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PubMed2004

Nanoscale organization of multiple GPI-anchored proteins in living cell membranes.

Cholesterol and sphingolipid-enriched "rafts" have long been proposed as platforms for the sorting of specific membrane components including glycosyl-phosphatidylinositol-anchored proteins (GPI-APs), however, their existence and physical properties have been controversial. Here, we investigate the size of lipid-dependent organization of GPI-APs in live cells, using homo and hetero-FRET-based experiments, combined with theoretical modeling. These studies reveal an unexpected organization wherein cell surface GPI-APs are present as monomers and a smaller fraction (20%-40%) as nanoscale (<5 nm) cholesterol-sensitive clusters. These clusters are composed of at most four molecules and accommodate diverse GPI-AP species; crosslinking GPI-APs segregates them from preexisting GPI-AP clusters and prevents endocytosis of the crosslinked species via a GPI-AP-selective pinocytic pathway. In conjunction with an analysis of the statistical distribution of the clusters, these observations suggest a mechanism for functional lipid-dependent clustering of GPI-APs.

Animals↗

PubMed2002

Rating dysthymia: an assessment of the construct and content validity of the Cornell Dysthymia Rating Scale.

BACKGROUND: Mason et al. developed the Cornell Dysthymia Rating Scale (CDRS), a 20-item clinician-rated inventory, and hypothesized that it may be superior to the commonly-used Hamilton Depression Rating Scale (HDRS) in assessing the symptoms of dysthymia, a form of chronic depression. The purpose of this study was to compare these instruments in an outpatient sample of dysthymic patients. METHOD: The CDRS and the HDRS and other inventories (including the Hopkins Symptom Check List (SCL)) were administered to 110 patients meeting DSM-IIIR diagnosis of dysthymia. RESULTS: There was a significant correlation between the CDRS and the HDRS at baseline and termination, indicating concurrent validity. Distributional statistics were compared for baseline and termination severity scores, showing that the CDRS has greater severity range scores than the HDRS. Furthermore, results of the DSM-IV Mood Disorders Field Trial suggest that the CDRS has better content validity than the HDRS when it comes to the dysthymic population. LIMITATIONS: The results are limited by the use of a homogeneous sample, the absence of observer ratings of divergent symptoms, and less than excellent validity of self-report divergent symptoms. CONCLUSIONS: Our results support the value of the CDRS in assessing symptoms of dysthymia.

Adolescent↗

PubMed1996

Positional nystagmus in asymptomatic human subjects.

Nystagmus produced by static placement of the head in different orientations is termed positional nystagmus and is known to occur in human subjects who are free of vestibular symptoms. This study provides quantitative data for horizontal positional nystagmus occurrence in 49 normal human subjects, in whom the number of nystagmus beats, the slow-phase velocity of each beat, and distribution statistics were determined. A metric for the possible differentiation of physiologic positional nystagmus from pathologic nystagmus is described.

Diagnosis, Differential↗

PubMed2002

A general methodology for structuring models to predict the long-term migration of radionuclides from catchments.

In the present paper a generic model for predicting the long-term migration of radionuclides and heavy metals from catchments is described. The model subdivides the catchment into a number of homogeneous, infinitesimal sub-catchments and integrates the radionuclide contributions from such sub-catchments to calculate the total flux of contaminant. It relates the radionuclide behaviour to the statistical distribution of the pollutant partition coefficient on the "ensemble" of sub-catchments. The methodology was validated for 90Sr and 137Cs by using data for water contamination in some European rivers. Values of migration parameters for Pu, Tc, I and Cd isotopes were obtained.

Cesium Radioisotopes↗

PubMed2003

Developing environmental quality standards for various pesticides and priority pollutants for French freshwaters.

The French Ministry of the Environment and Water Agencies have derived environmental quality standards following the existing French framework called SEQ-Eau, for 28 pesticides and seven priority substances listed in the Water Framework Directive. Like other existing frameworks, SEQ-Eau relies upon the use of standard toxicity test results and assessment factors. This approach made it possible to derive the desired quality standards, but due to the lack of chronic toxicity data many of the standards are only provisional. In addition, emerging issues such as endocrine disruption should be taken into account in this framework. Depending on the available data, more flexible derivation approaches, such as the statistical distribution of NOECs, are recommended for future versions of SEQ-Eau. A comparison is made using SEQ-Eau and the methodology currently being discussed in Europe to develop environmental quality standards, showing that the European approach is more conservative. Conversely, the proposed approach under the Water Framework Directive does not cover the entire range of required quality classes.

Environment↗

PubMed2002

Margins for translational and rotational uncertainties: a probability-based approach.

PURPOSE: To define margins for systematic rotations and translations, based on known statistical distributions of these deviations. METHODS AND MATERIALS: The confidence interval-based expansion method for translations, known as the "rolling ball algorithm," was extended to include rotations. This new method, which we call the Rotational and Translational Confidence Limit (RTCL) method, is exact for a point with arbitrary rotations and translations or for a finite shape with rotations only. The method was compared with two existing expansion methods: a rolling ball algorithm without rotations, and a convolution (blurring) method which included rotations. On the basis of these methods, planning target volumes (PTVs, expanded clinical target volumes [CTVs]) were constructed for a number of shapes (a sphere, a sphere with an extension, and three prostate cases), and evaluated in several ways by means of a Monte Carlo method. The accuracy of each method was measured by determining the probability of finding the CTV completely inside the PTV (P(CTVinPTV)), using parameters that yield a 90% probability for a sphere-shaped CTV without rotations. Furthermore, with the expansion parameters adjusted to give an equal P(CTVinPTV) for all methods, PTV volumes were compared. RESULTS: With the expansion algorithm parameters chosen to yield P(CTVinPTV) = 90% for a sphere, an average P(CTVinPTV) of 84%, 57%, and 46% was obtained for the other shapes, using the RTCL method, coverage probability, and rolling ball, respectively. With the parameters adjusted to yield an equal P(CTVinPTV) for all methods, the PTV volume was on average 8% larger for the coverage probability method and 15% larger for the rolling ball algorithm compared to the RTCL method. CONCLUSION: The RTCL method provides an accurate way to include the effects of systematic rotations in the margin. Compared to other algorithms, the method is less sensitive to the shape of the CTV, and, given a fixed probability of finding the CTV inside the PTV, a smaller PTV volume can be obtained.

Algorithms↗

PubMed1996

Testing for natural and synthetic anabolic agents in human urine.

This paper describes a comprehensive method for the detection of natural and synthetic anabolic agents, including some veterinary preparations such as trenbolone, zeranol (a non-steroidal agent) and clenbuterol (a beta 2-agonist). For the natural steroids such as testosterone, the precise determination of urinary androgens during routine procedures allowed the description of statistical distribution of relevant parameters of the endogenous steroid profile amongst male athletes. The validity of the results is discussed, taking into account some factors that may cause the degradation of the specimen.

Adolescent↗

PubMed2002

Linear and nonlinear transient evoked otoacoustic emissions in humans exposed to noise.

Transient evoked otoacoustic emissions (TEOAEs) have been analyzed in a population of 134 ears, divided into three classes: (1) nonexposed ears in bilaterally normal hearing subjects, (2) audiometrically normal ears of subjects exposed to noise and affected by unilateral high-frequency (f>3 kHz) hearing loss in the contralateral ear, and (3) the contralateral impaired ears of the exposed subjects. The statistical distributions of global and spectral signal-to-noise ratio (SNR) were analyzed. TEOAEs were recorded both in the linear and nonlinear acquisition mode to evaluate the effectiveness of two standard averaging techniques with respect to their sensitivity to the early effects of noise exposure. Good discrimination between nonexposed and exposed ears was obtained using either the linear or the nonlinear mode. Despite its intrinsically higher SNR, the linear mode is not more sensitive than the nonlinear mode for this purpose because it is not possible to find a window for effectively cancelling the linear artifact while keeping a suitable sensitivity to the short-latency high-frequency aspect of the response. Moreover, with respect to another measurable parameter, the TEOAE latency, good discrimination is obtained only by using the nonlinear mode because, again, the linear artifact masks the high-frequency TEOAE response.

Acoustic Stimulation↗

PubMed2003

Straightforward relative quantitation and age-related human standards of N-acetylaspartate at the centrum semiovale level by CSI (1)H-MRS.

1H-MRS was aimed to monitor metabolite concentrations in homogeneous interaxial slices of cerebral matter at the centrum semiovale level in healthy volunteers. NAA (N-acetylaspartate + N-acetylglutamate), Cr (creatine + phosphocreatine), and Cho (choline + acetylcholine) were evaluated by resonance integrations. Using Cr as an internal standard, NAA/Cr ratio was considered as a relative measure of concentration. CSI sequence explored volunteer's interaxial slices of white and gray matter by means of 8 x 8 matrices of (1)H-NMR spectra. NAA/Cr integral ratios were averaged over the whole spectral matrix to obtain the Index of NAA at Centrum Semiovale (INACS) of each individual. Indexes of the sixty-eight healthy volunteers, divided into three groups by age, showed good intraindividual reproducibility, and were virtually unaffected by small shifts or bendings of the interaxial slice analyzed. The INACSs were used to estimate Age-Sectorial INACS Ranges (ASIR), the intervals that, on the basis of a normal statistical distribution, should comprise 95% of the age-matched healthy population. Individual INACSs, compared to accurately defined ASIRs taken as standards, could early detect subtle, diffuse neuronal or axonal damage within centrum semiovale interaxial slices. Periodic inspection of INACS could also allow monitoring of progressive neuronal or axonal degeneration.

Adult↗

PubMed1996

Magnetic field nonuniformities and NMR of protons diffusing in a porous medium.

Magnetic field inhomogeneity can arise either because of an externally applied field gradient or because of spatial variations in magnetic susceptibility. The latter are most important when the solid matrix includes paramagnetic substances and when the uniform applied field, and, consequently, also the Larmor precession frequency are very large. Both types of field inhomogeneity add extra phase shifts to the precessing spins. These phase shifts vary with time and position in a complex and random fashion as a result of the diffusive motion of the spins. We have studied these effects by performing detailed calculations for the case of a fluid filled porous medium with a periodic microstructure. Special attention was devoted to the question of whether the statistical distribution of the phase shifts encountered in a Hahn spin echo experiment or in a Carr-Purcell-Meiboom-Gill (CPMG) spin-echo train can be approximated as a Gaussian. The mean square phase shift is measured in such experiments as an enhanced relaxation rate of the precessing transverse magnetization. We determine this mean square phase shift for periodic composites from the diffusion eigenstates, which were calculated using a previously developed Fourier expansion method. The enhanced relaxation rate depends on the echo spacing time tau in a way that can be correlated with important length scales of the porous microstructure. Those correlations can be extended also to disordered microstructures, like the ones that are found in natural rocks. We compare these theoretically predicted correlations with CPMG measurements performed on protons in laboratory samples of brine saturated sandstone.

Diffusion↗

PubMed1999

A global learning algorithm for a RBF network.

This article presents a new learning algorithm for the construction and training of a RBF neural network. The algorithm is based on a global mechanism of parameter learning using a maximum likelihood classification approach. The resulting neurons in the RBF network partitions a multidimensional pattern space into a set of maximum-size hyper-ellipsoid subspaces in terms of the statistical distributions of the training samples. An important feature of the algorithm is that the learning process includes both the tasks of discovering a suitable network structure and of determining the connection weights. The entire network and its parameters are thought of evolved gradually in the learning process.

Journal Article↗

PubMed1997

Antiviral activity of derivatized dextrans on HIV-1 infection of primary macrophages and blood lymphocytes.

The present study demonstrates at the molecular level that dextran derivatives carboxymethyl dextran benzylamine (CMDB) and carboxymethyl dextran benzylamine sulfonate (CMDBS), characterized by a statistical distribution of anionic carboxylic groups, hydrophobic benzylamide units, and/or sulfonate moieties, interact with HIV-1 LAI gp120 and V3 consensus clades B domain. Only limited interaction was observed with carboxy-methyl dextran (CMD) or dextran (D) under the same conditions. CMDBS and CMDB (1 microM) strongly inhibited HIV-1 infection of primary macrophages and primary CD4+ lymphocytes by macrophage-tropic and T lymphocyte-tropic strains, respectively, while D or CMD had more limited effects on M-tropic infection of primary macrophages and exert no inhibitory effect on M- or T-tropic infection of primary lymphocytes. CMDBS and CMDB (1 microM) had limited but significant effect on oligomerized soluble recombinant gp120 binding to primary macrophages while they clearly inhibit (> 50%) such binding to primary lymphocytes. In conclusion, the inhibitory effect of CMDB and the CMDBS, is observed for HIV M- and T-tropic strain infections of primary lymphocytes and macrophages which indicates that these compounds interfere with steps of HIV replicative cycle which neither depend on the virus nor on the cell.

Amino Acid Sequence↗

PubMed2002

A pH curve of human resting saliva sampled with a small paper slip and its medical application.

This paper described physiochemical characteristics of the pH curve of saliva that accompanied escape of CO(2) and that was recorded by a previously reported method. Monthly sample of the resting saliva was collected by a small paper slip from five adults (59.9+/-16.5 years old) over 36 months. The pH curves were examined to represent differences in secretion characteristics among individuals. The following results were obtained: (1) Three variables, pH(1), Delta pH(I), and Delta pH(L), that represent a saliva pH curve indicated secretory characteristics of each individual since the intra-individual variance of them was significantly smaller than the inter-individual variance. (2) These values (mean+/-S.D.) obtained from five adults were 7.03+/-0.54, 0.24+/-0.21, and -0.10+/-0.12, and those obtained from 663 young adults (21.7+/-2.4 years old) were 7.14+/-0.44, 0.26+/-0.23, and -0.08+/-0.13. (3) A characteristic about amplitude of the Delta pH(I) of each individual was maintained over 36 months under the healthy condition. Seasonal variation of the three pH variables and their statistical distribution were also investigated.

Journal Article↗

PubMed2001

The effect of powder type, free moisture and deformation behaviour of granules on the kinetics of fluid-bed granulation.

The effects of two types of powder, lactose and corn starch, and of free moisture on the kinetics of fluid-bed granulation have been investigated using population balance modelling. A coalescence kernel that considered the deformation behaviour of the granules was used. The best fit of the experimental data was obtained for both materials by assuming that the granules underwent plastic deformation. The predicted cumulative number fractions were in very good agreement with the experimental data. The effect of free moisture (in the range of 5-10%) was investigated with lactose. The process was independent of the statistical distribution in free moisture within the approximate range 5-10%. The results suggest a local plasticity in fluid-bed spray granulation caused by the deposition of spray droplets onto the granules, with their subsequent absorption into the voids leading to regions of saturated voids.

Lactose↗

PubMed1996

The concept of a random coil. Residual structure in peptides and denatured proteins.

Non-native states of proteins are of increasing interest because of their relevance to issues such as protein folding, translocation and stability. A framework for interpreting the wealth of experimental data for non-native states emerging from rapid advances in experimental techniques involves comparison with a "random coll' state, which possesses no structure except that inherent in the local interactions. We review here the concept of a random coil, from its global to its local properties. In particular, we focus on the description of a random coil in terms of statistical distributions in psi, phi space. We show that such a model, in combination with experimental data, provides insight into the structural properties of polypeptide chains and has significance for understanding protein folding and for molecular design.

Animals↗

PubMed2001

Segmentation of brain 3D MR images using level sets and dense registration.

This paper presents a strategy for the segmentation of brain from volumetric MR images which integrates 3D segmentation and 3D registration processes. The segmentation process is based on the level set formalism. A closed 3D surface propagates towards the desired boundaries through the iterative evolution of a 4D implicit function. In this work, the propagation relies on a robust evolution model including adaptive parameters. These depend on the input data and on statistical distribution models. The main contribution of this paper is the use of an automatic registration method to initialize the surface, as an alternative solution to manual initialization. The registration is achieved through a robust multiresolution and multigrid minimization scheme. This coupling significantly improves the quality of the method, since the segmentation is faster, more reliable and fully automatic. Quantitative and qualitative results on both synthetic and real volumetric brain MR images are presented and discussed.

Algorithms↗

PubMed1985

The population dynamics of competition between parasites.

A number of published studies of competition between parasite species are examined and compared. It is suggested that two general levels of interaction are discernible: these correspond to the two levels of competition recognized by workers studying free-living animals and plants: 'exploitation' and 'interference' competition. The former may be defined as the joint utilization of a host species by two or more parasite species, while the latter occurs when antagonistic mechanisms are utilized by one species either to reduce the survival or fecundity of a second species or to displace it from a preferred site of attachment. Data illustrating both levels of interaction are collated from a survey of the published literature and these suggest that interference competition invariably operates asymmetrically. The data are also used to estimate a number of population parameters which are important in determining the impact of competition at the population level. Theoretical models of host-parasite associations for both classes of competition are used to examine the expected patterns of population dynamics that will be exhibited by simple two-species communities of parasites that utilize the same host population. The analysis suggests that the most important factor allowing competing species of parasites to coexist is the statistical distribution of the parasites within the host population. A joint stable equilibrium should be possible if both species are aggregated in their distribution. The size of the parasite burdens at equilibrium is then determined by other life-history parameters such as pathogenicity, rates of resource utilization and antagonistic ability. Comparison of these theoretical expectations with a variety of sets of empirical data forms the basis for a discussion about the importance of competition in natural parasite populations. The models are used to assess quantitatively the potential for using competing parasite species as biological control agents for pathogens of economic or medical importance. The most important criterion for identifying a successful control agent is an ability to infect a high proportion of the host population. If such a parasite species also exhibits an intermediate level of pathology or an efficient ability to utilize shared common resources, antagonistic interactions between the parasite species contribute only secondarily to the success of the control. Competition in parasites is compared with competition in free-living animals and plants. The comparison suggests further experimental tests which may help to assess the importance of competition in determining the structure of more complex parasite-host communities.

Animals↗

PubMed2002

Crosslinking of 4.5S RNA to the Escherichia coli ribosome in the presence or absence of the protein Ffh.

Radioactively labeled 4.5S RNA containing statistically distributed 4-thiouridine residues in place of normal uridine was prepared by T7 transcription. The ability of this modified 4.5S RNA to form a complex with the protein Ffh was demonstrated by a gel shift assay. The modified 4.5S RNA, with or without Ffh, was added to Escherichia coli ribosomes under various conditions, and crosslinking from the thiouridine residues was induced by irradiation at 350 nm. The crosslinked ribosomal components were analyzed by our standard procedures. Two clearly defined types of crosslinking were observed. The first was a crosslink to 23S rRNA, which was entirely dependent both on the presence of Ffh and a nascent protein chain in the 50S subunit. This crosslink was localized to nt approximately 2828-2837 of the 23S rRNA, from position 84 of the 4.5S molecule. The second type of crosslinking, to the 30S ribosomal subunit, was independent of the presence of Ffh, and was found both with vacant 70S ribosomes or isolated 30S subunits. Here the crosslink was localized to the 3'-terminal region of the 16S rRNA, from positions 29-50 of the 4.5S RNA. Cross-linking to ribosomal protein S1 was also observed. The known crystal structure of the protein Ffh/4.5S RNA fragment complex was extrapolated by computer modeling so as to include the whole 4.5S molecule, and this was docked onto the ribosome using the crosslinking data. The results are discussed in terms of multiple functions and binding sites of the 4.5S RNA.

Base Sequence↗