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Tobacco leaf texture, appreciated by the difference of surface roughness of cured leaves, is studies with light microscopy and scanning electron microscopy (SEM). The leaf texture is obviously determined by the presence or absence of conical cellular protuberances on the adaxial side of the leaf. Considering the anatomic point of view, the leaf thickness, always more important when the leaf texture is open, is the only objective criterion which could be associated to the texture. The ultra-structural study with SEM and transmission electron microscopy (TEM) demonstrates that the expansion capacity of tobacco doesn't rely on cytological factors such as cellular reserves or debris. The expansion capacity could be inversely proportional with the relative importance of the mesophyll comparing to palisade parenchyma. On the studied material, no direct relation between the leaf texture and the expansion capacity has been noticed.

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopatherapy. Preclinical data in the 1‐methyl‐4‐phenyl‐1,2,3,6,‐tetrahydropyridine (MPTP) monkey suggest that alpha‐2 antagonists may reduce dihydroxyphenylalanine (L‐DOPA)‐induced dyskinesia. We assessed, in a pilot randomised placebo‐controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha‐2 antagonist, on motor parkinsonian disability and L‐DOPA‐induced dyskinesia following an acute oral challenge of L‐DOPA in 18 patients with Parkinson's disease. The severity of L‐DOPA‐induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L‐DOPA. These results suggest that blocking alpha‐2 receptors in patients with Parkinson's disease might improve L‐DOPA‐induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long‐term management of dyskinetic patients with Parkinson's disease. © 2001 Movement Disorder Society.

Background. Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD).Methods. Thirty‐nine stable patients on high‐flux dialysis were studied. Their mean age was 63±11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post‐dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months.Results. After 3 months, plasma homocysteine had decreased significantly by ≈23% from 31.1±12.7 to 24.5±9 μmol/l (P=0.0005), while folic acid concentrations had increased from 6.5±2.5 to 14.4±2.5 μg/l (P<0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by ≈2.5% (from 29.0±10.3 to 28.3±8.4 μmol/l, P=0.74), whereas in patients without OVD there was a significant reduction of ≈34% (from 32.7±14.4 to 21.6±8.6 μmol/l, P=0.0008). Plasma homocysteine levels were reduced by >15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P=0.001), and by >30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P=0.001).Conclusions. These results indicate that the homocysteine‐lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.

A single morning dose of dual-release formulation was compared with a slow-release formulation of l-dopa plus benserazide in a randomized, double-blind, cross-over study in 16 fluctuating patients with PD. The mean time to “on” was shorter with the dual-release formulation (43 ± 31 minutes) than with the slow-release formulation (81 ± 39 minutes) (p< 0.001), whereas the mean time to relapse to “off” was similar for both formulations. The dual-release formulation had a significantly shorter time to reach peak concentration (tmax) and greater maximum concentration (Cmax) and area under the plasma concentration time curve (AUC0–5 h) than the slow-release formulation, whereas apparent elimination half-life (t1/2) was similar for both formulations.

In this article, we prove the convergence of a splitting scheme of high order for a reaction-diffusion system of the form $u_t-M\Delta u +F(u)=0$ where $M$ is an $m \times m$ matrix whose spectrum is included in $\{{\mathfrak{R}} z > 0 \}$. This scheme is obtained by applying a Richardson extrapolation to a Strang formula.

Contradictory data are reported in the literature concerning the diffusion kinetics of inorganic phosphates (iPh) between red blood cells and plasma during haemodialysis. Accordingly, we performed mass balance and equilibration studies to analyze the diffusion kinetics of iPh in vivo and in vitro. Mass balance analysis shows that iPh is only cleared from the plasma volume and thus that it practically does not diffuse from red blood cells to plasma during the short time lapse of blood transit through the haemodialyzer. In vitro equilibration studies of blood drawn at the filter outlet show that at room temperature there is a slow, limited, and almost linear net efflux of iPh during the 4 h that follow blood drawing. Our results point out: (1) that the in vivo clearance of iPh should be exclusively determined as plasma clearance, and (2) that for accurate clearance determinations the iPh concentrations should be measured in blood samples centrifuged within at most 1 h after blood drawing. Whole-blood clearance determinations – as well as the in vitro dialyzer data – largely overestimate (>30%) the real in vivo dialyzer performance.

Nek2 is a mammalian cell cycle-regulated serine/threonine kinase that belongs to the family of proteins related to NIMA of Aspergillus nidulans. Functional studies in diverse species have implicated NIMA-related kinases in G(2)/M progression, chromatin condensation and centrosome regulation. To directly address the requirements for vertebrate Nek2 kinases in these cell cycle processes, we have turned to the biochemically-tractable system provided by Xenopus laevis egg extracts. Following isolation of a Xenopus homologue of Nek2, called X-Nek2B, we found that X-Nek2B abundance and activity remained constant through the first mitotic cycle implying a fundamental difference in Nek2 regulation between embryonic and somatic cell cycles. Removal of X-Nek2B from extracts did not disturb either entry into mitosis or the accompanying condensation of chromosomes providing no support for a requirement for Nek2 in these processes at least in embryonic cells. In contrast, X-Nek2B localized to centrosomes of adult Xenopus cells and was rapidly recruited to the basal body of Xenopus sperm following incubation in egg extracts. Recruitment led to phosphorylation of the X-Nek2B kinase. Most importantly, depletion of X-Nek2B from extracts significantly delayed both the assembly of microtubule asters and the recruitment of gamma-tubulin to the basal body. Hence, these studies demonstrate that X-Nek2B is required for efficient assembly of a functional zygotic centrosome and highlight the possibility of multiple roles for vertebrate Nek2 kinases in the centrosome cycle.

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT‐431 is the prodrug of A‐86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa‐responsive Parkinson's disease received five doses of ABT‐431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12‐hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT‐431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT‐431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT‐431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well‐tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease. Ann Neurol 1999;45:736–741

Let ρbe a nonnegative number; denote ⌈1/ρ⌉ as the smallest integer which is larger than 1/ρ. Let k=max(2⌈1/ρ⌉, 4), and let Vbe a positive potential on RNof class Cksuch that for all multi-index αsatisfying |α|⩽kwe have |∂αV(x)|⩽Cα(1+V(x))(1−ρ|α|)+. We prove that‖e−tVe2tΔe−tV−e2t(−V+Δ)‖L(L2)=O(t1+2inf(ρ, 1/2))as tdecreases to zero. Our techniques rely on estimates on commutators. Copyright 1999 Academic Press.

When studying complex cognitive tasks using functional magnetic resonance imaging (fMRI) one often encounters weak signal responses. These weak responses are corrupted by noise and artifacts of various sources. Preprocessing of the raw data before the application of test statistics helps to extract the signal and can vastly improve signal detection. Artifact sources and algorithms to handle them are discussed. In an empirical approach targeted to yield an optimal recovery of the hemodynamic response, we implemented a test bed for baseline correction and noise-filtering methods. A known signal is modulated onto foreground patches obtained from event-related fMRI experiments. Quantitative performance measures are defined to optimize the characteristics of a given filter and to compare their results. Marked improvements in the sensitivity and selectivity are achieved by optimized filtering. Examples using real data underline the usefulness of this preprocessing sequence.

In order to provide sophisticated access methods to the contents of video servers, it is necessary to automatically process and represent each video through a number of visual indexes. We focus on two tasks, namely the hierarchical representation of a video as a sequence of uniform segments (shots), and the characterization of each shot by a vector describing the camera motion parameters. For the first task we use a Bayesian classification approach to detecting scene cuts by analysing motion vectors. Adaptability to different compression qualities is achieved by learning different classification masks. For the second task, the optical flow is processed in order to distinguish between stationary and moving shots. A least-squares fitting procedure determines the pan/tilt/zoom camera parameters within shots that present regular motion. Each shot is then indexed by a vector representing the dominant motion components and the type of motion. In order to maximize processing speed, all techniques directly process and analyse MPEG-1 motion vectors, without the need for video decompression. An overall processing rate of 59 frames/s is achieved on software. The successful classification performance, evaluated on various news video clips for a total of 61 023 frames, attains 97.7% for the shot segmentation, 88.4% for the stationary vs. moving shot classification, and 94.7% for the detailed camera motion characterization.

Photodensitometry is known to provide high spatial resolution and continuous measurement of optical density for the analysis of dental radiographs, whereas digitization allows powerful image manipulations but, when using conventional video cameras, gives less spatial resolution and fewer grey levels. The aim of this study was therefore to develop a technique of high-resolution digital analysis for the measurement of bone density following the same principles as those of photodensitometry and based upon the use of a CCD Scanner Camera which provides up to 4096 grey levels and a spatial resolution of 4096 x 4096 pixels. Twenty-four zones were analysed with both techniques in five serial dental radiographs taken before and after periodontal therapy in eight patients. Statistical comparison of the results obtained by digital analysis and photodensitometry shows that the two techniques have the same accuracy.

The reliability of a paralleling instrument for dental radiographs was retrospectively evaluated in the course of a 6-month clinical study. The angular variation between successive exposures was precisely quantified. Ninety-one percent of the angular variations were below a 1.4 degree threshold, but some paired images were found unsuitable for quantitative analysis. A mathematic procedure to assess the global angular projection error of any similar coupled x-ray cone-film holder device is proposed. This mathematic procedure should be routinely used to check superimposability of serial radiographs before density quantification or subtraction.

Phosphoramidon, an endothelin converting enzyme inhibitor, is synthesized by coupling of a rhamnose derivative with a dichlorophosphate and a suitably protected dipeptide.

This paper addresses the issue of bottom-up recovery of structured 2-D geometric primitives from real, complex images. A novel approach for perceptual grouping is presented, using asynchrony whose fundamental principle is to process some primitives before some others, because they carry more information. The main contribution of this work lies in the reduction of the complexity of the grouping process to a problem linear with respect to the number of image contours. Another advantageous characteristic of the proposed method is that only two parameters need to be specified. The asynchronous perceptual grouping processes a data flow of ordered contour primitives, with a rank in the flow determined according to a measure of saliency. It sequentially attempts to group each contour primitive coming in the data flow with other neighboring ones having arrived earlier. Acceptance or rejection of the current contour depends on the geometrical configuration of its neighborhood in the image; properties tested include proximity, colinearity, curvilinearity, and parallelism. The topology as well as the morphology of the relevant structures emerging throughout the whole image are captured in a rigid graph. Junction and surface characteristics are easily extractable, which can help to choose pertinent primitives for an indexing or a recognition system.

In fMRI studies, Gaussian filtering is usually applied to improve the detection of activated areas. Such lowpass filtering enhances the signal to noise ratio. However, undesirable secondary effects are a bias on the signal shape and a blurring in the spatial domain. Neighboring activated areas may be merged and the high resolution of the fMRI data compromised. In the temporal domain, activation and deactivation slopes are also blurred. We propose an alternative to Gaussian filtering by restoring the signal using a spatiotemporal Markov Random Field which preserves the shape of the transitions. We define some interaction between neighboring voxels which allows us to reduce the noise while preserving the signal characteristics. An energy function is defined as the sum of the interaction potentials and is minimized using a simulated annealing algorithm. The shape of the hemodynamic response is preserved leading to a better characterization of its properties. We demonstrate the use of this approach by applying it to simulated data and to data obtained from a typical fMRI study.

Recently, we reported on the design, synthesis, and structure−activity relationships of a series of spiroimidazolines endowed with α-adrenergic agonist activities. Among the compounds described, (R,S)-spiro(1,3-diazacyclopent-1-ene)-[5,2‘](7‘-methyl-1‘,2‘,3‘,4‘-tetrahydronaphthalene) fumarate (5RS) was chosen for further development as a venotonic agent. The resolution of this compound, as well as the pharmacological characterization of the enantiomers, stereospecific synthesis of eutomer (5S, S 18149), and determination of absolute configuration by single-crystal X-ray diffraction analysis, are described.

The problem of flying with one engine inoperative is a very difficult one for pilots of twin-engined general aviation (GA) aircraft, particularly at take-off and during initial climb. This paper presents an account of some of the effects which occur as a result of an engine failure during take-off and also the details of a proposed automatic control system design to recover the aircraft's heading and to make the aircraft climb to a suitable height at which the pilot can safely resume full control. A number of digital simulation results are presented to illustrate the nature of the problem and the performance which can be obtained from the proposed system.

In this paper, we address the problem of estimating parameters of Markov random fields (MRFs). We consider polynomial energy functions. We show both theoretically and by using simulations that this model represents a wide class of MRFs. We then develop a general scheme for estimating the MRF parameters associated with the gradient of such an energy function. The degree of the polynomial energy function as well as a super-set of the neighborhood of pixels are assumed to be known. This method, based on Euler's lemma, requires a partition of the space of neighborhood configurations. Simulations allow us to give a texture interpretation of the parameters associated with polynomial MRFs. Some results of the estimation method are presented for short, middle, and long range interactions.

It has been suggested that English-speaking children have difficulty labeling pitch because of the multiple connotations of the terms “high” and “low.” In this study, we examined whether the use of single or multiple-meaning labels affects young children's identification of pitch changes. French-speaking children received instruction on the use of the single-meaning terms aigu and grave (which as a pair of opposite terms is only used to label high and low sounds) or the multiple-meaning words haut and bas (which as its English counterparts“high” and “low” are used to label pitch, space, and intensity). Children were asked to describe the instructor's high and low voice, strike a drum whenever they heard a two-octave pitch change in a melody, and label the melody's high and low fragments. Children identified most of the pitch changes of the melody and used the newly learned labels with a high degree of accuracy. Those who were taught the single-meaning terms labeled high and low stimuli more correctly than did those who were taught the multiple-meaning terms.

A pyridine group was linked to the tetrahydronaphthalene moiety of the derivatives described in the preceding paper, to afford new combined thromboxane receptor (TP-receptor) antagonists and synthase inhibitors. The most interesting compound 2finhibits TXA2 synthase with an IC50 value of 0.64 μM and the aggregation of human platelets with an IC50 value of 0.063 μM and shows a long duration of action in different species after oral administration.

New polysubstituted tetrahydronaphthalene derivatives were prepared as thromboxane receptor (TP-receptor) antagonists. Within this series of compounds S 18886has been identified as an orally active, highly potent antagonist with a very long duration of action in different species.

Human milk is the sole and recommended nutrition for the newborn infant and contains one of the largest constituents of diverse oligosaccharides, dubbed human milk oligosaccharides (HMOs). Preclinical and clinical association studies indicate that HMOs have multiple physiological functions largely mediated through the establishment of the gut microbiome. Until recently, HMOs were not available to investigate their role in randomized controlled intervention trials. To our knowledge, this is the first report on the effects of 2 HMOs on establishing microbiota in newborn infants. We provide a detailed description of the microbiota changes observed upon feeding a formula with 2 HMOs in comparison to breastfed reference infants' microbiota. Then, we associate the microbiota to long-term health as assessed by prescribed antibiotic use.

Fosfomycin is gaining renewed interest for treating urinary tract infections. Monitoring fosfomycin resistance is therefore important in order to detect the emergence of novel resistance mechanisms. Here, we used the Rapid Fosfomycin NP test to screen a collection of extended-spectrum-β-lactamase-producing Escherichia coliisolates from Switzerland and found a fosfomycin-resistant isolate in which a novel plasmid-mediated fosfomycin resistance gene, named fosL1, was identified.