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Interactions of selection, linkage and drift in the dynamics of polygenic characters.

We study the dynamics under directional truncation selection of the genetic variability of a quantitative character controlled by a finite number of possibly linked loci with additive effects. After the first generation of selection, the build-up of linkage disequilibria (Bulmer effect) is analytically demonstrated from a genetical point of view in an infinite population. In the following generations, the dynamics of the system in a finite population are predicted using analytic recurrences under a multi-normal approximation, and computer simulations. The effects of recombination on the dynamics of linkage disequilibria induced by selection and drift, and the consequences for the additive genetic variance are then analysed and discussed from the simulation results. Compared to the rapid exploitation of genetic variability promoted by high recombination rates, low recombination rates promote an early storage of genetic variability in repulsion associations of alleles and a possible late release of genetic variance in the population, so that the variability of the character may be maintained over a longer period of time. In some cases, favourable recombination events in tightly linked systems induce an increase of the additive variance of the character, which may explain some results observed in long-term selection experiments. Our results emphasize that the joint effects of selection, linkage and drift must not be neglected in theoretical quantitative genetics, and require further investigation.

Computer Simulation↗

X-ray dual-photon absorptiometry: a new method for the measurement of bone density.

A recently introduced method (dual-photon X-ray absorptiometry, DEXA) capable of measuring skeletal density in man (at present in the spine and hips, but ultimately for the whole body) has been evaluated in terms of its ability to perform long-term assessment of bone density changes. The method, which uses X rays rather than gamma rays as its photon source, represents a significant improvement over present systems both in image quality and precision (reproducibility) of results, which is better than 1% in vivo. Scanning time is approximately halved compared with present techniques and the radiation dose is reduced by 25%. First data on long-term drift of results and effects of changes in patient composition (i.e. thickness and fat content) are given and show the new method to be superior to present radionuclide systems. It is likely that this new method will become the standard for bone density measurements.

Bone and Bones↗

[Uncontrolled genetic processes in artificial populations: proving the leading role of selection in evolution].

The review considers studies examining artificially maintained populations as models for understanding biological evolution. The key factors of gene pool evolution-random processes, interspecific hybridization, migration, mutation, and selection--are analyzed. We present evidence indicating that selection is the leading evolutionary factor that regulates the operation of other factors, directly or through genetic systems.

Animals↗

A system for acquiring simultaneous electron energy-loss and X-ray spectrum-images.

A compositional imaging system based on simultaneous scanning electron energy-loss spectroscopy (EELS) and energy-dispersive X-ray spectroscopy (EDS) was developed. This system utilizes the combined power of EELS and EDS for quantitative compositional imaging at nanometre resolution. The system is particularly suitable for, but not limited to, biological research, as it simultaneously provides sensitive maps of an element such as Ca or P from EELS and of many other elements from EDS. Degradation of resolution by specimen drift is prevented by correcting for drift during data acquisition, using image cross-correlation. Several advanced features are implemented for real-time and/or off-line quantitative analysis, and the performance of the system is illustrated with practical applications to compositional imaging of cardiac muscle.

Animals↗

Re-entrant activity and its control in a model of mammalian ventricular tissue.

We characterize the meander of re-entrant excitation in a model of a sheet of mammalian ventricular tissue, and its control by resonant drift under feedback driven stimulation. The Oxsoft equations for excitability in a guinea pig single ventricular cell were incorporated in a two dimensional reaction-diffusion system to model homogeneous, isotropic tissue with a plane wave conduction velocity of 0.35 m s-1. Re-entrant spiral wave solutions have a spatially extended transient motion (linear core) that settles down into rotation with an irregular period of 100-110 ms around an irregular, multi-lobed spiky core. In anisotropic tissue this would appear as a linear conduction block. The typical velocity of drift of the spiral wave induced by low amplitude resonant forcing is 0.4 cm s-1.

Animals↗

Flow and transport in the drift shadow in a dual-continuum model.

The current concept for high-level radioactive waste disposal at Yucca Mountain is for the waste to be placed in underground tunnels (or drifts) in the middle of a thick unsaturated zone. Flow modeling and field testing have shown that not all flow encountering a drift will seep into the drift. The underlying reason for the diversion of unsaturated flow around a drift is that capillary forces in the fractures and matrix prevent water entry into the drift unless the capillary pressure in the rock decreases sufficiently to allow for gravity forces to overcome the capillary barrier. As a result of the capillary barrier effect, flow tends to be diverted around the drift, affecting the flow pattern beneath the drift. For some distance beneath the drift, water saturation and flux are reduced. This drift shadow zone is much more pronounced in the fractures than in the matrix due to dominance of gravity over capillary forces in the fractures. Moving downward, away from the drift, the shadow zone asymptotically re-equilibrates to the undisturbed flow conditions due to capillary forces. The behavior of radionuclide transport in this zone of reduced flow is investigated here because this will affect the amount of time required for radionuclides to penetrate the unsaturated zone. The delay of radionuclide movement in the geosphere is one aspect of the potential repository system that could limit public exposure to radioactive waste. The behavior of flow and transport is calculated using a two-dimensional, drift-scale dual-permeability model extending to nine drift diameters below the potential waste emplacement drift. The flow model is first compared with an analytical model for a single continuum. Then, the dual-continuum flow model is investigated with respect to drift-scale and mountain-scale property sets. Transport calculations are performed for a wide range of flow conditions and for different aqueous radionuclides and colloids. Findings indicate that transport times for dissolved or colloidal material released from a drift without seepage are several orders of magnitude longer than if the releases occurred in the undisturbed flow field. Furthermore, the calculations indicate that the transport rate for radionuclides released in the drift shadow is relatively insensitive to flow rates in the fractures, but is sensitive to the flow rate in the matrix.

Colloids↗

Integration of aquatic fate and ecological responses to linear alkyl benzene sulfonate (LAS) in model stream ecosystems.

An integrated model stream ecosystem fate and effect study of dodecyl linear alkylbenzene sulfonate (C(12)LAS) was performed in the summer and fall of 1996. The study addressed responses of periphytic microbes, immature benthic fauna including abundance, drift, and emergence of adult insects in a 56-day exposure. Exposures ranged from 126 to 2978 microg/L and were continuously presented in a single-pass, flow-through test system. Microbial heterotrophs acclimated to C(12)LAS exposure quickly (14 days) and biodegraded C(12)LAS at all concentrations. Blue-green algae responded by increasing in abundance with increasing C(12)LAS concentration. Invertebrates responded by increased drift and reduced benthic abundances at concentrations exceeding 293 microg/L. Emergence at 927 microg/L also declined relative to the control. Adverse responses for mayflies and chironomids were indicated using univariate statistical techniques. Multivariate techniques indicated these taxa plus mollusks, aquatic worms, caddisflies, and stoneflies were impaired at some concentrations. Bioavailability of C(12)LAS was investigated in streams as a function of the total suspended solid load in the water column driven by local weather and watershed patterns. A continuous bioavailability model indicated exposure was reduced by an average of 8.5+/-8.9%. A model ecosystem no-observed-effect concentration (NOEC) was concluded to be 293 microg/L based on measured water column exposure and adjusted to 268 microg/L by the bioavailability model. A literature review of 13 available model ecosystem studies was conducted and NOEC conclusions were adjusted by a structure-activity relationship to a dodecyl chain length (sulfophenyl position and distribution being ignored due to lack of information in the reviewed studies). Lentic studies (n=7) were found to have higher NOECs than lotic studies (n=6) and were more variable. Mean NOECs+/-SD for all studies, lentic studies only, and lotic studies only were 3320+/-6040, 5720+/-7640, and 530+/-430 microg/L, respectively. Interpretation of results for anomalies from specific studies suggests the importance of experimental design, use of laboratory versus natural surface water, biological complexity of the test system, and physical test system design as relevant factors for consideration. The specific results of the new model ecosystem study presented in this article can be well defended on the basis of a robust experimental and physical design and because the system contained a diverse and sensitive aquatic community. A low or no uncertainty factor could be applied to the result.

Adsorption↗

A motion illusion generated by afternystagmus suppression.

After a period of prolonged unidirectional smooth pursuit, the tracking target is seen to drift in the opposite direction when it is stopped, even though its retinal image is stationary. If, however, the tracking target is extinguished during the post-adaptive period, the eyes continue to drift in the tracking direction, a phenomenon known as pursuit afternystagmus. It is proposed that the visual system, in an effort to maintain fixation upon the target, produces a motor signal in the opposite direction in order to offset the residual afternystagmus. The perceptual registration of this efferent signal may then produce the motion illusion.

Humans↗

Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise.

INTRODUCTION: In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. PATIENTS AND METHODS: We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). RESULTS: The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. CONCLUSION: The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.

Adult↗

Protein tracking and detection of protein motion using atomic force microscopy.

Height fluctuations over three different proteins, immunoglobulin G, urease, and microtubules, have been measured using an atomic force microscope (AFM) operating in fluid tapping mode. This was achieved by using a protein-tracking system, where the AFM tip was periodically repositioned above a single protein molecule (or structure) as thermal drifting occurred. Height (z-piezo signal) data were taken in 1 - or 2-s time slices with the tip over the molecule and compared to data taken on the support. The measured fluctuations were consistently higher when the tip was positioned over the protein, as opposed to the support the protein was adsorbed on. Similar measurements over patches of an amphiphile, where the noise was identical to that on the support, suggest that the noise increase is due to some intrinsic property of proteins and is not a result of different tip-sample interactions over soft samples. The orientation of the adsorbed proteins in these preliminary studies was not known; thus it was not possible to make correlations between the observed motion and specific protein structure or protein function beyond noting that the observed height fluctuations were greater for an antibody (anti-bovine IgG) and an enzyme (urease) than for microtubules.

Animals↗

Diffusion, peer pressure, and tailed distributions.

We present a general, physically motivated nonlinear and nonlocal advection equation in which the diffusion of interacting random walkers competes with a local drift arising from a kind of peer pressure. We show, using a mapping to an integrable dynamical system, that on varying a parameter the steady-state behavior undergoes a transition from the standard diffusive behavior to a localized stationary state characterized by a tailed distribution. Finally, we show that recent empirical laws on economic growth can be explained as a collective phenomenon due to peer pressure interaction.

Economics↗

Temperature stability of a dichroic atomic vapor laser lock.

We have investigated the temperature stability of the dichroic atomic vapor laser lock laser frequency lock method. We find that, in general, the lock exhibits significant temperature sensitivity, leading to laser frequency drifts as large as tens of MHz/K. However, for certain configurations of the optical elements of the system, this temperature dependence is reduced to below 1 MHz/K. These temperature-independent points can be found across a broad range of frequencies. We present a numerical model that reproduces the general behavior of the system.

Journal Article↗

Spectrophotometric determination of Blue Procion HEGN in effluents of textile industry exploiting the dye aggregation effect and flow injection analysis.

A new spectrophotometric method involving flow injection analysis and textile dye aggregation effect is proposed. The method is based on the aggregation effect of Blue Procion HEGN at pH 3, which relocates its maximum absorption wavelength from 620 to 776 nm, avoiding the interference of other blue textile dyes. For this task, a simple and robust flow injection system was designed, which became a very stable analytical method. When the system was applied to Blue Procion determination in effluent of textile industry, precise results were observed (RSD < 2% within 1.0 and 5.0 mg l(-1) HEGN). The analytical frequency was 80 measurements per hour; the analytical curve was linear from 1.0 to 5.0 mg l(-1) HEGN; the detection limit considering three times the standard deviation of the blank solution (n = 10) was estimated as 0.03 mg l(-1) HEGN; and recoveries between 95% and 105% were found. The system consumes 20 mg of sodium citrate and 125 microl of the sample per determination. No baseline drift was observed during extended (5 h) operation periods.

Journal Article↗

High-purity selection and maintenance of gene expression in human neuroblastoma cells stably over-expressing GFP fusion protein. Application for opioid receptors desensitization studies.

Chronic use of opiates such as morphine is associated with drug tolerance, which is correlated with the desensitization of opioid receptors. This latter process involves phosphorylation of opioid receptors by G protein-coupled receptors kinases (GRKs) and subsequent uncoupling by beta-arrestins. To explore these molecular mechanisms, neuronal cell lines, endogenously expressing the opioid receptors, provide an ideal cellular model. Unfortunately, there are two major drawbacks: (1) these cells are refractory to cDNA introduction, resulting in low transfection efficiency; (2) continuous culturing of transfected cells invariably leads to phenotypic drift of the cultures even after an antibiotic selection. So, these cells were dropped in favor of heterologous expression systems, which are easier to transfect but whose relevance as adequate cellular model for studying opioid receptor regulation should be questioned, as recently demonstrated by [Haberstock-Debic, H., Kim, K.A.,Yu, Y.J., von Zastrow, M., 2005. Morphine promotes rapid, arrestin-dependent endocytosis of mu-opioid receptors in striatal neurons. J. Neurosci. 25, 7847-7857]. In this work, we describe a method, based on fluorescence-activated cell sorting (FACS), to select and maintain a high proportion of transfected SK-N-BE cells (a neuronal cell line endogenously expressing human Delta-Opioid Receptor (hDOR)), expressing the beta-arrestin1 fused to green fluorescent protein (GFP). While in functional experiments, we were not able to observe a major effect in non-sorted SK-N-BE cells expressing beta-arrestin1-GFP, the enrichment by 18-fold with FACS resulted in a robust increase of beta-arrestin1-GFP expression associated with strong hDOR desensitization. Moreover, this method also allows to counteract the phenotypic drift and to maintain a high-purity selection of SK-N-BE cells expressing beta-arrestin1-GFP. Thus, this approach provides a valuable tool for exploring opioid receptors desensitization in neuronal cells.

Analysis of Variance↗

Electromagnetic flow measurement using a magnetic resonance imaging static field.

RATIONALE AND OBJECTIVES: Electromagnetic flowmeters have been used for many years as a standard method to determine blood flow in animal models. The use of a modified probe to measure electromagnetic induction in response to an external, large direct current (DC) field magnetic resonance (MR) imaging system was investigated. METHODS: Extracted sheep iliac vessels were inserted into a pumped saline circuit with a modified probe and placed into a 2.0-T MR research imaging system. Voltage readings were collected at various flow rates ranging from 100 to 400 ml/min. Actual flows were measured with a graduated cylinder. RESULTS: A correlation of .937 (p < .001) was observed between the measured voltage changes and the actual flows. Baseline drift was also linear and within specified limits. CONCLUSION: The results indicate that electromagnetic induction in a conductive fluid can be accurately measured using electrodes and an MR imaging system and that this technique provides possible opportunities for in situ flow measurements in humans.

Animals↗

Analysis of the kinestatic charge detection system as a high detective quantum efficiency electronic portal imaging device.

Megavoltage x-ray imaging suffers from reduced image quality due to low differential x-ray attenuation and large Compton scatter compared with kilovoltage imaging. Notwithstanding this, electronic portal imaging devices (EPIDs) are now widely used in portal verification in radiotherapy as they offer significant advantages over film, including immediate digital imaging and superior contrast range. However video-camera-based EPIDs (VEPIDs) are limited by problems of low light collection efficiency and significant light scatter, leading to reduced contrast and spatial resolution. Indirect and direct detection-based flat-panel EPIDs have been developed to overcome these limitations. While flat-panel image quality has been reported to exceed that achieved with portal film, these systems have detective quantum efficiency (DQE) limited by the thin detection medium and are sensitive to radiation damage to peripheral read-out electronics. An alternative technology for high-quality portal imaging is presented here: kinesatic charge detection (KCD). The KCD is a scanning tri-electrode ion-chamber containing high-pressure noble gas (xenon at 100 atm) used in conjunction with a strip-collimated photon beam. The chamber is scanned across the patient, and an external electric field is used to regulate the cation drift velocity. By matching the scanning velocity with that of the cation (i.e., ion) drift velocity, the cations remain static in the object frame of reference, allowing temporal integration of the signal. The KCD offers several advantages as a portal imaging system. It has a thick detector geometry with an active detection depth of 6.1 cm, compared to the sub-millimeter thickness of the phosphor layer in conventional phosphor screens, leading to an order of magnitude advantage in quantum efficiency (>0.3). The unique principle of and the use of the scanning strip-collimated x-ray beam provide further integration of charges in time, reduced scatter, and a significantly reduced imaging dose, enhancing the imaging signal-to-noise ratio (SNR) and leading to high DQE. While thick detectors usually suffer from reduced spatial resolution, the KCD provides good spatial resolution due to high gas pressure that limits the spread of scattered electrons, and a strip-collimated beam that significantly reduces the inclusion of scatter in the imaging signal. A 10 cm wide small-field-of-view (SFOV) prototype of the KCD is presented with a complete analysis of its imaging performance. Measurements of modulation transfer function (MTF), noise power spectrum (NPS), and DQE were in good agreement with Monte Carlo simulations. Imaging signal loss from recombination within the KCD chamber was measured at different gas pressures, ion drift velocities, and strip-collimation widths. Image quality for the prototype KCD was also observed with anthropomorphic phantom imaging in comparison with various commercial and research portal imaging systems, including VEPID, flat-panel imager, and conventional and high contrast film systems. KCD-based imaging provided very good contrast and good spatial resolution at very low imaging dose (0.1 cGy per image). For the prototype KCD, measurements yielded DQE(0)=0.19 and DQE(1 cy/mm)=0.004.

Computer-Aided Design↗

Institutional and legislative issues of emergency management policy in Russia.

The emergency management policy as an organic component of the national development policy in contemporary Russia exists only for a slight more than a decade. However, its basic trends and directions could be revealed. In the legislative area covering technological accidents involving hazardous materials these include increasing differentiation of acts in terms of issue coverage, gradual integration of legislation via enforcement of the so-called systemic (umbrella) acts and increasing incorporation of specific acts, and keeping dominance of federal emergency acts. In addition, emergency legislation and policy programs on communities' protection against major hazards drift from alleviation-oriented towards more mitigation-focused. Meanwhile, the bulk of the existing acts are still specific laws and regulations, which consider most emergency response. In institutional realms the key direction of emergency policy development involved organization and progress of the Unified State System for Emergency Prevention and Elimination of the Russian Federation (USEPE) with EMERCOM as a key coordinator and actor in handling technological hazards and accidents. The detailed analysis of USEPE organizational pattern and operation modes including institutional structure, key functions, means and forces and operation routines is provided. It is argued that the system's logic and flexible organizational framework only to some extent contribute to effective mitigation of the major emergencies and/or disasters. In no less extent it depends on the existing socioeconomic conditions, which have been for a long time unfavorable in Russia and thus seriously constrain the USEPE effectiveness. This provides for ambiguous integral evaluation of the emergency management policy in the 1990s and early 2000s.

Disaster Planning↗

Determination of binding constants by equilibrium titration with circulating sample in a surface plasmon resonance biosensor.

A commercial surface plasmon resonance biosensor, BIACORE X, is employed as a detector in a closed loop of a small sample volume. The sample is continuously circulated by an external syringe pump over two sensor spots, one functionalized with immobilized binding sites to a soluble binding partner in the mobile phase and one serving as a reference surface. A binding isotherm for the interacting macromolecules can be obtained by a stepwise titration of the soluble reactant into the circulating loop, each step followed by observation of the signal increase until equilibrium is attained. Binding constants can be measured under conditions free of mass transport artifacts and without the requirement for regeneration of the immobilized binding sites. This procedure is similar to the stepwise titration procedure described for the cuvette-based sensor design (D. R. Hall and D. J. Winzor, 1997, Anal. Biochem. 244, 152-160). In the presented configuration, the high baseline stability of the instrument combined with the availability of a reference surface for the detection of nonspecific binding permits refractive index changes upon addition of the aliquots to be measured, as well as accounting for temperature or instrumental drifts, and allows for a very long experimental time. This feature extends the applicability of equilibrium titration to systems with higher affinity or slower dissociation rate constants. Furthermore a solution competition titration is described that avoids artifacts from the immobilization procedure to provide a method for measurement of binding constants in solution. Kinetic information on the complex dissociation can also be obtained by combination of sample delivery via the external pump with the injection of competitor via the microfluidics of the biosensor. The rapid injection of high concentrations of competitor allows the observation of fast dissociation processes under conditions minimizing rebinding.

Animals↗