduce the amount of transmission data to shorten delay. Point cloud compression is one method for reducing the amount of data. However, prior works addressing point cloud compression mainly focused on accuracy for the compression of an entire point cloud without considering its spatial characteristics. The more dynamically a spatial region changes, the more important it is when detecting moving objects such as cars, trucks, pedestrians, and bikes in smart monitoring. This paper proposes a prioritized transmission scheme that applies multiple point cloud compression methods to point cloud data according to the spatial importance of the data, i.e., how dynamically spatial regions change. This paper assumes data transmission of point cloud data from multiple LIDAR devices to an edge server and addresses the intra-frame geometry compression of point cloud data. The proposed scheme splits the point cloud into multiple classes according to the spatial importance and applies multiple point cloud compression methods to each class. A numerical study using a real point cloud dataset obtained at an intersection demonstrates the dependencies of quality, volume, and processing time on possible compression format options. The results verify that the proposed scheme reduces the amount of point cloud data drastically while satisfying the quality and processing time requirements.

Gonadal steroid hormone influences behavioral choice of adult animals toward pups, parental or aggressive. We previously reported that long-term administration of 17β-estradiol (E2) to male mice during sexual maturation induces aggressive behavior toward conspecific pups, which is called "infanticide," and significantly enhanced excitatory synaptic transmission in the rhomboid nucleus of bed nucleus of the stria terminalis (BSTrh), which is an important brain region for infanticide. However, it is unclear how estrogen receptor-dependent signaling after sexual maturity regulates neural circuits including the BSTrh. Here we revealed that E2 administration to gonadectomized mice in adulthood elicited infanticidal behavior and enhanced excitatory synaptic transmission in the BSTrh by increasing the probability of glutamate release from the presynaptic terminalis. Next, we performed whole-brain mapping of E2-sensitive brain regions projecting to the BSTrh and found that amygdalohippocampal area (AHi) neurons that project to the BSTrh densely express estrogen receptor 1 (Esr1). Moreover, E2 treatment enhanced synaptic connectivity in the AHi-BSTrh pathway. Together, these results suggest that reinforcement of excitatory inputs from AHi neurons into the BSTrh by estrogen receptor-dependent signaling may contribute to the expression of infanticide.

Scale-up of production is needed for industrial applications and clinical translation of human induced pluripotent stem cells (hiPSCs). However, in cryopreservation of hiPSCs, successful rewarming of vitrified cells can only be achieved by convective warming of small volumes (generally 0.2 mL). Here, we present a scalable nano-warming technology for hiPSC cryopreservation employing inductive heating of magnetic nanoparticles under an alternating magnetic field. The conventional method by water bath heating at 37 °C resulted in a decrease of cell viability owing to devitrification caused by slow warming of samples with large volumes (≥ 20 mL). Nano-warming showed uniform and rapid rewarming of vitrified samples and improved viability of hiPSCs in the 20-mL system. In addition to single cells, hiPSC aggregates prepared using a bioreactor-based approach were successfully cryopreserved by the nano-warming technique. These results demonstrate that nano-warming is a promising methodology for cryopreservation in mass production of hiPSCs.

The distribution of active pharmaceutical ingredients (APIs) in prescription medicines for human consumption in Japan was estimated using the public database of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). From the latest NDB, 2058 APIs were identified, and the prescription weight exceeded 1 tonne/year for 711 APIs. Of these, 298 APIs were selected for further analysis after removing 413 APIs that were not covered by current environmental risk assessment (ERA) directives or were combination products. Among the 298 APIs, 43 were relatively newly branded APIs that have been available on the Japanese market since 2001 or later and have no generic drugs, and only 5 of the branded APIs are used by more than 1% of the population. When prescription data from the 47 prefectures in Japan were analyzed, prescription weights for 257 of the 298 APIs were the highest in Tokyo, probably because of its large population. Though it has both advantages and limitations, this novel method based on a non-profit public database can provide a transparent, unbiased and cost-effective solution for the estimation of the environmental exposure of generic and branded human medicines distributed with prescriptions in Japan.

Real-time prediction of spatial information has attracted a lot of attention. Machine learning enables us to provide real-time prediction of spatial information such as road traffic by using aggregated sensor data. The amount of mobile traffic is forecasted to increase exponentially, thereby causing serious transmission delays when traffic loads are heavy. If a part of the data used for predicting spatial information in real time does not arrive on time, the prediction accuracy degrades because the prediction is done without the missing data. A utility-based scheduling technique has been suggested as a way of prioritizing such delay-sensitive data. However, no study has not addressed the utility-based scheduling for the real-time prediction of spatial information. Therefore, this paper proposes a scheme that enables modeling the utility function for real- time prediction of spatial information. The scheme is roughly composed of two steps: the first creates training data from original time-series data and a machine learning model using the data, while the second models the utility function using the feature selection method in the learning model. Feature selection method enables extracting the importance of data in terms of how much the data contributes to the prediction accuracy. This paper assumes the road traffic prediction as a scenario and shows the utility function modeled by the proposed scheme using real spatial datasets. A numerical study demonstrates how the model of the utility function works effectively in prioritizing data for real-time prediction in terms of accuracy.

The drag coefficients of freestream-aligned circular cylinders of fineness ratios of 0.75–2.0 were investigated with a magnetic suspension and balance system (MSBS). The objective was to find the critical geometry, that is, the fineness ratio at which the drag coefficient becomes the local maximum within this ratio range. The experiments were conducted using the 1-m MSBS at the low turbulence wind tunnel at the Institute of Fluid Science, Tohoku University. The drag and base pressure coefficients of various cylinders were measured. The freestream velocity was varied to produce flows with Reynolds numbers ranging from $$0.6\times 10^5$$ to $$1.0\times 10^5$$ . The drag coefficient monotonically decreases as the fineness ratio increases and no critical geometry or local maximum of the drag coefficient is found in the range we investigated. The base pressure coefficient decreases as the fineness ratio increases. The temporal fluctuations of the base pressure of the models with fineness ratios of 0.75, 1.0, and 1.2 are approximately twice as large as that of the model with a ratio of 2.0. The relationship between the fineness ratio and the drag coefficient is similar to that between the fineness ratio and the base pressure coefficient, similar to the findings of previous studies of two-dimensional bodies.

In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naive rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naive rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model.

In responses to looming objects, the praying mantis shows a defense behavior, which consists of retracting forelegs under the prothorax. The role of a looming-sensitive neuron in triggering this behavior was investigated by simultaneously recording the activity and behavioral responses of the neuron. The mantis initiated the defense behavior earlier in response to larger and slower looming stimuli. The time remaining to collision at defense initiation was linearly correlated with the ratio of the half-size of an approaching object to its speed ( l/| v|), suggesting that the defense behavior occurred a fixed delay after the stimuli had reached a fixed angular threshold. Furthermore, the results suggested that high-frequency spikes of the looming-sensitive neuron were involved in triggering the defense behavior: the distribution of maximum firing rate for trials with defense was shifted to larger rates compared with trials without defense; the firing rate of the neuron exceeded 150 Hz ∼100 ms before the defense initiation regardless of stimulus parameters; when a looming stimulus ceased approach prematurely, high-frequency spikes were removed, and the occurrence of defense was reduced.

Thalidomide (TM) induces limb defects in humans and some animal species including rabbits. Although the mechanism of TM-induced limb defects has been investigated for a long period, the limb development-related genes expressions have not been vigorously characterized in rabbits. In this study, we investigated the Fgf8, Bmp4 and Hoxa11 expressions in TM-treated JW rabbit embryos on gestation days (GDs) 10, 11 and 12 by whole mount in situ hybridization. On GDs 10 and 11, growth retardation of the embryo was induced by TM treatment. The Fgf8 expression lengths on GDs 10 and 11 in the forelimb bud were significantly or tended to be decreased in the TM-treated embryos, which was correlated to the growth retardation and was not considered to be directly relevant to the teratogenic effect of TM in the forelimb. The TM-induced characteristic changes in the expression pattern of Hoxa11 and Bmp4 on GDs 10 and/or 11 were not noted. On GD 12, TM-induced growth retardation was not noted and the Fgf8 and Bmp4 expressions were not changed. On the contrary, Hoxa11 expression was narrowed at the anterior region, which was located on the radial side, and was not changed at the middle and posterior regions in the forelimb bud and in all regions in the hindlimb bud. Because the radius malformations were induced by TM treatment, we concluded the decrease in the Hoxa11 expression was related to the TM-induced limb defects and can be a good marker for early prediction of the teratogenic effect of TM.

The effects of thalidomide on the embryo-fetal development (EFD) of rabbit fetuses and the sensitive periods (SP) for the various malformations were compared between Kbl:JW and Kbl:NZW rabbits to investigate possible strain differences. The post-implantation loss rate and number of placental remnants were increased and the number of live fetuses was decreased in both of the strains in the EFD study and in Kbl:NZW at 300 mg/kg dosed on GD 7-8 in the SP study. In the external and skeletal examinations, head, limb and tail malformations were observed in both the strains in the EFD and SP studies at the same dose levels in the same dosing period. In the visceral examination, hydrocephaly, cardiovascular malformations, absent pulmonary intermedial lobe, diaphragmatic hernia and/or abnormal liver lobation were also observed in both of the strains in the EFD and SP studies at the same dose levels and in the same dosing period. Plasma concentrations of thalidomide were equivalent between the two strains in the SP study. There were strain differences in some parameters, such as the post-implantation loss rate and the frequencies of malformations in forelimb and hindlimb and pulmonary intermedial lobe, but similar types of malformations or variations were induced at the same dose levels on the same dosing period in both strains. Therefore, it is concluded that there were no essential differences in sensitivity of the fetuses to thalidomide between Kbl:JW and NZW rabbits and both of the strains are useful to evaluate the teratogenic effects of thalidomide.

We retrospectively analyzed the reproductive variables and the spontaneous malformations in the historical control data from the embryo-fetal development studies conducted in our laboratories with Kbl:JW rabbits over two decades (1990-2010) and fetal malformations induced by thalidomide in 1988, 1995 and 2007. These analyses in the control animals revealed that the reproductive variables in dams, total frequencies and profile of external, visceral and skeletal abnormalities and/or variations in the fetuses were stable over two decades. In addition, the characteristics of the malformations induced by thalidomide were reproducible at the three time points. Therefore, it is concluded that Kbl:JW rabbit is one of the useful rabbit strains to evaluate the effects of test substances on embryo-fetal development, especially in view of the chronological stability of spontaneous or drug-induced malformations in the fetuses.

Pioglitazone hydrochloride (PIO), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, was administered orally for 85 weeks at 16 mg/kg/day to male rats fed either a diet containing 1.5% ammonium chloride (acid-forming diet) or a control diet to investigate the effects of urinary acidification induced by the acid-forming diet on the tumorigenic potential of PIO in the urinary bladder. The surviving animals at the end of the administration period were followed to the end of the 2-year study period without changes in the diet and were subjected to terminal necropsy on Week 104. The number of urinary microcrystals, evaluated by manual counting with light microscopy and by an objective method with a laser diffraction particle size analyzer, was increased by PIO on Weeks 12 and 25 and the increases were markedly suppressed by urinary acidification. Urinary citrate was decreased by PIO throughout the study period, but no changes were seen in urinary oxalate at any timepoint. The incidences of PIO-treated males bearing at least one of the advanced proliferative changes consisting of papillary hyperplasia, nodular hyperplasia, papilloma or carcinoma were significantly decreased from 11 of 82 males fed the control diet to 2 of 80 males fed the acid-forming diet. The acid-forming diet did not show any effects on the toxicokinetic parameters of PIO and its metabolites. Microcrystalluria appears to be involved in the development of the advanced stage proliferative lesions in bladder tumorigenesis induced by PIO in male rats.

The reactions of mixtures of zirconium alkoxide and cerium or yttrium acetate in 1,4-butanediol at 300°C (glycothermal reaction) yielded microcrystalline tetragonal zirconia–rare earth oxide solid solutions. The products maintained large surface areas even after calcination at high temperatures. The surface area of the products with low rare earth contents strongly depended on the drying conditions because of compaction at the drying stage, and the product dried by microwave irradiation had the highest surface area.

Circadian rhythmicity in the hypotensive effects of sodium nitroprusside (SNP) was determined to characterize the rhythmicity in hypotension mediated by nitric oxide (NO) donor in rats. When SNP was infused for 90 seconds every hour for 48 hours and the mean blood pressure was determined automatically by telemetry under light-dark conditions (LD), the degree of SNP-induced hypotension was shown to be minimal at the onset of the dark phase and to have marked circadian rhythmicity. The possible relationship between the circadian rhythm of the sympathetic nervous system (SNS) activity and SNP-induced hypotension was examined under LD conditions. The SNS activity assessed by blood pressure beat-to-beat variability analysis using the maximum entropy method (MEM) was higher at the preinfusion time at the onset of the dark phase than during the middle of the light phase. In addition, pretreatment with an alpha-blocker, phentolamine, followed by SNP infusion at the onset of the dark phase restored the SNP-induced hypotension and consequently dampened the daily variation in the degree of SNP-induced hypotension. The circadian rhythmicity determined by MEM was weakened, but persisted, in constant dark conditions (DD), suggesting partial involvement of endogenously driven circadian rhythms. In conclusion, the hypotensive effect of hourly infused SNP in rats was decreased in the dark phase in LD, especially at the onset of the dark phase, and clearly showed circadian rhythmicity in both LD and DD. The SNP-induced hypotension may be affected by rapid activation of the SNS at the onset of the dark phase in LD, and regulation of the circadian rhythm in SNP-induced hypotension in rats may be affected by both exogenous light stimuli and the endogenous biological clock.

A high incidence of maternal toxicity in rabbits characterized by uremia and death was observed when TCV-116, a novel angiotensin II subtype-1 (AT1) receptor antagonist, was orally administered to pregnant rabbits at dosage levels of 3 mg/kg/day or more. The effects of TCV-116 on blood pressure in nonpregnant or male rabbits and rats and on blood chemistry, renal circulation, and plasma renin activity in nonpregnant or male rabbits were examined to characterize the toxicity in rabbits. In a 2-week repeated dose study, most nonpregnant female rabbits receiving 3 or 100 mg/kg/day died or were sacrificed in a moribund state, indicating that toxicity could be caused independently of pregnancy. When these rabbits became moribund, marked hypotension, accompanied by increases in plasma concentrations of urea nitrogen, creatinine, and potassium, was observed, suggesting uremia. In a single-dose study, blood pressure in rabbits was decreased after administration of 10 or 100 mg/kg of TCV-116, and the hypotension was more marked and sustained than that in rats, as was the case with 30 mg/kg of enalapril. The sustained pharmacological effect in rabbits was also confirmed with regard to decreases in effective renal plasma flow and the glomerular filtration rate and increased plasma renin activity. Species differences in the hypotensive effect and mortality could not be explained by toxicokinetic data for the active metabolite of TCV-116 in various species, which supported a possibility that the differences in toxicity may be related to the species difference in sensitivity to the pharmacological effect of TCV-116. We conclude that the specific maternal toxicity of TCV-116 in rabbits may be mainly due to the higher sensitivity of rabbits to the pharmacological effects and is caused by marked and sustained hypotension resulting in the decrease in glomerular filtration rate, uremia, and death.

Thalidomide (TM) induces limb defects in humans and some animal species including rabbits. Although the mechanism of TM-induced limb defects has been investigated for a long period, the limb development-related genes expressions have not been vigorously characterized in rabbits. In this study, we investigated the Fgf8, Bmp4 and Hoxa11 expressions in TM-treated JW rabbit embryos on gestation days (GDs) 10, 11 and 12 by whole mount in situ hybridization. On GDs 10 and 11, growth retardation of the embryo was induced by TM treatment. The Fgf8 expression lengths on GDs 10 and 11 in the forelimb bud were significantly or tended to be decreased in the TM-treated embryos, which was correlated to the growth retardation and was not considered to be directly relevant to the teratogenic effect of TM in the forelimb. The TM-induced characteristic changes in the expression pattern of Hoxa11 and Bmp4 on GDs 10 and/or 11 were not noted. On GD 12, TM-induced growth retardation was not noted and the Fgf8 and Bmp4 expressions were not changed. On the contrary, Hoxa11 expression was narrowed at the anterior region, which was located on the radial side, and was not changed at the middle and posterior regions in the forelimb bud and in all regions in the hindlimb bud. Because the radius malformations were induced by TM treatment, we concluded the decrease in the Hoxa11 expression was related to the TM-induced limb defects and can be a good marker for early prediction of the teratogenic effect of TM.

The effects of thalidomide on the embryo-fetal development (EFD) of rabbit fetuses and the sensitive periods (SP) for the various malformations were compared between Kbl:JW and Kbl:NZW rabbits to investigate possible strain differences. The post-implantation loss rate and number of placental remnants were increased and the number of live fetuses was decreased in both of the strains in the EFD study and in Kbl:NZW at 300 mg/kg dosed on GD 7-8 in the SP study. In the external and skeletal examinations, head, limb and tail malformations were observed in both the strains in the EFD and SP studies at the same dose levels in the same dosing period. In the visceral examination, hydrocephaly, cardiovascular malformations, absent pulmonary intermedial lobe, diaphragmatic hernia and/or abnormal liver lobation were also observed in both of the strains in the EFD and SP studies at the same dose levels and in the same dosing period. Plasma concentrations of thalidomide were equivalent between the two strains in the SP study. There were strain differences in some parameters, such as the post-implantation loss rate and the frequencies of malformations in forelimb and hindlimb and pulmonary intermedial lobe, but similar types of malformations or variations were induced at the same dose levels on the same dosing period in both strains. Therefore, it is concluded that there were no essential differences in sensitivity of the fetuses to thalidomide between Kbl:JW and NZW rabbits and both of the strains are useful to evaluate the teratogenic effects of thalidomide.

A novel amorphous selenium (a-Se) detector with the hexagonal pixel has been developed for full-field digital mammography. The pixel area of the detector was designed to be same as that of the 68 μm square pixel detector, while the pixel pitch between neighboring pixels was set to be 73-75 μm in six directions. By applying the hexagonal pixels, the sensitivity of the detector has improved by 18% compared with a conventional square pixel. A simulation showed that the hexagonal pixel provided a more uniform electric field in the a-Se layer than the square pixel, which has lead to higher sensitivity. The modulation transfer function of the detector was 92 % at 2 mm -1 and 62 % at 5 mm -1 . These values were as high as that of a conventional a-Se detector with 50 μm square pixels. As a result, the detective quantum efficiency of this detector achieved 75 % with 5 mR and 72 % with 2.5mR at 2 mm -1 . The exposure conditions were 28 kV W/Rh with a 2 mm aluminum filter. Therefore, the new detector can reduce the exposure dose while maintaining a high image quality.

We retrospectively analyzed the reproductive variables and the spontaneous malformations in the historical control data from the embryo-fetal development studies conducted in our laboratories with Kbl:JW rabbits over two decades (1990-2010) and fetal malformations induced by thalidomide in 1988, 1995 and 2007. These analyses in the control animals revealed that the reproductive variables in dams, total frequencies and profile of external, visceral and skeletal abnormalities and/or variations in the fetuses were stable over two decades. In addition, the characteristics of the malformations induced by thalidomide were reproducible at the three time points. Therefore, it is concluded that Kbl:JW rabbit is one of the useful rabbit strains to evaluate the effects of test substances on embryo-fetal development, especially in view of the chronological stability of spontaneous or drug-induced malformations in the fetuses.

Left ventricular pressure (LVP) in free-moving rats was continuously measured for 2 weeks by a telemetry blood pressure measurement system. Prior to LVP measurement, a dummy transmitter was used to determine whether organ weights, including that of the heart and the lungs, or the stiffness of the left ventricular chamber were affected by the catheterization of the LV chamber. Organ weights did not increase, and no functional abnormalities were observed in the left ventricular pressure-volume relationship. The LVP transmitter was implanted in the left ventricle, and systolic LVP, end-diastolic LVP, LV dP/dt max, and heart rate were measured. All parameters were essentially stable during the 2-week observation period after implantation, and the values, especially the heart rate, in the dark phase tended to be higher than those in the light phase. Microscopic examination of the left ventricular wall revealed that implantation of the dummy or LVP transmitter caused no histological damage. We confirmed that LVP in free-moving rats can be measured continuously for 2 weeks without any harmful effect on cardiac function and that this telemetry system should be useful in pharmacological and toxicological studies.

In this study, we characterized the image quality of two types of indirect-conversion flat-panel detectors: an X-ray incident-side photo-detection system (IS) and an X-ray penetration-side photo-detection system (PS). These detectors consist of a Gd2O2S:Tb (GOS) scintillator coupled with a photodiode thin film transistor (PD-TFT) array on a glass substrate. The detectors have different X-ray incident directions, glass substrates, and scintillators. We also characterized the effects of layered scintillator structures on the image quality by using a single-layered scintillator containing large phosphor grains and a double-layered scintillator consisting of a layer of large phosphor grains and a layer of small phosphor grains. The IS system consistently demonstrated a higher MTF than the PS system for a scintillator of the same thickness. Moreover, the IS system showed a higher DQE than the PS system when a thick scintillator was used. While the double-layered scintillators were useful for improving the MTF in both systems, a thick single-layered scintillator was preferable for obtaining a high DQE when the IS system was applied. These results indicate that an IS system can efficiently utilize the light emitted from the phosphor at the far side of the PD without the occurrence of blurring. The use of IS systems makes it possible to increase the thickness of the scintillator layer for improving the sensitivity without reducing the MTF, which increases the DQE. The DQE of the IS system was 1.2 times that of the PS system, despite the absorption of X-rays at the glass substrate before entering the phosphor.

Users in peer-to-peer (P2P) content sharing can share their content by contributing their own resources to one another. However, since there is no incentive for contributing contents or resources to others, users may attempt to obtain content without any contribution. To motivate users to contribute their resources to the service, incentive-rewarding mechanisms have been proposed. On the other hand, emerging wireless technologies, such as IEEE 802.11 wireless local area networks, beyond third generation (B3G) cellular networks and mobile WiMAX, provide high-speed Internet access for wireless users. Using these high-speed wireless access, wireless users can use P2P services and share their content with other wireless users and with fixed users. However, this diversification of access networks makes it difficult to appropriately assign rewards to each user according to their contributions. This is because the cost necessary for contribution is different in different access networks. In this paper, we propose a novel incentive-rewarding mechanism called EMOTIVER that can assign rewards to users appropriately. The proposed mechanism uses an external evaluator and interactive learning agents. We also investigate a way of appropriately controlling rewards based on the system service's quality and managing policy.

Candesartan cilexetil (TCV-116), an angiotensin II receptor antagonist, was administered orally to male F344/Jcl and Crj:CD (SD) rats at 1000 mg kg(-1) day(-1) for 1-28 days, and the possible mechanism for the anemia induced by TCV-116 was investigated. In the TCV-116 group, the erythrocyte count, hematocrit value and hemoglobin concentration were decreased by 7-8% as compared with the values in the control group after dosing for 28 days. The plasma and renal erythropoietin levels, the reticulocyte count in the peripheral blood and the erythroid cell count upon bone marrow examination were decreased on day 7, but there were no accompanying histopathological renal lesions. Renal blood flow was increased, and mean blood pressure was decreased after TCV-116. These results suggest that the primary cause of the anemia induced by TCV-116 treatment is the increase in renal blood flow followed by a decrease in erythropoietin production.

Blood pressure and heart rate were measured by telemetry in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) to investigate the contribution of angiotensin II to the reflex tachycardia resulting from exaggerated hypotension caused by a high dose of a calcium channel blocker. Pre-treatment with TCV-116, an angiotensin II AT1 receptor antagonist, or enalapril partially attenuated the reflex tachycardia induced by manidipine, but TCV-116 had almost no effect on the sinus tachycardia induced by isoproterenol. The suppressive effects of TCV-116 against the reflex tachycardia tended to be more obvious in WKY than in SHR, though the difference was not statistically significant. Concurrent administration of propranolol almost completely inhibited both the reflex tachycardia and the sinus tachycardia in SHR and WKY, indicating that the sympathetic nervous system contributes to both types of tachycardia. We demonstrated that angiotensin II may be involved in the reflex tachycardia induced by calcium channel blockers probably via activation of some component of the sympathetic nervous system other than postsynaptic factors at the sinus node.

Blood pressure (BP) and heart rate (HR) were measured by telemetry in conscious unrestrained rabbits to clarify the profile of their variabilities. The variabilities were assessed for two periods, 24 h (circadian rhythm) and 1 h (short-term variability), and compared with those in rats. BP and HR in rabbits were lower than those in rats but the circadian rhythms in rabbits showed nocturnal patterns as is the case in rats. In contrast, short-term variabilities in BP in rabbits were considerably larger than those in rats. The short-term variability in BP in rabbits was suppressed by alpha-adrenergic blocking without changes in basal values but not by beta-adrenergic blocking or angiotensin converting enzyme inhibition. These results demonstrate the need to take the unique characteristics of short-term variability in BP in rabbit into consideration when the circadian rhythm is focused on and that the short-term variability in BP in rabbits is caused mainly by activation of alpha-adrenergic receptors.