bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental toxicity evaluation of berberine in rats and mice
Authors: Jahnke Gloria D. , Price Catherine J. , Marr Melissa C. , Myers Christina B. , George Julia D. 
Published: April 2006

AbstractBACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health‐related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice.METHODS: Berberine chloride dihydrate was administered in the feed to timed‐mated Sprague–Dawley (CD) rats (0, 3625, 7250, or 14,500 ppm; on gestational days [GD] 6–20), and Swiss Albino (CD‐1) mice (0, 3500, 5250, or 7000 ppm; on GD 6–17). Ingested doses were 0, 282, 531, and 1313 mg/kg/day (rats) and 0, 569, 841, and 1155 mg/kg/day (mice).RESULTS:There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1000 mg/kg/day was conducted in both species.CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7250 ppm (531 mg/kg/day) based on the feed study and the developmental toxicity NOAEL was raised to 1000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5–6% with no change in live litter size. The maternal toxicity LOAEL remained at 5250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1000 mg/kg/day BCD based on decreased fetal body weight. Birth Defects Research (Part B) 77:195–206, 2006. Published 2006 Wiley‐Liss, Inc.
Molecular and cellular contractile dysfunction of dystrophic muscle from young mice
Authors: Lowe Dawn A. , Williams Brian O. , Thomas David D. , Grange Robert W. 
Published: April 2006

AbstractThe purpose of this study was to determine whether contractile protein alterations are responsible for force deficits in young dystrophic muscle. Contractility of intact extensor digitorum longus muscles and permeabilized fibers from wild‐type (wt), dystrophin‐deficient (mdx), and dystrophin/utrophin‐deficient (mdx:utrn−/−) mice aged 21 and 35 days was determined. Myosin structural dynamics were assessed by site‐directed spin labeling and electron paramagnetic resonance spectroscopy. The principal finding was that force generation was depressed by ∼20% in mdx muscles, but fiber Ca2+‐activated force and myosin structure were not different from wt animals, suggesting that contractile proteins are not responsible for the force deficits in those muscles. For mdx:utrn−/− mice, muscle and fiber forces were ∼40% lower than wt and the fraction of strong‐binding myosin during contraction was reduced by 13%. These data indicate that contractile protein alterations, in addition to myosin dysfunction, cause force deficit in muscles from young mdx:utrn−/− mice. Elucidating the molecular mechanisms underlying muscle weakness at the onset of disease is important for designing treatment strategies. Muscle Nerve, 2006
Laminar mixing and chaotic mixing in several cavity flows
Authors: Chien W.-L. , Rising H. , Ottino J. M. 
Published: April 2006

The objective of this work is an experimental study of laminar mixing in several kinds of two-dimensional cavity flows by means of material line and blob deformation in a new experimental system consisting of two sets of roller pairs connected by belts. The apparatus can be adjusted to produce a range of aspect ratios (0.067–10), Reynolds numbers (0.1–100), and various kinds of flow fields with one or two moving boundaries. Flow visualization is conducted by marking underneath the free surface of the flow with a tracer solution of low diffusivity and of approximately the same density and viscosity as the flowing fluid. The effects of the initial location of the material blob, relative motion of the two bands, and minor changes in the geometry of the flow region are investigated experimentally.The alternate periodic motion of two bands in a cavity flow is an example of a laminar flow which might lead to chaotic mixing. The governing parameter is the dimensionless frequency of oscillation of the walls f which, under the proper conditions, is able to produce horseshoe functions of various types. The deformation of blobs is central to the understanding of mixing and can be studied to identify horseshoe functions. It is found that the efficiency of mixing depends strongly on the value of f and that there exists an optimal value of f that produces the best mixing in a given time.
On the skewness of sea-surface elevation
Authors: Srokosz M. A. , Longuet-Higgins M. S. 
Published: April 2006

Surface skewness is a statistical measure of the vertical asymmetry of the air-sea interface – exemplified by the sharp crests and rounded troughs of surface gravity waves. Some authors have proposed a constant ratio between surface skewness and the ‘significant slope’ of the waves. Here it is shown theoretically that no such simple relation is to be expected.Wave records are of at least two different types; Eulerian (as made with a fixed probe) or Lagrangian (as with a free-floating buoy). The corresponding statistical properties are examined. At first sight it might appear that the degree of skewness in corresponding records would be different. However it is shown that to lowest order the skewness is invariant; only the apparent mean level is different, at second order.
Numerical simulations of nonlinear axisymmetric flows with a free surface
Authors: Dommermuth Douglas G. , Yue Dick K. P. 
Published: April 2006

A numerical method is developed for nonlinear three-dimensional but axisymmetric free-surface problems using a mixed Eulerian-Lagrangian scheme under the assumption of potential flow. Taking advantage of axisymmetry, Rankine ring sources are used in a Green's theorem boundary-integral formulation to solve the field equation; and the free surface is then updated in time following Lagrangian points. A special treatment of the free surface and body intersection points is generalized to this case which avoids the difficulties associated with the singularity there. To allow for long-time simulations, the nonlinear computational domain is matched to a transient linear wavefield outside. When the matching boundary is placed at a suitable distance (depending on wave amplitude), numerical simulations can, in principle, be continued indefinitely in time. Based on a simple stability argument, a regriding algorithm similar to that of Fink & Soh (1974) for vortex sheets is generalized to free-surface flows, which removes the instabilities experienced by earlier investigators and eliminates the need for artificial smoothing. The resulting scheme is very robust and stable.For illustration, three computational examples are presented: (i) the growth and collapse of a vapour cavity near the free surface; (ii) the heaving of a floating vertical cylinder starting from rest; and (iii) the heaving of an inverted vertical cone. For the cavity problem, there is excellent agreement with available experiments. For the wave-body interaction calculations, we are able to obtain and analyse steady-state (limit-cycle) results for the force and flow field in the vicinity of the body.
An investigation of the growth of turbulence in a uniform-mean-shear flow
Authors: Rohr J. J. , Itsweire E. C. , Helland K. N. , Atta C. W. Van 
Published: April 2006

A uniform-mean-gradient shear flow was produced using a ten-layer closed-loop water channel, providing long enough dimensionless flow development times (τ = (x/Ū) (∂ Ū/∂z)) for the turbulence to grow. The rate of growth of the turbulence compares well with similar measurements in wind-tunnel-generated uniform shear flows for which the mean shears and centreline velocities are larger by an order of magnitude. Preliminary investigations were undertaken to study the growth of the turbulent intensity as functions of the mean shear, centreline velocity, and initial disturbance lengthscales. Initial disturbance lengthscales were varied by using grids of different mesh sizes.Turbulent intensities were found to increase nearly linearly with τ. Differences in grid mesh size produce different offsets in the turbulent intensity level, with a larger grid mesh producing a higher positive offset. This offset persists throughout the growth of the turbulent intensity. These observations provide valuable insight in interpreting previous wind-tunnel measurements, in particular the high-shear experiments of Karnik & Tavoularis (1983). Comparison with the theoretical predictions of Tavoularis (1985) allows for an improved universal characterization of evolving turbulence in a uniform mean shear.
Turbulent structure in low-concentration drag-reducing channel flows
Authors: Luchik T. S. , Tiederman W. G. 
Published: April 2006

A two-component laser-Doppler velocimeter was used to measure simultaneously velocity components parallel and normal to the wall in two fully developed, wellmixed, low-concentration (1-2 p.p.m.) drag-reducing channel flows and one turbulent channel flow of water. The mean velocity profiles, root-mean-square velocity profiles and the distributions of the ūv turbulent correlation confirm that the additives modify the buffer region of the flow. The principal influence of the additives is to damp velocity fluctuations normal to the wall in the buffer region.The structural results show that the average time between bursts increased for the drag-reducing flows. When compared to a water flow at the same wall shear stress, this increase in the timescale was equal to the increase in the average streak spacing. Conditionally averaged velocity signals of y+ = 30 centred on the leading edge of a burst, as well as those centred on the trailing edge, have the same general characteristics in all three flows indicating that the basic structure of the fundamental momentum transport event is the same in these drag-reducing flows. However, it was clearly shown that the lower-threshold Reynolds-stress-producing motions were damped while the higher-threshold motions were not damped. In the buffer region of the drag-reducing flows this yields a larger mean velocity gradient with damped fluctuations normal to the wall and increased fluctuations in the streamwise direction. It is hypothesized that some strong turbulent motions are required to maintain extended polymer molecules, which produce a solution with properties that can damp lower threshold turbulence and thereby reduce viscous drag.
On the stability of laminar boundary-layer flow over a flat plate with a compliant surface
Authors: Sen P. K. , Arora D. S. 
Published: April 2006

The problem has been examined using a kinematic model for wall pliability, wherein a kinematic postulation of the wall boundary conditions is made. A form of the normalized wall-displacement and its phase are used as additional parameters in an extended eigenvalue problem. Using this technique the entire gamut of possibilities regarding stability of flow past (normally) pliable walls can be examined, yet without recourse to any specific material properties for the wall. Rather, the results based on the kinematic model can be used to back-calculate the material properties corresponding to any chosen model for the dynamics of the wall. A sample back calculation is discussed herein for the Benjamin–Landahl wall model, and based on this some predictions are made regarding both stabilization of the flow and physical realizability of modes. It is believed that the kinematic model will prove useful in further understanding of the problem, and in the design of stabilizing coatings.The results show that there are three important ‘mode classes’ (distinct from ‘modes’), namely the Tollmien–Schlichting (TS), resonant (R) and Kelvin–Helmholtz (KH). Whereas the TS and R mode classes broadly agree with modes bearing similar names as found by earlier workers, the present KH mode class is difficult to classify based on earlier work. Moreover, there are also important transitional mode classes in the regions of bifurcations of the regular mode classes.Two important concepts evolve in connection with the TS and R mode classes, namely the existence of ‘stable pockets’ for the former and ‘unstable pockets’ for the latter. It is also confirmed herein that there are conflicting requirements on the damping d to stabilize TS and R modes. Considering these points it has been suggested that TS and R modes be avoided by keeping soft surfaces as compliant coatings. However, this in turn leads to instabilities from one of the transitional mode classes. It is also seen that a soft surface that is also marginally active (i.e. having a small negative value of d) could render even better stabilization.
A population pharmacokinetic model for cefuroxime using cystatin C as a marker of renal function
Authors: Viberg Anders , Lannergård Anders , Larsson Anders , Cars Otto , Karlsson Mats O. , Sandström Marie 
Published: April 2006

AimsSince cefuroxime mainly is excreted by renal filtration, dosing is currently based on serum creatinine (Scr) or creatinine clearance (CLcr). However, it has been suggested that cystatin C (CysC) is superior to Scr as a marker of renal function. The aim of this prospective study was to develop a population model that describes the pharmacokinetics of cefuroxime and to investigate the usefulness of CysC as a covariate of the model parameters.MethodsNinety‐seven patients were studied (CLcr range 6.5–115 ml min−1). Blood samples (n = 407) for the determination of cefuroxime were withdrawn according to a sparse data sampling schedule and analysed by liquid chromatography mass spectrometry. The population analysis was performed in NONMEM.ResultsA two‐compartment model described the data well. The biomarkers Scr, CLcr and CysC were evaluated as covariates on clearance (CL). The model that included CysC generated the best fit. In the final population model CL was a function of CysC and body weight, whereas V1 was only a function of body weight. Final parameter estimates (relative standard errors) were 6.00 (3.2%) l h−1, 11.4 (5.3%) l and 5.11 (11%) l for CL, V1 and V2, respectively.ConclusionsBased on the results of the present study, and because CysC is practical to use in the clinic, it is suggested that individual dosing of cefuroxime may be based on CysC rather than on Scr or CLcr. Furthermore, our final population model may be useful as a tool when designing new dosing schedules for cefuroxime.
Dose‐dependent effect of dobutamine on chemoreflex activity in healthy volunteers
Authors: Pathak Atul , Velez‐Roa Sonia , Xhaët Olivier , Najem Boutaina , Van De Borne Philippe 
Published: April 2006

Aims  β‐adrenergic agonists increase peripheral chemoreceptor sensitivity in humans. We tested the hypothesis that β1‐agonist‐related increase in peripheral chemoreflex sensitivity is selective and dose‐dependent.Methods  Using a double‐blind, placebo‐controlled, randomized, crossover study, we examined the effects of dobutamine (n = 17 healthy subjects) at perfusion rates of 2.5 µg kg−1 min−1 (D2.5) and 7.5 µg kg−1 min−1 (D7.5) on ventilation, haemodynamics and sympathetic nerve activity during normoxia, isocapnic hypoxia, posthypoxic maximal voluntary end‐expiratory apnoea, hyperoxic hypercapnia and cold pressor test (CPT). We analysed the effect of pretreatment with atenolol on dobutamine‐evoked chemosensitivity.Results  Dobutamine dose‐dependently increased ventilation (placebo 6.7 ± 0.5 vs. D2.5 7.8 ± 0.4 vs. D7.5 8.7 ± 0.4 l min−1, P < 0.005) during normoxia, enhanced the ventilatory (placebo 14.4 ± 0.6 vs. D2.5 17.3 ± 0.8 vs. D7.5 22.5 ± 1.9 l min−1, P < 0.0001) and sympathetic (placebo + 215 ± 31 vs. D2.5 + 285 ± 19 vs. D7.5 + 395 ± 50% of baseline, P < 0.03) responses at the fifth minute of isocapnic hypoxia and enhanced the sympathetic response to apnoea performed after hypoxia (increase after 5 min of hypoxia: + 290 ± 43% for placebo vs.+ 360 ± 21% for D2.5 vs. 537 ± 69% for D7.5, P < 0.05). No differences were observed between dobutamine and placebo in the responses to hyperoxic hypercapnia and CPT. Atenolol inhibited the dobutamine‐related hyperventilation and apnoea shortening during normoxia and hypoxia.Conclusion  Dobutamine enhances peripheral chemosensitivity at low infusion rates selectively and in a dose‐dependent manner. There is a β1 adrenoceptor component in dobutamine‐evoked increase in peripheral chemosensititivity; however, a contribution of additional adrenoceptor subtypes cannot be excluded.
Design of a complement mannose-binding lectin pathway-specific activation system applicable at low serum dilutions
Authors: Harboe M , Garred P , Borgen M S , Stahl G L , Roos A , Mollnes T E 
Published: April 2006

SummaryRecently we showed that alternative pathway (AP) amplification was responsible for more than 80% of specific classical pathway-induced terminal pathway activation under physiological conditions. The present study aimed to design a system for specific lectin pathway (LP) activation applicable at low serum dilutions with a fully functional AP. Comparison between activation of normal human serum (NHS), a mannose-binding lectin (MBL) homozygous D/D-deficient serum, and sera deficient in C1q and C2, all diluted 1 : 2, was essential to document optimal conditions for LP specificity. Mannan on the solid phase of enzyme-linked immunosorbent assay (ELISA) plates was used for activation, showing 0·5 µg mannan/well to give optimal conditions because at this concentration a good signal was preserved for C4 and TCC deposition in NHS, whereas the C3 deposition observed in C2-deficient serum at higher mannan concentrations reached nadir at 0·5 µg/well, indicating a lack of direct AP activation under these conditions. Pooled NHS and C1q-deficient serum gave the same degree of C4 and terminal complement complex (TCC) deposition, whereas deposition of these products was not obtained with MBL-deficient serum. Reconstitution with purified MBL, however, restored the depositions. A blocking anti-MBL monoclonal antibody (mAb) completely abolished the complement deposition, in contrast to a non-inhibiting anti-MBL mAb. Activation of C2-deficient serum induced C4 deposition similar to NHS, but negligible deposition of C3 and TCC, confirming the lack of direct activation of AP. Thus, this assay is unique in being LP-specific at low serum dilution and thus particularly suitable to study LP activation mechanisms and the role of AP amplification under physiological conditions.
GH replacement does not increase the risk of recurrence in patients with craniopharyngioma
Authors: Karavitaki Niki , Warner Justin T. , Marland Anne , Shine Brian , Ryan Fiona , Arnold Jayanth , Turner Helen E. , Wass John A. H. 
Published: April 2006

SummaryBackground  A significant number of patients with craniopharyngioma are GH deficient. The safety of GH replacement in these subjects has not been established.Objective  To assess the effect of GH replacement upon recurrence in patients with craniopharyngioma.Patients and methods  All the patients with craniopharyngioma followed‐up at the Departments of Endocrinology or Paediatrics in Oxford and treated or not with GH were studied retrospectively. These were recruited from the databases of the departments consisting of subjects diagnosed between January 1964 and July 2005. The impact of GH replacement upon recurrence was evaluated after adjusting for possible confounding factors.Results  Forty‐one subjects received GH replacement. Nine of them did not have follow‐up imaging during GH therapy and were not included in the statistical analyses. The remaining 32 (22 males/10 females) received GH for a mean period of 6·3 ± 4·6 years (median 5·1, range 0·8–22); 21 started during childhood (13 of them continued after the achievement of final height with an adult dose) and 11 during adult life. The mean duration of their follow‐up (from surgery until last assessment) was 10·8 ± 9·2 years (range 1·9–40). Fifty‐three subjects had not received GH therapy (30 men/23 women). The mean duration of their follow‐up (from surgery until last assessment) was 8·3 ± 8·8 years (range 0·5–36). During the observation period, 4 patients treated with GH and 22 non‐GH treated ones developed tumour recurrence. After adjusting for sex, age at tumour diagnosis and type of tumour therapy (gross total removal, partial removal, surgery + irradiation), GH treatment was not a significant independent predictor of recurrence (P = 0·06; hazard ratio = 0·309). Similar results were obtained when the impact of GH replacement was assessed according to its duration (P = 0·18; hazard ratio = 0·991/month of treatment). None of the nine patients with insufficient imaging data for inclusion in the statistical analyses [5 men/4 women, 3 treated with GH during childhood/6 during adult life, mean duration of GH therapy 2·9 ± 2·4 years (median 1·8, range 0·4–7)] showed clinical features suggestive of recurrence during the period of GH replacement.Conclusion  Based on the data of the craniopharyngiomas database in Oxford, there is no evidence that GH replacement is associated with an increased risk of tumour recurrence.
Helical distribution of the bacterial chemoreceptor via colocalization with the Sec protein translocation machinery
Authors: Shiomi Daisuke , Yoshimoto Masayuki , Homma Michio , Kawagishi Ikuro 
Published: April 2006

SummaryIn Escherichia coli, chemoreceptor clustering at a cell pole seems critical for signal amplification and adaptation. However, little is known about the mechanism of localization itself. Here we examined whether the aspartate chemoreceptor (Tar) is inserted directly into the polar membrane by using its fusion to green fluorescent protein (GFP). After induction of Tar–GFP, fluorescent spots first appeared in lateral membrane regions, and later cell poles became predominantly fluorescent. Unexpectedly, Tar–GFP showed a helical arrangement in lateral regions, which was more apparent when a Tar–GFP derivative with two cysteine residues in the periplasmic domain was cross‐linked to form higher oligomers. Moreover, similar distribution was observed even when the cytoplasmic domain of the double cysteine Tar–GFP mutant was replaced by that of the kinase EnvZ, which does not localize to a pole. Observation of GFP–SecE and a translocation‐defective MalE–GFP mutant, as well as indirect immunofluorescence microscopy on SecG, suggested that the general protein translocation machinery (Sec) itself is arranged into a helical array, with which Tar is transiently associated. The Sec coil appeared distinct from the MreB coil, an actin‐like cytoskeleton. These findings will shed new light on the mechanisms underlying spatial organization of membrane proteins in E. coli.