A therosclerosis, a progressive, chronic, inflammatory disease with specific, localized manifestations in the arterial wall, is a major health burden and is predicted to become the leading cause of mortality and morbidity worldwide. 1,2 Complications of atherosclerosis, such as myocardial infarction (MI), which is the largest single cause of death in developed countries, are caused by inflammation-driven rupture of atherosclerotic plaques. 3A major hurdle in research on mechanisms of plaque rupture is the lack of appropriate mouse models which exhibit plaque rupture and lesion characteristics of vulnerable, unstable, and thus rupture-prone plaques as found in humans.4 Such characteristics most importantly include a thin and ruptured fibrous cap, plaque inflammation, neovascularization within the plaque (vasa vasorum), plaque hemorrhage, and intravascular (often occlusive) thrombus formation. 2,3,[5][6][7] In addition, an animal model of plaque instability/rupture should include responsiveness to pharmacological agents known to reduce the risk of plaque rupture in humans. 8,9 Currently discussed animal models of atherosclerosis typically represent a few but not the full combination of the characteristics seen in human unstable/ruptured plaques. [10][11][12][13][14] An animal model of New Methods in Cardiovascular Biology© 2013 American Heart Association, Inc. Rationale: The high morbidity/mortality of atherosclerosis is typically precipitated by plaque rupture and consequent thrombosis. However, research on underlying mechanisms and therapeutic approaches is limited by the lack of animal models that reproduce plaque instability observed in humans.Objective: Development and use of a mouse model of plaque rupture that reflects the end stage of human atherosclerosis. Methods and Results:On the basis of flow measurements and computational fluid dynamics, we applied a tandem stenosis to the carotid artery of apolipoprotein E-deficient mice on high-fat diet. At 7 weeks postoperatively, we observed intraplaque hemorrhage in ≈50% of mice, as well as disruption of fibrous caps, intraluminal thrombosis, neovascularization, and further characteristics typically seen in human unstable plaques. Administration of atorvastatin was associated with plaque stabilization and downregulation of monocyte chemoattractant protein-1 and ubiquitin. Microarray profiling of mRNA and microRNA (miR) and, in particular, its combined analysis demonstrated major differences in the hierarchical clustering of genes and miRs among nonatherosclerotic arteries, stable, and unstable plaques and allows the identification of distinct genes/miRs, potentially representing novel therapeutic targets for plaque stabilization. The feasibility of the described animal model as a discovery tool was established in a pilot approach, identifying a disintegrin and metalloprotease with thrombospondin motifs 4 (ADAMTS4) and miR-322 as potential pathogenic factors of plaque instability in mice and validated in human plaques. Conclusions:The newly described mouse mod...
A series of experimental studies have been made of the fluid behaviour in a completely filled, precessing, right circular cylinder. The tank was spun about its axis of symmetry and subjected to a forced precession at various excitation frequencies ω, nutation angles θ and at various Ekman numbers. This forcing excites a subset of the modes, called inertia waves, that are made possible by the Coriolis force that arises in a spinning environment. In these experiments, the fluid flow breakdown phenomena are investigated. Here the fluid, when forced near a resonant frequency, exhibits a transition to disordered or turbulent flow. This paper presents a categorization of some of the breakdown regimes, of which the ‘resonant collapses’ (McEwan 1970) are the most catastrophic members.The studies reported in this paper used entirely visual observations and measurements. The experimental observations employed a visualization technique that gave no information on fluid velocities, but provided an excellent picture of the flow structure. Quantitative data were extracted in the form of the time for the breakdown to occur. The breakdown phenomena, while readily produced over a large region of parameter space, are complex and varied. The observations show that our system is extraordinarily rich, exhibiting, for example, recurrent breakdowns which may be explained in terms of chaotic intermittency. A detailed description of some of the different breakdown regimes indicates that no single model will explain the behaviour throughout parameter space. This research is motivated by the instability problems of spinning spacecraft containing liquid fuels.
This review details recent developments in nondestructive ultrasound separation techniques that can be used to separate, trap, or fractionate particles or emulsified droplets from bulk phase liquids. Whereas most previous reviews have focused on small scales or specific applications, this review groups different aspects of the acoustic separation technique and directs it at an audience with interests in separation technologies. The process has potential as an attractive alternative to common separation processes such as centrifugation, membrane filtration, sedimentation, or fluorescence activated cell sorting (FACS). The technology can achieve precise, gentle, and label-free separation in a system that involves no moving parts. The fundamental concepts are presented in detail and previous studies covering a range of different applications are reviewed. The challenges and opportunities for addressing large-scale industrial applications are evaluated.
The separation of milk fat from natural whole milk has been achieved by applying ultrasonic standing waves (1 MHz and/or 2 MHz) in a litre-scale (5L capacity) batch system. Various design parameters were tested such as power input level, process time, specific energy, transducer-reflector distance and the use of single and dual transducer set-ups. It was found that the efficacy of the treatment depended on the specific energy density input into the system. In this case, a plateau in fat concentration of ∼20% w/v was achieved in the creamed top layer after applying a minimum specific energy of 200 kJ/kg. In addition, the fat separation was enhanced by reducing the transducer reflector distance in the vessel, operating two transducers in a parallel set-up, or by increasing the duration of insonation, resulting in skimmed milk with a fat concentration as low as 1.7% (w/v) using raw milk after 20 min insonation. Dual mode operation with both transducers in parallel as close as 30 mm apart resulted in the fastest creaming and skimming in this study at ∼1.6 g fat/min.
A passive acoustic method of detecting breaking waves of different scales has been developed. The method also showed promise for measuring breaking severity.Sounds were measured by a subsurface hydrophone in various wind and wave states. A video record of the surface was made simultaneously. Individual sound pulses corresponding to the many individual bubble formations during wave-breaking events typically last only a few tens of milliseconds. Each time a soundlevel threshold was exceeded, the acoustic signal was captured over a brief window typical of a bubble formation pulse, registering one count. Each pulse was also analyzed to determine the likely bubble size generating the pulse.Using the time series of counts and visual observations of the video record, the sound-level threshold that detected bubble formations at a rate optimally discriminating between breaking and nonbreaking waves was determined by a classification-accuracy analysis. This diagnosis of breaking waves was found to be approximately 70%-75% accurate once the optimum threshold had been determined.The method was then used for detailed analysis of wave-breaking properties across the spectrum. When applied to real field data, a breaking probability distribution could be obtained. This is the rate of occurrence of wave-breaking events at different wave scales. With support from a separate, laboratory experiment, the estimated bubble size is argued to be dependent on the severity of wave breaking and thus to provide information on the energy loss due to the breaking at the measured spectral frequencies. A combination of the breaking probability distribution and the bubble size could lead to direct estimates of spectral distribution of wave dissipation.Corresponding author address: Richard Manasseh, Fluid Dynamics Cluster, CSIRO Manufacturing and Infrastructure Technology,
A series of experimental observations is presented of a flow in which inertial oscillations are excited. The homogeneous fluid is contained in a completely filled right circular cylinder. The cylinder is spun about its axis of symmetry and a small ‘forced precession’ (or coning motion) is impulsively started. The flow is visualized by an electrolytic dyeline method. The mathematical problem for linear inviscid inertial oscillations in this system, although ill-posed in general, admits a solution in terms of wave modes for the specific boundary conditions considered here. The experiments show that while this linear inviscid theory provides some facility for predicting the flow structure at early times, the flow rapidly and irreversibly distorts away from the predicted form. This behaviour is seen as a precursor to some of the more dramatic breakdowns described by previous authors, and it may be pertinent to an understanding of the breakdowns reported in experiments on elliptical flow instabilities.
Direct numerical simulations of flows in cylinders subjected to both rapid rotation and axial precession are presented and analysed in the context of a stability theory based on the triadic resonance of Kelvin modes. For a case that was chosen to provide a finely tuned resonant instability with a small nutation angle, the simulations are in good agreement with the theory and previous experiments in terms of mode shapes and dynamics, including long-time-scale regularization of the flow and recurrent collapses. Cases not tuned to the most unstable triad, but with the nutation angle still small, are also in quite good agreement with theoretical predictions, showing that the presence of viscosity makes the physics of the triadic-resonance model robust to detuning. Finally, for a case with 45• nutation angle for which it has been suggested that resonance does not occur, the simulations show that a slowly growing triadic resonance predicted by theory is in fact observed if sufficient evolution time is allowed.
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