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The dynamics of large gravity waves are known to be modified from the linear model by nonlinear physics. In this paper we analyse Eulerian surface elevation time histories measured from two sites, Lake George (Australia) and the North Sea, to examine how weak nonlinearity has modified the shape of extreme wave groups relative to linear theory. We analyse the asymmetry of the extreme wave groups and find that, on average, the wave in front of an extreme wave is smaller than the wave following it. We also observe a contraction in the envelope width of the wave group relative to linear theory. The departures from linear theory are strongly correlated with the steepness of the underlying sea state and are generally consistent with theoretical expectations, providing strong evidence that such nonlinear phenomena arise in naturally occurring water waves.
The lower-middle Hetang Formation (Cambrian Stage 2–3) deposited in slope-basinal facies in South China is well known for its preservation of the earliest articulated sponge fossils, providing an important taphonomic window into the Cambrian Explosion. However, the Hetang Formation also hosts a number of problematic animal fossils that have not been systematically described. This omission results in an incomplete picture of the Hetang biota and limits its contribution to the understanding of the early evolution of animals. Here we describe a new animal taxon, Cambrowania ovata Tang and Xiao, new genus new species, from the middle Hetang Formation in the Lantian area of southern Anhui Province, South China. Specimens are preserved as carbonaceous compressions, although some are secondarily mineralized. A comprehensive analysis using reflected light microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and micro-CT reveals that the new species is characterized by a spheroidal to fusoidal truss-like structure consisting of rafter-like crossbars, some of which are secondarily baritized and may have been internally hollow. Some specimens have aperture-like structures that are broadly similar to oscula of sponges, whereas others show evidence of a medial split reminiscent of gaping carapaces. While the phylogenetic affinity of Cambrowania ovata Tang and Xiao, n. gen. n. sp. remains problematic, we propose that it may represent carapaces of bivalved arthropods or more likely sponges in early life stages. Along with other problematic metazoan fossils such as hyolithids and sphenothallids, Cambrowania ovata Tang and Xiao, n. gen. n. sp. adds to the diversity of the sponge-dominated Hetang biota in an early Cambrian deepwater slope-basinal environment.
The problem of homogeneous isotropic turbulence (HIT) is revisited within the analytical framework of the Navier–Stokes equations, with a view to assessing rigorously the consequences of the scale invariance (an exact property of the Navier–Stokes equations) for any Reynolds number. The analytical development, which is independent of the 1941 (K41) and 1962 (K62) theories of Kolmogorov for HIT for infinitely large Reynolds number, is applied to the transport equations for the second- and third-order moments of the longitudinal velocity increment,
. Once the normalised equations and the constraints required for complying with the scale-invariance property of the equations are presented, results derived from these equations and constraints are discussed and compared with measurements. It is found that the fluid viscosity,
, and the mean kinetic energy dissipation rate,
(the overbar denotes spatial and/or temporal averaging), are the only scaling parameters that make the equations scale-invariant. The analysis further leads to expressions for the distributions of the skewness and the flatness factor of
and shows that these distributions must exhibit plateaus (of different magnitudes) in the dissipative and inertial ranges, as the Taylor microscale Reynolds number
increases indefinitely. Also, the skewness and flatness factor of the longitudinal velocity derivative become constant as
increases; this is supported by experimental data. Further, the analysis, backed up by experimental evidence, shows that, beyond the dissipative range, the behaviour of
, 3 and 4 cannot be represented by a power law of the form
when the Reynolds number is finite. It is shown that only when
-thirds law (i.e.
) emerge, which is consistent with the onset of a scaling range.
Sufficient amino acid (AA) transport is essential to ensure the normal physiological function and growth of growing animals. The processes of AA sensing and transport in humans and murine animals, but rarely in goats, have been arousing great interest recently. This study was conducted to investigate the messenger RNA expression patterns of lysophosphatidic acid receptor 5 (LPAR5), guanine nucleotide-binding protein α-transducing 3 (GNAT3) and important partial AA transporters in digestive tracts, metabolic organs and muscles of growing goats. The results showed that these genes were widely expressed in goats, and had different expression patterns. LPAR5, GNAT3, solute carrier (SLC38A2), SLC7A7, SLC7A1 and SLC3A1 were rarely expressed in the rumen, but were highly expressed in the abomasum and intestine which are the main sites of AA absorption. GNAT3, SLC38A1, SLC38A2, SLC6A19, SLC7A7 and SLC7A1 showed comparatively high expression in the pancreas and the vital digestive glands, and the relatively high expression of these nine genes were noted in the tibialis posterior, the active muscle in energy metabolism. The correlation analysis showed that there were certain positive correlation among most genes. The current results indicate that the AA sensing and transport occur extensively in the abomasum and small intestine, metabolic organs and muscle tissues of ruminants, and that related genes have tissue specificity.
Hydrogen is an important intermediate that is produced during carbohydrate fermentation to volatile fatty acid and utilized by methanogens to produce methane in the rumen. Ruminal volatile fatty acid and dissolved methane concentrations are more than 500 times greater than dissolved hydrogen concentration. Therefore, we hypothesized that dissolved hydrogen might have a higher sensitivity in response to dietary changes compared with volatile fatty acid and dissolved methane. Using goats, we investigated the effects of increasing dietary starch content (maize replaced with wheat bran) and supplementing with rhubarb rhizomes and roots on the relationships among dissolved hydrogen, dissolved methane and other fermentation end products. The study was conducted in a replicated 4×4 Latin square with a 2×2 factorial arrangement of four treatments: two starch levels (220 v. 320 g/kg dry matter (DM)), without and with rhubarb supplement (0% v. 2.8% of total mixed ration). Increased dietary starch and rhubarb supplementation did not alter volatile fatty acid concentrations or methane emissions in terms of g/day, g/g DM intake and g/g organic matter digested. However, goats fed the high-starch diet had greater dissolved hydrogen (P=0.005) and relative abundance of Selenomonas ruminantium (P<0.01), and lower (P=0.02) copy number of protozoa than those fed the low-starch diet. Rhubarb increased ruminal dissolved H2 (P=0.03) and total volatile fatty acid concentration (P<0.001), but decreased copies of bacteria (P=0.002). In conclusion, dissolved hydrogen appears to be more sensitive to dietary changes with starch content and rhubarb supplementation, when compared with volatile fatty acid concentrations and methane production.
The gastrointestinal tract (GIT) of animals is capable of sensing various kinds of nutrients via G-protein coupled receptor-mediated signaling transduction pathways, and the process is known as ‘gut nutrient chemosensing’. GPR40, GPR41, GPR43 and GPR119 are chemoreceptors for free fatty acids (FFAs) and lipid derivatives, but they are not well studied in small ruminants. The objective of this study is to determine the expression of GPR40, GPR41, GPR43 and GPR119 along the GIT of kid goats under supplemental feeding (S) v. grazing (G) during early development. In total, 44 kid goats (initial weight 1.35±0.12 kg) were slaughtered for sampling (rumen, abomasum, duodenum, jejunum, ileum, cecum, colon and rectum) between days 0 and 70. The expression of GPR41 and GPR43 were measured at both mRNA and protein levels, whereas GPR40 and GPR119 were assayed at protein level only. The effects of age and feeding system on their expression were variable depending upon GIT segments, chemoreceptors and expression level (mRNA or protein), and sometimes feeding system × age interactions (P<0.05) were observed. Supplemental feeding enhanced expression of GPR40, GPR41 and GPR43 in most segments of the GIT of goats, whereas G enhanced expression of GPR119. GPR41 and GPR43 were mainly expressed in rumen, abomasum and cecum, with different responses to age and feeding system. GPR41 and GPR43 expression in abomasum at mRNA level was greatly (P<0.01) affected by both age and feeding system; whereas their expression in rumen and abomasum at protein level were different, feeding system greatly (P<0.05) affected GPR41 expression, but had no effect (P>0.05) on GPR43 expression; and there were no feeding system×age interactions (P>0.05) on GPR41 and GPR43 protein expression. The expression of GPR41 and GPR43 in rumen and abomasum linearly (P<0.01) increased with increasing age (from days 0 to 70). Meanwhile, age was the main factor affecting GPR40 expression throughout the GIT. These outcomes indicate that age and feeding system are the two factors affecting chemoreceptors for FFAs and lipid derivatives expression in the GIT of kids goats, and S enhanced the expression of chemoreceptors for FFAs, whereas G gave rise to greater expression of chemoreceptors for lipid derivatives. Our results suggest that enhanced expression of chemoreceptors for FFAs might be one of the benefits of early supplemental feeding offered to young ruminants during early development.
Background: A need exists to characterise the long-term cognitive outcomes in patients who recovered from autoimmune encephalitis and to identify the modifiable factors associated with improved outcomes. Methods: We retrospectively analysed data from patients diagnosed with autoimmune encephalitis in our outpatient autoimmune encephalitis clinic over a 5-year period, where the Montreal Cognitive Assessment (MoCA) is routinely administered. Results: In total, 21 patients met the inclusion criteria, of whom 52% had persistent cognitive impairment at their latest follow-up (median delay to testing=20 months, range 13-182). Visuospatial and executive abilities, language, attention, and delayed recall were predominantly affected. Patients with status epilepticus at presentation had lower total MoCA scores at their last follow-up (median total score 21, range 15-29) compared with patients without status epilepticus at presentation (median total score 27.5, range 21-30; r2=0.366, p=0.004). Patients who experienced delays of more than 60 days from symptom onset to initiation of treatment (either immunosuppression or tumour removal) were more likely to have a MoCA score compatible with cognitive impairment at their last follow-up (r2=0.253, p=0.0239; z-score=−2.01, p=0.044). Conclusions: Our study suggests that the MoCA may be used to evaluate cognition in recovering patients with autoimmune encephalitis. Delays to treatment shorter than 60 days and absence of status epilepticus at onset were associated with better performance on the MoCA obtained more than 1 year after symptom onset, and may predict better long-term cognitive outcomes.
We first analytically show, starting with the Navier–Stokes equations, that the value of the derivative flatness is controlled by pressure diffusion of energy, viscous destructive effects and large-scale effects (decay and/or production). The latter two terms tend to zero when the Taylor-microscale Reynolds number
is sufficiently large. We argue that the pressure-diffusion term should also tend to a constant at large
. Available data for the velocity derivative flatness,
, in different turbulent flows are re-examined and interpreted in the light of the finite-Reynolds-number effect. It is found that
can differ from flow to flow at moderate
; for a given flow,
may also depend on the initial conditions. The data for
in various flows, e.g. along the axis in the far field of plane and circular jets, and grid turbulence, show that it approaches a constant, with a value slightly larger than 10, when
is sufficiently large. This behaviour for
is supported, at least qualitatively, by our analytical considerations. The constancy of
violates the refined similarity hypothesis introduced by Kolmogorov (J. Fluid Mech., vol. 13, 1962, pp. 82–85) to account for the intermittency of the energy dissipation rate. It is not, however, inconsistent with Kolmogorov’s original similarity hypothesis (Dokl. Akad. Nauk SSSR, vol. 30, 1941, pp. 299–303), although we contend that the power-law relation
(Kolmogorov 1962), which is widely accepted in the literature, has in reality been almost invariably used to ‘model’ the finite-Reynolds-number effect for the laboratory data and has been strongly influenced by the weighting given to the atmospheric surface layer data. The inclusion of the latter data has misled previous investigations of how
Influenza is a long-standing public health concern, but its transmission remains poorly understood. To have a better knowledge of influenza transmission, we carried out a detailed modelling investigation in a nosocomial influenza outbreak in Hong Kong. We identified three hypothesised transmission modes between index patient and other inpatients based on the long-range airborne and fomite routes. We considered three kinds of healthcare workers’ routine round pathways in 1140 scenarios with various values of important parameters. In each scenario, we used a multi-agent modelling framework to estimate the infection risk for each hypothesis and conducted least-squares fitting to evaluate the hypotheses by comparing the distribution of the infection risk with that of the attack rates. Amongst the hypotheses tested in the 1140 scenarios, the prediction of modes involving the long-range airborne route fit better with the attack rates, and that of the two-route transmission mode had the best fit, with the long-range airborne route contributing about 94% and the fomite route contributing 6% to the infections. Under the assumed conditions, the influenza virus was likely to have spread via a combined long-range airborne and fomite routes, with the former predominant and the latter negligible.
Introduction: Accurate identification of children with a concussion by emergency department (ED) physicians is important to initiate appropriate anticipatory guidance and management. In children meeting international criteria for concussion, we aimed to determine the proportion who were provided this diagnosis by the ED physician and which variables were associated with a physician-diagnosed concussion. We also compared persistent symptoms in concussion cases versus those with alternative diagnoses. Methods: This was a planned secondary analysis of a prospective, multicenter cohort study. Participants were children aged 5 through 17 years and met Zurich/Berlin International Consensus Statement criteria for concussion. The primary outcome was the proportion of study participants who were assigned a diagnosis of concussion by the treating ED physician. Based on available evidence, between 50% and 90% of children meeting international concussion criteria are also diagnosed by an ED physician as having a concussion. Assuming a worst case scenario that 50% of physicians would diagnose concussion, our anticipated study sample size of 2946 would be accompanied by a +2% margin of error at the 95% confidence level for the primary outcome. Results: Among the 2946 eligible children, 2340 [79.4% (95% CI 78.0, 80.8)] were diagnosed with a concussion by an ED physician. Twelve variables were associated with this ED diagnosis, five of which had an odds ratio (OR) > 1.5: older age (13-17 vs 5-7 years, OR=2.9), longer time to presentation (>16 vs. <16 hours, OR=2.1), nausea (OR=1.7), sport mechanism (OR=1.7), and amnesia (OR=1.6). In those with physician-diagnosed concussion versus no concussion, the frequency of persistent symptoms was 62.5% vs. 38.8% (p<0.0001) at one week, 46.3% vs. 25.8% (p<0.0001) at two weeks and 33.0% vs. 23.0% (p<0.0001) at four weeks. Conclusion: Most children meeting international criteria for concussion were provided this diagnosis by the ED physician. There were five variables which increased the odds of this diagnosis by at least 1.5-fold. Relative to international criteria, the more selective assignment of concussion by ED physicians was associated with a greater frequency of persistent concussion symptoms. Nevertheless, many patients with alternative diagnoses exhibited persistent concussive symptoms at all time points. Clinicians should therefore weigh the benefits and risks of strictly applying the Zurich/Berlin international criteria versus individual discretion.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
Li4Ti5O12 (LTO) represents a promising anode material for lithium ion batteries, however, it suffers from limitations associated with poor intrinsic electron conductivity as well as moderate ionic conductivity. Hence, to achieve the goal of creating LTO anodes with improved high-rate performance, we have put forth a number of targeted fundamental strategies. Herein we discuss the roles of controllably tuning (i) morphology, (ii) attachment modalities of carbon, and (iii) ion doping of the LTO material. In addition, we also demonstrated in situ studies of lithiation-driven structural transformations in LTO via a combination of X-ray absorption spectroscopy and ab initio calculations, which have been proven to be powerful tools to probe the negligible volume change and extraordinary stability of LTO upon repeated charge/discharge cycles.
In this paper, a new type of fixed-wing vertical take-off and landing, unmanned aerial vehicle (UAV) has been designed. Thrust-vector direct force control has been introduced in three axes to make UAV exhibit superior manoeuverability in transition flight. Considering the characteristics of UAV's dynamic model, which are non-linear, non-affine, and have redundant input, a two-stage progressive optimal control allocation method is developed, which can optimise position and attitude control in synthetical, and motivate effectors to generates desired force and moments. A task-oriented weight selection scheme is proposed to make objective function suitable for different tasks and flight conditions. In addition, a general constraint strategy is designed to guarantee the feasibility of optimal allocation results, which can largely reduce the onboard computation time. Simulations show that UAV can adjust flight attitude and use control effectors in an optimal way, and demonstrating satisfactory tracking of low-speed high-manoeuver flight paths.
The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.
Honeybee foraging can transfer exogenous genes from genetically modified (GM) oilseed rape (Brassica napus L.) to closely related plants, which not only induces potential ecological risks but also contaminates non-GM seeds or honey products with GM ingredients. These events may lead to international trade disputes. Chinese honeybees (Apis cerana cerana Fabricius) and a herbicide (glufosinate)-resistant GM strain of B. napus (Z7B10) were studied to examine the effects of honeybee short-range foraging on oilseed rape gene flow and honey ingredients. Results showed variable frequencies of gene flow between GM and non-GM oilseed rape cultivars, with the highest frequency under nylon net isolation with artificially stocked honeybees, the lowest frequency under nylon net isolation alone, and an intermediate frequency under natural pollination, suggesting the important role of honeybee foraging in gene flow frequency. Additionally, GM pollen grains were found in honey collected from honeybees foraging on both GM and non-GM oilseed rape cultivars. The phosphinothricin acetyltransferase protein was also detected in both unbroken pollen-containing and pollen-free honey by protein testing strips, suggesting that honeybee foraging on GM oilseed rape could lead to contamination with GM ingredients. Overall, the results provide a direct scientific basis for the ecological risk assessment and safety management of GM oilseed rape.
RNA interference (RNAi) is a very effective technique for studying gene function and may be an efficient method for controlling pests. Trehalose-6-phosphate synthase (TPS), which plays a key role in the synthesis of trehalose and insect development, was cloned in Tribolium castaneum (Herbst) (TcTPS) and the putative functions were studied using RNAi via the injection of double-stranded RNA (dsRNA) corresponding to conserved TPS and trehalose-6-phosphate phosphatase domains. Expression analyses show that TcTPS is expressed higher in the fat body, while quantitative real-time polymerase chain reaction results show that the expression of four trehalase isoforms was significantly suppressed by dsTPS injection. Additionally, the expression of six chitin synthesis-related genes, such as hexokinase 2 and glutamine-fructose-6-phosphate aminotransferase, was suppressed at 48 and 72 h post-dsTPS-1 and dsTPS-2 RNA injection, which were two dsTPS fragments that had been designed for two different locations in TcTPS open reading frame, and that trehalose content and trehalase 1 activity decreased significantly at 72 h post-dsRNA injection. Furthermore, T. castaneum injected with dsTPS-1 and dsTPS-2 RNA displayed significantly lower levels of chitin and could not complete the molting process from larvae to pupae, revealing abnormal molting phenotypes. These results demonstrate that silencing TPS gene leads to molting deformities and high mortality rates via regulation of gene expression in the chitin biosynthetic pathway, and may be a promising approach for pest control in the future.
Based on unstructured hybrid grid and dynamic overlapping grid technique, numerical simulations of Unsteady Reynolds Averaged Navier-Stokes equations were performed and investigation on isolated propeller aerodynamic characteristics and effects of propeller slipstream on turboprops were undertaken. The computational grid consisted of rotational subzone of propeller and stationary major-zone of aircraft, and walls criterion was used in the automatic hole-cutting procedure. Distance weight interpolation and tri-linear interpolation were developed to transfer information between the rotational and stationary subzones. The boundaries of overlapping grids were optimized for fixed axis rotation. The governing equations were solved by dual-time method and Lower Upper-Symmetric Gauss-Seidel method. The method and grid technique were verified by isolated propeller configuration and the computational results were in well agreement with the experimental data. The grid independence was studied to establish the numerical results. Finally, the flow around a turboprop case was simulated and the influence of propeller slipstream was presented by analyzing the surface pressure contours, profile pressure distribution, vorticity contours and profile streamline. It's indicated that the slipstream accelerates and rotates the free stream flow, changing the local angle of attack, enhancing the downwash effects, affecting the pressure distribution on wing and horizontal tail, as well as increasing the drag coefficient, pitching moment coefficient and the slope of lift coefficient.
The effects of high-Z dopant on the laser-driven ablative Richtmyer–Meshkov instability (RMI) are investigated by theoretical analysis and radiation hydrodynamics simulations. It is found that the oscillation amplitude of ablative RMI depends on the ablation velocity, the blow-off plasma velocity and the post-shock sound speed. Owing to enhancing the radiation at the plasma corona and increasing the radiation temperature at the ablation front, the high-Z dopant in plastic target can significantly increase the ablation velocity and the blow-off plasma velocity, leading to an increase in oscillation frequency and a reduction in oscillation amplitude of the ablative RMI. The high-Z dopant in plastic target is beneficial to reduce the seed of ablative Rayleigh–Taylor instability. These results are helpful for the design of direct drive inertial confinement fusion capsules.
The effect of large-scale forcing on the second- and third-order longitudinal velocity structure functions, evaluated at the Taylor microscale
, is assessed in various turbulent flows at small to moderate values of the Taylor microscale Reynolds number
. It is found that the contribution of the large-scale terms to the scale by scale energy budget differs from flow to flow. For a fixed
, this contribution is largest on the centreline of a fully developed channel flow but smallest for stationary forced periodic box turbulence. For decaying-type flows, the contribution lies between the previous two cases. Because of the difference in the large-scale term between flows, the third-order longitudinal velocity structure function at
differs from flow to flow at small to moderate
. The effect on the second-order velocity structure functions appears to be negligible. More importantly, the effect of
on the scaling range exponent of the longitudinal velocity structure function is assessed using measurements of the streamwise velocity fluctuation
in the range 500–1100, on the axis of a plane jet. It is found that the magnitude of the exponent increases as
increases and the rate of increase depends on the order
. The trend of published structure function data on the axes of an axisymmetric jet and a two-dimensional wake confirms this dependence. For a fixed
, the exponent can vary from flow to flow and for a given flow, the larger
is, the closer the exponent is to the value predicted by Kolmogorov (Dokl. Akad. Nauk SSSR, vol. 30, 1941a, pp. 299–303) (hereafter K41). The major conclusion is that the finite Reynolds number effect, which depends on the flow, needs to be properly accounted for before determining whether corrections to K41, arising from the intermittency of the energy dissipation rate, are needed. We further point out that it is imprudent, if not incorrect, to associate the finite Reynolds number effect with a consequence of the modified similarity hypothesis introduced by Kolmogorov (J. Fluid Mech., vol. 13, 1962, pp. 82–85) (K62); we contend that this association has misled the vast majority of post K62 investigations of the consequences of K62.