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Discrimination of the direction of motion on the human hand: a psychophysical study of stimulation parameters.

1. In these experiments we assess the relative importance of the spatial and temporal properties of a moving tactile stimulus in determining the ability of humans to discriminate its direction of motion. Movement along the finger was simulated by applying a series of pulses to adjacent locations on the skin using the tactile array of an OPTACON stimulator. Simulated motion permitted us to vary independently the overall distance moved as well as the spacing, timing, and number of sequential stimuli. Different combinations of spatiotemporal parameters allowed us to further examine the relationship of apparent velocity of motion and sweep duration to behavioral performance. Discrimination accuracy was measured using signal detection techniques to calculate the discrimination parameter d' and PCmax, a bias-free measure of the percent correct identification of the direction of motion. 2. In experiments where the path length was constant, discriminability of the direction of motion increased as the spacing between successive pulses narrowed. Similarly, for a given interpulse spacing, the accuracy of discrimination increased linearly with distance, saturating at perfect performance. These apparent spatial effects on performance actually reflect the total number of stimuli presented to the skin rather than their proximity. Sweeps containing the same number of pulses are equally discriminable regardless of either their spacing or the total distance crossed on the skin. d' values obtained at 1.2-, 2.4-, and 4.8-mm spacings appear indistinguishable when plotted as a function of the total number of pulses in a sweep. 3. Experiments in which both the distance moved and the spacing between pulses was varied randomly confirmed that discrimination accuracy depends on the total number of pulses in a sweep rather than the spatial dimensions of the path traversed. Stimulation of only two points that mark the start and stop locations on the skin appears insufficient to enable subjects to discriminate correctly the direction of motion. Two-point stimulation elicits random performance whether the points lie 1.2 or 4.8 mm apart. Discriminability rises linearly to near-perfect performance when eight or more pulses are delivered sequentially. Extrapolation of the d' and PCmax curves suggests a mean threshold of approximately three points for 75% correct discrimination of the direction of motion across the skin. 4. The relationship of stimulus spacing to discriminability over a fixed path suggests that direction discrimination does not simply involve computation of the location of the start and stop points on the skin or their spatial disparity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Linkage analysis of neointimal hyperplasia and vascular wall transformation after balloon angioplasty.

Neointimal hyperplasia (NIH), a result of vascular injury, is due to the migration and proliferation of smooth muscle cells through the media and internal elastic lamina leading to vascular occlusion. We used a rat model to find the genetic regions controlling NIH after endothelial denudation in two divergent inbred strains of rats. The Brown Norway (BN) and spontaneously hypertensive rat (SHR) strains have a 2.5-fold difference in injury-induced NIH. A population of 301 F2 (SHR x BN) rats underwent a standard vascular injury followed by phenotyping 8 wk after injury to identify quantitative trait loci (QTL) responsible for this strain difference. Interval mapping identified two %NIH QTL on rat chromosomes 3 and 6 [logarithm of odds (LOD) scores 2.5, 2.2] and QTL for other injured vascular wall changes on rat chromosomes 3, 4, and 15 (LOD scores 2.0-4.6). Also, QTL for control vessel media width (MW) and media area (MA) were found on chromosome 6 with LOD scores of 2.3 and 2.5, suggesting that linkage exists between these control vessel parameters and NIH production. These results represent the first genetic analysis for the identification of NIH QTL and QTL associated with the vascular injury response.

Angioplasty, Balloon↗

Atypical enzyme kinetics: their effect on in vitro-in vivo pharmacokinetic predictions and drug interactions.

The most common method for estimating a drug's in vivo clearance from in vitro data has involved using the classical Michaelis-Menten model to describe the observed in vitro data and from this estimate intrinsic clearance. This process assumes that the drug obeys standard enzyme kinetics that can be described by this model. However, the observation of atypical enzyme kinetics, particularly involving cytochrome P450 enzymes, has become relatively common, and occurrences have been reported with virtually all of the cytochrome P450 isoforms. Since predictions of a drug's in vivo clearance are made based on kinetic parameters observed during in vitro experiments (in vitro estimated intrinsic clearance), mis-identification of the drug's kinetic profile can lead to inaccurate predictions of intrinsic clearance. In addition to these potential ramifications of in vitro-in vivo predictions, information is becoming available concerning the in vivo implications of drugs that exhibit atypical kinetic profiles. This review will discuss the various types of atypical kinetic profiles that may be observed during in vitro experiments, hypotheses for why they may occur, examples of how a drug's intrinsic clearance may be mis-estimated when atypical kinetics are incorrectly assessed, and the potential ramifications of these issues for prediction of drug interactions. Furthermore, potential, artifactual causes of atypical kinetic phenomena will be described.

Algorithms↗

[Allele polymorphism of molecular-genetic individualizing systems based on tetranucleotide tandem repeats LPL, vWA and TH01 among the population of Russia].

Until recently, data bases on incidence rates of alleles STR (LPL, vWA and THO1 loci) have not been introduced in Russia. To obtain information on the above rates in Russia, a large scale research of distribution of LPL, vWA and Tho1 loci has been performed among a sample of 442 blood-unrelated persons from 57 regions of the Russian Federation to specify basic assessment characteristics of these loci and to raise efficiency of expert use of identifying systems on their base. Relevant parameters (allele frequencies) are presented for each polymorphic locus as well as basic population characteristics of polymorphism in the studied sample of RF population. These results can be used as key parameters for standard probability estimations in assessing the results of molecular-genetic identification.

Alleles↗

A sequential method for discovering probabilistic motifs in proteins.

OBJECTIVES: This paper proposes a greedy algorithm for learning a mixture of motifs model through likelihood maximization, in order to discover common substrings, known as motifs, from a given collection of related biosequences. METHODS: The approach sequentially adds a new motif component to a mixture model by performing a combined scheme of global and local search for appropriately initializing the component parameters. A hierarchical clustering scheme is also applied initially which leads to the identification of candidate motif models and speeds up the global searching procedure. RESULTS: The performance of the proposed algorithm has been studied in both artificial and real biological datasets. In comparison with the well-known MEME approach, the algorithm is advantageous since it identifies motifs with significant conservation and produces larger protein fingerprints. CONCLUSION: The proposed greedy algorithm constitutes a promising approach for discovering multiple probabilistic motifs in biological sequences. By using an effective incremental mixture modeling strategy, our technique manages to successfully overcome the limitation of the MEME scheme which erases motif occurrences each time a new motif is discovered.

Algorithms↗

[Laboratory methods of examination of porous vascular prostheses].

The author discusses applied methods of investigation of porous vascular prostheses with special attention to physical methods and proposes some heretofore unused criteria for the evaluation of polyester prostheses such as: quantitative determination of oligomers catalist residues, inor ganic fillers and manufacturer's oil and identification of the degree of crystallization and molecular orientation. The evaluation of these parameters in conjunction with the results of physical, mechanical, hematological, toxicologic and preclinical testing may form the basis for further improvement of vascular prostheses.

Biomechanical Phenomena↗

[Dissociated symptoms of the progressive course of brain injury].

Hypotension of the cerebrospinal fluid (CSF) was detected in 18% of 856 patients with brain trauma examined in the study. Three syndromes of dissociated hypotension of the CSF were described: (1) at the level of the Magendie-Luschka openings; (2) at the level of the aqueduct of Sylvius; (3) at the level of the third ventricle. Each level of hypotension of the CSF was attended by a specific clinical syndrome. The parameters of the progressive course of the disease made it possible upon their identification to begin the rehabilitation of patients at the earliest stage which led to a faster compensation. Special attention was given to apitherapy, phytococtails and instillations of special coctails for controlling the dissociation between CSF hypotension and hydrocephaly. The conducted rehabilitation made it possible to significantly reduce the incidence of crises indicative of the decompensation of brain injury.

Acute Disease↗

[Study of the kinetics of anion metabolism in the erythrocytes of patients with various forms of hereditary neuromuscular diseases].

The authors have shown an increase in the rate of the anion transport in erythrocytic membranes in patients with hereditary neuromuscular diseases, as well as in probable heterozygotic carriers of Duchenne's progressive muscular dystrophy. It is suggested that the kinetic parameters of chlorine-bicarbonate exchange be used for the early diagnosis and identification of the heterozygotic carriership of Duchenne's myodystrophy gene.

Adolescent↗

Kinetics of platelets, megakaryocytes and their precursors: what to measure?

A sequential exploration of the kinetics of platelets, megakaryocytes, and their progenitors is devised, wherein abnormalities at one level of differentiation are the subject of further analysis at the preceding level. Platelet kinetics yield estimates of mean platelet life span, fraction of platelet mass in circulation and daily production, making it possible to recognize the disorders of hyperdestruction, hypersequestration, hypoproduction, and hyperproduction. Theoretical considerations and regression analysis of a variety of computer-simulated survival tests show that sufficient information is contained in the first four days of the disappearance curve of population labeled platelets to provide an estimate of mean life span with an error of 9%--15%. Identifying the type of destruction disorder depends on developing tests and parameters which will make it possible to integrate into a coherent model such indices as the rate of senescence, the rates of reversible and irreversible aggregation, and the rates of adhesion to and phagocytosis by the reticuloendothelial system. Foremost among the existing models is the multiple-hit theory, although its validity rests on the unproved assumption that platelets keep a permanent memory of their injuries. Identifying the type of production disorder is the purpose of megakaryocyte kinetics. The daily production of megakaryocytes could be derived from the daily platelet production and the number of platelets released per megakaryocyte; determining megakaryocyte number would also yield the mean megakaryocyte maturation time. All these parameters could be obtained by combining a simple radioiron dilution method with cytochemical identification of megakaryocytes and with advanced, automated morphometric techniques. Abnormalities of megakaryocyte number and size can be further analyzed by studying the kinetics of thrombocytic precursors in tissue culture, i.e., by recording the distribution of precursor doublings and megakaryocyte ploidy histograms. The application of these techniques to cultures of bone marrow suggest that endomitosis may be initiated by any megakaryocyte precursor and that the kinetics of this process influence the number and final ploidy level of megakaryocytes.

Blood Platelets↗

[Characterization of the involvement of respiratory diseases in sheep herds in the Sahelian zone in Senegal].

A study was applied in traditionally raised small ruminants in the Senegal Sahelian zone, in order to define the breeding factors linked to respiratory disorders, and to suggest an efficient prevention scheme. A first analysis, which took into account the season, age, and sex effects, led to a definition of the importance of the disease in sheep using different parameters to characterize the pathology. The between-group variability will allow the identification of the factors linked to the disorder, among which breeding techniques may be of great importance.

Age Factors↗

[Echocardiographic assessment of alcohol consumers in different clinical stages].

In relation to the importance of cardiac damage in alcohol drinkers this study aims to check the modifications of some cardiac sonographic parameters in drinkers examined at different stages of alcohol intoxication. Seventy-seven male subjects (43 +/- 9 years old) were divided into 3 groups in relation to the biohumoral alterations used for the diagnosis of chronic alcoholism (increase of GGT and MGV). EF, interventricular septum hypertrophy, LVEdD and the presence of left ventricular diastolic failure were considered. All these cardiac sonographic parameters "in toto" were first compared with the same parameters of a group of normal subjects and then the differences of these sonographic parameters between the 3 groups of drinkers were evaluated. These data confirm the early onset of cardiac damage and also that the cardiac alterations may occur before the modifications of the biohumoral parameters considered too. The alterations of the cardiac sonographic parameters considered in this study seem to be a good marker for the identification, quantification and staging of cardiac damage. Interventricular septum hypertrophy, EF and EDV (in this sequence) are to be considered usefull for the diagnosis of cardiac damage in alcohol drinkers. However also LVEdD and the presence of left ventricular diastolic failure are to be evaluated before any therapy.

Adult↗

Identifiability study of the proteins degradation model, based on ADM1, using simultaneous batch experiments.

The objective of the present study is to analyse kinetic and stoichiometric parameter values of gelatine anaerobic degradation at thermophilic range, based on an experiment designed to elucidate if volatile fatty acids (VFA) are inhibitors of the hydrolysis process. Results showed that VFA are not inhibiting the hydrolysis process. The ADM1 model adequately expressed the consecutive steps of hydrolysis and acidogenesis, with estimated kinetic values corresponding to a fast acidogenesis and slower hydrolysis. The hydrolysis was found to be the rate limiting step of anaerobic degradation. Estimation of yield coefficients based on the relative initial slopes of VFA profiles obtained in a simple batch experiment produced satisfactory results. From the identification study, it was concluded that it is possible to determine univocally the related kinetic parameter values for protein degradation if the evolution of amino acids is measured in simultaneous batch experiments, with different initial protein and amino acids concentrations.

Algorithms↗

A method for constructing data-based models of spiking neurons using a dynamic linear-static nonlinear cascade.

This paper describes a general nonlinear dynamical model for neural system identification. It describes an algorithm for fitting a simple form of the model to spike train data, and reports on this algorithm's performance in identifying the structure and parameters of simulated neurons. The central element of the model is a Wiener-Bose dynamic nonlinearity that ensures that the model is able to approximate the behaviour of an arbitrary nonlinear dynamical system. Nonlinearities associated with spike generation and transmission are treated by placing the Wiener-Bose system in cascade with pulse frequency modulators and demodulators, and the static nonlinearity at the output of the Wiener-Bose system is decomposed into a rectifier and a multinomial. This simplifies the model without reducing its generality for neuronal system identification. Model elements can be characterised using standard methods of dynamical systems analysis, and the model has a simple form that can be implemented and simulated efficiently. This model bears a structural resemblance to real neurons; it may be regarded as a connectionist "neuron" that has been generalized in a realistic way to enable it to mimic the behaviour of an arbitrary nonlinear system, or conversely as a general nonlinear model that has been constrained to make it easy to fit to spike train data. Tests with simulated data show that the identification algorithm can accurately estimate the structure and parameters of neuron-like nonlinear dynamical systems using data sets containing only a few hundred spikes.

Animals↗

Computer-assisted simulation of conventional roentgenograms from three-dimensional computed tomography (CT) data--an aid in the identification of unknown corpses (FoXSIS).

A computer simulation program (Forensic X-ray Simulation and Identification System, FoXSIS) is presented. FoXSIS calculates conventional X-ray summation images using any scanning parameters from three-dimensional CT data records. All those parameters decisive for X-ray morphology are freely selectable for realistic simulations: focus-object distance, object-film distance, centering of the X-ray beam, the location of the object in the patch of rays, brightness and contrast, as well as parallel and central projection. In addition, distance and angle measurements, as well as enlargements of details are possible. The program may be expected to help in the identification of unknown corpses now, and even more in the future on account of the increased use of clinical computed tomographies.

Forensic Medicine↗

Rapid species identification and biotyping of respiratory isolates of Haemophilus spp.

Three commercially available systems, the 4-h Minitek Enterobacteriaceae III, the Haemophilus Trio-Tube, and the Micro-ID, were evaluated for their capacities to identify and biotype 308 respiratory isolates of Haemophilus spp. When compared with aminolevulinic acid test results, the definitive identification method used in this study, these systems demonstrated no significant differences in their capacities to differentiate Haemophilus influenzae from Haemophilus parainfluenzae. They were in agreement with the standard method of species identification approximately 50% of the time. When sucrose was added to the Minitek and Trio-Tube configurations, the efficiency rate of species identification increased to more than 95%. The Micro-ID could not be modified to incorporate this additional biochemical parameter. The performance of the sucrose-supplemented Minitek and Trio-Tube systems, compared to the combined results of Micro-ID and aminolevulinic acid, produced correlations of 94 and 90%, respectively. Rapid and accurate methodologies are available for combined species identification and biotyping of Haemophilus spp.

Haemophilus↗

Sensitivity analysis for evaluating nonlinear models of lung mechanics.

We present a combined theoretical and numerical procedure for sensitivity analyses of lung mechanics models that are nonlinear in both state variables and parameters. We apply the analyses to a recently proposed nonlinear lung model which incorporates a wide range of potential nonlinear identification conditions including nonlinear viscoelastic tissues, airway inhomogeneities via a parallel airway resistance distribution function, and a nonlinear block-structure paradigm. Additionally, we examine a system identification procedure which fits time- and frequency-domain data simultaneously. Model nonlinearities motivate sensitivity analyses involving numerical approximation of sensitivity coefficients. Examination of the normalized sensitivity coefficients provides direct insight on the relative importance of each model parameter, and hence the respective mechanism. More formal quantification of parameter uniqueness requires approximation of the paired and multidimensional parameter confidence regions. Combined with parameter estimation, we use the sensitivity analyses to justify tissue nonlinearities in modeling of lung mechanics for healthy and airway constricted conditions, and to justify both airway inhomogeneities and tissue nonlinearities during bronchoconstriction. The tools in this paper are general and can be applied to a wide class of nonlinear models.

Airway Resistance↗

Identification and differentiation of Panax species using ELISA, RAPD and eastern blotting.

Immunochemical and genetic methods have been developed in order to distinguish Panax spp. With the aim of establishing immunochemical methods, two hybridomas (3H4 and 5H8), each secreting a monoclonal antibody (MAb) against proteins of Panax ginseng, were prepared by fusing splenocytes immunized with two kinds of ginseng water-soluble fractions and a hypoxanthine-thymidine-aminopterin-sensitive mouse myeloma cell line, P3-X63-Ag8-U1. MAb 3H4 cross-reacted with four Panax spp., whereas the MAb 5H8 cross-reacted with P. ginseng in the enzyme-linked immunosorbent assay (ELISA). ELISA and western blotting methods using a ginseng water-soluble fraction as the solid-phase antigen were developed for the unambiguous authentication of P. ginseng. A combination of random amplified polymorphic DNA (RAPD) and eastern blotting analyses using anti-ginsenoside Rb1 and Rgl monoclonal antibodies was used for the identification of P. notoginseng, P. quinquefolius and P. japonicus. RAPD can be used to differentiate the species of Panax from each other. An important parameter used for differentiating P. notoginseng is the absence of ginsenoside Rc in the extract of P. notoginseng with eastern blotting. The combination of these methods enabled a reliable identification of Panax spp.

Antibodies, Monoclonal↗

Cognitive sequelae of subthalamic nucleus deep brain stimulation in Parkinson's disease: a meta-analysis.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) is an increasingly common treatment for Parkinson's disease. Qualitative reviews have concluded that diminished verbal fluency is common after STN DBS, but that changes in global cognitive abilities, attention, executive functions, and memory are only inconsistently observed and, when present, often nominal or transient. We did a quantitative meta-analysis to improve understanding of the variability and clinical significance of cognitive dysfunction after STN DBS. METHODS: We searched MedLine, PsycLIT, and ISI Web of Science electronic databases for articles published between 1990 and 2006, and extracted information about number of patients, exclusion criteria, confirmation of target by microelectrode recording, verification of electrode placement via radiographic means, stimulation parameters, assessment time points, assessment measures, whether patients were on levodopa or dopaminomimetics, and summary statistics needed for computation of effect sizes. We used the random-effects meta-analytical model to assess continuous outcomes before and after STN DBS. FINDINGS: Of 40 neuropsychological studies identified, 28 cohort studies (including 612 patients) were eligible for inclusion in the meta-analysis. After adjusting for heterogeneity of variance in study effect sizes, the random effects meta-analysis revealed significant, albeit small, declines in executive functions and verbal learning and memory. Moderate declines were only reported in semantic (Cohen's d 0.73) and phonemic verbal fluency (0.51). Changes in verbal fluency were not related to patient age, disease duration, stimulation parameters, or change in dopaminomimetic dose after surgery. INTERPRETATION: STN DBS, in selected patients, seems relatively safe from a cognitive standpoint. However, difficulty in identification of factors underlying changes in verbal fluency draws attention to the need for uniform and detailed reporting of patient selection, demographic, disease, treatment, surgical, stimulation, and clinical outcome parameters.

Chi-Square Distribution↗