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Results for “Models, Theoretical”

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At least 1,063 records · Page 59Linked to original sources

PubMed2000

Polarization of scatter and fluorescence signals in flow cytometry.

BACKGROUND: The pulses of light scatter and fluorescence measured in flow cytometers exhibit varying degrees of polarization. Flow cytometers are heterogeneously sensitive to this polarization, depending on the light source(s), the optical layout, and the types of mirrors and filters used. Therefore, fluorescence polarization can affect apparent intensity ratios between particles and interfere with schemes for interlaboratory standardization. METHODS: We investigate the degree to which polarization affects common flow cytometry measurements. Our technique for determining polarization differs from previous methods because complete distributions of intensity versus polarization angle are measured, rather than intensities at just two orthogonal polarization angles. Theoretical models for scatter and fluorescence are presented and verified by making polarization measurements of calibration beads. RESULTS: Measurements of cells stained with a variety of dyes illustrate that fluorescence polarization occurs frequently in flow cytometry. CONCLUSIONS: Consequences for quantitative cytometry are discussed, and the use of the "magic angle" to make a flow cytometer insensitive to fluorescence polarization is proposed.

Animals↗

PubMed1999

2D multislice and 3D MRI sequences are often equally sensitive.

A simple theoretical model was developed to compare the sensitivities (i.e., signal-to-noise ratios per unit imaging time) of two-dimensional (2D) multislice and 3D imaging sequences. The model shows that the sensitivities of 3D and 2D multislice MRI sequences are usually similar. Sensitivities are identical in T2-weighted sequences when the T(R)s of the two sequences are the same. In T1-weighted gradient-echo sequences, sensitivities are very similar when Ernst angle excitation is used and the T(R) of the 2D sequence is less than T1. The predictions of the model are confirmed in phantom and animal experiments.

Animals↗

PubMed2001

Social support as a buffer to the psychological impact of stressful life events in women with breast cancer.

BACKGROUND: Three theoretical models by which social support may influence the impact of stressful life events on cancer patients' psychological state were tested: 1) the additive model, in which social support and stressful life events each directly influence cancer patients' adjustment, irrespective of the magnitude of the other; 2) the buffering hypothesis, in which stressful events occurring in the presence of social support should produce less distress than if they occur in its absence; and 3) both additive and buffering models. METHODS: One hundred seventy-nine patients who had Stage II breast cancer (median age, 56 yrs; 68% disease free), treated a mean of 6.8 years since entry to Cancer and Leukemia Group B (CALGB) 8541, were interviewed by telephone concerning their psychosocial adjustment. The following measures were used: Medical Outcome Study Social Support Survey (MOS-SSS), Life Experience Survey (LES) a measure of stressful life events within the past 12 months, European Organization for Research on the Treatment of Cancer (EORTC QLQ-C30) a measure of quality of life, Mental Health Inventory (MHI), and the Systems of Belief Inventory (SBI) a measure of spiritual and religious involvement. RESULTS: Hierarchical regression analyses revealed that less than excellent levels of social support (P < 0.01), greater negative impact of LES fateful life events (e.g., death of family member) (P < 0.05), personal illness or injury (P < 0.05), and all other negative life events in the past year (< 4; P < 0.01) were significant predictors of greater MHI psychological distress, in addition to being divorced or separated (P < 0.001), and more recently treated for cancer on CALGB 8541 (P < 0.05). The interaction of LES scores with MOS-SSS or SBI social support, used to test the buffering hypothesis, did not significantly improve the prediction of MHI psychological distress. CONCLUSIONS: The results supported the additive model, with both stressful life events and social support independently and significantly affecting patients' emotional state. However, the level of social support needed to be very high to reduce the likelihood of severe psychological distress.

Adult↗

PubMed2002

Quantification and evaluation of Joule heating in on-chip capillary electrophoresis.

We present the use of a novel, picoliter volume interferometer to measure, for the first time, the extent of Joule heating in chip-scale capillary electrophoresis (CE). The simple optical configuration for the on-chip interferometric backscatter detector (OCIBD) consists of an unfocused laser, an unaltered silica chip with a half-cylinder channel and a photodetector. Using OCIBD for millidegree-level noninvasive thermometry, temperature changes associated with Joule heating (2.81 degrees C above ambient) in on-chip CE have been observed in 90 microm wide and 40 microm deep separation channels. The temporal response of Joule heating in isotropically etched channels was exponential, with it taking an excess of 2.7 s to reach equilibrium. Buffer viscosity changes have also been derived from empirical on-chip thermometry data, allowing for the determination of diffusion coefficients for solutes when separated in heated buffers. In addition, OCIBD has allowed the reduction in separation efficiency to be estimated in the absence of laminar flow and due to increased molecular diffusion and lower buffer viscosity. A 7% reduction in separation efficiency was determined for a high current drawing buffer such as Tris-boric acid under an applied field of just 400 V/cm. Results indicate that heating effects in on-chip CE have been underestimated and there is a need to readdress the theoretical model.

Buffers↗

PubMed2004

The psychosocial work environment and musculoskeletal disorders: design of a comprehensive interviewer-administered questionnaire.

BACKGROUND: Psychosocial working conditions are likely to contribute to work-related musculoskeletal disorders (WRMSDs), but a lack of standardized measurement tools reflects both the theoretical and methodological limitations of current research. METHODS: An interdisciplinary team including biomedical, behavioral, and social science researchers used an iterative process to adapt existing instruments for an interviewer-administered questionnaire assessing psychosocial workplace exposure related to musculoskeletal disorders. RESULTS: The resulting questionnaire included measures of psychosocial workplace factors based on two theoretical models (the demand-control-support and the effort-reward imbalance models), supplemented by the additional constructs of "emotional demands," and "experiences of discrimination." Other psychosocial and physical measures selected for questionnaire inclusion address physical workload, sociodemographic and anthropometric characteristics, social relations and life events, health behaviors, and physical and psychological health. CONCLUSION: Using an interdisciplinary approach facilitated the development of a comprehensive questionnaire inclusive of key measures of psychosocial factors that may play a role in the complex mechanisms leading to WRMSDs.

Humans↗

PubMed2004

Good practices in managing work-related indoor air problems: a psychosocial perspective.

BACKGROUND: Indoor air problems at workplaces are often exceedingly complex. Technical questions are interrelated with the dynamics of the work community, and the cooperation and interaction skills of the parties involved in the problem solving process are also put to the test. The objective of our study was to analyze the process of managing and solving indoor air problems from a psychosocial perspective. METHODS: This collective case study was based on data from questionnaires, interviews and various documentary materials. Technical inspections of the buildings and indoor air measurements were also carried out. RESULTS: The following four factors best differentiated successful cases from impeded cases: extensive multiprofessional collaboration and participative action, systematic action and perseverance, investment in information and communication, and process thinking and learning. The study also proposed a theoretical model for the role of the psychosocial work environment in indoor air problems. CONCLUSIONS: The expertise related to social and human aspects of problem solving plays a significant role in solving indoor air problems. Failures to properly handle these aspects may lead to resources being wasted and result in a problematic situation becoming stagnant or worse.

Air Pollutants, Occupational↗

PubMed2004

Theoretical aspects of genomic variation screening using DNA microarrays.

We present a theoretical model for typical microarray-based single nucleotide polymorphism (SNP) assay of small genomic DNA amount. We derived the adsorption isotherm expressing the on-array hybridization efficiency in terms of genomic target sequence and concentration, oligonucleotide probe sequence and surface density, hybridization buffer, and temperature. This isotherm correctly describes the surface probe density effects, the sensitivity peak, and the melting temperature depression, and is in accord with published experiments. We discuss optimization of parallel SNP genotyping. Our estimates show that SNP detection at a single temperature in aqueous hybridization buffer is restricted by DNA regions that differ by less than 20% in GC content. We predict that the variety of genotyped SNPs could be substantially extended using an assay design with high probe density and a large fraction of probes hybridized.

Genetic Testing↗

PubMed2005

Theoretical analysis of selection-based strain improvement for microorganisms with growth dependent upon extracytoplasmic enzymes.

This study analyzes selection in continuous culture as a means to improve the growth of microorganisms dependent upon the expression of extracytoplasmic enzymes. A quantitative, theoretical model was developed that considers increases in enzyme activity and/or expression due to mutation in conjunction with reaction and diffusion at the cell surface and in the surrounding boundary layer. This model was applied to a system consisting of a recombinant yeast cell growing on either soluble or insoluble substrates by virtue of extracytoplasmic enzymes either with or without tethering to the cell surface. Our results indicate that selection of faster-growing cells can be effective, arbitrarily defined as a faster-growing mutant representing 1% of the population in < or =3 months, but only under some conditions. For both soluble and insoluble substrates, tethering of enzymes to the cell surface is required for selection to be effective under the conditions examined. Significant increases in heterologous enzyme expression (2.5-fold for mutants as compared to the parent strain) are also required. In the soluble substrate/enzyme tethered case, the value of k(S) must also be low in order for selection to be effective. Cells growing on non-native substrates by virtue of extracytoplasmic enzyme production are expected to experience selective pressure in response to several additional factors, including cell shape, distance of the cell-substrate gap, properties of the gap, and perhaps mutation frequency. However, these factors exert a smaller impact on selection time and it is not clear that favorable values for these factors are required in order for selection to be effective.

Biotechnology↗

PubMed1994

Fluorescence lifetime measurements in a flow cytometer by amplitude demodulation using digital data acquisition technique.

We have developed a method for fluorescence lifetime measurements in a flow cytometer based upon the amplitude demodulation of the fluorescence signals using digital data acquisition techniques. Amplitude demodulation is one of the two methods by which excited state lifetimes may be investigated in the frequency domain. The other method involves the phase-shift measurements. In frequency-domain measurement techniques, the amplitude-demodulation and phase-shift data serve mutually complementary roles to enhance the analytical capabilities of the measurements. The purpose of having amplitude demodulation measurement capability is to obtain information that supplements, rather than replaces, that obtained by the phase-shift method alone. Application of amplitude demodulation measurements has been widely explored in static, cuvette-based, frequency domain systems. However, due to time dependence of the amplitude of the modulated fluorescence signal in a flow cytometer, the amplitude demodulation measurements in flow turns out to be more complicated than similar measurements in a static system. The goal of the present work is to explore the problems involved in amplitude demodulation measurements in flow (using digital method), through detailed theoretical modeling and use the model to develop a practical method that can be incorporated into a flow cytometer to measure amplitude modulation lifetimes. We experimentally verify the amplitude demodulation measurement capability of this method using fluorescent microspheres. The experimental measurements show good agreement with static frequency-domain measurements on microspheres in bulk suspensions.

Analog-Digital Conversion↗

PubMed2004

Effect of Joule heating on efficiency and performance for microchip-based and capillary-based electrophoretic separation systems: a closer look.

An attempt is made to revisit the main theoretical considerations concerning temperature effects ("Joule heating") in electro-driven separation systems, in particular lab-on-a-chip systems. Measurements of efficiencies in microfabricated devices under different Joule heating conditions are evaluated and compared to both theoretical models and measurements performed on conventional capillary systems. The widely accepted notion that planar microdevices are less susceptible to Joule heating effects is largely confirmed. The heat dissipation from a nonthermostatically controlled glass microdevice was found to be comparable to that from a liquid-cooled-fused silica capillary. Using typically dimensioned glass and glass/silicon microdevices, the experimental results indicate that 5-10 times higher electric field strengths can be applied than on conventional capillaries, before detrimental effects on the separation efficiency occur. The main influence of Joule heating on efficiency is via the establishment of a radial temperature profile across the lumen of the capillary or channel. An overall temperature increase of the buffer solution has only little influence on the quality of the separation. Still, active temperature control (cooling, thermostatting) can help prevent boiling of the buffer and increase the reproducibility of the results.

Electrophoresis↗

PubMed2003

Spot overlapping in two-dimensional polyacrylamide gel electrophoresis maps: relevance to proteomics.

Proteomics requires a large-scale, simultaneous separation of proteins from a mixture, assessment of the relative abundance of these molecules, and identification and characterization of each component. In 2-D PAGE separations, the best method of choice for protein analysis, separation of all the proteins present in the sample is still far to be achieved and comigrating proteins in the same spot are in general present. A statistical estimation of the degree of spot overlapping present in a 2-D PAGE separation is here described: for different conditions of spot overcrowding in the map, the degree of overlapping can be quantified in terms of purity degree of each spot or percentage of proteins that will appear in the map as a single spot. A computer simulation approach is described: it is based on the protein separation pattern present in the experimental maps. The results thus obtained are compared to a theoretical model (statistical degree of peak overlapping model) based on random spot position. The described procedures were applied to an experimental reference map of human plasma. The severity of spot overlapping in 2-D PAGE maps is estimated and the influence of different experimental conditions (strip dimension, detector system performance, pI range) is discussed. These informations are useful to quantitatively estimate the degree of error associated with identification and quantitation of each protein and to set-up experimental conditions which will increase resolution and greatly decrease the probability of spot overlapping.

Computer Simulation↗

PubMed2003

Capillary electrophoresis-mass spectrometry of peptides from enzymatic protein hydrolysis: simulation and optimization.

Two important limitations still exist for the characterization of protein digests by capillary electrophoresis-mass spectrometry (CE-MS): (i) the buffer choice (i.e., the buffer must provide an adequate CE separation without ruining the MS signal), and (ii) the frequent generation of "unexpected" peptidic fragments during the enzymatic protein hydrolysis. In this work, a new approach is used to solve these difficulties, namely a theoretical model that relates the electrophoretic behavior of peptides to their sequence. The effectiveness of this procedure is demonstrated by the fast attainment of good CE-MS conditions for analyzing the peptides obtained from an enzymatic protein hydrolysate in a single run. This strategy can provide useful information for helping to characterize "unexpected" fragments from protein digests.

Amino Acid Sequence↗

PubMed1989

Segregation analysis of quantitative traits in nuclear families: comparison of three program packages.

Segregation analysis frequently is used to test for the presence of major gene effects and to estimate the various genetic and environmental components contributing to diseases. Recent advances in both theoretical models and computational algorithms have provided a number of new programs for performing segregation analyses. We compared two newer programs: REGC (part of the package "SAGE") and FISHER/MENDEL with an older established program (PAP) to determine relative accuracy in recovering parameter values and asymptotic standard errors, ability to discriminate between alternative transmission models, and execution speeds. Each program was applied to a set of computer simulations of a quantitative trait generated under a variety of genetic models. The results of these comparisons indicated that all the programs provided very similar parameter estimates, but that they differed in their abilities to identify the correct mode of transmission. In our simulations, PAP more often led to the selection of the correct transmission model, whereas REGC frequently indicated the presence of a major gene in simulations of purely polygenic transmission. Relative speeds for the programs differed, and their rank ordering varied with the complexity of the model being fitted. Although REGC was the fastest program for fitting a major gene or mixed model, it was by far the slowest program for estimating parameters in a sporadic or polygenic model.

Computer Simulation↗

PubMed1995

Role of cyclic plastic deformation in the wear of UHMWPE acetabular cups.

The mechanisms of wear in ultra-high-molecular-weight polyethylene (UHMWPE) acetabular cups were investigated on both laboratory simulator-tested cups and a clinically retrieved component. Two different levels of wear process were identified: one characterized by the formation and detachment of platelet-like flakes from initial machining marks, and the other by the formation of fine ripple and fibrils by repeated passes of microscopic asperities on the femoral head. Both wear processes could be described by a criterion of critical plastic strain. A theoretical model was developed to account for the generation of the microscopic wear particles based on such a critical strain criterion. Its predictions of the dependence of the UHMWPE wear rate on surface roughness and applied load were in excellent agreement with previously published experimental correlations.

Acetabulum↗

PubMedDate not supplied

Protein folding and binding in confined spaces and in crowded solutions.

Simple theoretical models are presented to illustrate the effects of spatial confinement and macromolecular crowding on the equilibria and rates of protein folding and binding. Confinement is expected to significantly stabilize the folded state, but for crowding only a marginal effect on protein stability is expected. In confinement the unfolded chain is restricted to a cage but in crowding the unfolded chain may explore different interstitial voids. Because confinement and crowding eliminate the more expanded conformations of the unfolded state, folding from the compact unfolded state is expected to speed up. Crowding will shift the binding equilibrium of proteins toward the bound state. The significant slowing down in protein diffusion by crowding, perhaps beneficial for chaperonin action, could result in a decrease in protein binding rates.

Models, Theoretical↗

PubMedDate not supplied

Theoretical analysis of gadopentetate dimeglumine enhancement in T1-weighted imaging of the brain: comparison of two-dimensional spin-echo and three-dimensional gradient-echo sequences.

By using a theoretical model, the signal difference-to-noise ratios between simulated lesions and normal white matter and gray matter were calculated as a function of lesion concentration of gadopentetate dimeglumine (GD) for two-dimensional (2D) T1-weighted spin-echo (SE), three-dimensional (3D) steady-state spoiled gradient-echo (GRE) (FLASH [fast low-angle shot]), and 3D magnetization-prepared rapid gradient echo (MP-RAGE) pulse sequences. The 3D GRE sequences provided greater contrast enhancement at relatively high [GD], and the 2D SE sequence demonstrated greater enhancement and a higher rate of enhancement at low [GD]. The results predict that at low [GD], certain lesions could probably be detected with the 2D SE sequence but possibly not with one or both of the 3D GRE sequences. At high [GD], certain lesions could probably be detected with one or both of the 3D GRE sequences but possibly not with the 2D SE sequence. This provides a potential explanation for the clinical observation that certain contrast agent-enhanced lesions appear less conspicuous on 3D GRE images than on 2D SE images and vice versa. Modified parameter values were derived for the 3D FLASH and 3D MP-RAGE sequences that are predicted to produce contrast enhancement behavior equivalent or superior to that of a conventional 2D SE sequence.

Brain↗

PubMedDate not supplied

Experimental and theoretical studies of vessel contrast-to-noise ratio in intracranial time-of-flight MR angiography.

CNR studies were performed for human intracranial vessels in 3D MRA data sets. The CNR dependency of different imaging parameters, such as flip angle, field of view, echo time, repetition time, and echo readout symmetry, was studied for vessels in the region of the circle of Willis. A theoretical model was developed for MR vascular imaging based on the Bloch equations and Fourier imaging theory. This model predicts the MR image intensity of vessels from basic subject parameters, such as the relaxation times of blood and stationary tissue, vessel dimension, and flow velocity, and the parameters of the imaging technique, such as flip angle, voxel volume, repetition time, and echo time. For most experiments, the model was found to fit the experimental results well. The validity of this model allows the optimization of imaging parameters to maximize vessel CNR in MR angiography.

Adult↗

PubMed2005

Transverse relaxation effect of MRI contrast agents: a crucial issue for quantitative measurements of cerebral perfusion.

Quantitative cerebral perfusion imaging using dynamic susceptibility contrast (DSC) MRI requires the dynamic measurement of changes in contrast agent concentration in cerebral tissue and its feeding artery. In this work the tracer kinetics approach to general tracer-based perfusion imaging is reviewed. In the typical practical setting, measurements of change in transverse relaxation (DeltaR(2)) derived from MR signals are assumed to be substitutes for true concentration measurements. The implications and limitations of this assumption are reviewed in the light of various results obtained in theoretical, simulated, and experimental studies. The mechanisms of R(2) changes in biological media are discussed. These mechanisms operate over different spatial scales and differentially influence gradient-echo (GE) and spin-echo (SE) MRI signals. This differential sensitivity can be used to assess vessel size in the microvasculature. Finally, the need for well controlled experimental data to provide input parameters and/or experimental tests of theoretical models is emphasized.

Brain↗