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Dynamics of cytonuclear disequilibria in finite populations and comparison with a two-locus nuclear system.

We study the behavior of cytonuclear disequilibria in a finite monoecious population due to (1) random drift alone, (2) random drift and mutation, and (3) random drift and migration, using exact results on the RUZ (Random Union of Zygotes) model and diffusion approximations. We also show that the RUG (Random Union of Gametes) model is not suitable for a cytonuclear system. The study is also accompanied by a comparison with a two-locus nuclear system. We show that in a finite population of size N without mutation, the rate of decrease of the cytonuclear allelic disequilibrium is the same as that in the corresponding unlinked two-locus nuclear system. The principal rate of decrease of variance in allelic disequilibrium in a cytonuclear system is slightly faster than that in the corresponding nuclear system. However, the expected value of the variance in cytonuclear disequilibria is larger than that in a two-locus nuclear system for at least the first N generations. With mutation, the expected value of steady state variances of both systems are about the same; however, the normalized variance in linkage disequilibrium sigma 2d of the cytonuclear system is about twice as large as that for the corresponding nuclear system. For the migration process, two sets of steady state solutions are provided, one for the variables before migration and the other for the variables after migration. Diffusion approximations for both the principal rate of decay and steady state solutions in both systems are found to be satisfactory. A more accurate backward diffusion equation for a two-locus nuclear system is provided when the recombination fraction R is large.

Animals↗

Automatic control of external carbon source addition for nitrogen removal in sewage with low C/N ratios.

For cost-effective nitrogen removal from sewage with low C/N ratios, an automatic control system for the addition of external carbon based on oxidation-reduction potential (ORP) data in an anoxic reactor has been developed. In this study, it was carried out with a pilot-scale modified Bardenpho process. This consisted of anoxic1, aerobic1, anoxic2 and aerobic2 stages with an external recycle ratio of 150% (Q/Qinf), and a media packing ratio of 2.4%-2.9% (v/v) in the aerobic reactor. As a result of applying the automatic control system for the minimization of the external carbon source dosage, the dosage was decreased by about 20%. This estimate was based on ORP compared with a stable dosage of 75 mg/L based on the C/NOx-N ratio of the anoxic influent. It was necessary that the ORP set-value be regulated from -120 mV to -80 mV because influent NH4+-N concentration varied from 12 to 15 mg/L due to rainfall. Correspondingly, the demanded dosages were decreased. Drift of the the real-time value in control system was more stable after changing the ORP set-value from -120 mV to -80 mV.

Automation↗

Optical monitoring of bubble size and shape in a pulsating bubble surfactometer.

The pulsating bubble surfactometer (PBS) is often used for in vitro characterization of exogenous lung surfactant replacements and lung surfactant components. However, the commercially available PBS is not able to dynamically track bubble size and shape. The PBS therefore does not account for bubble growth or elliptical bubble shape that frequently occur during device use. More importantly, the oscillatory volume changes of the pulsating bubble are different than those assumed by the software of the commercial unit. This leads to errors in both surface area and surface tension measurements. We have modified a commercial PBS through the addition of an image-acquisition system, allowing real-time determination of bubble size and shape and hence the accurate tracking of surface area and surface tension. Compression-expansion loops obtained with the commercially available PBS software were compared with those provided by the image-analysis system for dipalmitoylphosphatidylcholine, Infasurf, and Tanaka lipids (dipalmitoylphosphatidylcholine-palmitoyloleoylphosphatidyl-glycerol-palmitic acid, 68:22:9) at concentrations of 0.1 and 1.0 mg/ml and at frequencies of 1 and 20 cycles/min. Whereas minimum surface tension as determined by the image-analysis system is similar to that measured by the commercially available software, the maximum surface tension and the shapes of the interfacial area-surface tension loops are quite different. Differences are attributable to bubble drift, nonsinusoidal volume changes, and variable volume excursions seen with the modified system but neglected by the original system. Image analysis reveals that the extent of loop hysteresis is greatly overestimated by the commercial device and that an apparent, rapid increase in surface tension upon film expansion seen in PBS loops is not observed with the image-analysis system. The modified PBS system reveals new dynamic characteristics of lung surfactant preparations that have not previously been reported.

Equipment Design↗

Gaze failure, drifting eye movements, and centripetal nystagmus in cerebellar disease.

Three abnormalities of eye movement in man are described which are indicative of cerebellar system disorder, namely, centripetally beating nystagmus, failure to maintain lateral gaze either in darkness or with eye closure, and slow drifting movements of the eyes in the absence of fixation. Similar eye movement signs follow cerebellectomy in the primate and the cat. These abnormalities of eye movement, together with other signs of cerebellar disease, such as rebound alternating, and gaze paretic nystagmus, are explained by the hypothesis that the cerebellum helps to maintain lateral gaze and that brain stem mechanisms which monitor gaze position generate compensatory biases in the absence of normal cerebellar function.

Adult↗

Mitochondrial DNA variation is an indicator of austronesian influence in Island Melanesia.

Past studies have shown a consistent association of a specific set of mitochondrial DNA 9 base pair (bp) deletion haplotypes with Polynesians and their Austronesian-speaking relatives, and the total lack of the deletion in a short series of New Guinea Highlanders. Utilizing plasma and DNA samples from various old laboratory collections, we have extended population screening for the 9-bp deletion into "Island Melanesia," an area notorious for its extreme population variation. While the 9-bp deletion is present in all Austronesian, and many non-Austronesian-speaking groups, it is absent in the more remote non-Austronesian populations in Bougainville and New Britain. These results are consistent with the hypothesis that this deletion was first introduced to this region about 3,500 years ago with the arrival of Austronesian-speaking peoples from the west, but has not yet diffused through all populations there. The pattern cannot be reconciled with the competing hypothesis of a primarily indigenous Melanesian origin for the ancestors of the Polynesians. Although selection clearly has operated on some other genetic systems in this region, both migration and random genetic drift primarily account for the remarkable degree of biological diversity in these small Southwest Pacific populations.

Anthropology↗

Measurement of phycocyanin fluorescence as an online early warning system for cyanobacteria in reservoir intake water.

Cyanobacterial blooms in drinking water reservoirs may cause a variety of water quality problems, including those of taste and odor, and can compromise the water supply destined for human consumption. In response to this problem an online monitoring tool for analyzing the cyanobacterial concentration in intake water is of practical value. This study demonstrated a positive correlation between phycocyanin fluorescence and cyanobacterial biomass during Microcystis aeruginosa blooms in a lowland drinking water reservoir, using online detection. The highest correlation coefficients were found for a cyanobacterial biomass concentration below 15 mg freshweight/L, indicating that this method can be an effective early warning system. Rapid changes in fluorescence were observed when wind drift moved higher cyanobacterial concentrations into the water intake, indicating that fluorescence could be employed as a quick warning for changed requirements for plant operations.

Biomass↗

Cumulant dynamics of a population under multiplicative selection, mutation, and drift.

We revisit the classical population genetics model of a population evolving under multiplicative selection, mutation, and drift. The number of beneficial alleles in a multilocus system can be considered a trait under exponential selection. Equations of motion are derived for the cumulants of the trait distribution in the diffusion limit and under the assumption of linkage equilibrium. Because of the additive nature of cumulants, this reduces to the problem of determining equations of motion for the expected allele distribution cumulants at each locus. The cumulant equations form an infinite dimensional linear system and in an authored appendix Adam Prügel-Bennett provides a closed form expression for these equations. We derive approximate solutions which are shown to describe the dynamics well for a broad range of parameters. In particular, we introduce two approximate analytical solutions: (1) Perturbation theory is used to solve the dynamics for weak selection and arbitrary mutation rate. The resulting expansion for the system's eigenvalues reduces to the known diffusion theory results for the limiting cases with either mutation or selection absent. (2) For low mutation rates we observe a separation of time-scales between the slowest mode and the rest which allows us to develop an approximate analytical solution for the dominant slow mode. The solution is consistent with the perturbation theory result and provides a good approximation for much stronger selection intensities.

Alleles↗

Temporal and spatial frequency tuning of the flicker motion aftereffect.

The motion aftereffect (MAE) was used to study the temporal and spatial frequency selectivity of the visual system at supra-threshold contrasts. Observers adapted to drifting sine-wave gratings of a range of spatial and temporal frequencies. The magnitude of the MAE induced by the adaptation was measured with counterphasing test gratings of a variety of spatial and temporal frequencies. Independently of the spatial or temporal frequency of the adapting grating, the largest MAE was found with slowly counterphasing test gratings (at approximately 0.125-0.25 Hz). The largest MAEs were also found when the test grating was of similar spatial frequency to that of the adapting grating, even at very low spatial frequencies (0.125 c/deg). These data suggest that MAEs are dominated by a single, low-pass temporal frequency mechanism and by a series of band-pass spatial frequency mechanisms. The band-pass spatial frequency tuning even at low spatial frequencies suggests that the "lowest adaptable channel" concept [Cameron et al. (1992). Vision Research, 32, 561-568] may be an artifact of disadvantaged low spatial frequencies using static test patterns.

Adaptation, Ocular↗

Determination of left ventricular dimensions with ultrasound.

A new ultrasonic measuring system (UM 3) is described. In addition, the construction of simple piezoelectric transducers is outlined. These can be implanted either in the epicardium or in the endocardium of the left ventricle in anesthetized or conscious dogs. The total system has a high accuracy and linearity, and zero drift is small. An automatically controlled floating window excludes most artifacts due to unwanted echoes. Together with a modified delay-time measuring circuit, better recordings of dimensions are obtained. Sources of error due to the technique of implantation or due to electrical disturbances are described. A modified technique of implantation of endocardial transducers is presented.

Animals↗

[Immunopathological mechanisms of human immunodeficiency virus infection].

Human immunodeficiency virus (HIV) infection usually elicits an early, strong and efficient immune response, despite which the virus can persist in the organism by using a complex strategy. It escapes immune surveillance through direct and indirect effects on cells of the immune system; by modifying its biological properties; and by antigenic drift as a result of the immune response selective pressure. The immune response to the virus could also lead to detrimental immunopathological mechanisms. In particular, any immune stimulation may increase the viral load, and specific immunisation may lead to enhancement of infection. However, reports that some "at risk" non HIV-infected individuals present markers of cell-mediated immunity to the virus, and occurrence of "long-term survivors" strongly suggests that the immune response to HIV may sometimes be protective. Understanding the immunological mechanisms involved in this infection is thus essential.

Antibody Formation↗

A split microchannel design and analytical model to compensate for electroosmotic instabilities in micro-separations.

Organic polymers offer many advantages as materials for the construction of microfluidic devices but suffer frequently from the limitation that the electrodynamic flow they support can exhibit considerable instability. This article describes a split-channel microfluidic device that can be used to compensate for changes in electroosmotic flow. The design of the separation system divides an analyte plug after injection between two separation channels of differing length. The two channels are later recombined for single point detection, eliminating the need for a scanning optical detection system. The utility of this simple design lies in the fact that the migration time of any analyte can be referenced to its twin in the parallel separation channel. This eliminates the need for a separate electroosmotic marker and allows mobilities measured in multiple devices to be compared quantitatively. Using a model adopted from the literature, the data from the split channel system can be used to precisely account for the drift that characterizes electrophoretic separations made in a polymer chip. The relative standard deviations of the analyte mobilities measured for replicate runs on multiple devices were reduced from values as high as 20% to ca. 1% RSD. This internal standardization procedure also appears to address other sources of drift in the electroosmotic flow (EOF) supported by the polymer microchannel, eliminating the need for careful monitoring of either the temperature or reservoir pH between separation runs.

Journal Article↗

Assessment of Actin FS and Actin FSL sensitivity to specific clotting factor deficiencies.

We present a two centre study designed to assess the sensitivity of Actin FS and Actin FSL to deficiencies of factor VIII, IX, XI or XII. The study was undertaken at two centres to avoid bias due to the investigations being undertaken on one analyser. Samples from patients with a factor VIII (n = 36, F VIII = < 1.0-50 iu/dl), factor IX (n = 22, F IX = 2-48 iu/dl), factor XI (n = 23, F XI = 5-50 u/dl) or a factor XII (n = 18, F XII = 1-50 u/dl) deficient state were studied. Activated partial thromboplastin times (APTT) were determined using two batches of Actin FS and of Actin FSL; comparison of APTT results between centres was facilitated by the conversion of clotting times to ratios (test divided by geometric mean normal clotting time). APTT ratios were considered to be elevated if greater than two standard deviations above the mean normal. The factor deficient status of each sample was verified by assaying all samples for factors VIII, IX, XI and XII. Clotting factor assays were performed on a Sysmex CA-1000 fitted with research software, which permitted the auto-dilution and testing of three serial dilution of both a reference preparation and each patient's sample. Assay results were calculated using parallel-line Bioassay principles. This procedure allowed for variation in clotting times due to the effect of temporal drift of any of the reagents within the assay system. Actin FS and Actin FSL demonstrate acceptable sensitivity to factor VIII deficiency, however, both reagents failed to detect a large proportion of factor XI (17.4% and 30.4% of samples, respectively) and factor XII (66.7% and 72.2%, respectively) deficiencies. The detection rate with Actin FSL for factor IX deficiency was also poor (36.4% not detected). As factor IX and XI deficiencies are both associated with haemorrhagic disorders, the inability of these reagents to detect such abnormalities gave cause for concern.

Actins↗

On treating the chromosome as the unit of selection.

A simple method is presented for approximating the behavior of a multiple genetic system under the action of selection and linkage. The effects of genetic drift and mutation are left out. It is found that the results are close to those obtained from a computer simulation of the same problem by Franklin and Lewontin (1970). It is possible to describe the system in terms of a correlation length on the chromosome which measures the degree to which the different parts are bound by linkage. There is also a brief discussion about the higher order correlation coefficients as a measure of the interaction effects.

Alleles↗

The maintenance of genetic polymorphism in small island populations: large mammals in the Hebrides.

Conventionally, small populations living on islands are expected to lose genetic variation by drift. Fluctuations in population size, combined with polygynous mating systems, are expected to contribute to the process by increasing sampling effects on genetic variation. However, in individually monitored populations of Red deer on Rum and Soay sheep on St. Kilda, which experience fluctuations in population size, two processes have been identified which mitigate loss of genetic variation. First, in a number of examples, population reductions are associated with selection. Selection may be in favour of heterozygotes, or, as we have documented in several cases, it may fluctuate in direction temporally. Second, in Soay sheep, in which mortality over population crashes is male-biased, ostensibly leading to low effective numbers of males, molecular studies show that there are systematic changes in the reproductive success of young males, and in variance in male success, that broaden genetic representation compared with expectation.

Adenosine Deaminase↗

Optical sensor based on fluorescent quenching and pulsed blue LED excitation for long-term monitoring of dissolved oxygen in NASA space bioreactors.

There is a need to monitor the concentration of dissolved oxygen (DO) present in the culture medium for NASA's space cell biology experiments, as well as in earth-based cell cultures. Continuous measurement of DO concentration in the cell culture medium in perfused bioreactors requires that the oxygen sensor provide adequate sensitivity and low toxicity to the cells, as well as maintain calibration over several weeks. Although there are a number of sensors for dissolved oxygen on the market and under development elsewhere, very few meet these stringent conditions. An in-house optical oxygen sensor (HOXY) based on dynamic fluorescent quenching of Tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) chloride and a pulsed blue LED light source was developed in our laboratory to address these requirements. The sensing element consisted of the fluorescent dye embedded in a silicone matrix and coated onto a glass capillary. Photobleaching was minimized by a pulsed LED light source. The total noise in the sensor output is 2% and the sensor dynamic range is 0 to 200 mm Hg. The resolution of the sensor is 0.1 mm Hg at 50 mm Hg, and 0.25 mm Hg at 130 mm Hg, while the accuracy is 5%. The LED-based oxygen sensor exhibited stable performance and low drift, making it compatible for space-flight bioreactor systems.

Bioreactors↗

Camino intracranial pressure monitor: prospective study of accuracy and complications.

OBJECTIVES: The fibreoptic device is a type of intracranial pressure monitor which seems to offer certain advantages over conventional monitoring systems. This study was undertaken to analyse the accuracy, drift characteristics, and complications of the Camino fibreoptic device. METHODS: One hundred and eight Camino intracranial pressure (ICP) devices, in their three modalities, were implanted during 1997. The most frequent indication for monitoring was severe head injury due to road traffic accidents. RESULTS: Sixty eight probe tips were cultured; 13.2% of the cases had a positive culture without clinical signs of infection, and 2.9% had a positive culture with clinical signs of ventriculitis. The most common isolated pathogen was Staphylococcus epidermidis. All patients were under cephalosporin prophylaxis during monitoring. Haemorrhage rate in patients without coagulation disorders was 2.1% and 15.3% in patients with coagulation abnormalities. Drift characteristics were studied in 56 cases; there was no drifting from the values expected according to the manufacturer's specifications in 34 probes. There was no relation between direction of the drift and duration of placement, nor between drift and time. CONCLUSIONS: Although the complication and drift rates were similar to those reported elsewhere, there was no correlation between the direction of the drift and long term monitoring despite the fact that some published papers refer to overestimation of values with time with this type of device.

Adolescent↗

3-D position measurement for microsurgical evaluation.

A compact system for high-resolution three-dimensional measurement of microsurgical instrument tip position in the laboratory is under development. The system is useful for quantification of tremor, wander, and drift, as well as for other studies characterizing surgeons' motion in microsurgery, and for evaluation of engineered devices for enhancement of microsurgical positioning accuracy. Preliminary results are presented.

Equipment Design↗

Genetic studies in three South American black populations.

Twenty-one genetic systems were investigated in three relatively isolated South American Black populations. Unexpected allele frequencies were found in different systems in all populations, suggesting the occurrence of genetic drift and/or founder effects. The estimates of racial admixture indicate 50% to 79% of Black ancestry, with various degrees of White (18%-28%) and Amerindian (3%-32%) ancestry.

Adolescent↗