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Inter-subject variability of cerebral activations in acquiring a motor skill: a study with positron emission tomography.

Cerebral structures activated during sequential right-hand finger movements were mapped with regional cerebral blood flow (rCBF) measurements by positron emission tomography (PET) in individual subjects. Nine healthy volunteers were examined twice; after initial learning and after practicing the finger movement sequence for more than 1 h. Task-specific activation sites were identified by statistical distributions of maximal activity and region size in rCBF subtraction images. A consistent task-specific activation in all nine subjects was detected in the contralateral sensorimotor cortex at an average movement rate of 3.2 Hz reached after practice. This corresponded to a significant increase of the mean rCBF in the left primary sensorimotor cortex in spatially standardised and averaged PET images. Additional task-specific activation sites detected by individual analysis were found in the lateral and medial premotor, parietal, and cingulate areas, and in subcortical structures including the basal ganglia of both cerebral hemispheres. These activations showed no or little spatial overlap from subject to subject, thus being obscured in the analysis of pooled data. The observed activity patterns were related to movement rate and accuracy in individual subjects. It is suggested that the rCBF changes associated with acquisition of a motor skill in individual humans may correspond to plasticity of sensorimotor representations reported in monkeys.

Adult↗

Relationship between EPSP shape and cross-correlation profile explored by computer simulation for studies on human motoneurons.

We used a computer model (making several simplifying assumptions) to explore the relationship between the characteristics of an excitatory postsynaptic potential (EPSP) and the profile of the change in firing probability that occurred when that EPSP was delivered to a rhythmically discharging neuron. In circumstances applicable to studies on human motoneurons we found that the magnitude of the period of increased firing probability in the cross-correlation (produced by the rising phase of the EPSP) was related to the number of stimuli and to the proportion of the interspike interval that the EPSP was within reach of threshold. The interstimulus interval and the statistical distribution of the motoneuron interspike intervals were of little consequence. For this model the subsequent period of reduced firing probability was proportional to the amplitude of the EPSP and not to the duration of its falling phase.

Afferent Pathways↗

Red blood cell acid phosphatase: ambiguity in phenotype and activity estimations in the proof of the "single allele" states.

A population sample of sick children was analyzed for the phenotypes and enzymatic activity of the erythrocyte acid phosphatase. These data were statistically examined for the reliability with which the enzymatic activity of a given phenotype, supposed to be derived from a single allele in the phosphatase gene locus, may be used as a decisive criterion in distinguishing such an event from the normal states with the fully functioning pair of alleles. Due to the overlapping of the statistical distribution curves of the normal and defective kins os isozymes, dependent on the relation of x and s, ranges of activity are shown where the measured enzymic activity is not conclusive for the judgement on the number of acting alleles, on the chosen probability level. On the same basis a time saving screening system is proposed for the inteded search for the single-allele states of the phosphatase isozymes; some consequences for the paternity tests with the RBC phosphatase are also mentioned.

Acid Phosphatase↗

Ataxia telangiectasia resists gene cloning: an account of parameters determining gene transfer into human recipient cells.

A subclone of an SV40-transformed fibroblast cell line from a patient with Ataxia telangiectasia (AT) with a relatively high rate of DNA uptake was isolated. However, more than 65000 independent genomic transfectants (using wild-type human DNA) did not contain the functional AT gene. This number represents the statistical distribution of an amount of DNA equivalent to more than three times the haploid human genome. The transfectants were screened by an X ray selection protocol that could rescue a single wild-type cell out of a population of 10(6) AT cells. This suggests a reversion frequency for AT of below 10(-8). The DNA uptake into human cells is compared with that into NIH3T3 cells and future possibilities for the isolation of human repair genes are discussed.

Ataxia Telangiectasia↗

A study of the motor unit action potential by means of computer simulation.

In order to study the motor unit action potential a computer stimulation model was developed. It is based on the superposition of single muscle fibre potentials of the fibres belonging to the motor unit. The parameters which characterize each fibre (spatial position, diameter, and a dispersion of arrival time of the potential at the electrode) are chosen from statistical distributions which can be derived from anatomical and physiological data. The electrode type, position and dimensions can be specified. Simulated motor unit action potentials are presented in the time and frequency domain. The stimulation results refer to (1) the influence of the electrode position and dimensions with respect to the motor unit territory, (2) the meaning of this model for the study of pathological phenomena, (3) the variability of some parameters characterizing the motor unit, (4) the selectivity of uni- and bipolar electrodes and finally (5) the influence of the geometrical situation of the motor end-plates within the muscle, on the shape of motor unit action potentials.

Action Potentials↗

Hematological findings among styrene-exposed workers in the reinforced plastics industry.

A cross-sectional survey of hematological parameters was carried out among 221 workers exposed to styrene in the reinforced plastics industry and 104 controls. Styrene exposure was assessed in both groups by monitoring urinary excretion of styrene metabolites (i.e. mandelic and phenylglyoxylic acids) in post-shift urinary samples collected over five consecutive days. Blood tests were performed with the same counter for all subjects. Information on factors liable to affect hematological parameters was collected from personal questionnaires completed by the workers. Urinary excretion of styrene metabolites varied from 15 to 3740 mg/g creatinine. Exposed subjects exhibited significantly lower mean values of neutrophils and mean corpuscular hemoglobin concentration (MCHC) than controls, and significantly higher mean values for monocytes and mean corpuscular volume. A dose-effect relationship was found for MCHC which decreased with urinary metabolite concentrations. These results remained statistically significant for all parameters after adjustment for age, sex, tobacco and alcohol consumption, place of residence (rural or urban) and time of blood sampling (morning or afternoon) with the exception of neutrophils whose relationship with exposure was essentially explained by smoking. These results are suggestive of a direct effect of styrene-exposure--in the range considered--on the statistical distribution of some hematological parameters.

Adult↗

Orgons and biolons in theoretical biology: phenomenological analysis and quantum analogies.

In this paper we define two types of formal biological entities corresponding to biological levels of organization, the biolons and the orgons, the properties of which are phenomenologically analyzed and discussed. We examine then, in a rather speculative manner, how some characteristics of these entities may suggest analogies between properties of biological systems and some special features of quantum systems. These analogies are principally related to the specific roles played by these entities (relatively to matter-energy, for orgons, and to information, for biolons) in a biological system. They are funded on the formal equivalence between the temporal variations associated to the development of the orgons and the biolons, respectively, and the statistical distribution over the available energy levels of the two main types of quantum entities, the fermions and the bosons (the former being associated to the constitution of matter and the latter to the effects of interactions). This formal comparison leads us to put into correspondences the developmental duration in biological systems with the energetic structuration in quantum ones and the related characteristic times of the former with the temperature of the latter. We discuss briefly these correspondences.

Animals↗

A priori lithium dosage regimen using population characteristics of pharmacokinetic parameters.

The important problem of initiation of long-term lithium treatment is tackled by means of the selection of an a priori dosage regimen based on the presumed efficacy of lithium and absence of toxicity. The pharmacokinetics of Li+ ion is represented by a four-compartment open model including the supposed first-order processes for the release of the active compound from the dosage form and its absorption. Experimental protocols for measurements of serum concentrations and of urinary amounts after single and multiple dosing to healthy volunteers were derived with several oral dosage forms. Estimation of the pharmacokinetic parameters for each subject made it possible to validate the model for the various dosage forms. The interindividual variability of these parameters is taken into account by estimating the characteristics of the statistical distribution for the whole population. A dosage regimen is considered optimum when serum concentration profiles at steady state range from the threshold of efficacy (0.8 mmol/liter) to the threshold of toxicity (2.0 mmol/liter). When the number of daily intakes is fixed, the search for the optimum dose for the whole population is effected by minimizing the expected value of the random variable which characterizes the risks of excursion out of the therapeutic range. By this means universal dosages are shown to be unsatisfactory. However, certain dosage regimens individualized with respect to the renal clearance value of lithium and based on two or three daily intakes can give excellent results even when conventional dosage forms are used.

Adolescent↗

An experimental study of the esthetic effect of facial profiles.

In this study good-looking "male" and "female" as well as ugly facial profiles were shaped by 104 lay persons using an especially constructed device according to specific instructions. These profiles were photographed and subsequently evaluated using a series of parameters from soft tissue profile analyses. Although some significant mean value differences were found between the good-looking and ugly profile variants, they were not substantial. In contrast, markedly significant differences were revealed between the variances of all variables. In some instances the variance of the ugly profiles was more than 3 to 4 times higher than that of the good-looking profiles. These findings were convincingly confirmed when statistical distribution of the data was established and compared. This implies that perception of beauty is associated with regularity of facial features and is conveyed by measurement values which are located close to the mean. Ugliness is associated with extreme deviations from the latter in either direction. Apart from the facial proportions, the degree of convexity or concavity of facial profile and their sequence seem to be important for the esthetic effects. "Male" profiles in contrast to "female" profiles exhibited more conspicuous facial features such as pronounced convexity and concavity.

Adolescent↗

[Application of the mechanical oscillator technique for the measurement of blood density and hematocrit (author's transl)].

Density measurements were performed with an accuracy of 0.01 g/l by means of a density meter based on the "mechanical oscillator technique", on human whole blood, on plasma, and on erythrocyte concentrates. A highly significant correlation between blood density and hematocrit was found. If plasma and red cell densities are known, hematocrit can be estimated more precisely than using the centrifugation method. This fact is important if small variations of the hematocrit are to be determined. Such variations can be produced, e.g., by alteration of the transcapillary filtration equilibrium. Furthermore, the statistical distribution of plasma and erythrocyte densities allows to determine the range of variation of blood densities for certain hematocrit values and vice versa.

Blood↗

Tables of critical values for examining compositional non-randomness in proteins and nucleic acids.

A binomially distributed statistic pchi2i is defined which in conjunction with a set of critical tables permits, for peptides or proteins of arbitrary lengths, a well-defined answer to the question: Does the proportion of a particular amino acid iota present in that protein deviate significantly from random expectation? An analogous statistic is defined for nucleic acids. This statistic is simply related to the classical chi-squared test. The classical chi2 and the pchi2i are supplementary in that the former permits one to determine that a non-randomness in amino acid composition exists in a protein, while the latter permits one to localize that non-randomness to particular amino acids. The pchi2i statistic takes into account explicity the compositional fluctuations imposed by the finite length of proteins. The tables are more exact than any hitherto existing, and require no intermediate calculations for their use: from the direct experimental measurement of the number of residues of amino acid iota, one immediately reads from the tables whether the number observed is within random expectation or not. These statistics are used to analyze eight proteins of diverse length, function, and origin in an accompanying paper.

Amino Acids↗

An analysis of protein folding type prediction by seed-propagated sampling and jackknife test.

In the development of methodology for statistical prediction of protein folding types, how to test the predicted results is a crucial problem. In addition to the resubstitution test in which the folding type of each protein from a training set is predicted based on the rules derived from the same set, cross-validation tests are needed. Among them, the single-test-set method seems to be least reliable due to the arbitrariness in selecting the test set. Although the leaving-one-out (or jackknife) test is more objective and hence more reliable, it may cause a severe information loss by leaving a protein in turn out of the training set when its size is not large enough. In order to overcome the above drawback, a seed-propagated sampling approach is proposed that can be used to generate any number of simulated proteins with a desired type based on a given training set database. There is no need to make any predetermined assumption about the statistical distribution function of the amino acid frequencies. Combined with the existing cross-validation methods, the new technique may provide a more objective estimation for various protein-folding-type prediction methods.

Amino Acids↗

Structure of rat tail tendon collagen examined by atomic force microscope.

The Atomic Force Microscope (AFM) was used to inspect collagen fibrils deposited on mica sheets at different fibrillogenesis times. Collagen was obtained from rat tail tendon fibers. Various fibril forms were observed, together with the characteristic periodic intra-fibril structure (D-bands). The fibril thickness, width, D-band periodicity and depth were measured and the statistical distribution of these parameters at 1, 2, 5, 10 and 15 days of in vitro fibril formation time was calculated. The fibrils showed an increasing size with time, but the band interval measure remained stable. The band depth, after an initial increase, exhibited a relative steadiness. The results indicate that AFM offers, at low resolution, images qualitatively similar to those obtained with electron microscopy, but with less manipulation of the sample. A quantitative evaluation of collagen structural features in the nanometer scale is made possible by AFM.

Animals↗

A system to project injury and illness incidence during military operations.

Modeling of medical resource requirements during military operations requires projections of disease and non-battle injury (DNBI) and wounded-in-action (WIA) rates. Historical data were extracted from unit diaries of infantry and support troops deployed during four previous combat engagements. A planning tool (FORECAS) was developed that uses the statistical distributions of DNBI and WIA incidence from previous operations to simulate injury and illness arrival rates under future scenarios. Output of the simulated data reflects the nuances of the empirical data.

Decision Support Systems, Management↗

Concentrations of delta 9-tetrahydrocannabinol, cocaine and 6-monoacetylmorphine in hair of drug abusers.

Hair samples taken from 850 individuals with presumed drug abuse were tested simultaneously for delta 9-tetrahydrocannabinol (THC), cocaine, heroin, the primary heroin metabolite 6-monoacetylmorphine (6-MAM) and morphine. The drugs were extracted with methanol under sonication. Compared to other extraction procedures this solvent extraction technique provides high extraction yields and less experimental effort. The analyses were carried out using gas chromatography-mass spectrometry (GCMS) in selected ion monitoring (SIM) mode. This procedure allows the simultaneous detection of amphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxylamphetamine (MDE). THC was found in 104 (12.2%), cocaine in 230 (27%) and 6-MAM in 141 (16.6%) samples. In addition to 6-MAM, morphine was detected in 87 (10.2%) and heroin in 38 samples (4.5%). The concentrations found were in a range 0.009-16.7 ng/mg for THC, 0.037-129.68 ng/mg for cocaine, 0.028-79.82 ng/mg for 6-MAM, 0.045-53.14 ng/mg for heroin and 0.011-7.800 ng/mg for morphine. The statistical distribution of the drug concentrations compared with the self-reported consumption behaviour of the users may possibly lead to a better understanding of the relationship between drug dosage and corresponding concentrations in hair.

3,4-Methylenedioxyamphetamine↗

[Improvement of transrectal ultrasound. Artificial neural network analysis (ANNA) in detection and staging of prostatic carcinoma].

As a result of the enhanced clinical application of prostate specific antigen (PSA), an increasing number of men are becoming candidates for prostate cancer work-up. A high PSA value over 20 ng/ml is a good indicator of the presence of prostate cancer, but within the range of 4-10 ng/ml, it is rather unreliable. Even more alarming is the fact that prostate cancer has been found in 12-37% of patients with a "normal" PSA value of under 4 ng/ml (Hybritech). While PSA is capable of indicating a statistical risk of prostate cancer in a defined patient population, it is not able to localize cancer within the prostate gland or guide a biopsy needle to a suspicious area. This necessitates an additional effective diagnostic technique that is able to localize or rule out a malignant growth within the prostate. The methods available for the detection of these prostate cancers are digital rectal examination (DRE) and Transrectal ultrasound (TRUS). DRE is not suitable for early detection, as about 70% of the palpable malignancies have already spread beyond the prostate. The classic problem of visual interpretation of TRUS images is that hypoechoic areas suspicious for cancer may be either normal or cancerous histologically. Moreover, about 25% of all cancers have been found to be isoechoic and therefore not distinguishable from normal-appearing areas. None of the current biopsy or imaging techniques are able to cope with this dilemma. Artificial neural networks (ANN) are complex nonlinear computational models, designed much like the neuronal organization of a brain. These networks are able to model complicated biologic relationships without making assumptions based on conventional statistical distributions. Applications in Medicine and Urology have been promising. One example of such an application will be discussed in detail: A new method of Artificial Neural Network Analysis (ANNA) was employed in an attempt to obtain existing subvisual information, other than the gray scale, from conventional TRUS and to improve the accuracy of prostate cancer identification.

Adult↗

The lineage-specific base-pair contents in the stem regions of ribosomal RNAs and their influence on the estimation of evolutionary distances.

The base-pair changes in the stem regions of ribosomal RNAs provide a useful measure for resolving the phylogeny of organisms. In the present study, how the biased base-pair content influences the estimation of evolutionary distances is theoretically investigated. By regarding the biased base-pair content as a result of the difference in selective strength between A:U and G:C base pairs, the evolutionary distance empirically obtained by enumerating base-pair changes is theoretically expressed in terms of selective strength, base-pair change rate, and divergence time. Its application to nuclear-coded large subunit ribosomal RNAs (LSU rRNAs) reveals the followings. LSU rRNAs from most organisms have moderate base-pair contents and the empirical evolutionary distances obtained by the comparison of these LSU rRNAs are approximately proportional to their divergence times. In the comparison of these moderate LSU rRNAs with the GC-rich LSU rRNAs such as those from Mycoplasma, Crenarchaeota, and Giardia, however, the empirically calculated distances are considerably smaller than the true evolutionary distances, while the comparison with AU-rich LSU rRNAs from Microsporidia overestimates their distances. With this result in mind, the relative base-pair change probabilities among three kingdoms are carefully estimated from the statistical distribution of base-pair change ratios enumerated for LSU rRNAs showing almost the same base-pair contents, leading to the result that prokaryotes and eukaryotes first diverged and that archaebacteria and eubacteria diverged on the line of prokaryotes slightly later, by about 0.3 billion years.

Animals↗

Basic aspects of photon transport through matter with respect to track structure formation.

After a short summary of the most important physical aspects of photon interaction with matter and of the main elements of photon transport simulation, some basic features of photon tracks in liquid water are discussed. These include the statistical distribution of the number of photon interactions caused during the complete photon slow-down, the corresponding mean value, the distance distribution of photon interactions, and the spectral distribution of secondary electrons or, which is the same, the spectral distribution of the start energy of secondary electron tracks. The latter distribution can easily be interpreted in terms of the track entity concept of Mozumder and Magee, which, therefore, proves to be the most natural concept of track structure analysis in the case of photon irradiation.

Electrons↗