408,228 research outputs found
Outer layer turbulence intensities in smooth- and rough-wall boundary layers
Clear differences in turbulence intensity profiles in smooth, transitional and fully rough zero-pressure-gradient boundary layers are demonstrated, using the diagnostic plot introduced by Alfredsson, Segalini & Örlü (Phys. Fluids, vol. 23, 2011, p. 041702) – u?/U versus U/Ue, where u? and U are the local (root mean square) fluctuating and mean velocities and Ue is the free stream velocity. A wide range of published data are considered and all zero-pressure-gradient boundary layers yield outer flow u?/U values that are roughly linearly related to U/Ue, just as for smooth walls, but with a significantly higher slope which is completely independent of the roughness morphology. The difference in slope is due largely to the influence of the roughness parameter (?U+ in the usual notation) and all the data can be fitted empirically by using a modified form of the scaling, dependent only on ?U/Ue. The turbulence intensity, at a location in the outer layer where U/Ue is fixed, rises monotonically with increasing ?U/Ue which, however, remains of O(1) for all possible zero-pressure-gradient rough-wall boundary layers even at the highest Reynolds numbers. A measurement of intensity at a point in the outer region of the boundary layer can provide an indication of whether the surface is aerodynamically fully rough, without having to determine the surface stress or effective roughness height. Discussion of the implication for smooth/rough flow universality of differences in outer-layer mean velocity wake strength is include
Review article: Linaclotide for the management of irritable bowel syndrome with constipation
BACKGROUND:
Irritable bowel syndrome with constipation (IBS-C) represents a significant burden to patients and healthcare systems due to its prevalence and lack of successful symptomatic resolution with established treatment options. Linaclotide 290 μg has recently been approved by the European Medicines Agency (EMA) for moderate-to-severe IBS-C and by the US Food and Drug Administration for IBS-C (290 μg dose) and for chronic constipation (145 μg dose).
AIM:
To summarise data leading to the approval of linaclotide for IBS-C, with focus on EMA-pre-specified outcome measures.
METHODS:
Literature search of a peer-review database (PubMed) and review of congress abstracts on linaclotide preclinical and clinical trial data in IBS-C.
RESULTS:
Preclinical studies suggest that the guanylate cyclase C agonist (GCCA) linaclotide acts through elevation of cyclic guanosine monophosphate (cGMP) levels, leading to accelerated gastrointestinal (GI) transit through increased fluid secretion and reduced visceral hypersensitivity. Clinical trial data demonstrate that linaclotide improves abdominal symptoms (pain, bloating) and bowel symptoms (constipation) compared with placebo in patients with IBS-C. The most frequent side effect, diarrhoea, results from the therapeutic action of linaclotide. Linaclotide acts locally in the GI tract with minimal systemic exposure, resulting in low oral bioavailability and thus a low risk of relevant systemic adverse effects.
CONCLUSION:
Linaclotide, a first-in-class GCCA, is a promising new drug with a novel, dual mechanism of action that, unlike more well-established agents, can relieve the abdominal pain, bloating and constipation associated with IBS-C and has a low propensity for systemic side effects
The minimal seed of turbulent transition in the boundary layer
This paper describes a scenario of transition from laminar to turbulent flow in a spatially developing boundary layer over a flat plate. The base flow is the Blasius non-parallel flow solution; it is perturbed by optimal disturbances yielding the largest energy growth over a short time interval. Such perturbations are computed by a nonlinear global optimization approach based on a Lagrange multiplier technique. The results show that nonlinear optimal perturbations are characterized by a localized basic building block, called the minimal seed, defined as the smallest flow structure which maximizes the energy growth over short times. It is formed by vortices inclined in the streamwise direction surrounding a region of intense streamwise disturbance velocity. Such a basic structure appears to be a robust feature of the base flow since it is practically invariant with respect to the initial energy of the perturbation, the target time, the Reynolds number and the dimensions of the computational domain. The minimal seed grows very rapidly in time while spreading, and it triggers nonlinear effects which bring the flow to turbulence in a very efficient manner, through the formation of a turbulence spot. This evolution of the initial optimal disturbance has been studied in detail by direct numerical simulations. Using a perturbative formulation of the Navier–Stokes equations, each linear and nonlinear convective term of the equations has been analysed. The results show the fundamental role of the streamwise inclination of the vortices in the process. The nonlinear coupling of the finite amplitude disturbances is crucial to sustain such streamwise inclination, as well as to generate dislocations within the flow structures, and local inflectional velocity distributions. The analysis provides a picture of the transition process characterized by a sequence of structures appearing successively in the flow, namely, 3 vortices, hairpin vortices and streamwise streaks. Finally, a disturbance regeneration cycle is conceived, initiated by the fast nonlinear amplification of the minimal seed, providing a possible scenario for the continuous regeneration of the same fundamental flow structures at smaller space and time scales
Tertiary patterns in inclined layer convection
Convection in an inclined layer generates various types of spatio-temporal patterns due to interaction of buoyancy and shear. At small angles of incline, the secondary instability of the uniform base state occurs in the form of buoyancy dominated longitudinal rolls. Above a critical angle of incline marking a co-dimension 2 point, shear driven transverse roll instabilities take over as the secondary instabilities. Computing the location of the co-dimension 2 point for varying thermal driving and inclination angle and determining all secondary bifurcations together with the resulting tertiary states allows to characterize the nonlinear phase diagram of inclined layer convection system. The semi-analytically computed phase diagram quantitatively matches experimental observations by Daniels et al. Close to the co-dimension 2 point, a subcritical secondary bifurcation leading to bistability is identified. In the bistable region, heteroclinic cycles generate bursting behavior
Measurements in an urban-type boundary layer.
Wind tunnel measurements of the boundary layer flow over a very rough surface comprising a staggered array of cubes are presented and discussed. Attention is concentrated on the near-wall region, including the canopy region below the tops of the roughness elements. Particle image velocimetry (PIV) and laser Doppler anemometry were used to identify the dominant features of the mean and turbulent flow and these are compared with the better-known features of the flow above the roughness. Spatial correlation data, extracted from the PIV images, are used to provide information about eddy structures and it is shown that these differ in some crucial respects from those typical of more classical boundary layers. The implications of the results are discussed in terms of their relevance to flows within the urban environment
The s-layer glycome-adding to the sugar coat of bacteria
This work was supported by the Austrian Science Fund FWF, projects P19047-B12, P20605-B12, P21954-B20 (to C. Sch¨affer), and P20745-B11 (to P. Messner). Zarschler and Ristl were supported by the Hochschuljubil¨aumsstiftung der Stadt Wien, Projects H-2229-2007 (to K. Zarschler) and H-1897-2008 (to R. Ristl).The amazing repertoire of glycoconjugates present on bacterial cell surfaces includes lipopolysaccharides, capsular polysaccharides, lipooligosaccharides, exopolysaccharides, and glycoproteins. While the former are constituents of Gram-negative cells, we review here the cell surface S-layer glycoproteins of Gram-positive bacteria. S-layer glycoproteins have the unique feature of self-assembling into 2D lattices providing a display matrix for glycans with periodicity at the nanometer scale. Typically, bacterial S-layer glycans are O-glycosidically linked to serine, threonine, or tyrosine residues, and they rely on a much wider variety of constituents, glycosidic linkage types, and structures than their eukaryotic counterparts. As the S-layer glycome of several bacteria is unravelling, a picture of how S-layer glycoproteins are biosynthesized is evolving. X-ray crystallography experiments allowed first insights into the catalysis mechanism of selected enzymes. In the future, it will be exciting to fully exploit the S-layer glycome for glycoengineering purposes and to link it to the bacterial interactome.Peer reviewe
Experimental application of a dynamic observer to capture and predict the dynamics of a flat-plate boundary layer
The recent approach, proposed by Guzman-Inigo et al. \cite{GuzmanInigo2014}, using System Identification to derive a Reduced Order Model from snapshots of a flow is applied to a transitional boundary layer growing over a flat-plate. It is shown that such an approach can indeed be applied to experimental PIV snapshots. Using a proper learning dataset and a proper local sensor, it is shown that the evolution of boundary layer can be properly estimated from the time evolution of the local probe and with no more than ten POD modes for the Reduced Order Model. The influence of the various parameters on the efficiency of the system identification technique is discussed
Optimal wave packets in a boundary layer and initial phases of a turbulent spot
The three-dimensional global optimal dynamics of a flat-plate boundary layer is studied by means of an adjoint-based optimization in a spatial domain of long – but finite – streamwise dimension. The localized optimal initial perturbation is characterized by a pair of streamwise-modulated counter-rotating vortices, tilted upstream, yielding at the optimal time elongated streaks of alternating sign in the streamwise direction. This indicates that perturbations with non-zero streamwise wavenumber have a role in the transient dynamics of a boundary layer. A scaling law is provided, describing the variation of the streamwise modulation of the optimal initial perturbation with respect to the streamwise domain length and to the Reynolds number. For spanwise-extended domains, a near-optimal three-dimensional perturbation is extracted during the optimization process; it is localized also in the spanwise direction, resulting in a wave packet of elongated disturbances modulated in the spanwise and streamwise directions. The nonlinear evolution of the optimal and near-optimal perturbations is investigated by means of direct numerical simulations. Both perturbations are found to induce transition at lower levels of the initial energy than local optimal and suboptimal perturbations. Moreover, it is observed that transition occurs in a well-defined region of the convected wave packet, close to its centre, via a mechanism including at the same time oscillations of the streaks of both quasi-sinuous and quasi-varicose nature. Hairpin vortices are observed before transition; they have an active role in the breakdown of the streaks and result in a turbulent spot which spreads out in the boundary layer
A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms
We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms (SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds (a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines--in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases
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