SEARCH · PubMed Health

Results for “Equilibrium optimization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2003

An optimization algorithm for intensity modulated radiotherapy--the simulated dynamics with dose-volume constraints.

We have developed a new method for optimization in intensity modulated radiation therapy (IMRT) that makes use of simulated dynamics in a classical system of interacting particles. An analogy is drawn between intensity profile optimization in IMRT and relaxation to the equilibrium configuration in a dynamic system. The intensities of beamlets are equivalent to the positions of the virtual particles. The potential energy of the system is defined by the objective function, which determines the equations of motion for the virtual particles. In this paper, we present the implementation of dose constraints and dose-volume constraints. Our strategy is to optimize the dose to the planned target volume (PTV) while keeping all constraints to the organs at risk (OARs) satisfied rigorously. A simple quadratic objective function is used that only includes terms for PTV voxels. By this approach, no additional parameters other than that for prescribing desired dose and constraints, such as importance factors, are needed. The hard constraints that require non-negative beamlet intensities and that the dose at any voxel in an OAR cannot exceed a maximum tolerance, are implemented as semi-transmittable potential barriers of infinite height. Dose-volume constraints are handled by placing hard constraints on partial volumes. Handling of the clinically applied constraints was tested using phantoms and clinical cases. Our results show that the dose-volume histogram (DVH) type of plan prescription can be fulfilled with satisfactory PTV coverage. In addition to the convenience of implementation, our method can achieve a high computational efficiency with the understanding of the dynamic behavior of the system.

Algorithms↗

PubMed1981

Kinetic analysis of relationship between partition coefficient and biological response.

Both nonequilibrium and equilibrium models were proposed to explain the optimal biological response to a set of congeners with respect to the oil-water partition coefficient (P). A detailed analysis of the kinetic model proposed by Hansch demonstrates the bilinear form of the model, with the initial slope of the logarithm of the concentration for 50% receptor binding versus log P having a slope of greater than one. This result is in contrast to the equilibrium model for an initial slope of less than one. Thus, a criterion is established for deciding whether equilibrium or nonequilibrium processes apply.

Biological Transport↗

PubMed1976

Optimal conditions and specificity of interaction of a distinct class of nonhistone chromosomal proteins with DNA.

A subclass of nonhistone chromatin proteins with high DNA affinity has been isolated from rat liver. The interaction of the isolated proteins with DNA in vitro was characterized utilizing a nitrocellulose filter binding technique. The temperature, time, concentration, ionic strength, and pH dependence were characterized. Optimal interaction was observed at 0.19 M naCl, pH 7.5 with a protein to DNA ratio of 13 (w/w). Equilibrium and kinetic competition experiments indicated that these proteins interact optimally with A-T rich and single-stranded DNA. The data also suggest that these proteins might affect the helixcoil transiton of DNA.

Animals↗

PubMed1984

On the optimal sex-ratio: a stability analysis based on a characterization for one-locus multiallele viability models.

Theoretical one-locus multiallele sex-determination models are found to admit even sex ratio equilibrium surfaces besides the equilibria for corresponding one-locus multiallele viability models. Both types of equilibria can be defined in terms of a single spectral radius function, the former corresponding to level surfaces and the latter to critical points. The stable equilibria in the corresponding viability models are associated with the local maxima, and the equilibrium structures for the sex-determination models can be fully described. Several optimality properties of the even-sex-ratio equilibrium surfaces can be deduced.

Alleles↗

PubMed2001

Molecular dynamics used in radiation therapy.

In this Letter, classical molecular dynamics is used to deal with optimization problems occurring in intensity modulated radiation therapy. By introducing the concepts of virtual atom and virtual cluster, the optimization process in this kind of therapy can be considered as an analogy to finding the equilibrium configuration of a cluster. This viewpoint gives great insight into the optimization problems. To show how the idea works, a dose-based objective function is adopted to obtain the optimized intensity profiles. The results and high computational efficiency show that molecular dynamics is applicable clinically for this therapy. The idea presented here also could be inspiring to other fields where optimization problems exist.

Algorithms↗

PubMed2002

Role of entropy in protein thermostability: folding kinetics of a hyperthermophilic cold shock protein at high temperatures using 19F NMR.

We used (19)F NMR to extend the temperature range accessible to detailed kinetic and equilibrium studies of a hyperthermophilic protein. Employing an optimized incorporation strategy, the small cold shock protein from the bacterium Thermotoga maritima (TmCsp) was labeled with 5-fluorotryptophan. Although chaotropically induced unfolding transitions revealed a significant decrease in the stabilization free energy upon fluorine labeling, the protein's kinetic folding mechanism is conserved. Temperature- and guanidinium chloride-dependent equilibrium unfolding transitions monitored by (19)F NMR agree well with the results from optical spectroscopy, and provide a stringent test of the two-state folding character of TmCsp. Folding and unfolding rate constants at high temperatures were determined from the (19)F NMR spectra close to the midpoint of thermal unfolding by global line shape analysis. In combination with results from stopped-flow experiments at lower temperatures, they show that the folding rate constant of TmCsp and its temperature dependence closely resemble those of its mesophilic homologue from Bacillus subtilis, BsCspB. However, the unfolding rate constant of TmCsp is two orders of magnitude lower over the entire temperature range that was investigated. Consequently, the difference in conformational stability between the two proteins is solely due to the unfolding rate constant over a wide temperature range. A thermodynamic analysis points to an important role of entropic factors in the stabilization of TmCsp relative to its mesophilic homologues.

Bacterial Proteins↗

PubMed1997

Phosphate Adsorption on Hematite, Kaolinite, and Kaolinite-Hematite (k-h) Systems As Described by a Constant Capacitance Model

The constant capacitance model was used to describe phosphate adsorption on hematite, kaolinite, and a kaolinite-hematite system (k-h). The model assumes a ligand exchange mechanism and considers the charge on both adsorbate and adsorbent. The model is shown to provide a quantitative description of phosphate adsorption on these, including the effect of varying pH values. The computer program Ma-Za 2, a program that fits equilibrium constants to experimental data using an optimization technique, was used to obtain optimal values for the anion surface complexation constants on hematite, kaolinite, and a kaolinite-hematite system, while the PC program Ma-Za 1 in Q-Basic language was used for the application of the constant capacitance model. The model represented adsorption of phosphate anions well over the entire pH range studied (3.8-9.0). The main advantage of the model is its ability to represent changes in anion adsorption occurring with changes in pH. Extension of the model to describe phosphate adsorption in a mixed system, such as the kaolinite-hematite system, using the surface protonation-dissociation constant of hematite was qualitatively successful. In mixed system the model reproduced the shape of the adsorption isotherms well over the pH range 3.8-9.0. However, phosphate adsorption was overestimated. The hematite and the kaolinite-hematite system were synthesized and identified by X-ray, NMR, and FT-IR spectroscopy.

Journal Article↗

PubMed1995

Development of a binding assay for the B1 receptors for kinins.

A novel binding assay to kinin B1 receptors was developed, based on the design of a high-affinity agonist ligand, [125I]Tyr-Gly-Lys-Aca-Lys-des-Arg9-BK. Binding to rabbit aortic smooth muscle cells is highly temperature-dependent (optimal at 37 degrees C); apparent binding equilibrium is reached within 30 min, and competition by kinin analogs reveals the expected correlation with the B1 receptor pharmacology. The dissociation constant (Kd) of the labeled ligand is approx. 0.2 nM and this value does not change significantly as a function of cytokine pretreatment. However, the receptor abundance (Bmax) is significantly increased (1.5-fold) by pretreating the cells with interleukin-1 (IL-1), while oncostatin M (OSM) produces a marginal increase of the Bmax. This assay may be useful in documenting the regulation of B1 receptors in pathology.

Amino Acid Sequence↗

PubMed1999

Levels of human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte effector and memory responses decline after suppression of viremia with highly active antiretroviral therapy.

Therapeutic suppression of human immunodeficiency virus type 1 (HIV-1) replication may help elucidate interactions between the host cellular immune responses and HIV-1 infection. We performed a detailed longitudinal evaluation of two subjects before and after the start of highly active antiretroviral therapy (HAART). Both subjects had evidence of in vivo-activated and memory cytotoxic T-lymphocyte precursor (CTLp) activity against multiple HIV-1 gene products. After the start of therapy, both subjects had declines in the levels of in vivo-activated HIV-1-specific CTLs and had immediate increases in circulating HIV-1-specific CTL memory cells. With continued therapy, and continued suppression of viral load, levels of memory CTLps declined. HLA A*0201 peptide tetramer staining demonstrated that declining levels of in vivo-activated CTL activity were associated with a decrease in the expression of the CD38(+) activation marker. Transient increases in viral load during continued therapy were associated with increases in the levels of virus-specific CTLps in both individuals. The results were confirmed by measuring CTL responses to discrete optimal epitopes. These studies illustrate the dynamic equilibrium between the host immune response and levels of viral antigen burden and suggest that efforts to augment HIV-1-specific immune responses in subjects on HAART may decrease the incidence of virologic relapse.

Anti-HIV Agents↗

PubMed1992

Binding of platelet-activating factor to oviductal membranes during early pregnancy in the rabbit.

The present study explores the ability of rabbit oviductal membranes to bind tritiated platelet-activating factor [3H]PAF on days 3 and 6 of pregnancy. Under optimal conditions (25 degrees C, 120 min) equilibrium saturation analysis revealed only one class of binding sites, characterized by Kd s(nM), 80.03 +/- 11.60 and 11.17 +/- 7.09 and Bmaxs, (pmol/mg protein), 5.25 +/- 2.23 and 1.08 +/- 0.22 (N = 3, mean +/- SEM) for ampullar membranes on days 3 and 6, respectively. The corresponding values for isthmic membranes were Kds, 86.56 +/- 12.01 and 52.43 +/- 30.49 and Bmaxs, 9.41 +/- 0.67 and 2.88 +/- 1.96 for days 3 and 6, respectively. Significant differences between days 3 and 6 were observed only in the binding affinities for the ampullar membranes and the binding capacities for the isthmic binding sites. [3H]PAF binding was inhibited in the following order of decreasing potency: lyso-PAF greater than PAF C18:0 greater than U66985 greater than PAF C16:0 for day 3 ampullar membranes; and lyso-PAF C16:0 greater than PAF C18:0 greater than U66985 greater than PAF C16:0 for day 6 ampullar membranes. These studies show the existence of specific oviductal membrane PAF binding sites, the binding parameters of which may be related to the stage of pregnancy, rather than to the spatial location along the oviduct. The relative proportion of endosalpinx to myosalpinx between the ampulla and isthmus may have masked inherent differences and account for the relatively low affinity binding. The physiological significance of oviductal membrane PAF binding is yet to be established.

Animals↗

PubMed1988

Conformational restrictions of the sheep testicular receptor discriminates pituitary lutropin and placental gonadotropins.

A membrane preparation from the testis of maturing Dorset-Leicester-Suffolk sheep, capable of discriminating pituitary LH (lutropin) from placental gonadotropins human choriogonadotropin (hCG) and equine choriogonadotropin is described. Maximum binding of 125I-oLH (ovine lutropin) to the testicular receptors occurred at 4 degrees C in a rapid manner, attaining equilibrium in 12-16 h. Under such optimal conditions, only unlabeled ovine LH or the structurally identical bovine LH effectively competed for receptor occupation. Other highly purified pituitary LH preparations from rat and human pituitaries were weakly (4-10%) active in displacement assays. Purified hCG or equine choriogonadotropin, which were highly potent in rat testicular LH receptor assays, could not compete with 125I-oLH for binding to the sheep LH receptor at 4 degrees C. Thus, the sheep testicular LH receptor was highly specific in recognizing pituitary LH conformation. The presence of an ovine/bovine LH alpha- or beta-subunit in recombinants with hCG subunit counterparts was required to generate an effective conformation capable of receptor recognition. Chemically deglycosylated hCG, containing 75% less carbohydrate and which showed greater binding to other LH receptors, failed to recognize sheep LH receptor, suggesting that excess carbohydrate in hCG was not a factor in hindering binding of the native placental hormone. Scatchard analysis using 125I-hCG/125I-oLH revealed that there were separate sites with similar affinities but vastly different capacities. The hCG binding sites, which could also be effectively occupied by oLH, were less than 10% of oLH binding sites. Thus, the Dorset-Leicester-Suffolk sheep testicular receptor provides an important and unique in vitro test system to distinguish pituitary LH from placental LH-like hormones. We infer that temperature-dependent conformational restrictions of the sheep testicular LH receptor are involved in recognizing differences in these highly similar and structurally homologous hormones.

Animals↗

PubMed1977

A pregnenolone-binding protein in soluble fraction of guinea pig adrenal cortex.

A pregnenolone-binding component has been detected in the soluble fraction of the guinea pig adrenal cortex. Enzymatic degradation studies revealed that the binding component was a protein. The binding was destroyed at 60 degrees but was not inhibited by sulfhydryl reactants. Pregnenolone was bound optimally at pH 7 to 7.5 The equilibrium association constant at 0 degrees was 10(7) M-1. The pregnenolone-binding protein had an apparent molecular weight of 58,000, as determined by gel filtration. With the exception of pregnenolone sulfate, structurally similar steroids did not interfere with pregnenolone binding. No such binding activity was detected in the guinea pig liver and kidney. Serum contained pregnenolone-binding activity which was distinguishable from the adrenal cytosol factor by a variet of physicochemical means. The physiological importance of this finding remains to be determined.

Adrenal Cortex↗

PubMed2000

Life history evolution: successes, limitations, and prospects.

Life history theory tries to explain how evolution designs organisms to achieve reproductive success. The design is a solution to an ecological problem posed by the environment and subject to constraints intrinsic to the organism. Work on life histories has expanded the role of phenotypes in evolutionary theory, extending the range of predictions from genetic patterns to whole-organism traits directly connected to fitness. Among the questions answered are the following: Why are organisms small or large? Why do they mature early or late? Why do they have few or many offspring? Why do they have a short or a long life? Why must they grow old and die? The classical approach to life histories was optimization; it has had some convincing empirical success. Recently non-equilibrium approaches involving frequency-dependence, density-dependence, evolutionary game theory, adaptive dynamics, and explicit population dynamics have supplanted optimization as the preferred approach. They have not yet had as much empirical success, but there are logical reasons to prefer them, and they may soon extend the impact of life history theory into population dynamics and interspecific interactions in coevolving communities.

Aging↗

PubMed1996

The evolution of begging: signaling and sibling competition.

In many species, young solicit food from their parents, which respond by feeding them. Because of the difference in genetic make-up between parents and their offspring and the consequent conflict, this interaction is often studied as a paradigm for the evolution of communication. Existent theoretical models demonstrate that chick signaling and parent responding can be stable if solicitation is a costly signal. The marginal cost of producing stronger signals allows the system to converge to an equilibrium: young beg with intensity that reflects their need, and parents use this information to maximize their own inclusive fitness. However, we show that there is another equilibrium where chicks do not beg and parents' provisioning effort is optimal with respect to the statistically probable distribution of chicks' states. Expected fitness for parents and offspring at the nonsignaling equilibrium is higher than at the signaling equilibrium. Because nonsignaling is stable and it is likely to be the ancestral condition, we would like to know how natural systems evolved from nonsignaling to signaling. We suggest that begging may have evolved through direct sibling fighting before the establishment of a parental response, that is, that nonsignaling squabbling leads to signaling. In multiple-offspring broods, young following a condition-dependent strategy in the contest for resources provide information about their condition. Parents can use this information even though it is not an adaptation for communication, and evolution will lead the system to the signaling equilibrium. This interpretation implies that signaling evolved in multiple-offspring broods, but given that signaling is evolutionarily stable, it would also be favored in species which secondarily evolved single-chick broods.

Animal Communication↗

PubMed1974

Purification and properties of malyl-coenzyme A lyase from Pseudomonas AM1.

1. Malyl-CoA lyase was purified 20-fold from extracts of methanol-grown Pseudomonas AM1. 2. Preparations of the enzyme were essentially homogeneous by electrophoretic and ultracentrifugal criteria. 3. Malyl-CoA lyase has a molecular weight of 190000 determined from sedimentation-equilibrium data. 4. Within the range of compounds tested, malyl-CoA lyase is specific for (2S)-4-malyl-CoA or glyoxylate and acetyl-CoA or propionyl-CoA. 5. A bivalent cation is essential for activity, Mg(2+) or Co(2+) being most effective. 6. Malyl-CoA lyase is inhibited by (2R)-4-malyl-CoA and by some buffers, but thiol-group inhibitors are without effect. 7. Optimal activity was recorded at pH7.8. 8. An equilibrium constant of 4.7x10(-4)m was determined for the malyl-CoA cleavage reaction. 9. The Michaelis constants for the enzyme are: 4-malyl-CoA, 6.6x10(-5)m; acetyl-CoA, 1.5x10(-5)m; glyoxylate, 1.7x10(-3)m; Mg(2+), 1.2x10(-3)m.

Centrifugation, Density Gradient↗

PubMedDate not supplied

A strategy for efficient characterization of macromolecular heteroassociations via measurement of sedimentation equilibrium.

A method is proposed for the selection of experimental conditions for sedimentation equilibrium experiments that will provide maximal information about the values of equilibrium association constants within a given scheme for heteroassociation of two solute components. A discriminator function is proposed that indicates the sensitivity of the experimentally observed gradient or gradients to alterations in the underlying association constants. The value of this function is plotted or tabulated as a function of the concentrations of the two components, over a broad range of solution compositions. It is suggested that experiments performed with loading compositions corresponding to large absolute values of the discriminator function will yield the most information with respect to determination of the underlying association constants. This method was tested by predicting optimal conditions for three different types of sedimentation equilibrium experiments: (i) measurement of total (natural) solute absorbance; (ii) measurement of individual component gradients via measurement of tracer absorbance; and (iii) global analysis of multiple experiments. Experimental data resulting from sedimentation equilibrium experiments carried out under the specified conditions were simulated by addition of realistic levels of random error to calculated equilibrium gradients. The simulated data were then analyzed exactly as real experimental data, i.e., without prior knowledge of the underlying association constants. It was found that the highest accuracy and precision in determination of heteroassociation constants are obtained by global analysis of multiple experiments performed using significantly different loading compositions, each of which is selected from 'sensitive' regions of the discriminator map.

Centrifugation, Density Gradient↗

PubMed1976

Hydrolysis-resynthesis equilibrium of the lysine-15--alanine-16 peptide bond in bovine trypsin inhibitor (Kunitz).

Catalytic amounts of bovine beta-trypsin, bovine alpha-chymotrypsin and porcine plasmin establish a true thermodynamic equilibrium between virgin (I) (reactive site Lys15-Ala16 peptide bond intact) and modified (I) (this bond hydrolyzed) bovine trypsin/kallikrein inhibitor (Kunitz). The very slow reaction rates for attaining equilibrium are pH-dependent and differ for different enzymes. Optimal rates are for beta-trypsin at pH 3.75, for alpha-chymotrypsin at pH 5.5, and for plasmin at pH 5.0. Under conditions of optimum pH the equilibrium is reached with the highest rate by plasmin. In 10(-5)M inhibitor solutions the equilibrium concentrations of virgin and modified inhibitor are established by plasmin after almost 300 days starting from either pure virgin or pure modified inhibitor. Thus, the hydrolysis constant KHyd = [I]/[I] is determined to be 0.33 at pH 5.0. In spite of many unsuccessful attempts, this demonstrates that the reactive site peptide bond Lys15-Ala16 in the bovine trypsin inhibitor (Kunitz) can be hydrolyzed by catalytic amounts of endopeptidase. It further confirms that the hydrolyzed Lys15-Ala16 peptide bond in modified inhibitor is subject to thermodynamic control resynthesis.

Alanine↗

PubMed1985

Synthesis of ATP catalyzed by the (Ca2+ + Mg2+)-ATPase from erythrocyte ghosts. Energy conservation in plasma membranes.

The (Ca2+ + Mg2+)-ATPase from erythrocyte ghosts catalyzed the hydrolysis of ATP together with the synthesis of ATP or ATP in equilibrium 'Pi exchange. The modulation of the ATPase reaction cycle was controlled by high- and low-affinity calcium-binding sites asymmetrically located on the enzyme. Calmodulin accelerated the reaction cycle in both directions, stimulating the overall turnover of the enzyme. Calcium transport was achieved utilizing optimal conditions for the expression of the ATP in equilibrium Pi exchange system.

Adenosine Triphosphate↗