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The relationship between infantile strabismus and latent nystagmus.

The so-called infantile strabismus syndrome consists, among other signs, of (1) strabismus, (2) a defect of pursuit and optokinetic tracking with particular involvement of temporally directed responses on monocular viewing, (3) latent nystagmus and (4) adduction preference of the fixating eye. The following causal relationship between these three phenomena is suggested. (1) Binocularity in the visual cortex is impaired, either as a primary defect or as a consequence of misalignment of the eyes. (2) The reduced binocularity prevents maturation of signal transmission from the visual cortex to the brainstem such that slip control is evident in poor pursuit and optokinetic responses, particularly to monocular, temporally directed stimuli. (3) The asymmetry of the pursuit and optokinetic systems is also evident in latent nystagmus which reflects a tonic preponderance, directed nasally with reference to the fixating eye. The directional preponderance drives the slow phases of latent nystagmus if the visual input is unbalanced in favour of one eye. Because of the maldeveloped slip control latent nystagmus is not inhibited by visual contours. When both eyes are open the better-functioning nasally directed pursuit and optokinetic control systems of the two eyes complement each other and largely prevent drifting of the eyes. The defect responsible for the abnormal motor control cannot be located between the retina and the visual cortex because perception of motion is only slightly impaired and a nasal-temporal asymmetry of the motion VEP, typically encountered in infantile strabismus, does not correlate quantitatively with the asymmetry of the motor control. Rather, the defect is located between the cortex and the brainstem. (4) Adduction preference of the fixating eye with a compensatory headturn is due to a gaze-evoked component added to the latent component of the nystagmus. The gaze-evoked component is a purposeful reaction that allows dampening of the nystagmus in adduction at the expense of an increase in abduction.

Electrophysiology↗

The deterministic behavior of self-incompatibility alleles.

For a system of n self-incompatibility alleles, neglecting mutation and random drift, it is shown that the completely symmetric equilibrium is locally stable, and any allelic frequency less than q equals 1 + a minus the square root of 1 + a-2, where a equals [2(n minus 1)]- minus 1, will increase. For all n, q greater than (2n)- minus 1, but if n greater than 1, q is approximately equal to (2n)- minus 1.

Alleles↗

Advantages of continuous measurement of cardiac output 24 h a day.

To test the hypothesis that continuous measurement of cardiac output 24 h a day would provide a better day-by-day reproducibility of the daily average cardiac output than acute measurements, we developed a computer-assisted method to monitor cardiac output continuously using an electromagnetic flow transducer. Because the diastolic aortic flow, which is used as a zero-flow reference, can drift significantly with electromagnetic flow probes, automatic tracking of the diastolic flow baseline was considered essential for long-term measurements. To accomplish this, the analog pulsatile flow signal was digitally converted and processed by an IBM PC to correct for signal drift on a beat-per-beat basis. Using this computerized system in 19 chronically instrumented dogs, we compared the values of cardiac output during 5 consecutive control days, measured either for 20 h each day (allowed 4 h for special care) or for 30 min in the morning when the trained dogs were required to lie quietly in their cages. The results show that the coefficient of variation of the five daily averages in cardiac output for each individual dog was three times smaller when cardiac output was measured 20 h each day (2.9 +/- 0.3 vs. 9.7 +/- 1.0%). Whole-day coefficients of variation were also smaller for mean arterial pressure, heart rate, stroke volume, and total peripheral resistance. Because of this greater day-by-day reproducibility, continuous monitoring of cardiac output is likely to be more sensitive to small changes in cardiac output induced by experimental protocols.

Animals↗

Synovectomy of the hand and wrist.

Synovectomy of tendons gives excellent results with rare recurrence. This is because the local environment is altered from a closed space into a decompressed area of healthy fat. The synovium can invade and destroy tendon, cartilage or bone when in a closed space and under pressure. Unfortunately, the environment can not be so altered in a joint. Joint synovectomy, however, is the only procedure available to prolong function of the patient's own joint (and relieve pain) for an "X" amount of time, which depends upon the course of the generalized disease. After two to three years, the result of a synovectomy is dependent upon the course of the general disease activity and not the surgery. It is absolutely necessary that general medical treatment be carried on before, during, and after surgery, as the surgery is only one incident, often dramatic, in total care of the patient. Chemical synovectomy of the hand has been shown to have variable results with only short-term gains being noted. Surgical synovectomy is indicated when synovitis persists in spite of adequate medical management and there is pain and early correctible deformities. Besides removing the synovium, it is necessary to reconstruct the capsular support and correct alignment. Flexor tenosynovitis in the fingers should be treated with decompression of the digital sheath, not incising the pulley system due to the possibility of accentuating the forces causing ulnar drift. Dorsal tenosynovitis in the wrist is treated by tenosynovectomy, synovectomy, resection of the distal ulna, reconstruction of the ulnar side of the wrist and transposition of the dorsal carpal ligament beneath the extensor tendons.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

Modeling slow correcting gaze movements.

Recent experimental results show evidence for the corrective role of postsaccadic drifts. This paper addresses the modeling of these slow correcting gaze movements (SCMs). Classical arguments to explain drifts are presented, both in the head fixed condition (pulse-step mismatch) and in the head free condition (vestibulo-ocular reflex (VOR)). The most significant behavioral and electrophysiological experimental data related to SCMs are then briefly reported, with the conclusion that SCMs have a clear corrective role, incompatible with classical explanations of drifts. Based on these experimental data, existing models of the saccadic system are then compared. A theoretical comparison of the classical Robinson model with an alternative model is proposed. Two possible (slow and fast) pathways involved in the control of SCMs are examined, and simulation results are presented. Finally, the discussion addresses the observed species differences in SCMs. The link between natural SCMs and electrical SC stimulations, and the interactions between saccades, VOR, and SCMs are also discussed.

Animals↗

Genetic consequences of polygyny and social structure in an Indian fruit bat, Cynopterus sphinx. II. Variance in male mating success and effective population size.

Variance in reproductive success is a primary determinant of genetically effective population size (Ne), and thus has important implications for the role of genetic drift in the evolutionary dynamics of animal taxa characterized by polygynous mating systems. Here we report the results of a study designed to test the hypothesis that polygynous mating results in significantly reduced Ne in an age-structured population. This hypothesis was tested in a natural population of a harem-forming fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae), in western India. The influence of the mating system on the ratio of variance Ne to adult census number (N) was assessed using a mathematical model designed for age-structured populations that incorporated demographic and genetic data. Male mating success was assessed by means of direct and indirect paternity analysis using 10-locus microsatellite genotypes of adults and progeny from two consecutive breeding periods (n = 431 individually marked bats). Combined results from both analyses were used to infer the effective number of male parents in each breeding period. The relative proportion of successfully reproducing males and the size distribution of paternal sibships comprising each offspring cohort revealed an extremely high within-season variance in male mating success (up to 9.2 times higher than Poisson expectation). The resultant estimate of Ne/N for the C. sphinx study population was 0.42. As a result of polygynous mating, the predicted rate of drift (1/2Ne per generation) was 17.6% higher than expected from a Poisson distribution of male mating success. However, the estimated Ne/N was well within the 0.25-0.75 range expected for age-structured populations under normal demographic conditions. The life-history schedule of C. sphinx is characterized by a disproportionately short sexual maturation period scaled to adult life span. Consequently, the influence of polygynous mating on Ne/N is mitigated by the extensive overlap of generations. In C. sphinx, turnover of breeding males between seasons ensures a broader sampling of the adult male gamete pool than expected from the variance in mating success within a single breeding period.

Animals↗

A dual-respiration chamber system with automated calibration.

This study characterizes respiration chambers with fully automated calibration. The system consists of two 14-m3 pull-type chambers. Care was taken to provide a friendly environment for the subjects, with the possibility of social contact during the experiment. Gas analysis was automated to correct for analyzer drift and barometric pressure variations and to provide ease of use. Methods used for checking the system's performance are described. The gas-analysis repeatability was within 0.002%. Results of alcohol combustion (50-350 ml/min CO2) show an accuracy of 0.5 +/- 2.0 (SD) % for O2 consumption and -0.3 +/- 1.6% for CO2 production for 2- to 24-h experiments. It is concluded that response time is not the main factor with respect to the smallest practical measurement interval (duration); volume, mixing, gas-analysis accuracy, and levels of O2 consumption and CO2 production are at least equally important. The smallest practical interval was 15-25 min, as also found with most chamber systems described in the literature. We chose to standardize 0.5 h as the minimum measurement interval.

Atmosphere Exposure Chambers↗

Development and evaluation of a new bicycle instrument for measurements of pedal forces and power output in cycling.

Determination of pedal forces is a prerequisite to analyse cycling performance capability from a biomechanical point of view. Comparing existing pedal force measurement systems, there are methodological or practical limitations regarding the requirements of scientific sports performance research and enhancement. Therefore, the aim of this study was to develop and to validate a new bicycle instrument that enables pedal forces as well as power output measurements with a free choice of pedal system. The instrument (Powertec-System) is based on force transducer devices, using the Hall-Effect and being mounted between the crank and the pedal. Validation of the method was evaluated by determining the accuracy, the cross talk effect, the influence of lateral forces, the reproducibility and, finally, a possible drift under static conditions. Dynamic tests were conducted to validate the power output measurement in reference to the SRM-System. The mean error of the present system was -0.87 +/- 4.09 % and -1.86 +/- 6.61 % for, respectively, the tangential and radial direction. Cross talk, lateral force influence, reproducibility and drift mean values were < +/- 7 %, < or = 2.4 %, < 0.8 % and 0.02 N x min (-1), respectively. In dynamic conditions, the power output measurement error could be kept below 2.35 %. In conclusion, this method offers the possibility for both valid pedal forces and power output measurements. Moreover, the instrument allows measurements with every pedal system. This method has an interesting potential for biomechanical analyses in cycling research and performance enhancement.

Bicycling↗

The distribution of human genetic diversity: a comparison of mitochondrial, autosomal, and Y-chromosome data.

We report a comparison of worldwide genetic variation among 255 individuals by using autosomal, mitochondrial, and Y-chromosome polymorphisms. Variation is assessed by use of 30 autosomal restriction-site polymorphisms (RSPs), 60 autosomal short-tandem-repeat polymorphisms (STRPs), 13 Alu-insertion polymorphisms and one LINE-1 element, 611 bp of mitochondrial control-region sequence, and 10 Y-chromosome polymorphisms. Analysis of these data reveals substantial congruity among this diverse array of genetic systems. With the exception of the autosomal RSPs, in which an ascertainment bias exists, all systems show greater gene diversity in Africans than in either Europeans or Asians. Africans also have the largest total number of alleles, as well as the largest number of unique alleles, for most systems. GST values are 11%-18% for the autosomal systems and are two to three times higher for the mtDNA sequence and Y-chromosome RSPs. This difference is expected because of the lower effective population size of mtDNA and Y chromosomes. A lower value is seen for Y-chromosome STRs, reflecting a relative lack of continental population structure, as a result of rapid mutation and genetic drift. Africa has higher GST values than does either Europe or Asia for all systems except the Y-chromosome STRs and Alus. All systems except the Y-chromosome STRs show less variation between populations within continents than between continents. These results are reassuring in their consistency and offer broad support for an African origin of modern human populations.

Africa↗

Nonlinear dynamics of a zonal flow near marginal stability.

The predator-prey model of the coupled spectral dynamics of drift-wave-zonal-flow turbulence is extended to the regime near the instability threshold. The problem reduces to a nonlinear integral equation, which is similar to that for the mode-particle system [H. L. Berk, Phys. Rev. Lett. 76, 1256 (1996)]], but contains two additional terms due to drift-wave self-nonlinearity. The possibility of pulsating solutions of this equation is investigated. The critical parameter for the Hopf bifurcation and the pulsation period are in reasonable agreement with the bursting behavior recently observed in the global gyrokinetic simulations [Z. Lin, Phys. Rev. Lett. 83, 3545 (1999)]].

Journal Article↗

Determination of geometric orientation of adsorbed cinchonidine on Pt and Fe and quiphos on Pt nanoclusters via DRIFTS.

Platinum nanoclusters modified with cinchonidine have been employed as 'quasi-homogeneous' catalysts for the hydrogenation of ethyl pyruvate and have demonstrated exceptional activities while the ee's of these systems are currently inferior to the traditional Pt/Al2O3 heterogeneous system. For the bulk systems it has been shown that the orientation of the modifier on the metal surface is a critical parameter influencing catalytically induced enantioselectivity. It has been speculated that the lower observed ee's for the nanocluster systems are a result of the modifier assuming an orientation unfavorable for inducing enantioselectivity due to the lack of large numbers of planar metal atoms. Using DRIFTS (diffuse reflectance infra-red Fourier transform spectroscopy) analysis of samples together with geometry optimization and IR modelling we have studied the orientation of cinchonidine on Pt and Fe nanoclusters and additionally the man-made ligand quiphos on Pt nanoclusters. It has been determined that cinchonidine can adsorb on Pt and Fe nanoclusters in both 'flat' and 'tilted' modes, while quiphos can be adsorbed on Pt only via the 'pi-bonded' mode. These studies thus provide an insight into modifier orientation on nanocluster surfaces that can be extended to a wide range of potential modifiers and facilitate a better understanding of the origin of enantioselectivity with these 'quasi-homogeneous' catalyst systems.

Journal Article↗

Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein.

The distribution of fitness effects of protein mutations is still unknown. Of particular interest is whether accumulating deleterious mutations interact, and how the resulting epistatic effects shape the protein's fitness landscape. Here we apply a model system in which bacterial fitness correlates with the enzymatic activity of TEM-1 beta-lactamase (antibiotic degradation). Subjecting TEM-1 to random mutational drift and purifying selection (to purge deleterious mutations) produced changes in its fitness landscape indicative of negative epistasis; that is, the combined deleterious effects of mutations were, on average, larger than expected from the multiplication of their individual effects. As observed in computational systems, negative epistasis was tightly associated with higher tolerance to mutations (robustness). Thus, under a low selection pressure, a large fraction of mutations was initially tolerated (high robustness), but as mutations accumulated, their fitness toll increased, resulting in the observed negative epistasis. These findings, supported by FoldX stability computations of the mutational effects, prompt a new model in which the mutational robustness (or neutrality) observed in proteins, and other biological systems, is due primarily to a stability margin, or threshold, that buffers the deleterious physico-chemical effects of mutations on fitness. Threshold robustness is inherently epistatic-once the stability threshold is exhausted, the deleterious effects of mutations become fully pronounced, thereby making proteins far less robust than generally assumed.

Epistasis, Genetic↗

Dual-capillary backscatter interferometry for high-sensitivity nanoliter-volume refractive index detection with density gradient compensation.

A simple, stable, ultrasensitive dual-capillary dual-bicell (DCDB) microinterferometic backscattering detection (MIBD) system was developed. In DCDB MIBD, a He-Ne laser beam passes through a half-wave plate onto the cross section of two capillaries, one for reference and another for sensing analyte. The position of the backscattered fringe from each capillary, which are in proximity or essentially identical thermal environments, was detected with matched bicell photodetectors. The configuration was found to effectively compensate for thermal drift, which is normally the major source of noise in refractive index (RI) detection systems. It is shown that passive environmental compensation leads to greatly enhanced signal in nanoscale refractometry preformed by MIBD. An order of magnitude improvement in detection limits over single channel configurations is possible. Performance reaches the 10(-9) RIU level for like solvents in the presence in extremely large thermally induced RI gradients. At this level of detectability, DCDB MIBD could facilitate nanoliter-volume, femtomole-level universal detection in applications ranging from mu-HPLC and on-chip CE to scanning microcalorimetry.

Journal Article↗

Oculomotor disturbances during visual-vestibular interaction in Wallenberg's lateral medullary syndrome.

Transient and lasting oculomotor disturbances during visual-vestibular interaction are described in 9 patients with Wallenberg's lateral medullary syndrome. In all patients magnetic resonance imaging (MRI) demonstrated a single focal area of pathological signal intensity in the (dorso)-lateral medulla suggesting infarction. In 2 of these 9 patients and in 3 further patients with no medullary signs, the infarction involved the cerebellar territory of the posterior inferior cerebellar artery (PICA). Acutely, all patients with Wallenberg's syndrome (except 1) had saccadic lateropulsion and spontaneous nystagmus in light with the horizontal fast component beating to the contralateral normal side. The velocity of the slow drift to the side of the lesion was dependent on eye position and induced a characteristic asymmetry of the visually and vestibularly elicited slow eye movements. In most patients smooth pursuit, optokinetic nystagmus and visual suppression of the vestibulo-ocular reflex were still impaired when this spontaneous drift was minimal or absent. The oculomotor disturbances in patients with and without cerebellar infarction are compared. The following conclusions are made. (1) The spontaneous drift that is dependent on eye position is mostly created by 'ocular lateropulsion', that is, a tonic bias within the oculomotor system which may have several sources. (2) The abnormalities and asymmetries of oculomotor responses during visual-vestibular stimulation cannot solely be explained by this spontaneous drift and its interaction with otherwise normal eye movements. Instead, structures and pathways are damaged in Wallenberg's syndrome which mediate visual and/or motor signals important for the cerebellar control of visually-guided slow eye movements. (3) Damage to these pathways occurs in the lateral medulla, as the MRI findings show that in most patients the cerebellum is rarely involved, but no definite conclusion can be made as to which of the fibres travelling in the inferior peduncle to the cerebellum may be interrupted.

Adult↗

Testing of nonlinear electrofrictiophoresis in agarose gel.

It was theoretically predicted earlier that if a periodic force without constant component is applied to a particle, then the particle can produce a directed drift in some direction. The effect is named nonlinear electrofrictiophoresis, because it is crucial for its appearance that the friction force depends on the particle's velocity in a nonlinear manner. We test a possibility to observe this effect when a mixture of fragments of DNA (the DNA ladder) moves in the agarose gel. For this purpose, we study the nonlinear characteristics of a DNA ladder movement in the gel. The gels with the ladder were run under various electric field strengths. It was found that the friction coefficient for each DNA fragment in the ladder depends on the migration velocity, suggesting that energy dissipation during migration is a nonlinear function of velocity. This nonlinearity makes the system under consideration suitable for observing nonlinear electrofrictiophoresis. A possible velocity of directed drift under periodic electric drive without constant component was estimated numerically for experimentally observed dependencies. The velocity appeared to be comparable with that of migration under a constant field of moderate strength. A possible mechanism of energy dissipation during movement of DNA through the gel is discussed.

Electrophoresis, Agar Gel↗

Accuracy and repeatability of the Pedar Mobile system in long-term vertical force measurements.

Portable insole pressure systems can be used to measure the vertical force during long-term (hours) measurements to determine the patient's amount of weight bearing during daily activities in the hospital and at home. Especially for long-term measurements, the amount and duration of loading pressure insoles can have a large influence on the accuracy, as previous studies found a time-dependent behavior after a relatively short period (minutes) of constant loading. Therefore, this study assessed the accuracy and repeatability of a portable capacitive insole system (Pedar, Novel(GmbH)) to measure vertical force during long-term loading. Static loading experiments were performed during which the Pedar insoles were loaded with 5 and 10 N/cm2 for 7 h. Dynamic loading experiments were performed with one Pedar insole which was cyclically loaded with 300, 500 and 1000 N during two sessions of 1200 load cycles. The static and dynamic experiments were repeated 3 days later. Accuracy, due to offset drift, decreased in time during the start of the static experiments (percent error: -1.9% to 0.3% at hour 0; 26.3% to 34% at hour 7). The percent error for the dynamic experiments ranged from -16% to -19%, from -3% to -7% and from -8% to approximately 0% when the insole was loaded with 300, 500 and 1000 N, respectively. The amount of drift ranged from 12 to 62 N for the 500 and 1000 N loads, respectively. The mean day-to-day percentage difference for the static and dynamic experiments ranged from -2.3% to 0.5%, and from -2.9% to 3.0%, respectively. The results indicate that drift correction is necessary for accurate assessment of vertical force by the Pedar Mobile system to determine the amount of weight bearing during long-term measurements.

Humans↗

Spike trains in a stochastic Hodgkin-Huxley system.

We consider a standard Hodgkin-Huxley model neuron with a Gaussian white noise input current with drift parameter mu and variance parameter sigma(2). Partial differential equations of second order are obtained for the first two moments of the time taken to spike from (any) initial state, as functions of the initial values. The analytical theory for a 2-component (V,m) approximation is also considered. Let mu(c) (approximately 4.15) be the critical value of mu for firing when noise is absent. Large sample simulation results are obtained for mu mu(c), for many values of sigma between 0 and 25. For the time to spike, the 2-component approximation is accurate for all sigma when mu=10, for sigma>7 when mu=5 and only when sigma>15 when mu=2. When mu >mu(c), most paths show similar behavior and the moments exhibit smoothly changing behavior as sigma increases. Thus there are a different number of regimes depending on the magnitude of mu relative to mu(c): one when mu is small and when mu is large; but three when mu is close to and above mu(c). Both for the Hodgkin-Huxley (HH) system and the 2-component approximation, and regardless of the value of mu, the CV tends to about 1.3 at the largest value (25) of sigma considered. We also discuss in detail the problem of determining the interspike interval and give an accurate method for estimating this random variable by decomposing the interval into stochastic and almost deterministic components.

Action Potentials↗

Applicability of quadratic and threshold models to motion discrimination in the rabbit retina.

Computational and behavioral studies suggest that visual motion discrimination is based on quadratic nonlinearities. This raises the question of whether the behavior of motion sensitive neurons early in the visual system is actually quadratic. Theoretical studies show that mechanisms proposed for retinal directional selectivity do not behave quadratically at high stimulus contrast. However, for low contrast stimuli, models for these mechanisms may be grouped into three categories: purely quadratic, quadratic accompanied by a rectification, and models mediated by a high level threshold. We discriminated between these alternatives by analyzing the extracellular responses of ON-OFF directionally selective ganglion cells of the rabbit retina to drifting periodic gratings. The data show that purely-quadratic or high-threshold systems do not account for the behavior of these cells. However, their behavior is consistent with a rectified-quadratic model.

Animals↗