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PubMed1987

[Population genetics study of hemoglobinopathies in Uzbekistan. II. Population dynamics of hemoglobinopathies].

It was shown that on comparing variability of selective neutral genetic marker systems with that of the beta-thalassemia system for the populations of different hierarchical level, the relative importance of selection and genetic drift could be evaluated. The genetic differentiation of the beta-thalassemia gene frequencies in elementary populations (villages) could be solely explained by genetic drift. On the other hand, the differentiation of district populations (the sizes of the populations being 10(6] for beta-thalassemia gene frequencies could be explained by selection forces. This is supported by the fact that the genetic distances and FST values are only significant for the beta-thalassemia gene and not for the neutral genetic systems, when the district populations are compared.

Genetic Markers↗
PubMed2006

Fed-batch mode in shake flasks by slow-release technique.

Most industrial production processes are performed in fed-batch operational mode. In contrast, the screenings for microbial production strains are run in batch mode which results in completely different physiological conditions than relevant for production conditions. This may lead to wrong selections of strains. Silicone elastomer discs containing glucose crystals were developed to realize fed-batch fermentation in shake flasks. No other device for feeding was required. Glucose was fed in this way to Hansenula polymorpha cultures controlled by diffusion. Two strains of H. polymorpha were investigated in shake flasks: the wild-type strain (DSM 70277) and a recombinant strain pC10-FMD (P(FMD)-GFP). The oxygen transfer rate (OTR) and respiratory quotient (RQ) of the cultures were monitored online in shake flasks with a Respiration Activity Monitoring System (RAMOS). Formation of biomass and green fluorescent protein (GFP), pH-drift and the metabolite dynamics of glucose, ethanol and acetic acid were measured offline. With the slow-release technique overflow metabolism could be reduced leading to an increase of 85% in biomass yield. To date, 23.4 g/L cell dry weight of H. polymorpha could be achieved in shake flask. Biomass yields of 0.38-0.47 were obtained which are in the same magnitude of laboratory scale fermentors equipped with a substrate feed pump. GFP yield could be increased by a factor of 35 in Syn6-MES mineral medium. In fed-batch mode 88 mg/L GFP was synthesized with 35.9 g/L fed glucose. In contrast, only 2.5 mg/L with 40 g/L metabolized glucose was revealed in batch mode. In YNB mineral medium over 420-fold improvement in fed-batch mode was achieved with 421 mg/L GFP at 41.3 g/L fed glucose in comparison to less than 1 mg/L in batch mode with 40 g/L glucose.

Biomass↗
PubMed2003

Embryological origins of developmental stability: size, shape and fluctuating asymmetry in prenatal random bred mice.

Ontogenetic patterns of fluctuating asymmetry (FA) can be used to test models for the mechanisms underlying stability during embryonic development (developmental stability). In this study, we ask whether developmental processes initially show high levels of instability that are subsequently dampened through active compensatory mechanisms or passive properties of developmental systems or whether the effects of instability accumulate during embryonic development causing random drift away from an earlier stable state. Previous work on this question has dealt with postnatal skeletal growth and thus been unable to effectively distinguish developmental instability from the effects of mechanically mediated variation in bone modeling and remodeling. Here, we report that FA variances of limb skeletal elements in CD1 mice decrease with gestational age from day 14 to birth (day 20.5). Thus, in mouse limbs, skeletal development is characterized by a high level of developmental instability initially that is reduced during subsequent prenatal development. These results are consistent with the existence of active mechanisms that compensate for the effects of minor perturbations or deviations during development. However, they are also consistent with Soule's model of allomeric variation in which the variance of structures is reduced as the number of independent developmental events that produce them increases. This study illustrates that predictions based on morphometric analyses can yield insights into general properties of developmental systems in cases where specific developmental mechanisms are not yet known.

Animals↗
PubMed1994

Inbreeding: one word, several meanings, much confusion.

Because conservation biologists must frequently deal with small populations, inbreeding (a frequent consequence of small population size) has played a central role in many genetic management programs. However, the word "inbreeding" has several, often contradictory meanings, and a failure to distinguish among these meanings has caused much misunderstanding on the role of inbreeding in genetic management. Three different biological meanings of inbreeding are discussed in this paper: (1) inbreeding as a measure of shared ancestry in the paternal and maternal lineages of an individual; (2) inbreeding as a measure of genetic drift in a finite population, and (3) inbreeding as a measure of system of mating in a reproducing population. The distinction and use of these different measures of inbreeding are discussed and illustrated with a worked example, the North American captive population of Speke's gazelle (Gazella spekei). It is shown that these different meanings of the word inbreeding must be kept separated, otherwise erroneous management recommendations and evaluations can occur. On the positive side, the different measures of inbreeding when used jointly can be a powerful management tool precisely because they measure different biological phenomena.

Animals↗
PubMed1981

Oculomotor changes in cats reared without experiencing continuous retinal image motion.

Eye movements recorded with the magnetic-field search coil technique from six cats raised in an 8 Hz stroboscopically illuminated environment were found to be normal with the exception of fixation and optokinetic nystagmus. Fixation eye movements were characterized by a 4-5 Hz conjugate pendular nystagmus superimposed on a wandering drift. Optokinetic nystagmus was very asymmetrical on monocular tests. Depriving the oculomotor system of experience differentially effects fixation and smooth pursuit.

Animals↗
PubMed1993

Visual processing delays alter the perceived spatial form of moving gratings.

This study shows that there are delays in processing high spatial frequencies relative to low frequencies, and that these may affect the perceived brightness profile of drifting waveforms. The stimuli were complex waveforms consisting of 2-3 sinusoidal components, either drifting or stationary. The phase of the components was varied until the brightness profile of the waveform appeared as a square, triangle, ramp or bar. The results indicate that stationary waveforms are perceived veridically, but drifting waveforms are not. The harmonics of a drifting complex wave must be phase advanced, relative to the fundamental, in order to cancel motion-induced waveform distortions. This suggests that during visual processing the harmonics must be phase delayed, indicating that they are being processed more slowly than the fundamental. The most significant delays appear to be those between the fundamental and its second and third harmonic. Furthermore, the results show that the magnitude of the delays is dependent on the phase relationship between the components at perceptually significant points in the waveform: delays are less when the components are in sine phase than when they are in cosine phase. Separate experiments show that the detectability of phase shifts is least when the components are in sine phase. Together, these results may explain why drifting "sharp-edged" stimuli are not perceptually distorted: the human visual system appears to be relatively insensitive to phase shifts around square-wave phase and may therefore tolerate differences in the processing times of certain harmonics. A discussion of the possible origin of these processing delays is presented, together with the hypothesis that frequency dependent delays may reflect the spatiotemporal inseparability of cortical visual units.

Form Perception↗
PubMed1977

Two-stage operation for anatomical correction of transposition of the great arteries with intact interventricular septum.

To allow redevelopment of the posterior ventricle in an infant with transposition of the great arteries and intact interventricular septum, at the age of 4 weeks the pulmonary artery was banded, an aortopulmonary shunt was fashioned proximal to the band, and atrial septectomy was performed. Peak systolic posterior ventricular pressure immediately rose to systemic level (70 mm Hg.) During the next 4 months the pressure drifted back to 55 mm Hg but rose to 72 mm Hg after angiography without a rise in end-diastolic pressure. When the child was six months old anatomical correction of the transposition was successfully performed, the aorta, pulmonary, and coronary arteries being reattached to the appropriate ventricles. Debanding was performed at the same time. For the first 48 hours after operation phenoxybenzamine was given to reduce overload. At 6-month follow-up the child remained symptomless and was not on any cardiac drugs; left-ventricular function was good. This two-stage technique should widen the application of anatomical correction from a small selected group with additional defects to include most patients with transposition of the great arteries.

Aorta↗
PubMedDate not supplied

In vitro and in vivo methods to determine the interactions of osteogenic cells with biomaterials.

To assess new biomaterials for possible use as bone graft substitutes, a number of techniques allow interactions with osteoblastic cells to be studied, with respect to effects on proliferation and differentiation of osteoprogenitors. In vitro models include the use of bone explant cultures, fetal rat calvarial-derived osteoblast cells, primary stromal populations, transformed and non-transformed cell lines and immortalized osteoblast cell lines. However, these assessments are limited by the extent of osteogenic differentiation and bone formation that can be observed in vitro, species differences and phenotypic drift of cells cultured in vitro. The use of in vivo experimental systems such as the segmental/calvarial bone defect model, the subcutaneous implant model and the diffusion chamber implantation model circumvent some of these issues and, in the appropriate model, provide data on efficacy, biocompatibility and osteointegration of a biomaterial. The combination of in vitro and in vivo approaches together with the development of new cell labeling techniques, in particular the ability to genetically mark and select specific human bone cell populations provides new avenues for their potential evaluation in combination with appropriate biomaterials for clinical use. These in vitro and in vivo techniques are reviewed and those recently developed for assessment of human osteogenic cells should be applicable to many other cell systems where knowledge of specific human tissue or cell interactions with biomaterials is required.

Journal Article↗
PubMed2000

Evidence for a novel affinity mechanism of motor-assisted transport along microtubules.

In microtubule (MT) translocation assays, using colloidal gold particles coupled to monoclonal tubulin antibodies to mark positions along MTs, we found that relative motion is possible between the gold particle and an MT, gliding on dynein or kinesin. Such motion evidently occurred by an affinity release and rebinding mechanism that did not require motor activity on the particle. As the MTs moved, particles drifted to the trailing edge of the MT and then were released. Sometimes the particles transferred from one MT to another, moving orthogonally. Although motion of the particles was uniformly rearward, movement was toward the (-) or (+) end of the MT, depending on whether dynein or kinesin, respectively, was used in the assay. These results open possibilities for physiological mechanisms of organelle and other movement that, although dependent on motor-driven microtubule transport, do not require direct motor attachment between the organelle and the microtubule. Our observations on the direction of particle drift and time of release may also provide confirmation in a dynamic system for the conclusion that beta tubulin is exposed at the (+) end of the MT.

Animals↗
PubMed2003

r8s: inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock.

SUMMARY: Estimating divergence times and rates of substitution from sequence data is plagued by the problem of rate variation between lineages. R8s version 1.5 is a program which uses parametric, nonparametric and semiparametric methods to relax the assumption of constant rates of evolution to obtain better estimates of rates and times. Unlike most programs for rate inference or phylogenetics, r8s permits users to convert results to absolute rates and ages by constraining one or more node times to be fixed, minimum or maximum ages (using fossil or other evidence). Version 1.5 uses truncated Newton nonlinear optimization code with bound constraints, offering superior performance over previous versions. AVAILABILITY: The linux executable, C source code, sample data sets and user manual are available free at http://ginger.ucdavis.edu/r8s.

Algorithms↗
PubMed1989

[Stage IV renal cell carcinoma producing alpha-fetoprotein treated with multimodal treatment. A case report].

A 63 year old man, having right renal cell carcinoma which was found after initial symptoms of left supraclavicular tumor and gross hematuria, is presented. The points to note with this case are; (1) An unusual production of alpha-fetoprotein (AFP), (2) Being discovered at a very advanced stage and that the disease progressed rapidly (at initial presentation the patient had lymph nodes metastases from the paraaorta, mediastinum to the left supraclavicular region. Later the patient had a recurrent tumor in the left supraclavicular area and multiple cutaneous metastases), (3) Various modalities of treatment were given (right nephrectomy, abdominal lymph nodes dissection, resection of the supraclavicular and mediastinal lymph nodes metastases, hyperthermia combined with irradiation for the recurrent tumor in the supraclavicular region and systemically adoptive immunotherapy with tumor infiltrating lymphocytes). During this treatment course, the drift of serum AFP showed a good correlation. The possibility of AFP as a tumor marker of renal cell carcinoma in selected cases was presented and the suitability of the treatments performed to this patient was discussed.

Carcinoma, Renal Cell↗
PubMed1990

Population structure of the Peljesac Peninsula, Yugoslavia.

We gathered serogenetic and parent-offspring migration data from 604 residents of 7 villages on the Peljesac peninsula in southern Yugoslavia. A variety of population genetics and multivariate statistics models and procedures give a concordant picture of the population structure of this region. Extensive migration is the dominant microevolutionary force patterning the variation seen today. Multiple population bottlenecks have also occurred over the past few centuries as a result of disease, famine, war, economic failure, and founder events, making it likely that genetic drift has been an important factor in the history of this population system.

Adult↗
PubMed1990

Performance goals for internal quality control of multichannel haematology analysers.

Performance goals for analytic bias and analytic imprecision are presented for multichannel haematology analysers. These goals represent a compromise between limits that would cause minimal degradation in the information content for clinical decisions and limits that are achievable by current instruments. For midrange measurements the maximal limits for total analytic bias are +/- 14.6% for WBC, +/- 5.3% for RBC, +/- 4.5% for Hb concentration, +/- 4.2% for MCV, and +/- 22% for platelet counts. The limits include error inherent in calibrator value assignment, instrument calibration, instrument drift, and instrument non-linearity as well as the quality control systems necessary to monitor each of these processes. If analytic biases are held within the proposed limits, the clinical specificities of the assays will be decreased by less than 7% for all assays except that platelet counts will have a decrease in specificity of about 15%. Analytic imprecision has minimal direct effect on clinical decisions because the influence of within-person and across-person biological variation dominates. However, analytic imprecision is a major factor in the control of analytic bias and thereby remains an important quality control factor.

Blood Cell Count↗
PubMed1997

A new automated computerized analyzing system simplifies readings and reduces the variability in ultrasound measurement of intima-media thickness.

BACKGROUND AND PURPOSE: A computerized analyzing system with manual tracing of echo interfaces for measurement of intima-media thickness and lumen diameter in carotid and femoral arteries was previously developed by our research group and has been used for many years in several laboratories. However, manual measurements are not only time consuming, but the results from these readings are also dependent on training and subjective judgement. A further problem is the observed drift in measurements over time. A new computerized technique for automatic detection of echo interfaces was therefore developed. The aim of this study was to evaluate the new automated computerized analyzing system. METHODS: The new system is based on dynamic programming and includes optional interactive modification by the human operator. Local measurements of vessel echo intensity, intensity gradient, and boundary continuity are extracted by image analysis techniques and included as weighed terms in a cost function. The dynamic programming procedure is used for determining the optimal location of the vessel interfaces in a way that the cost function is minimized. RESULTS: With the new automated computerized analyzing system the measurement results were less dependent on the reader's experience, and the variability between readers was less compared with the old manual analyzing system. The measurements were also less time consuming. CONCLUSIONS: The new automated analyzing system will not only greatly increase the speed of measurements but also reduce the variability between readers. It should also reduce the variability between different laboratories if the same analyzing program is used. Furthermore, the new system will probably prevent the problem with drift in measurements over time.

Automation↗
PubMed1979

Performance assessment of the GammafloTM automated radioimmunoassay system by assaying for digoxin.

We report an evaluation of the GammafloTM automated continuous-flow radioimmunoassay instrument in which we used a digoxin assay to assess system performance. System operation was based on combined continuous-flow and column-chromatographic techniques. No drift or carryover was detectable in 180 within-assay consecutive determinations performed at a rate of 42 determinations per hour (5 h of continuous operation). Within-assay and between-assay precision were less than 6% (coefficient of variation). The automated method correlated well (r = 0.960 and 0.952, respectively) with two established manual digoxin radioimmunoassay procedures. The data suggest this automated system offers a valid alternative to manual radioimmunoassay procedures in terms of overall precision, simplicity of operation, and sample throughout capacity.

Autoanalysis↗
PubMed1995

Sharpening of drifting, blurred images.

The perceived blur of moving images is less than expected given the sluggish temporal response of the visual system. This suggests that a motion deblurring mechanism may exist to preserve the positional acuity and sharpness of moving images. Furthermore, when sequences of blurred stills are presented, observers report that the moving image is in sharp focus raising the possibility that there is a mechanism which may sharpen the appearance of moving, blurred images. We have measured the effects of velocity and contrast on the perceived blur of drifting, blurred images (sine gratings and blurred edges). Subjects matched the perceived blur of drifting, blurred images to that of static, blurred images in a dimly lit room. It was found that perceived blur was inversely related to drift speed and contrast. The results confirm that moving, blurred images may appear sharper than when they are static. This finding is not consistent with some models of motion deblurring since these account only for the preservation of sharp contours that are present in the image and not for the sharp appearance of images that are in fact blurred.

Contrast Sensitivity↗
PubMed2005

Unidirectional drift of bistable front under asymmetrically oscillating zero-mean force.

The unidirectional drift of bistable fronts (BFs) that separate two stable uniform states of a bistable system under the action of an asymmetrically oscillating zero-mean force (driver) is considered within the "pseudolinear" (piecewise-linear) model of the system. The particular case of the symmetrical (symmetrically shaped) rate functions is studied. To perform a rigorous analytic treatment for arbitrary strengths of the driving force we assume that the applied ac force is quasistatically slow. Both cases of the initially static and the initially propagating BFs are examined; various types of the "unforced" dc motion are found. We show that the unforced transport of BF takes place in any case of the asymmetric driver, whether Maxwellian construction of the rate function was balanced or not. In particular, progressive (accelerated) dc drift of the initially static BFs occurred. In contrast, both progressive and regressive (decelerated) types of unforced dc drift of the initially propagating BFs take place. Moreover, reversal of the directed motion of the initially propagating BF occurred, if the deviation of Maxwellian construction from the strictly balanced situation was relatively small; by tuning the strength of the driving force the dc drift of BF exhibits the reversal. The symmetry properties of the biharmonic driver are discussed. The biharmonic ac force consisting of a superposition of the fundamental mode and its even (odd) superharmonics is an asymmetrically (symmetrically) oscillating one. The reversal type of the unforced dc drift occurred only in the case of the even superharmonic "mixing," when the superharmonic mode of the biharmonic driver was even.

Journal Article↗
PubMed2004

Comprehensive study of phase transitions in relaxational systems with field-dependent coefficients.

We present a comprehensive study of phase transitions in single-field systems that relax to a nonequilibrium global steady state. The mechanism we focus on is not the so-called Stratonovich drift combined with collective effects, but is instead similar to the one associated with noise-induced transitions in the manner of Horsthemke-Lefever in zero-dimensional systems. As a consequence, the noise interpretation (e.g., Itô vs Stratonovich) merely shifts the phase boundaries. With the help of a mean-field approximation, we present a broad qualitative picture of the various phase diagrams that can be found in these systems. To complement the theoretical analysis we present numerical simulations that confirm the findings of the mean-field theory.

Journal Article↗