Side Chain Structure Determines Unique Physiologic and Therapeutic Properties of norUrsodeoxycholic Acid in Mdr2(-/-) Mice

24-norursodeoxycholic acid (norUDCA), a side chain-modified ursodeoxycholic acid derivative, has dramatic therapeutic effects in experimental cholestasis and may be a promising agent for the treatment of cholestatic liver diseases. We aimed to better understand the physiologic and therapeutic properties of norUDCA and to test if they are related to its side chain length and/or relative resistance to amidation. For this purpose, Mdr2-/- mice, a model for sclerosing cholangitis, received either a standard diet or a norUDCA-, tauro norursodeoxycholic acid (tauro- norUDCA)-, or di norursodeoxycholic acid (di norUDCA)-enriched diet. Bile composition, serum biochemistry, liver histology, fibrosis, and expression of key detoxification and transport systems were investigated. Direct choleretic effects were addressed in isolated bile duct units. The role of Cftr for norUDCA-induced choleresis was explored in Cftr-/- mice. norUDCA had pharmacologic features that were not shared by its derivatives, including the increase in hepatic and serum bile acid levels and a strong stimulation of biliary HCO3- -output. norUDCA directly stimulated fluid secretion in isolated bile duct units in a HCO3- -dependent fashion to a higher extent than the other bile acids. Notably, the norUDCA significantly stimulated HCO 3- -output also in Cftr-/- mice. In Mdr2-/- mice, cholangitis and fibrosis strongly improved with norUDCA, remained unchanged with tauro- norUDCA, and worsened with di norUDCA. Expression of Mrp4, Cyp2b10, and Sult2a1 was increased by norUDCA and di norUDCA, but was unaffected by tauro- norUDCA. Conclusion:The relative resistance of norUDCA to amidation may explain its unique physiologic and pharmacologic properties. These include the ability to undergo cholehepatic shunting and to directly stimulate cholangiocyte secretion, both resulting in a HCO3- -rich hypercholeresis that protects the liver from cholestatic injury.

Asymptotic analysis for the coupled wavenumbers in an infinite fluid-filled flexible cylindrical shell: The beam mode

Using asymptotics, the coupled wavenumbers in an infinite fluid-filled flexible cylindrical shell vibrating in the beam mode (viz. circumferential wave order n = 1) are studied. Initially, the uncoupled wavenumbers of the acoustic fluid and the cylindrical shell structure are discussed. Simple closed form expressions for the structural wavenumbers (longitudinal, torsional and bending) are derived using asymptotic methods for low- and high-frequencies. It is found that at low frequencies the cylinder in the beam mode behaves like a Timoshenko beam. Next, the coupled dispersion equation of the system is rewritten in the form of the uncoupled dispersion equation of the structure and the acoustic fluid, with an added fluid-loading term involving a parameter mu due to the coupling. An asymptotic expansion involving mu is substituted in this equation. Analytical expressions are derived for the coupled wavenumbers (as modifications to the uncoupled wavenumbers) separately for low- and high-frequency ranges and further, within each frequency range, for large and small values of mu. Only the flexural wavenumber, the first rigid duct acoustic cut-on wavenumber and the first pressure-release acoustic cut-on wavenumber are considered. The general trend found is that for small mu, the coupled wavenumbers are close to the in vacuo structural wavenumber and the wavenumbers of the rigid-acoustic duct. With increasing mu, the perturbations increase, until the coupled wavenumbers are better identified as perturbations to the pressure-release wavenumbers. The systematic derivation for the separate cases of small and large mu gives more insight into the physics and helps to continuously track the wavenumber solutions as the fluid-loading parameter is varied from small to large values. Also, it is found that at any frequency where two wavenumbers intersect in the uncoupled analysis, there is no more an intersection in the coupled case, but a gap is created at that frequency. This method of asymptotics is simple to implement using a symbolic computation package (like Maple). (C) 2008 Elsevier Ltd. All rights reserved.

Simulation of Dust Loaded V-I Characteristics of a Commercial Thermal Power Plant Precipitator

A new approach based on finite difference method, is proposed for the simulation of electrical conditions in a dc energized wire-duct electrostatic precipitator with and without dust loading. Simulated voltage-curren characteristics with and without dust loading were compared with the measured characteristics for analyzing the performance of a precipitator. The simple finite difference method gives sufficiently accurate results with reduced mesh size. The results for dust free simulation were validated with published experimental data. Further measurements were conducted at a thermal power plant in India and the results compares well with the measured ones.

Improvement in solar air collector performance with vaned diffuser

Modifications made in a solar air collector inlet duct to achieve uniform velocity of air in the absorber duct are described. Measurements of temperature and pressure at various points in the duct gave information on the distribution of air in the absorber duct. A thermal performance test conducted on the collector with a vaned diffuser showed some significant improvement compared with a diffuser without vanes.

An experimental study of suddenly expanded rectangular jet flow field

Flow through a rectangular Passage which is expanded suddenly into another rectangular duct of larger Cross-sectional area has been studied experimentally with stagnation Pressures from 3.5 atmospheres to 1.25 atmospheres. The length to height ratio of the enlarged duct varied from 5.769 to 1.923 and three models with length to height ratios 5.769, 3.846, and 1.923 were studied. The influence of stagnation Pressures and length to height ratio of the enlarged duct on base pressure and flow field mean pressures in the enlarged duct is discussed. The results of the present investigation indicate that the oscillatory nature of the mean pressure flow field in the enlarged portion with rectangular cross-section is appreciably different from that for circular cross-section at similar flow conditions.

Effect of wall thickness on the end corrections of the extended inlet and outlet of a double-tuned expansion chamber

Simple expansion chambers, the simplest of the muffler configurations, have very limited practical application due to the presence of periodic troughs in the transmission loss spectrum which drastically lower the overall transmission loss of the muffler. Tuned extended inlet and outlet can be designed to nullify three-fourths of these troughs, making use of the plane wave theory. These cancellations would not occur unless one altered the geometric lengths for the extended tube in order to incorporate the effect of evanescent higher-order modes (multidimensional effect) through end corrections or lumped inertance approximation at the area discontinuities or junctions. End corrections of the extended inlet and outlet have been studied by several researchers. However the effect of wall thickness of the inlet/outlet duct on end correction has not been studied explicitly. This has significant effect on the tuning of an extended inlet/outlet expansion chamber. It is investigated here experimentally as well as numerically (through use of 3-D FEM software) for stationary medium. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.

Blade manipulators in turbulent channel flow

We report here the results of a series of careful experiments in turbulent channel flow, using various configurations of blade manipulators suggested as optimal in earlier boundary layer studies. The mass flow in the channel could be held constant to better than 0.1%, and the uncertainties in pressure loss measurements were less than 0.1 mm of water; it was therefore possible to make accurate estimates of the global effects of blade manipulation of a kind that are difficult in boundary layer flows. The flow was fully developed at the station where the blades were mounted, and always relaxed to the same state sufficiently far downstream. It is found that, for a given mass flow, the pressure drop to any station downstream is always higher in the manipulated than in the unmanipulated flow, demonstrating that none of the blade manipulators tried reduces net duct losses. However the net increase in duct losses is less than the drag of the blade even in laminar flow, showing that there is a net reduction in the total skin friction drag experienced by the duct, but this relief is only about 20% of the manipulator drag at most.

Flow-Acoustic Performance of Perforated Element Mufflers With Application to Design

A fairly comprehensive computer program incorporating explicit expressions for the four-pole parameters of concentric-tube resonators, plug mufflers, and three-duct cross-flow perforated elements has been used for parametric studies. The parameters considered are hole diameter, the center-to-center distance between consecutive holes (which decides porosity), the incoming mean flow Mach number, the area expansion ratio, the number of partitions of chambers within a given overall shell length, and the relative lengths of these partitions or chambers, all normalized with respect to the exhaust pipe diameter. Transmission loss has been plotted as a function of a normalized frequency parameter. Additionally, the effect of the tail pipe length on insertion loss for an anechoic source has also been studied. These studies have been supplemented by empirical expressions for the normalized static pressure drop for different types of perforated-element mufflers developed from experimental observations.

A note on the effect of wall compliance on lowest?order mode propagation in fluid?filled/submerged impedance tubes

Wave propagation in fluid?filled/submerged tubes is of interest in large HVAC ducts, and also in understanding and interpreting the experimental results obtained from fluid?filled impedance tubes. Based on the closed form analytical solution of the coupled wave equations, an eigenequation, which is the determinant of an 8×8 matrix, is derived and solved to obtain the axial wave number of the lowest?order longitudinal modes for cylindrical ducts of various diameter and wall thickness. The dispersion behavior of the wave motion is analyzed. It is observed that the larger the diameter of the duct and/or the smaller its wall thickness, the more flexible the impedance tube leading to more coupling between the waves in the elastic media. Also, it is shown that the wave motion in water?filled ducts submerged in water exhibits anomalous dispersion behavior. The axial attenuation characteristics of plane waves along water?filled tubes submerged in water or air are also investigated. Finally, investigations on the sound intensity level difference characteristics of the wall of the air?filled tubes are reported.

Experimental studies of a distorted turbulent spot in a three-dimensional flow

We report here on the results of a series of experiments carried out on a turbulent spot in a distorted duct to study the effects of a divergence with straight streamlines preceded by a short stretch of transverse streamline curvature, both in the absence of any pressure gradient. It is found that the distortion produces substantial asymmetry in the spot: the angles at which the spot cuts across the local streamlines are altered dramatically (in contradiction of a hypothesis commonly made in transition zone modelling), and the Tollmien-Schlichting waves that accompany the wing tips of the spot are much stronger on the outside of the bend than on the inside. However there is no strong effect on the internal structure of the spot and the eddies therein, or on such propagation characteristics as overall spread rate and the celerities of the leading and trailing edges. Both lateral streamline curvature and non-homogeneity of the laminar boundary layer into which the spot propagates are shown to be strong factors responsible for the observed asymmetry. It is concluded that these factors produce chiefly a geometric distortion of the coherent structure in the spot, but do not otherwise affect its dynamics in any significant way.

An experimental study of reverse transition in two-dimensional channel flow

An experimental investigation on reverse transition from turbulent to laminar flow in a two-dimensional channel was carried out. The reverse transition occurred when Reynolds number of an initially turbulent flow was reduced below a certain value by widening the duct in the lateral direction. The experiments were conducted at Reynolds numbers of 625, 865, 980 and 1250 based on half the height of the channel and the average of the mean velocity. At all these Reynolds numbers the initially turbulent mean velocity profiles tend to become parabolic. The longitudinal and vertical velocity fluctuations ($\overline{u^{\prime 2}}$ and $\overline{v^{\prime 2}}$) averaged over the height of the channel decrease exponentially with distance downstream, but $\overline{u^{\prime}v^{\prime}} $ tends to become zero at a reasonably well-defined point. During reverse transition $\overline{u^{\prime}}\overline{v^{\prime}}/\sqrt{\overline{u^{\prime 2}}}\sqrt{\overline{v^{\prime 2}}}$ also decreases as the flow moves downstream and Lissajous figures taken with u’ and v’ signals confirm this trend. There is approximate similarly between $\overline{u^{\prime 2}} $ profiles if the value of $\overline{u^{\prime 2}_{\max}} $ and the distance from the wall at which it occurs are taken as the reference scales. The spectrum of $\overline{u^{\prime 2}} $ is almost similar at all stations and the non-dimensional spectrum is exponential in wave-number. All the turbulent quantities, when plotted in appropriate co-ordinates, indicate that there is a definite critical Reynolds number of 1400±50 for reverse transition.

Analysis of Lined Ducts With Mean Flow, With Application to Dissipative Mufflers

Mufflers with at least one acoustically absorptive duct are generally called dissipative mufflers. Generally, for want of systems approach, these mufflers are characterized by transmission loss of the lined duct with overriding corrections for the terminations, mean flow, etc. In this article, it is proposed that dissipative duct should be integrated with other muffler elements, source impedance and radiation impedance, by means of transfer matrix approach. Towards this end, the transfer matrix for rectangular duct with mean flow has been derived here, for the least attenuated mode. Mean flow introduces a coupling between transverse wave numbers and axial wave number, the evaluation of which therefore calls for simultaneous solution of two or three transcendental equations. This is done by means of a Newton-Raphson iteration scheme, which is illustrated here for square ducts lined with porous ceramic tiles.

Analysis of a linear one-dimensional active noise control system by means of block diagrams and transfer functions

In arriving at the ideal filter transfer function for an active noise control system in a duct, the effect of the auxiliary sources (generally loudspeakers) on the waves generated by the primary source has invariably been neglected in the existing literature, implying a rigid wall or infinite impedance. The present paper presents a fairly general analysis of a linear one-dimensional noise control system by means of block diagrams and transfer functions. It takes into account the passive as well as active role of a terminal primary source, wall-mounted auxiliary source, open duct radiation impedance, and the effects of mean flow and damping. It is proved that the pressure generated by a source against a load impedance can be looked upon as a sum of two pressure waves, one generated by the source against an anechoic termination and the other by reflecting the rearward wave (incident on the source) off the passive source impedance. Application of this concept is illustrated for both the types of sources. A concise closed-form expression for the ideal filter transfer function is thus derived and discussed. Finally, the dynamics of an adaptive noise control system is discussed briefly, relating its standing-wave variables and transfer functions with those of the progressive-wave model presented here.

Transfer matrix modeling of hyperbolic and parabolic ducts with incompressible mean flow

A general differential equation for the propagation of sound in a variable area duct or nozzle carrying incompressible mean flow (of low Mach number) is derived and solved for hyperbolic and parabolic shapes. Expressions for the state variables of acoustic pressure and acoustic mass velocity of the shapes are derived. Self‐consistent expressions for the four‐pole parameters are developed. The conical, exponential, catenoidal, sine, and cosine ducts are shown to be special cases of hyperbolic ducts. Finally, it is shown that if the mean flow in computing the transmission loss of the mufflers involving hyperbolic and parabolic shapes was not neglected, little practical benefit would be derived.

Mixing enhancement in a compact trapped vortex combustor

Previous studies on a single-cavity, compact trapped vortex combustor concept showed good flame stability for a wide range of flow conditions. However, achieving good mixing between cavity products and mainstream flow was still a major challenge. In the present study, a passive mixing enhancement strategy of using inclined struts along with a flow guide vane is presented and experimentally tested at atmospheric pressure conditions. Results show excellent mixing and consequently low values of the combustor exit pattern factor in the range of 0.1 and small flame lengths (57 times the main-duct depth). The pressure drop is small in the range of 0.35%, and NOx levels of the order of 12ppm are achieved. The flame stability is excellent, and combustion efficiency is reasonable in the range of 96%. The effectiveness of the proposed strategy is explained on the basis of in-situ OH chemiluminescence images and prior numerical simulations of the resulting complex flow field. The flow guide vane is observed to lead to a counterclockwise cavity vortex, which is conducive to the rise of cavity combustion products along the inclined struts and subsequent mixing with the mainstream flow.