CREB-binding protein (CBP) is a transcriptional co-activator which is required by many transcription factors. Rubinstein-Taybi syndrome (RTS), which is an autosomal dominant syndrome characterized by abnormal pattern formation, is associated with mutations in the human CBP gene. Various abnormalities occur at high frequency in the skeletal system of heterozygous Cbp-deficient mice, but some features of RTS such as cardiac anomalies do not, suggesting that some symptoms of RTS are caused by a dominant-negative mechanism. Here we report the characterization of homozygous Cbp-deficient mice. Homozygous mutants died around E10.5-E12.5, apparently as a result of massive hemorrhage caused by defective blood vessel formation in the central nervous system, and exhibited apparent developmental retardation as well as delays in both primitive and definitive hematopoiesis. Cbp-deficient embryos exhibited defective neural tube closure which was similar to those observed in twist-deficient embryos. However, a decrease in the level of twist expression was not observed in Cbp-deficient embryos. Anomalous heart formation, a feature of RTS patients and mice mutated in the CBP-related molecule, p300, was not observed in Cbp-deficient embryos. Since both Cbp and p300 are ubiquitously expressed in embryonic tissues including the developing heart, these results suggest that cardiac anomalies observed in RTS patients may be caused by a dominant negative effect of mutant CBP.
Mouse newborns find their mother’s nipples and suckle milk by themselves. It has been argued which sense organ they use when locating their mother’s nipples to suckle milk. Olfactory or tactile sensory systems are primary candidates. In the present study, we investigated the trigeminal-whisker sensory and olfactory systems in genetic arhinencephaly mouse embryos (Pdn/Pdn). Pdn/Pdn newborns do not suckle milk and die within 1 day after birth. Dysfunction of nipple-searching behavior was clear in Pdn/Pdn newborns. Pdn/Pdn newborns had a complete developmental failure in the olfactory nerve projection to the central nervous system and no olfactory bulb architecture. The trigeminal-whisker system was intact in this strain. From the results of these experiments, it was suggested that the olfactory system is essential for nipple-searching behavior and suckling milk and that the trigeminal-whisker system is not able to substitute for the lack of olfactory input in mouse newborns.
Non invasive fractional flow reserve derived from CT coronary angiography (CT-FFR) has to date been typically performed using the principles of fluid analysis in which a lumped parameter coronary vascular bed model is assigned to represent the impedance of the downstream coronary vascular networks absent in the computational domain for each coronary outlet. This approach may have a number of limitations. It may not account for the impact of the myocardial contraction and relaxation during the cardiac cycle, patient-specific boundary conditions for coronary artery outlets and vessel stiffness. We have developed a novel approach based on 4D-CT image tracking (registration) and structural and fluid analysis, to address these issues. In our approach, we analyzed the deformation variation of vessels and the volume variation of vessels, primarily from 70% to 100% of cardiac phase, to better define boundary conditions and stiffness of vessels. We used a statistical estimation method based on a hierarchical Bayes model to integrate 4D-CT measurements and structural and fluid analysis data. Under these analysis conditions, we performed structural and fluid analysis to determine pressure, flow rate and CT-FFR. The consistency of this method has been verified by a comparison of 4D-CT-FFR analysis results derived from five clinical 4D-CT datasets with invasive measurements of FFR. Additionally, phantom experiments of flexible tubes with/without stenosis using pulsating pumps, flow sensors and pressure sensors were performed. Our results show that the proposed 4D-CT-FFR analysis method has the potential to accurately estimate the effect of coronary artery stenosis on blood flow.
Non invasive fractional flow reserve derived from CT coronary angiography (CT-FFR) has to date been typically performed using the principles of computational fluid analysis in which a lumped parameter coronary vascular bed model is assigned to represent the impedance of the downstream coronary vascular networks absent in the computational domain for each coronary outlet. This approach may have a number of limitations. It may not account for the impact of the myocardial contraction and relaxation during the cardiac cycle, patient-specific boundary conditions for coronary artery outlets and vessel stiffness. We have developed a novel approach based on 4D-CT image tracking (registration) and structural and fluid analysis based on one dimensional mechanical model, to address these issues. In our approach, we analyzed the deformation variation of vessels and the volume variation of vessels to better define boundary conditions and stiffness of vessels. We focused on the blood flow and vessel deformation of coronary arteries and aorta near coronary arteries in the diastolic cardiac phase from 70% to 100 %. The blood flow variation of coronary arteries relates to the deformation of vessels, such as expansion and contraction of the cross-sectional area, during this period where resistance is stable, pressure loss is approximately proportional to flow. We used a statistical estimation method based on a hierarchical Bayes model to integrate 4D-CT measurements and structural and fluid analysis data. Under these analysis conditions, we performed structural and fluid analysis to determine pressure, flow rate and CT-FFR. Furthermore, the reduced-order model based on fluid analysis was studied in order to shorten the computational time for 4D-CT-FFR analysis. The consistency of this method has been verified by a comparison of 4D-CT-FFR analysis results derived from five clinical 4D-CT datasets with invasive measurements of FFR. Additionally, phantom experiments of flexible tubes with and without stenosis using pulsating pumps, flow sensors and pressure sensors were performed. Our results show that the proposed 4D-CT-FFR analysis method has the potential to accurately estimate the effect of coronary artery stenosis on blood flow.
Two-phase thermosyphons, which use sodium at 960 K as a refrigerant for heat transportation in small nuclear reactors, are promising for manned exploration to Mars. This is because the concentric-tube type thermosyphon may not have a flooding limit, and so the heat transfer performance per unit volume is comparatively large. Moreover, since its external form is a single tube by inserting a pipe through which the liquid flows into a pipe through which the gas flows, the reactor core can be made smaller. Experimental investigations of heat transport characteristics using water, R113, ethanol, and nitrogen as refrigerants and development of prediction formulas are progressing for establishing the design of the concentric-tube two-phase thermosyphon. However, it is necessary to use sodium at 960 K for application to heat transportation of a reactor, and further elucidation of the flow phenomenon is necessary to establish its performance prediction model. We have proposed a model based on bubble pump theory in order to take into consideration the rise of liquid level of the heating section. We conducted an experimental study on the flow inside a thermosyphon made of transparent material, and evaluated the maximum heat transfer rate using a low boiling point refrigerant, HFE-7100. As a result, even when the heat transfer rate was close to the maximum, it was shown that the flow regime in the outer tube of the adiabatic section of the concentric tube is two-phase flow. However, the experimental value of the maximum heat transfer rate was found to be about 17 % smaller than the calculated value. We therefore investigated the cause of this difference by making pressure measurements and flow observations, and found that bubble entrainment in the inner tube of the concentric tube of the adiabatic section greatly influences the pressure distribution. It is thought that taking mixing into consideration would help improve the model.
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