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Cardiopulmonary resuscitation in a hospitalized population: prospective study of factors associated with outcome.

A prospective study of advanced cardiopulmonary resuscitation (CPR) was carried out on 226 patients in order to examine factors predicting successful resuscitation and 6 month survival. The mean age of all patients was 70 years and median age was 74. Cardiopulmonary resuscitation was successful in 40.5% (137) of all arrests and in 48.7% (110) of the first arrests. Thirty of 207 patients with one or more cardiac arrests were discharged alive (14%). Twenty-one of our patients were alive at 6 months (10.3%). Patients in ventricular fibrillation and/or ventricular tachycardia at the time of arrest were more likely to have successful outcomes. When the patient required Isuprel or bicarbonate, cardiopulmonary resuscitation was significantly less successful. We found no correlation of immediate outcome with the following variables: location of arrest; time of day; pre-existence of shock; coma; stroke; malignancy. Uremia and/or chronic obstructive pulmonary disease was not significantly associated with failed resuscitation. Most notable in our results of specific treatments was the evidence for the need to improve the initial pH, particularly when it was less than 7.2. Failure to do so by the time the second blood gas was drawn was associated with failure of cardiopulmonary resuscitation. Our results also suggest that the adequate treatment of metabolic acidosis, and improved ventilatory management with improved PO2 and optimization of PCO2, play a role in the better outcome of cardiopulmonary resuscitation.

Acid-Base Equilibrium↗

[Problems in the preoperative treatment of old patients].

Because of a higher duration of life the age surgical operations get higher importance also in the gynaecology. In elderly patients careful pre-operative treatment gives a reduction of lethality and morbidity. You must consider the shorted functional resources of the heart circulation system and the lungs and kindeys. Disturbances in electrolyte metabolism, water balance and acid-base regulation should optimally be compensated pre-operatively. At the same time the thrombosis prophylactic is a very important fact in the pre-operative treatment.

Acid-Base Equilibrium↗

[The status of the newborns from mothers in a risk group for fetal distress depending on the method of delivery].

Use of an algorithm for assessment of the severity of antenatal fetal distress and prediction of intranatal complications helped choose the optimal mode of delivery individually for each parturient and develop the strategy of rational management of spontaneous labor, which was confirmed by measurements of hydrocortisone levels in umbilical blood during delivery by different modes. Rational management of labor and optimization of delivery were conducive to a reduction of the incidence of grave distress in the newborns.

Acid-Base Equilibrium↗

Intrasubject correlation between static scan and distribution volume images for [11C]flumazenil PET.

Accumulation of [11C]flumazenil (FMZ) reflects central nervous system benzodiazepine receptor (BZR). We searched for the optimal time for a static PET scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal subjects, a dynamic series of decay-corrected PET scans was performed for 60 minutes, and the arterial blood was sampled during the scan to measure radioactivity and labeled metabolites. We generated 13 kinds of "static scan" images from the dynamic scan in each subject, and analyzed the pixel correlation for these images versus distribution volume (DV) images. We also analyzed the time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra-subject pixel correlation demonstrated that the "static scan" images for the period centering around 30 minutes post-injection had the strongest linear correlation with the DV image. The ratio of radioactivity in the cortex to that in the plasma reached a peak at 40 minutes after injection. Considering the physical decay and patient burden, we conclude that the decay corrected static scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be optimally acquired from 20 to 40 minutes after injection.

Adult↗

The thermodynamic efficiency of the Ca2+-Mg2+-ATPase is one hundred percent.

The thermodynamic efficiency of the Ca2+ -Mg2+ -ATPase of skeletal sarcoplasmic reticulum has been evaluated by comparing the Ca2+ gradient established with the ATP/(ADP*Pi) ratio. The evaluation was made at an external Ca2+ level (4.7 X 10(-8) M) which is below the Km value of 7 X 10(-8) M. The Mg-ATP and phosphate concentrations were held constant (0.1 mM) and the ADP concentration was varied. Maximal uptake to an internal free Ca2+ concentration of 17 mM was observed at infinite ATP/(ADP*Pi) ratio (absence of ADP). This corresponds to a [Ca2+] i/[Ca2+] 0 gradient of 3.6 X 10(5). A Ca2+ gradient one-half as large was observed at an ATP/(ADP*Pi) ratio of 3.5 X 10(3) M-1. The square of the Ca2+ gradient is shown to be proportional to the ATP/(ADP*Pi) ratio, for finite values of the latter. The proportionality constant is identical to the equilibrium constant for hydrolysis of ATP (9.02 X 10(6) M) under these conditions (0.1 mM Mg2+, 30 degrees C). The intrinsic thermodynamic efficiency of the pump is shown to be 100%, with a maximal uncertainty of 3%. The efficiency is lower under less optimal conditions, when the pump is inhibited and passive leak processes compete.

Adenosine Diphosphate↗

Mixed state on a sparsely encoded associative memory model.

We analyzed symmetric mixed states corresponding to the so-called concept formation on a sparsely encoded associative memory model with 0-1 neurons. Three types of mixed states--OR, AND, and a majority decision--are described as typical examples. Each element of the OR mixed state is composed of corresponding memory pattern elements by means of the OR operation. The other two types are similarly defined. By analyzing their equilibrium properties through self-consistent signal-to-noise analysis and computer simulation, we found that the storage capacity of the OR mixed state diverges in a sparse limit, but that the other states do not diverge. In addition, we found that the optimal threshold values, which maximize the storage capacity for the memory pattern and the OR mixed state, coincide with each other in the spare limit. We conclude that the OR mixed state is a reasonable representative of mixed state in the sparse limit.

Computer Simulation↗

Radiation damping in microcoil NMR probes.

Radiation damping arises from the field induced in the receiver coil by large bulk magnetization and tends to selectively drive this magnetization back to equilibrium much faster than relaxation processes. The demand for increased sensitivity in mass-limited samples has led to the development of microcoil NMR probes that are capable of obtaining high quality NMR spectra with small sample volumes (nL-microL). Microcoil probes are optimized to increase sensitivity by increasing either the sample-to-coil ratio (filling factor) of the probe or quality factor of the detection coil. Though radiation damping effects have been studied in standard NMR probes, these effects have not been measured in the microcoil probes. Here a systematic evaluation of radiation damping effects in a microcoil NMR probe is presented and the results are compared with similar measurements in conventional large volume samples. These results show that radiation-damping effects in microcoil probe is much more pronounced than in 5 mm probes, and that it is critically important to optimize NMR experiments to minimize these effects. As microcoil probes provide better control of the bulk magnetization, with good RF and B0 inhomogeneity, in addition to negligible dipolar field effects due to nearly spherical sample volumes, these probes can be used exclusively to study the complex behavior of radiation damping.

Journal Article↗

Universality and diversity of the protein folding scenarios: a comprehensive analysis with the aid of a lattice model.

BACKGROUND: The role of intermediates in protein folding has been a matter of great controversy. Although it was widely believed that intermediates play a key role in minimizing the search problem associated with the Levinthal paradox, experimental evidence has been accumulating that small proteins fold fast without any detectable intermediates. RESULTS: We study the thermodynamics and kinetics of folding using a simple lattice model. Two folding sequences obtained by the design procedure exhibit different folding scenarios. The first sequence folds fast to the native state and does not exhibit any populated intermediates during folding. In contrast, the second sequence folds much slower, often being trapped in misfolded low-energy conformations. However, a small fraction of folding molecules for the second sequence fold on a fast track avoiding misfolded traps. In equilibrium at the same temperature the second sequence has a highly populated intermediate with structure similar to that of the kinetics intermediate. CONCLUSIONS: Our analysis suggests that intermediates may often destabilize native conformations and derail the folding process leading it to traps. Less-optimized sequences fold via parallel pathways involving misfolded intermediates. A better designed sequence is more stable in the native state and folds fast without intermediates in a two-state process.

Amino Acid Sequence↗

Aquatic passive sampling of herbicides on naked particle loaded membranes: accelerated measurement and empirical estimation of kinetic parameters.

Water-sampler equilibrium partitioning coefficients and aqueous boundary layer mass transfer coefficients for atrazine, diuron, hexazionone and fluometuron onto C18 and SDB-RPS Empore disk-based aquatic passive samplers have been determined experimentally under a laminar flow regime (Re = 5400). The method involved accelerating the time to equilibrium of the samplers by exposing them to three water concentrations, decreasing stepwise to 50% and then 25% of the original concentration. Assuming first-order Fickian kinetics across a rate-limiting aqueous boundary layer, both parameters are determined computationally by unconstrained nonlinear optimization. In addition, a method of estimation of mass transfer coefficients--therefore sampling rates--using the dimension-less Sherwood correlation developed for laminar flow over a flat plate is applied. For each of the herbicides, this correlation is validated to within 40% of the experimental data. The study demonstrates that for trace concentrations (sub 0.1 microg/L) and these flow conditions, a naked Empore disk performs well as an integrative sampler over short deployments (up to 7 days) for the range of polar herbicides investigated. The SDB-RPS disk allows a longer integrative period than the C18 disk due to its higher sorbent mass and/or its more polar sorbent chemistry. This work also suggests that for certain passive sampler designs, empirical estimation of sampling rates may be possible using correlations that have been available in the chemical engineering literature for some time.

Environmental Monitoring↗

Variable-temperature X-ray crystallographic and DFT computational study of the N-H...O/N...H-O tautomeric competition in 1-(Arylazo)-2-naphthols. Outline of a transition-state hydrogen-bond theory.

Phenyl-substituted 1-arylazo-2-naphthols (AAN) display ...HN-N=C-C=O... <==>...N=N-C=C-OH... ketohydrazone-azoenol tautomerism and can form intramolecular resonance-assisted H-bonds from pure N-H...O to pure N...H-O through tautomeric and dynamically disordered N-H...O <==>N...H-O bonds according to the electronic properties of their substituents. Three compounds of this series (m-OCH(3)-AAN = mOM; p-Cl-AAN = pCl; and p-NMe(2)-AAN = pNM2) have been studied by X-ray crystallography at four temperatures (100-295 K), showing that the remarkably short H-bonds formed (2.53 < or = d(N...O) < or = 2.55 A) are a pure N-H...O in mOM, a dynamically disordered mixture in pCl (N-H...O:N...H-O = 69:31 at 100 K), and a statically disordered mixture in pNM2 (N-H...O:N...H-O = 21:79 at 100 K). These compounds, integrated by the p-H-, p-NO(2)-, p-F-, and p-O(-)-substituted derivatives, have been emulated by DFT methods (B3LYP/6-31+G(d,p) level) with full geometry optimization of the stationary points along the proton-transfer (PT) pathway: N-H...O and N...H-O ground states and N...H...O transition state. Analysis of DFT-calculated energies and geometries by the methods of the rate-equilibrium Marcus theory shows that all H-bond features (stability and tautomerism, as well as position and height of the PT barrier) can be coherently interpreted in the frame of the transition-state (or activated-complex) theory by considering the bond as a chemical reaction N-H...O <==> N...H...O <==> N...H-O which is bimolecular in both directions and proceeds via the N...H...O PT transition state (the activated complex).

Journal Article↗

Aromatic dienophiles. 1. A theoretical study of an inverse-electron demand Diels-Alder reaction between 2-aminopyrrole and 1,3,5-triazine.

This study is devoted to a detailed theoretical study of an inverse-electron demand Diels-Alder reaction (IDA) with 1,3,5-triazine as the diene and 2-aminopyrrole 1A(alpha) as the dienophile, which is a key step in a cascade reaction for the one-pot synthesis of purine analogues. Geometries were optimized with the B3LYP/6-31G* method and energies were evaluated with the MP2/6-311++G** method. This IDA reaction occurs through a stepwise mechanism, where the first step corresponds to the nucleophilic attack of 2-aminopyrrole to triazine to form a zwitterionic intermediate, which is in equilibrium with a neutral intermediate through a hydrogen transfer process, followed by a rate-determining ring-closure step. It is shown that the B3LYP method significantly overestimates the activation energy, whereas the MP2 method offers a reasonable activation barrier of 27.9 kcal/mol in the gas phase. The solvation effect has been studied by the PCM model. In DMSO, the calculated activation energy of the IDA reaction is decreased to 24.0 kcal/mol with a strong endothermicity of 17.4 kcal/mol due to the energy penalty of transforming two aromatic reactants into a nonaromatic IDA adduct. The possible stepwise [2+2] pathway is ruled out based on its higher activation and reaction energies than those of the [4+2] pathway. By comparing the IDA reactions of triazine to 2-aminopyrrole and pyrrole, we address two crucial roles of the alpha-amino substituent in lowering activation and reaction energies and controlling the reaction regiochemistry.

Journal Article↗

Diffusion dynamics of the Li+ ion on a model surface of amorphous carbon: a direct molecular orbital dynamics study.

Diffusion processes of the Li+ ion on a model surface of amorphous carbon (Li+C96H24 system) have been investigated by means of the direct molecular orbital (MO) dynamics method at the semiempirical AM1 level. The total energy and energy gradient on the full-dimensional AM1 potential energy surface were calculated at each time step in the dynamics calculation. The optimized structure, where Li+ is located in the center of the cluster, was used as the initial structure at time zero. The dynamics calculation was carried out in the temperature range 100-1000 K. The calculations showed that the Li+ ion vibrates around the equilibrium point below 200 K, while the Li+ ion moves on the surface above 250 K. At intermediate temperatures (300 K < T < 400 K), the ion moves on the surface and falls in the edge regions of the cluster. At higher temperatures (600 K < T), the Li+ ion transfers freely on the surface and edge regions. The diffusion pathway of the Li+ ion was discussed on the basis of theoretical results.

Journal Article↗

Binding constants and stability of dexamethasone-binding protein from rat heart.

A pronounced decrease in specific dexamethasone binding capacity of heart cytosol was observed. The inactivation of unbound glucocorticoid receptor was not due to the action of proteases since the rat of albumin digestion was very slow in the particulate preparations. The rate of inactivation of glucocorticoid binding capacity depends on cytosol protein concentration and temperature. Addition of hormone and glycerol to cytosol markedly slow binding capacity inactivation. The rapid loss of binding activity, especially in the cytosol with high protein concentration, makes difficult to perform equilibrium studies for simultaneous determination of binding affinity and a number of binding sites. Under various conditions the apparent dissociation constants were measured and compared with the dissociation constants, calculated from the rate of constants of association and dissociation, in order to find out optimal conditions for simultaneous determination of KD and [R0].

Animals↗

Waddington's canalization revisited: developmental stability and evolution.

Most species maintain abundant genetic variation and experience a range of environmental conditions, yet phenotypic variation is low. That is, development is robust to changes in genotype and environment. It has been claimed that this robustness, termed canalization, evolves because of long-term natural selection for optimal phenotypes. We show that the developmental process, here modeled as a network of interacting transcriptional regulators, constrains the genetic system to produce canalization, even without selection toward an optimum. The extent of canalization, measured as the insensitivity to mutation of a network's equilibrium state, depends on the complexity of the network, such that more highly connected networks evolve to be more canalized. We argue that canalization may be an inevitable consequence of complex developmental-genetic processes and thus requires no explanation in terms of evolution to suppress phenotypic variation.

Evolution, Molecular↗

A dynamic model of the knee and lower limb for simulating rising movements.

A two-dimensional dynamical model of the human body was developed and used to simulate muscle and knee-ligament loading during a fast rising movement. The hip, ankle, and toes were each modeled as a simple hinge joint. Relative movements of the femur, tibia, and patella in the sagittal plane were described using a more detailed representation of the knee. The geometry of the model bones was adapted from cadaver data. Eleven elastic elements described the geometric and mechanical properties of the knee ligaments and joint capsule. The patella was assumed to be massless. Smooth hypersurfaces were constructed and used to calculate the position and orientation of the patella during a forward integration of the model. Each hypersurface was formed by applying the principle of static equilibrium to approximate patellofemoral mechanics during the simulation. The model was actuated by 22 musculotendinous units, each unit represented as a three-element muscle in series with tendon. A first-order process was assumed to model muscle excitation-contraction dynamics. Dynamic optimization theory was used to calculate the pattern of muscle excitations that produces a coordinated rising movement from an initial squatting position in minimum time. The calculations support the contention that squatting is a relatively safe exercise for rehabilitation following ACL reconstruction. ACL forces remain less than 20 N for the duration of the task.

Adult↗

Methodology of radon monitoring and dose estimates in Postojna Cave, Slovenia.

Due to the specific work regime in the Postojna Cave, which depends primarily on the daily number of visitors, and on seasonal variations in air radon concentrations, an optimal methodology for radon and progeny measurement and dose calculation was sought. The program of measurement throughout the years was optimized, and now comprises 3-mo exposures of etched-track detectors, and twice a year, 8-10-d measurements using continuous monitors. Radon concentrations range from about 500 Bq m(-3) in winter to about 6,000 Bq m(-3) in summer, and equilibrium factors range from 0.42 to 0.69 in winter and from 0.33 to 0.86 in summer. Radiation doses from radon decay products for employees in the cave were calculated according to the ICRP 65 methodology. The basic input data are radon concentrations and equilibrium factors at two selected locations in the cave and the records of the time spent by a worker in the cave. Effective doses received by employees annually ranged from 0.02 to 8.4 mSv.

Environmental Exposure↗

Valine dehydrogenase from Streptomyces fradiae: purification and properties.

Valine dehydrogenase (VDH) was purified to homogeneity from cell-free extract of Streptomyces fradiae, which produces tylosin. The enzyme was purified 1508-fold in a 17.7% yield using a combination of hydrophobic chromatography and ion-exchange fast protein liquid chromatography. The Mr of the native enzyme was determined to be 218,000 and 215,000, by equilibrium ultracentrifugation and size-exclusion high-performance liquid chromatography, respectively. The enzyme is composed of 12 subunits of Mr 18,000. Using analytical isoelectric focusing the isoelectric point of VDH was found to be 4.7. Oxidative deamination of L-valine was optimal at pH 10.6. Reductive amination of 2-oxoisovalerate was optimal at pH 8.8. The Michaelis constants (Km) were 1 mM for L-valine and 0.029 mM for NAD+. Km values for reductive amination were 0.80 mM for 2-oxoisovalerate, 0.050 mM for NADH and 22 mM for NH4+.

Amino Acid Oxidoreductases↗

Evaluation of a candidate reference measurement procedure for serum free testosterone based on ultrafiltration and isotope dilution-gas chromatography-mass spectrometry.

BACKGROUND: To assess the analytical validity of free testosterone (FTe) measurements, a reference measurement procedure (RMP) is required. For steroids, isotope dilution-mass spectrometry is accepted as state-of-the-art technology. Because FTe is defined as the hormone fraction in serum water in equilibrium with the protein-bound fraction, the RMP should include a physical separation step. The use of equilibrium dialysis (ED) or ultrafiltration (UF) is advocated. Our objective was to develop such a candidate RMP. METHODS: We selected UF combined with isotope dilution-gas chromatography-mass spectrometry (ID-GC/MS) for direct measurement of Te in the ultrafiltrate. After optimization of the UF process, the complete procedure was validated by use of split-sample comparisons with indirect ED (iED) and symmetric dialysis (SyD). RESULTS: The candidate RMP gave maximum within-day, between-day, and total CVs of 3.0%, 3.1%, and 4.3%. The Deming regression equations for the respective method comparisons were: UF-ID-GC/MS = 0.98(iED) - 53 pmol/L (r = 0.94; S(y|x)= 42 pmol/L) and UF-ID-GC/MS = 0.92(SyD) + 21 pmol/L (r = 0.97; S(y|x)= 31 pmol/L). CONCLUSIONS: We achieved the objective of a state-of-the-art candidate RMP, which agreed well with iED and SyD. However, we also demonstrated that a degree of discordance remains, which may require a decision from an authoritative organization on the recommended procedure to measure free hormone concentrations.

Blood Proteins↗