Search

Despite the human 5-HT5A receptor being cloned in 1994, the biological function of this receptor has not been extensively characterized due to a lack of specific ligands. We recently reported that the selective 5-HT5A receptor antagonist ASP5736 ameliorated cognitive impairment in several animal models of schizophrenia. Given that areas of the brain with high levels of 5-HT5A receptor expression, such as the hippocampus and cerebral cortex, have important functions in cognition and memory, we evaluated the chemically diverse, potent and brain-penetrating 5-HT5A receptor antagonists ASP5736, AS2030680, and AS2674723 in rodent models of cognitive dysfunction associated with dementia. Each of these compounds exhibited a high affinity for recombinant 5-HT5A receptors that was comparable to that of the non-selective ligand of this receptor, lysergic acid diethylamide (LSD). Although each compound had a low affinity for other receptors, 5-HT5A was the only receptor for which all three compounds had a high affinity. Each of the three compounds ameliorated scopolamine-induced working memory deficit in mice and improved reference memory impairment in aged rats at similar doses. Further, ASP5736 decreased the binding of LSD to 5-HT5A receptors in the olfactory bulb of rats in a dose-dependent manner and occupied 15%–50% of brain 5-HT5A receptors at behaviorally effective doses. These results indicate that the 5-HT5A receptor is involved in learning and memory and that treatment with 5-HT5A receptor antagonists might be broadly effective for cognitive impairment associated with not only schizophrenia but also dementia.

Sirolimus (SRL) is widely used to prevent restenosis after percutaneous coronary intervention. However, its beneficial effect is hampered by complications of thrombosis. Several studies imply that reactive oxygen species (ROS) play a critical role in endothelial dysfunction and thrombus formation. The present study investigated the protective effect of nicorandil (NIC), an anti-angina agent, on SRL-associated thrombosis. In human coronary artery endothelial cells (HCAECs), SRL stimulated ROS production, which was prevented by co-treatment with NIC. The preventive effect of NIC on ROS was abolished by 5-hydroxydecanoate but not by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. NIC also inhibited SRL-induced up-regulation of NADPH oxidase subunit p22phox mRNA. Co-treatment with NIC and SRL significantly up-regulated superoxide dismutase 2. NIC treatment significantly improved SRL-induced decrease in viability of HCAECs. The functional relevance of the preventive effects of NIC on SRL-induced ROS production and impairment of endothelial viability was investigated in a mouse model of thrombosis. Pretreatment with NIC inhibited the SRL-induced acceleration of FeCl3-initiated thrombus formation and ROS production in the testicular arteries of mice. In conclusion, NIC prevented SRL-induced thrombus formation, presumably due to the reduction of ROS and to endothelial protection. The therapeutic efficacy of NIC could represent an additional option in the prevention of SRL-related thrombosis.

The recurrence of urothelial carcinoma in an orthotopic neobladder is rare. We report the case of a 61-year-old man with a muscle-invasive bladder tumor that was treated using radical cystectomy and the creation of a Studer's orthotopic neobladder. However, nine years after the cystectomy, we detected a mass at the left ureteroileal anastomosis. We successfully performed Studer's neobladder resection, urethrectomy, and left nephroureterectomy to remove the entire mass. Pathological examination revealed urothelial carcinoma with adenocarcinoma in the neobladder and adenocarcinomatous metastasis in the mesenteric lymph node.

The ability to maintain the body relative to the external environment is important for adaptation to altered gravity. However, the physiological limits for adaptation or the disruption of body orientation are not known. In this study, we analyzed postural changes in mice upon exposure to various low gravities. Male C57BL6/J mice (n = 6) were exposed to various gravity-deceleration conditions by customized parabolic flight-maneuvers targeting the partial-gravity levels of 0.60, 0.30, 0.15 and μ g (

Wind-tunnel experiments are the most effective approaches both to elucidate the flows around runners in track-and-field athletics, and to evaluate their air resistances. In the present study, we develop a moving-belt system, and show its basic performance, such as the distributions of time-mean flow velocity and turbulent intensity above the moving-belt using a hot-wire anemometer. As a result, we have confirmed the effective improvement of the velocity distributions in terms of flow uniformity and turbulence reduction, especially near the moving-belt surface. Following, using this the developed moving-belt system, we investigate the air resistance on a runner in solo running and in duet running. For solo running, we reveal an increase in air resistance of more than 10% in comparison with the conventional result with no moving-belt system. For duet running, we reveal the optimum duet-running formation where a following runner behind a pacemaker experiences small air resistances or strong drafts.

It is known that parity violation can be enhanced in compound nuclei due to mixing of s- and p-waves, and it is suggested that time reversal invariance (T) violation is enhanced by the same mechanism. We are planing a T-violation search using compound nuclei produced in neutron capture reactions. Although 81Br is one of the candidate target nuclei, its sensitivity to T-violation has not yet been determined. For an estimate of the latter, a measurement of the angular distribution of γ-rays emitted in the 81Br(n,γ) reaction was carried out in November 2017, of which we report first results.

This experimental research concerns a simple air-bubblejet from a bottom nozzle in water. We try to conduct the measurements of the flow by applying a three-dimensional particle tracking velocimetry (3D-PTV) technique, in order to specify both bubble (air) and liquid (water) velocities. As tracer particles, we regard bubbles themselves in bubble-velocity measurements, and polyethylene particles suspended in water in liquid-velocity measurements. Then, we visualise the three-dimensional motions of the bubbles and the liquid. As we record stereo images using a pair of high-speed video cameras, we can get temporally-consecutive spatial information of both the bubbles' and liquid's motions. As a result, we quantitatively reveal the three-dimensional and instantaneous behaviour of the unsteady bubble-jet flow. And, using the obtained three-dimensional information, we show the fundamental flow structure of the bubble jet from a statistical view point.

In the present study, we consider the air entrainment into a suction pipe which is vertically inserted down into a suction sump across a mean free-water surface. This configuration is often referred to as the “vertical wet-pit pump”, and has many practical advantages in construction, maintenance and operation. In particular, we focus our concern upon the critical submergence depth Sc, which is one of the prime and conventional indicators for the air-entrainment occurrence. By a systematic approach, we experimentally investigate the influences of kinetic and geometric parameters upon Sc. As the kinetic parameters, we consider the Reynolds number Re and the Weber number We, in addition to the Froude number Fr, on such a basis as Fr is not much larger than unity in many actual cases. As the geometric parameters, we consider back clearance X, sump breadth B and bottom clearance Z. Here, all parameters are non-dimensionalised by the outside diameter D and the intake velocity Vi of the suction pipe. As a result, we reveal the effects of such six parameters upon Sc. The We effect, namely, the surface-tension effect can be ignored at We > 12. And, the Re effect, namely, the viscous effect becomes negligibly small at Re > 3×104. Under such conditions for We and Re, we could consider only the Fr effect, namely, the gravitational effect. Concerning the X/D and B/D effects, Sc/D attains the maximum at a certain X/D or B/D. On the other hand, the Z/D effect is monotonic, and becomes small at Z/D > 2.5. Some aspects of these geometric effects can be evaluated by a local-Froude-number effect on the basis of the global relation between Sc/D and Fr. And, the other aspects is necessarily considered to be related with the flow structure in the suction sump.

The present aim is to reveal the flow past a pipe which is immersed parallel to the mainstream at high Reynolds numbers. In a wind tunnel, we carry out (1) base-pressure measurements, (2) velocity-fluctuation measurements using a hot-wire anemometer and (3) flow visualisations by a smoke-wire method with PIV analyses, where we take consecutive picutures using a high-speed camcorder to obtain quantitative flow-field information such as velocity vector and vorticity. The tested parameter ranges are as follows: Re = 2.0×103 - 1.3×104, d/t = 4.0 - 10.0 and l/t = 1.0 - 10.0, where Re, d, t and l are the Reynolds number, mean diameter, thickness and length of the pipe, respectively. As a result, the Re effects are negligible. The base-suction coefficient -Cpb monotonically decreases with decreasing d/t, or with increasing l/t. We propose a unified formula to predict -Cpb, which are consistent with both a two-dimensional prism and a rod for l/t < 4.0 in addition to a ring. In contrast, the Strouhal number St almost coincides with that for a two-dimensional prism at any l/t, if we can detected any dominant frequencies. In addition, we conduct flow visualisations, and reveal the effects upon axisymmetry of wake. Finally, we classify the flow into three modes based on both periodicity and axisymmetry. Such a modal classification reveals that the enhancement of flow's irregularity corresponds to the decrease of -Cpb.

In this study, the authors numerically investigate the frequency response on the three-dimensional thermal convection in a cubic cavity heated below in the gravitational field, concerning flow characteristics such as flow structure and a global quantity the spatially-averaged kinetic energy K. The authors assume incompressible fluid with a Prandtl number Pr = 7.1 (water) and with a Rayleigh number Ra = 1.0×104 or 4.0×104. The direction of a forced sinusoidal oscillation is parallel to the terrestrial gravity. The authors especially focus upon the influences of both the forced-oscillation amplitude η and frequency ω in non-dimensional forms, whose test ranges are 1.5 ≤ η ≤ 15 and 10 ≤ ω ≤ 103. The obtained results are as follows. For Ra = 4.0×104, as well as Ra = 1.0×104 (Tanigawa et al., 2009), we can observe the optimum frequency ωKmax where the amplitude of K attains the maximum, each η. And, for both Ra's, ωKmax becomes the minimum at η = 1.5 - 2.0. Especially for Ra = 4.0×104, ωKmax is affected by the initial conditions. For both Ra's, the maximum of the K amplitude uniquely exists at ω= ωKmax each η, when η < 1.5. On the other hand, we can observe not single but plural peak frequencies with locally-maximum K's each η, when η ≥ 1.5. It is confirmed that such plural frequencies are related with the appearances of various flow structures such as S1, S2, S4, S5, S6 and S8. Especially for Ra = 4.0×104, this relation is also affected by the initial conditions. In addition, the details of a new flow structure S8 is reported.

The authors numerically investigate the forced-oscillation-frequency responses on flow and thermal characteristics of the thermal convection in a cubic cavity heated from below in the gravitational field, concerning global quantities such as spatially-averaged kinetic energy and so on. The authors assume incompressible fluid with a Prandtl number Pr = 7.1 (water) and a Rayleigh number Ra = 1.0×104. The direction of a forced sinusoidal oscillation is parallel to that of the terrestrial gravity. The authors focus their special attention on the amplitude effects of the forced oscillation upon kinetic energy, the optimum frequency for response and flow structure. The obtained results are as follows. Even at large acceleration amplitudes, the optimum frequency exists. At the optimum frequency, periodicity is exact, while the wave form is far from sinusoidal at a non-dimensional acceleration amplitude η ≥ 1. A boundary exists at η = 1.5, where both the increasing rate of a spatially-averaged kinetic energy and the flow structure change abruptly, and where the optimum frequency attains the minimum. This abrupt change in the flow structure can be explained by an indicial response.

Our aim is to understand the complicated flow inside a suction sump in the vertical-wet-pit-pump configuration. The information of unsteady and three-dimensional flow structures is useful, not only for this complicated flow but also for other complicated flows which are commonly seen in various practical applications. To acquire such information, a three-dimensional particle tracking velocimetry (3D-PTV) technique is one solution. However, this technique includes more unknown factors in reliability and accuracy than other well-established measuring techniques. In the present study, we examine the simultaneous measurement using both of the 3D-PTV and another velocimetry, namely, an ultrasonic velocity profiler (UVP) with common tracer particles. This simultaneous measurement is expected to become an effective method to dissolve the above fatal defect of the 3D-PTV. As a result, we have successfully found out the suitable condition for the simultaneous measurement with high accuracy. Then, under this condition, we have revealed the time-mean and instantaneous velocity vectors of the unsteady and three-dimensional flow inside the suction sump.

BACKGROUND:There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. METHODS AND RESULTS:Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. CONCLUSIONS:NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic modality for IR injury in acute myocardial infarction.

In the present study, the authors consider a control of the flow past a semi-infinite plate with a blunt front. The flow is one of the simplest separated-and-reattaching flows, and can be a model such as heat exchangers and flow straighteners commonly seen inside power plants, chemical plants and household appliances. As a control device, a rotating object, which is a small flat plate, is placed in the upstream of the semi-infinite plate. In a wind tunnel, the authors conduct flow-velocity-fluctuation measurements using a hot-wire anemometer for various control-object positions and rotation speeds, showing (1) root-mean-squared values near the leading edge of the semi-infinite plate and (2) dominant frequencies in the downstream. The present test range of the control-object rotation speed is low; specifically, the object's tip velocity is less than the uniform mainstream velocity. Referring to such results, we can classify the controlled flow into four regions. Moreover, in order to clarify the characteristics for each region, the authors carry out (1) flow visualisations with particle-image-velocimetry analyses, and (2) velocity-profile measurements concerning time-mean and turbulence-intensity values.

In the present study, we investigate a self-excited oscillatory phenomenon of a two-dimensional confined jet with a rectangular-cross-section cylinder as a downstream target. More specifically, in order to reveal the effects of a kinematic parameter the Reynolds number Re and various geometric parameters upon the jet-oscillation frequency fD, we conduct experiments at Re < 5000 in water and in air by an ultrasonic velocity profiler and a hot-wire anemometer, respectively. As a result, we specify the effects of Re and four non-dimensional geometric parameters upon fD, which is non-dimensionalised as the Strouhal number St. As the four geometric parameters, we consider (1) the streamwise target size, (2) the channel breath, (3) the cross-streamwise target size and (4) the target distance in non-dimensional forms with a length scale of the jet's breadth. It is found that the Re effect is negligible. This guarantees a wide-range workability as flowmeters. All the results can be summarised in an empirical formula describing the relation of St with the four geometric parameters.

In this study, we experimentally deal with the tumbling, which is a rotating motion of a plate with its axis perpendicular to the falling direction. As the plate, we consider a rectangular-cross-section prism with a depth-to-width ratio λ = 0.3, an aspect ratio AR = 10, and inertia moment ratios I* = 0.75 - 43, together with a wide range of a non-dimensional control parameter C = 7.2×101 - 1.6×103. As a result, we specify fundamental aerodynamic characteristics in terminal condition, like the reduced rotating rate Ω*, the lift coefficient CL, the drag coefficient CD and the lift-to-drag ratio CL/CD as functions of both C and I*. Moreover, the relation between the actual Reynolds number Re and the Reynolds number Re(Vd) based on Vd can be approximately determined, being independent of C and I*. Eventually, we successfully propose a series of empirical formulae to predict Ω*, CL, CD and CL/CD as functions of Re(Vd) alone, which is available for a wide parameter range except for large C and small I*.

Abstract.: The present research investigated the effect of the oxidative phenoxazines, 2-amino-4,4α-dihydryo-4α-7H-phenoxazine-3-one (Phx-1) and 2-amino-phenoxazine-3-one (Phx-3) on apoptosis induction and apoptosis-related early events in human neutrophils. When Phx-1 or Phx-3 was administered to freshly drawn human blood for 18 h, these phenoxazines caused apoptotic cell death morphologically characterized by condensation of the nucleus in neutrophils, without causing it in lymphocytes and monocytes. Apoptosis, which was detectable by microscopic analysis and by using flow-cytometry, occurred significantly in human neutrophils isolated from freshly drawn blood, 6 h after the administration of 50 μM Phx-1 and Phx-3. After 24 h, every isolated neutrophil treated with Phx-1 or Phx-3 fell into apoptosis or lost its morphology, while many of the neutrophils without these phenoxazines remained alive, with normal morphology. Apoptosis-related early events including a decrease in intracellular pH (pHi) and depolarization of the mitochondria occurred in the isolated neutrophils, 30 min and 6 h after the administration of Phx-1 or Phx-3, respectively. Superoxide generation from the isolated neutrophils mimicked by phorbol myristate acetate (PMA) was very markedly inhibited by 100 μM Phx-1 or Phx-3. This result could be explained, in part, by the fact that the insufficient supply of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) was caused by pHi decrease in neutrophils treated with Phx-1 or Phx, because NADPH is necessary for NADPH oxidase responsible for generating superoxide in the cells. The present results suggest that Phx-1 and Phx-3 have the capacity of selectively inducing apoptosis in human neutrophils and that these phenoxazines may be useful as specific drugs to induce apoptotic cell death of human neutrophils and thereby prevent inflammation caused by these phagocytic cells. Keywords:: neutrophil, phenoxazine, apoptosis, mitochondria, pHi

The aerodynamic characteristics of airfoils have been researched in higher Reynolds-number ranges more than 106, in a historic context closely related with the developments of airplanes and fluid machineries in the last century. However, our knowledge is not enough at low and middle Reynolds-number ranges. So, in the present study, we investigate such basic airfoils as a NACA0015, a flat plate and the flat plates with modified fore-face and after-face geometries at Reynolds number Re < 1.0×105, using two- and three-dimensional computations together with wind-tunnel and water-tank experiments. As a result, we have revealed the effect of the Reynolds number Re upon the minimum drag coefficient CDmin. Besides, we have shown the effects of attack angle α upon various aerodynamic characteristics such as the lift coefficient CL, the drag coefficient CD and the lift-to-drag ratio CL/CD at Re = 1.0×102, discussing those effects on the basis of both near-flow-field information and surface-pressure profiles. Such results suggest the importance of sharp leading edges, which implies the possibility of an inversed NACA0015. Furthermore, concerning the flat-plate airfoil, we investigate the influences of fore-face and after-face geometries upon such effects.

A wireless camera sensor network is useful for surveillance and monitoring for its visibility and easy deployment. However, it suffers from the limited capacity of wireless communication and a network is easily overflown with a considerable amount of video traffic. In this paper, we propose an autonomous video coding rate control mechanism where each camera sensor node can autonomously determine its coding rate in accordance with the location and velocity of target objects. For this purpose, we adopted a biological model, i.e., reaction-diffusion model, inspired by the similarity of biological spatial patterns and the spatial distribution of video coding rate. Through simulation and practical experiments, we verify the effectiveness of our proposal.

Vertical sloshing is the liquid surface motion in a container forced to oscillate in the vertical direction. The present paper concerns the vertical sloshing in various equilateral-polygonal-section containers such as octagonal-, heptagonal-, hexagonal-, pentagonal-, square- and triangular-section containers together with a circular-section container, in order to generalise their sloshing modes. As a result, the authors classify the sloshing modes on the basis of the conventional circular-section-container sloshing modes. It is revealed that this modal classification has some advantages over that based on the conventional square-section-container sloshing modes. Furthermore, the stability diagrams for all the equilateral-polygonal-section containers are investigated by both experiments and computations. The present computation is based on a discrete singularity method. The proposed modal classification is useful to predict the eigen frequencies. Specifically speaking, it is found that the equivalent diameter de1 based on the hydraulic mean depth is the most adequate as a characteristic length scale to classify all the sloshing modes. The authors show a unified formula to predict the eigen frequencies, using de1 together with the proposed modal classification.

Cerebral vasospasm is a persistent arterial narrowing typically observed during the 3 – 14 days after subarachnoid hemorrhage (SAH). Vasospasm is frequently associated with ischemic neurological deficits or even death, resulting in a poor prognosis for patients with SAH. However, the mechanism underlying cerebral vasospasm remains elusive, and no effective therapeutic strategies have been established. A large amount of thrombin is produced during SAH. Recent investigations have uncovered a key role of the thrombin receptor in the pathogenesis of cerebral vasospasm. Thrombin has little contractile effect in the normal cerebral artery, but it induces an enhanced and prolonged contraction after SAH, owing to the up-regulation of thrombin receptor PAR1 (proteinase-activated receptor 1) and the impairment of receptor desensitization in arterial smooth muscle. Thrombin-mediated activation of PAR1 is an irreversible process, as it is initiated by the proteolytic removal of the N-terminal region. Since the mechanism of receptor desensitization is impaired after SAH, the thrombin-induced contraction irreversibly persists even after terminating thrombin stimulation. Intrathecal administration of a PAR1 antagonist prevents the PAR1 up-regulation and the increased reactivity to thrombin. PAR1 is suggested to play a key role in cerebral vasospasm and may be useful as a therapeutic target for prevention and treatment of cerebral vasospasm. Keywords:: desensitization, proteinase-activated receptor, up-regulation, subarachnoid hemorrhage, vasoconstriction

Pulsating jets are very common and sometimes useful in industrial fields, due to some differences in basic characteristics from steady jets. In this research, the authors focus upon the mechanism of the frequency effect on a finite-amplitude pulsating jet. Experiments are conducted at a Reynolds number of 5,000, Strouhal numbers of 0.13, 0.20 and 0.27, and a velocity-amplitude ratio of 0.5. Using olive-oil smoke, the authors visualise the flow from a nozzle exit with a circular cross section, and get quantitative information by a PIV technique. As a result, the authors have succeeded in defining the locations of main and subsidiary ring vortices. And, the authors have revealed the vortices' convection manners at three frequencies. Besides, the instantaneous measurements on entraining flow with a conditional-sampling technique have shown the complexity of the frequency effect, which is affected by two factors in a trade-off relation.

A confined jet sometimes causes a self-exited oscillation due to the existence of a downstream target. In this work, the authors study this phenomenon. More specifically, the authors deal with a simple fluidic oscillator; namely, a two-dimensional confined jet into an abruptly-expanding channel with a downstream target of a square cylinder. The authors conduct the velocity measurements by an UVP (ultrasonic velocity profiler). Besides, the flow patterns in the fluidic oscillator are observed by a PIV (particle image velocimetry). As a result, the authors reveal the geometrical effects upon the range of stable jet's oscillation, such as the aspect-ratio effect, the channel-breadth effect, the cylinder-size effect and the cylinder-distance effect, together with the Re effect.

Pulsating jets are very common and useful in various industrial aspects. However, they have some different basic characteristics from steady jets. In this research, the authors reveal both the frequency and the amplitude effects of pulsations on a jet, including large-amplitude cases. Experiments are conducted at a Reynolds number of 5,000, Strouhal numbers of 0.011 - 0.27 and velocity-amplitude ratios of 0.1 - 1.0. Using a hot-wire anemometry, the authors show centre velocities, radial profiles, half widths and total flow rates at several positions downward a nozzle exit. From centre velocities and radial profiles, we can see that the streamwise scale of the potential core is less than three times the diameter. From half widths and total flow rates, we can see that the pulsation enhances mixing, and confirm the frequency and the amplitude effects specifically. On the other hand, from centre velocities and radial profiles, we cannot see the both effects clearly. As a result, the authors show the combined frequency-and-amplitude effect upon total flow rate, which consists with small-amplitude results by Crow and Champagne (1971), and find the optimum frequencies.

This experimental research concerns the air-bubble-jet flow in water. We try to apply three-dimensional particle tracking velocimetry to the flow. Air bubbles are regarded as tracer particles. Then, we visualise the three-dimensional motions of the bubbles. As we record the stereo images using two high-speed video cameras, we can get timely-consecutive information of the bubbles' motions. As a result, the three-dimensional structure of two simple bubble-jet plumes with different nozzle's tilting angles has been quantitatively revealed near the nozzle exit.

In this study, we deal with the tumbling, which is a rotating motion with the axis perpendicular to the falling direction. Our purpose is to reveal the fundamental aerodynamic characteristics of the tumbling, experimentally. Regarding a test plate, we consider a prism with a rectangular cross section with a depth-to-width ratio λ of 0.3. The results are as follows. The reduced terminal rotating rate Ω*, the lift coefficient CL, the drag coefficient CD and the lift-to-drag ratio CL/CD are independent of the aspect ratio AR, when AR is greater than 10. As the inertia moment ratio I* increases from zero to 50, Ω*, CL and CD increase. However, Ω*, CL and CD become almost constant, at I* greater than 50. We propose the empirical formulae to predict them. At low I*, the tumbling shows a dominant periodicity of 360 deg.

In order to get accurate measurements of air entrainment in a suction sump, we design a new and simple conductance-type electric bubble sensor, which can detect the existence of air bubbles inside a suction pipe with no disturbances by the sensor probe and with a fine spatial resolution. We focus on occurrence-time ratio γ of the air entrainment, and compare the result by the present sensor with those by conventional two methods; namely, visual and auditory ones. As a result, we show the criteria which specify lower-accuracy conditions in the conventional methods. By the visual method, the accuracy of γ becomes low, when γ is less than 0.05. By the auditory method, the accuracy of γ becomes low, when submergence depth S of the suction pipe is close to the critical one Sc.

Mean flow quantities have been investigated for the equilibrium boundary layer evolving over the rough wall with a roughness height that is proportional to streamwise distance. The wall shear stress measured by drag balance with a floating element device of a zero displacement mechanism. The local skin friction coefficient is independent of both streamwise distance and momentum thickness Reynolds number and has a value of 0.00826. The boundary layer thickness is proportional to the streamwise distance. The relative roughness height then maintains a constant value. The log-law profile has the same slope of that of the smooth wall turbulent boundary layer in the logarithmic liner part. The value of the roughness function increases in the streamwise direction. The wake parameter approaches to a constant value of approximately 0.70. In addition, the value is consistent with the result determined from the analytical method using the momentum integral equation and Coles's wake law. For the analytical result, the wake parameter decreases with increasing friction parameter.

In the present study, to reveal the air entrainment mechanism into a suction pipe in a suction sump, the authors conduct flow-velocity measurements by UDM (Ultrasonic Doppler Method). Here, we consider the simplest geometry as a suction sump, that is, a straight channel with rectangle-cross section and a simple suction pipe near the end of the channel. Ultrasonic transducers are fixed outside the side, bottom and back walls with right/near-right angles and, we get three-dimensional time-mean velocity distributions and equi-vorticity contours. At first, measurement accuracy is checked by comparing velocity profiles by UDM with hydrogen bubble method. As a result, the authors show typical flow fields in the sump, and show the relation between flow pattern and air entrainment. Especially, we compare two cases where the air entrainment is often observed.

Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage (SAH). The prevention and treatment of cerebral vasospasm thus plays a critical role in the management of SAH patients. However, the mechanism of cerebral vasospasm still remains elusive, while effective therapeutic strategies also remain to be established. The role of thrombin and its receptor proteinase-activated receptor 1 (PAR1) in cerebral vasospasm was investigated using a rabbit double hemorrhage SAH model. The expression of PAR1 was up-regulated and the contractile response to thrombin was markedly enhanced in the basilar artery of SAH models. The intrathecal administration of a PAR1 antagonist prevented the up-regulation of PAR1 and the enhancement of the contractile responses to thrombin in SAH. These observations thus suggest that PAR1 may play a pivotal role in post-hemorrhagic cerebral vasospasm in SAH. Following SAH, thrombin activates PAR1, thereby up-regulating the expression of PAR1, which culminates in the increased contractile response to thrombin in the basilar artery. PAR1 antagonists are thus anticipated to be a novel therapeutic strategy for cerebral vasospasm. However, further studies are needed before establishing the clinical usefulness of PAR1 antagonists. Keywords:: subarachnoid hemorrhage, cerebral vasospasm, thrombin, proteinase-activated receptor, 1 (PAR1), antagonist

This research deals with the switching mechanism of a flip-flop jet nozzle with a connecting tube, being based on the measurements of pressure in two chambers, velocity in the connecting tube and velocity distribution between two inside walls of the nozzle, i.e., reattachment walls. The authors particularly focus upon the details of switching flow field inside the nozzle, using a ultrasound-velocity-profile monitor (UVP monitor). As a result, two re-circulating flows, viz., two vortical structures, are shown on both side walls inside the nozzle. By means of the simultaneous observation of chamber pressures and connecting-tube velocity with UVP results, we show a coherent scenario of the jet-oscillation phenomenon in concern.

The Ca2+ signal is the primary determinant of the contraction of the vascular smooth muscle. However, the alteration of the Ca2+ sensitivity of the contractile apparatus also plays an essential role. The regulation of the myosin light chain phosphatase (MLCP) activity is considered to be the most important mechanism underlying the regulation of Ca2+ sensitivity. The investigations during the last 15 years have identified many proteins that participate in the regulation of the MLCP activity. Recently, the Ca2+ signal has also been shown to cross-talk with the mechanisms regulating the Ca2+ sensitivity. Consequently, Rho kinase, protein kinase C, CPI-17, and MYPT1 have all been suggested to play a physiologically important role in the regulation of the MLCP activity. We are now close to elucidating the major rules regulating the MLCP activity and the Ca2+ sensitivity during vascular contractions. This article will give an overview of the current understanding of the biochemical basis for the regulation of the MLCP activity, while also discussing their functional roles from a physiological point of view. I hope this article will help to develop new pharmacological strategies for the prevention and treatment of the pathological vasoconstriction often seen in vascular diseases. Keywords:: vascular smooth muscle, contraction, calcium, Ca2+ sensitivity, signal transduction

We conducted a study related to sound absorbing materials created by folding thin material in the shape of a Japanese folding fan. In order to conduct a calculation of the shape of a clearance in the folding fan-shaped test sample, we performed an approximation of element decomposition in both the incidence direction of the sound wave and the lateral direction. In a theoretical analysis, we considered sound wave attenuation due to boundary layer friction in the clearance between two surfaces. We compared experimental and calculated values for the sound absorption coefficient. Trends in both matched closely. Errors in the calculated values for large clearances could be attributed mainly to irregularity in the size of the clearances. Frequency shift of the calculated values for small clearances were due to errors in estimating the sound attenuation. Sound absorbing structures shaped like a folding fan possess sound absorption characteristics are similar to the wedge-shaped sound absorbing structures shown in previous reports. This was also shown in calculated values based on theoretical analysis. In cases with an appropriate back air space, sound absorption peak frequencies decreased relative to cases without a back air space, and sound absorption characteristics were superior across a wide frequency range.

We numerically study the forced-oscillation-frequency responses on the three-dimensional thermal convection in a cubic cavity heated from one wall and chilled from its opposite wall in the non-gravitational field at vibrational Rayleigh number (the Rayleigh number based on the cavity's acceleration amplitude instead of the gravitational acceleration) Raη = 5.0×103 - 1.1×105, Plandtl number Pr = 7.1 (water) and non-dimensional forced-oscillation frequency ω = 1.0×100 - 1.0×103. The direction of the forced sinusoidal oscillation is parallel to the temperature gradient inside the cubic cavity. We especially focus upon the influences of both Raη and ω. As a result, five kinds of structures S2 (with a single roll), S4 (with a toroidal roll), S5 (with four roll), S6 (with four roll) and Sα (with six roll) appear in the tested ranges of Raη and ω. The Sα consists of a pair of trident currents, namely, three ascending streams and three matching descending streams in the cubic cavity. And, such flow structures are revealed in detail. Whenever it is not conductive but convective for ω < 5.0×10 2, convective motion always starts with the S4 from the rest at each forcing cycle. We find out the optimum frequency ω|K|max where the amplitude of a spatially-averaged kinetic energy K, which is defined by the difference between the maximum K and the minimum K over one forcing cycle, attains the maximum at each Raη. At ω = ω|K|max max, the flow structure is characterised by the S4. So, this fact suggests that the optimum frequency can be related with the S4. In addition, we show the occurrence condition for convection as a function of Raη and ω, and the boundary for the quasi-steady approximation which is permissible at ω ≲ 100 from a quantitative viewpoint.

We reveal the fundamental and dominant flow structures of thermal convection in a cubic cavity under forced oscillation heated differentially by analysing the flow field with the proper orthogonal decomposition (referred to as POD). The database is made of consequtive series of three-dimensional results obtained by the direct numerical simulation based on the Boussinesq approximation for a forcedly-oscillating cube under the zero-gravity environment, at vibrational Rayleigh number (the Rayleigh number based on the cavity's acceleration amplitude instead of the gravitational acceleration) Raη = 5.0×104 - 1.1×105, Plandtl number Pr = 7.1 (water) and non-dimensional forced-oscillating frequency ω = 1.0×100 - 2.0×102. The direction of the forced sinusoidal oscillation is parallel to the temperature gradient. It appears that the most energetic POD modes, or the first POD eigenfunctions with large eigenvalues, account for the transient process on flow structures during one forcing cycle. The first eigenfunctions correspond to the steady and laminar flow structures which appear inside a non-oscillating cube in the terrestrial environments. The POD expansion coefficient is found to be useful for predicting a consecutive series of the dominant flow structures.

The level of receptors expressed on the cell surface determines the cellular responsiveness to agonists. Proteinase-activated receptors (PARs) have been reported to be either upregulated or down-regulated in response to various types of stimulation and pathological situations. In addition, the transcriptional regulation plays a major role in the alteration of the expression of PARs under pathological conditions, while post-translational mechanisms such as phosphorylation, arresting-binding, internalization, and lysosomal degradation, which desensitize activated PARs and terminate intracellular signaling, also play an important role in regulating the expression of PARs and the cellular responsiveness to the agonists. Elucidating the mechanisms related to the expression of PARs is a critical step to understand the pathophysiology of various diseases and establish new therapeutic strategies. However, the molecular mechanism regulating the expression of PARs still remains to be elucidated. This minireview discusses our current understanding of the mechanisms regulating the expression of PARs. The transcription factors and the regulatory elements in the promoter regions, and the proteins that interact with the receptors and thereby regulate their trafficking and desensitization are the main problems that need to be elucidated. Keywords:: expression, transcription, trafficking, proteinase-activated receptor

Adenosine A1 receptors in the brain are believed to play an important role in brain functioning. We have discovered a novel adenosine A1 receptor antagonist, FR194921 (2-(1-methyl-4-piperidinyl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-3(2H)-pyridazinone), and characterized the pharmacological activity in the present study. FR194921 showed potent and selective affinity for the adenosine A1 receptor without affinity for A2A and A3 receptors and did not show any species differences in binding affinity profile among human, rat, and mouse. Pharmacokinetic study in rats revealed that FR194921 was orally active and highly brain penetrable. Oral administration of FR194921 dose-dependently ameliorated the hypolocomotion induced by the A1 receptor agonist N6-cyclopentyladenosine in rats, indicating this compound exerts A1-antagonistic action in vivo. In the passive avoidance test, scopolamine (1 mg/kg)-induced memory deficits were significantly ameliorated by FR194921 (0.32, 1 mg/kg). In two animal models of anxiety, the social interaction test and elevated plus maze, FR194921 showed specific anxiolytic activity without significantly influencing general behavior. In contrast, FR194921 did not show antidepressant activity even at a dose of 32 mg/kg in the rat forced swimming test. These results indicate that the novel, potent, and selective adenosine A1 receptor antagonist FR194921 exerts both cognitive-enhancing and anxiolytic activity, suggesting the therapeutic potential of this compound for dementia and anxiety disorders. Keywords:: adenosine A1 receptor, hypolocomotion, memory deficit, anxiety, depression

We investigated the sound absorption coefficient within a sound-absorbing structure made of layered clearances between two planes. We discussed the experimental results from the existing literature and conducted a theoretical analysis on several different sound-absorbing structures that take into account the viscosity of the boundary layer at the clearances. First, we examined the case of thin sheets placed in parallel. Then, we examined the case where the size of the clearance continuously changed perpendicular to the direction of incidence of the sound waves. Subsequently, we examined the case where the clearance continuously decreased in the direction of incidence of the sound waves. In latter two cases, the transfer matrix used in the calculations was divided into elements perpendicular or coincident to the direction of incidence of the sound waves and the size of the clearance for each element was changed in a stepwise fashion. We then calculated the sound absorption coefficients for various structures and dimensions and observed that the calculated and experimental data agreed well. On the basis of the calculation simulation, the differences between the calculated and experimental absorption coefficient data were attributed mainly to the changes in the flexure of the sheet materials. The proposed calculation methods will be useful in determining the absorption coefficient of such shapes, and in the design of sound-absorbing materials that use such shapes.

Concerning most of track-and-field athletics such as the marathon, it is important to clarify the flow around track runners and to evaluate their air resistances (or wind resistances, drags). In wind-tunnel experiments which are the most effective approaches to such a problem as well as field observasions and numerical analyses the moving-belt system is indispensable for precise aerodynamic measurements, if the so-called “ground effect” is negligible. In the present study, we develop a moving-belt system, and show its basic performance such as the distributions of time-mean velocity and turbulent intensity above the moving-belt system using a hot-wire anemometer. Then, the authors investigate the air resistance of a runner in solo running and of a runner in duet running in various duet-running formations. Especially for duet-running formations, the authors reveal the optimum one.

In many fluid-structure interaction problems, the virtual mass, namely, the added mass is one of important interests. In the present study, the authors investigate the validity of a numerical method previously proposed by them in order to specify the added mass coefficient of arbitrary two-dimensional solid bodies efficiently and conveniently. In this method, we consider a two-dimensional incompressible viscous fluid under the assumption of an infinitesimal oscillation amplitude of the body, and properly modify the Navier-Stokes equations into linear equations the Brinkman equations. The solving method is based on a discrete singularity method. In order to show the method's effectivity and validity, the authors compute some flows around the bodies with fundamental cross sections with/without sharp edges, which oscillate in infinite flow fields. In addition, the authors solve the full Navier-Stokes equations by a finite difference method, and compare with each other to specify the valid range for the method. Then, the authors confirm the nonlinear amplitude effect and specify the valid range for the method.

Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated muscle atrophy. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. Methods. Mice were fed either 20% casein diet, 20% soy protein isolate diet, 10% glycinin diet containing 10% casein, or 20% glycinin diet. One week later, the right sciatic nerve was cut. The wet weight, cross sectional area (CSA), IGF-1 signaling, and atrogene expression in hindlimb muscles were examined at 1, 3, 3.5, or 4 days after denervation. Results. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Furthermore, dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Dietary soy glycinin partially suppressed the denervation-mediated expression of atrogenes, such as MAFbx/atrogin-1 and MuRF-1, through the protection of IGF-1 signaling estimated by phosphorylation of Akt-1. Conclusions. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice.

The effects of orally administered dipeptidyl peptidase IV (DPP-IV) inhibitor on the glucose-lowering effect of glibenclamide are still unknown. We evaluated the effects of combination treatment with a long-lasting DPP-IV inhibitor, K579 ((S)-1-[4-methyl-1-(2-pyrimidinyl)-4-piperidylamino]acetyl-2-pyrrolidinecarbonitrile), and glibenclamide on the glycemic responses to glucose loading in rats. Treatment with K579 inhibited the plasma DPP-IV activity even 8 h after the administration. K579 significantly suppressed the blood glucose elevation in glibenclamide-pretreated rats without excessive hypoglycemia. These profiles of K579 indicate that it could be useful agent to correct the postprandial glucose excursion in type 2 diabetes patients by combination treatment with glibenclamide. Keywords:: dipeptidyl peptidase IV, glibenclamide, glucose tolerance

Large-scale data sets of protein-protein interactions (PPIs) are a valuable resource for mapping and analysis of the topological and dynamic features of interactome networks. The currently available large-scale PPI data sets only contain information on interaction partners. The data presented in this study also include the sequences involved in the interactions (i.e., the interacting regions, IRs) suggested to correspond to functional and structural domains. Here we present the first large-scale IR data set obtained using mRNA display for 50 human transcription factors (TFs), including 12 transcription-related proteins. The core data set (966 IRs; 943 PPIs) displays a verification rate of 70%. Analysis of the IR data set revealed the existence of IRs that interact with multiple partners. Furthermore, these IRs were preferentially associated with intrinsic disorder. This finding supports the hypothesis that intrinsically disordered regions play a major role in the dynamics and diversity of TF networks through their ability to structurally adapt to and bind with multiple partners. Accordingly, this domain-based interaction resource represents an important step in refining protein interactions and networks at the domain level and in associating network analysis with biological structure and function.