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PubMed2000

A new explicit stability criterion for human periodic breathing.

The aim of this paper is to carry out a stability analysis for periodic breathing in humans that incorporates the dynamic characteristics of ventilation control. A simple CO2 model that takes into account the main elements of the respiratory system, i.e. the lungs and the ventilatory controller with its dynamic properties, is presented. This model results in a three-dimensional non-linear delay differential system for which there exists a unique equilibrium point. Our stability analysis of this equilibrium point leads to the definition of a new explicit stability criterion and to the demonstration of the existence of a Hopf bifurcation. Numericall simulations illustrate the influence of physiological parameters on the stability of ventilation. and particularly the major role of the dynamic characteristics of the respiratory controller.

Carbon Dioxide↗
PubMed1991

Size analysis and stability study of lipid vesicles by high-performance gel exclusion chromatography, turbidity, and dynamic light scattering.

Vesicles of egg phosphatidylcholine (EPC) and phosphatidic acid (EPA) were prepared by reverse-phase evaporation (REV) followed either by sequential extrusion through polycarbonate membranes with pore diameters of 0.8, 0.4, 0.2, 0.1, and 0.05 micron or by filtration through 0.8-micron cellulosic or 0.22-micron polyvinylidene fluoride (PVF) membranes. The resulting vesicles ranging from 130 to 640 nm in mean diameter (REVs) were characterized by high-performance liquid chromatography (HPLC) using a TSK G6000 PW gel exclusion column. The efficiency of this technique to determine vesicle size parameters was studied by the analysis of the chromatograms in combination with dynamic light scattering (DLS) determination of the mean diameters (MD) of the fractionated vesicles in the region of the elution profile maxima. The HPLC TSK G6000 PW gel exclusion provides a reproducible and fast method of size characterization for lipid vesicles having MD up to 1 micron, the best selectivity being obtained in the 20- to 500-nm MD range. HPLC analysis of REV's demonstrates that: (i) both the average size and polydispersity of the vesicles decrease with decreasing pore size of the membranes, cellulosic or PVF "tortuous" ones being less efficient than "straight bores" polycarbonate ones; (ii) mixed EPC/EPA REVs sequentially extruded down through 0.2-micron polycarbonate membranes are highly deformable without rupture of the bilayer; and (iii) the mean size of extruded REV's is stable for at least 1 week. The role of EPA on the size stability of mixed EPC/EPA vesicles was studied by coupling HPLC gel exclusion and turbidity analysis of pure EPC and EPC/EPA (mole ratio: 91/9) sonicated small unilamellar vesicles as a function of time. The apparent size variation of EPC vesicles observed over a week, is mainly due to their aggregation which is significantly reduced by the introduction of a small amount of EPA in the vesicle membrane.

Chromatography, High Pressure Liquid↗
PubMed1993

Analysis of stability of human upright posture based upon the measurement of the head sway.

The paper is dealing with the description of a simple and inexpensive technique for recording and measuring of the head sway during upright stance. In particular the recording system and the evaluation of the body sway data are highlighted. The objectives of the head sway signal analysis are the determination of sway components in the side-to-side (lateral) direction and forward-backward (anteroposterior) direction. It is anticipated that it will be possible to extract from the digitized data some information about the transfer characteristic and stability margin of the neuromuscular control system concerned with the maintenance of equilibrium. Additional information of potential clinical significance could be obtained by correlating the measured sway data with electromyographically determined changes in the activity of the main postural muscles. The information obtained is comparable to that gathered by more sophisticated, and more expensive conventional devices. A special feature is the easy portability of the system which permits collection of stabilometric data even in remote locations, while the analysis on which the diagnostic assessment is based can be performed at a later date in a central facility equipped with the necessary instrumentation.

Head↗
PubMed1997

Stability and analysis of 2-chloro-2'-deoxyadenosine, 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine and 2-chloroadenine in human blood plasma.

Cladribine (2-chloro-2'-deoxyadenosine, CdA) is a purine nucleoside analog with activity against lymphoproliferative and autoimmune disorders. 2-Chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA), a derivative of CdA with better acid stability, shows a similar in vitro spectrum of activity as CdA. 2-Chloroadenine (CAde) is the major catabolite of both CdA and CAFdA. We have developed a high performance liquid chromatography method to measure CdA, CAFdA and their metabolite CAde in plasma. This method employees an internal standard, chloroadenosine (CAdo), and a C8 solid-phase extraction to isolate and concentrate the substances. Chromatographic separation was achieved using a C8 reverse-phase column, with UV detection at 265 nm, which gives a limit of detection of 1 nmol/l for all substances. The method was reproducible with intra- and inter-assay coefficients of variations below 6% at 50 nmol/l and at 5 nmol/l below 23%. The average recoveries of CdA, CAde, CAFdA and the internal standard were higher than 70%. Stability studies of authentic patient samples show that samples containing CdA should be kept in a refrigerator or on ice to prevent degradation. Plasma containing CAde should not be kept at -20 degrees C for longer than 10 weeks before analysis. CdA and CAFdA remain almost stable during storage at -20 degrees C for 12 weeks.

Adenine↗
PubMed2001

Shape stability of sonoluminescence bubbles: comparison of theory to experiments.

Single bubble sonoluminescence (SBSL) is the brief flash of light emitted from a single, stable, acoustically forced bubble. In experiments, the maximum pressure amplitude with which a bubble may be forced is limited by considerations of spherical stability. The traditional linear stability analysis predicts a threshold for SBSL at a much lower pressure amplitude than experimental observations. This work shows that if one constructs an accurate model of the radial dynamics, the traditional linear stability analysis predicts a boundary that is in excellent agreement with experimental data.

Journal Article↗
PubMed2000

Analysis and stability study of retinoids in pharmaceuticals by LC with fluorescence detection.

Liquid chromatographic (HPLC) methods with fluorescence detection at different wavelengths were developed for measurements of retinoic acids (13-cis and all-trans) in pharmaceutical dosage forms and components of 'retinoid solution' (all-trans retinoic acid, vitamin A palmitate and beta-carotene), a galenical of 'Di Bella therapy', using reversed phase columns under isocratic conditions. The stability of all-trans retinoic acid in cream and all-trans retinoic acid and vitamin A palmitate in 'retinoid solution' was investigated. Solid-phase extraction (SPE), using C18 sorbent was applied to the analysis of retinoic acids (9-cis, 13-cis and all-trans) in the 'retinoid solution' to obtain a practical and reliable sample clean-up. The results showed that these preparations (cream and solution) can be conveniently stored in the dark (t.a. or 2-8 degrees C): under these conditions about 86-87% of the all-trans retinoic acid initial concentration in both formulations and about 73-78% of vitamin A palmitate in the 'retinoid solution' remained after 90 days, while under sunlight exposure rapid degradation of the drugs was observed.

Chromatography, High Pressure Liquid↗
PubMed1993

Analysis and stability of phenylglyoxylic and mandelic acids in the urine of styrene-exposed people.

In this work a high-performance liquid chromatographic method is described that is reliable and practical for use in routine biological monitoring of exposure to styrene. The method uses a modern diode array detection technique by which mandelic and phenylglyoxylic acids can be measured simultaneously using different wavelengths. The liquid chromatographic method was compared to a gas chromatographic method developed for the analysis of mandelic, phenylglyoxylic and para-hydroxymandelic acids. The methods gave results consistent with each other. These two methods were then used to check the stability of the main metabolites of styrene, especially of phenylglyoxylic acid, in urine samples stored at +6 degrees C or at -18 degrees C for periods up to 70 days. None of the frozen samples showed any significant decrease in the phenylglyoxylic acid concentration, whereas at 6 degrees C one of the samples showed a reduction of 46% after 1 month.

Chromatography, Gas↗
PubMed1992

The folding of an enzyme. I. Theory of protein engineering analysis of stability and pathway of protein folding.

The theory, assumptions and limitations are outlined for a simple protein engineering approach to the problem of the stability and pathway of protein folding. It is a general procedure for analysing structure-activity relationships in non-covalent bonding, including enzyme catalysis, that relates experimentally accessible data to changes in non-covalent bonding. Kinetic and equilibrium measurements on the unfolding and refolding of mutant proteins can be used to map the formation of structure in transition states and folding intermediates. For example, the ratio of the changes in the activation energy of unfolding and the free energy of unfolding on mutation is measured to give a parameter phi. There are two extreme values of phi that are often found in practice and may be interpreted in a simple manner. A value of phi = 0 implies that the structure at the site of mutation is as folded in the transition state as it is in the folded state. Conversely, phi = 1 shows that the structure at the site of mutation is as unfolded in the transition state as it is in the unfolded structure. Fractional values of phi are more difficult to interpret and require a more sophisticated approach. The most suitable mutations involve truncation of side-chains to remove moieties that preferably make few interactions with the rest of the protein and do not pair with buried charges. Fractional values of phi found for this type of mutation may imply that there is partial non-covalent bond formation or a mixture of states. The major assumptions of the method are: (1) mutation does not alter the pathway of folding; (2) mutation does not significantly change the structure of the folded state; (3) mutation does not perturb the structure of the unfolded state; and (4) the target groups do not make new interactions with new partners during the course of reaction energy. Assumptions (2) and (3) are not necessarily essential for the simple cases of phi = 0 or 1, the most common values, since effects of disruption of structure can cancel out. Assumption (4) may be checked by the double-mutant cycle procedure, which may be analysed to isolate the effects of just a pair of interactions against a complicated background. This analysis provides the formal basis of the accompanying studies on the stability and pathway of folding of barnase, where it is seen that the theory holds very well in practice.

Bacterial Proteins↗
PubMed2001

Global stability, local stability and permanence in model food webs.

The dynamical theory of food webs has been based typically on local stability analysis. The relevance of local stability to food web properties has been questioned because local stability holds only in the immediate vicinity of the equilibrium and provides no information about the size of the basin of attraction. Local stability does not guarantee persistence of food webs in stochastic environments. Moreover, local stability excludes more complex dynamics such as periodic and chaotic behaviors, which may allow persistence. Global stability and permanence could be better criteria of community persistence. Our simulation analysis suggests that these three stability measures are qualitatively consistent in that all three predict decreasing stability with increasing complexity. Some new predictions on how stability depends on food web configurations are generated here: a consumer-victim link has a smaller effect on the probabilities of stability, as measured by all three stability criteria, than a pair of recipient-controlled and donor-controlled links; a recipient-controlled link has a larger effect on the probabilities of local stability and permanence than a donor-controlled link, while they have the same effect on the probability of global stability; food webs with equal proportions of donor-controlled and recipient-controlled links are less stable than those with different proportions.

Animals↗
PubMed2026

Pattern Formation in a Spatial Public Goods Dilemma due to Diffusive or Directed Motion.

The costly provision of public goods serves as a model problem for the evolution of cooperative behavior, presenting a social dilemma between the collective benefits of shared resources and the individual incentive to free-ride in resource production. The spatial structure of populations can also impact cooperation over public goods, as diffusion of public goods and intentional motion of individuals towards regions with greater resources can interact with population and public goods dynamics to produce heterogeneous patterns in the spatial distribution of strategies and resources. In this paper, we build off a model introduced by Young and Belmonte for the reaction dynamics of interacting individuals and an explicit public good, deriving a system of PDEs that describes the spatial profiles of strategies and the public good in the presence of both diffusive motion of individuals and resources and chemotaxis-like directed motion of individuals in response to gradients in the concentration of public goods. Through linear stability analysis, we show that spatial patterns in strategic and public goods profiles can emerge due to either Turing instability with high defector diffusivity or a directed-motion instability through strong sensitivity of cooperators towards increasing resource concentration. We further explore the emergent spatial patterns with a mix of weakly nonlinear stability analysis and numerical simulation, showing that, for a wide range of reaction parameters, diffusion-driven instability appears to increase cooperation and public goods across the spatial domain, while directed motion of cooperators towards public goods tends to decrease cooperation and environmental quality across the environment.

Models, Biological↗
PubMed2002

Rayleigh-Bénard convection with rotation at small Prandtl numbers.

We present experimental and theoretical results near the onset of the Rayleigh-Bénard convection with rotation about a vertical axis in a fluid with a Prandtl number sigma close to 0.18. In the experiment we used a H2-Xe gas mixture with a separation ratio Psi=0.22 and a Lewis number L=1.22 at various pressures and dimensionless rotation rates Omega up to 400. On the basis of a standard weakly nonlinear stability analysis, we found a supercritical, stationary bifurcation for Omega < than approximately 13, which became subcritical over the range 13 < than approximately Omega < or approximately 160. For Omega > than approximately 160 a supercritical Hopf bifurcation precedes the stationary instability of the uniform state. Following the unstable straight-roll fixed point in the subcritical regime by Galerkin methods we determined the location of the saddlenode and the stability of the nonlinear two-dimensional straight-roll state. The rolls were found to be unstable to three-dimensional Küppers-Lortz perturbations for 3.8 < than approximately Omega < than approximately 160. Theoretical results for a pure fluid with the same sigma were qualitatively similar. Measurements using shadowgraph flow visualization yielded a bifurcation line and an Omega range of subcriticality, which agreed with the stability analysis. In the subcritical range the experiment revealed a discontinuity of the pattern amplitude at onset, but was unable to find any hysteresis. Patterns at onset fluctuated irregularly between the ground state and the finite-amplitude state. In this parameter range the convection pattern further above onset was chaotically time dependent. Investigation of the Hopf bifurcation line was difficult because of a wall mode that, for large Omega, preceded the bulk instability. For Omega approximately equal to 400, patterns were found in the sample interior only when the expected Hopf bifurcation was exceeded by about 10%. This is consistent with the convective nature of the bifurcation. However, the observed structure, although time periodic, was spatially disordered and had a frequency that was considerably larger than the expected Hopf frequency. In a separate sample cell with a radial ramp in the spacing no structure was observed at all in the cell interior until the expected stationary instability was reached.

Journal Article↗
PubMed1999

Effects of protein-polyphenol interactions on beverage haze, stabilization, and analysis.

The haze-forming activity of a polypeptide depends greatly on its proline content. Haze-forming polyphenols have at least two binding groups, each of which has at least two hydroxy groups on an aromatic ring. The protein/polyphenol ratio has a strong influence on the amount of haze formed; the largest amount occurs when the numbers of polyphenol binding ends and protein binding sites are nearly equal. This has important consequences for turbidimetric methods used to measure haze-active proteins and polyphenols in beverages. The ratio also influences the effectiveness of a number of stabilization procedures.

Beverages↗
PubMed1998

[Alterations in postural control: the use of spectral analysis in stability measurement].

UNLABELLED: Static posturography studies the frequency at which the center of gravity in the human body oscillates. There is no universal agreement as to the importance of this index or whether it is specific in identifying alterations in the postural control systems (vestibular, proprioceptive and visual). Nevertheless, some hypotheses appear generally accepted: a) visual information dominates; b) proprioception affects anterior-posterior oscillation; c) relatively low frequency body oscillation is affected by vestibular input while higher frequency oscillations are controlled by proprioceptive information. In order to check these hypotheses, four groups of patients underwent spectral analysis of bodily oscillations recorded with static posturography. The four groups of patients were similar in terms of age and broken down as follows: Group A-peripheral diabetic neuropathy (10 cases); Group B-diabetic neuropathy-free patients (10 cases); Group C-pure peripheral vestibulopathy (10 cases); Group D-normal subjects (20 cases). Analysis was performed dividing the frequency spectrum (FFT) into three groups: gr. I) 0.01-0.7 Hz; gr. II) 0.7-1 Hz; gr. III) > 1 Hz. Analysis of the spectra for Group A showed a significant increase in high frequency bodily oscillation (gr. III) with the eyes open in the anterior-posterior direction (M = 8.6 +/- 5.5; p < 0.05) and in the lateral direction (M = 4.0 +/- 2.0; p < 0.05); an increase was also found in both directions with the eyes closed (M = OCX II: 7.4 +/- 1.5; p < 0.05) (M = OCX III: 5.6 +/- 1.6; p < 0.01) (M = OCY II: 16.8 +/- 5.0; p < 0.05) (M = OCY II: 9.2 +/- 4.4; p < 0.05). In Group B the increase was limited to high frequency anterior-posterior oscillations (gr. III) at open eyes (M = 3.6 +/- 1.6; p < 0.05) and at closed eyes (M = 4.4 +/- 1.5; p < 0.05). In Group C there was an increase in high frequency lateral oscillations (gr. III) at open eyes (M = 4.2 +/- 0.5; p < 0.01) and panfrequency oscillations at closed eyes (M = OCX I: 47.7 +/- 5.6; p < 0.01) (M = OCX II: 23.2 +/- 4.9; p < 0.01) (M = OCX III: 7.2 +/- 2.3; p < 0.05). CONCLUSIONS: The diabetic proprioceptive deficit appears to lead to multiplanar destabilization at the medium-to-high frequency range. The labyrinthine deficit, on the other hand, appears to cause lateral destabilization at all frequencies. The method of analysis used appears to provide useful parameters with which to evaluate static posture since they can specifically identify alterations in orthostatic bodily control of various origins.

Adult↗
PubMed2001

High-performance liquid chromatographic analysis and stability of anti-tumor agent temozolomide in human plasma.

Temozolomide (SCH 52365; TEMODAL) is an antineoplastic agent with activity against a broad spectrum of murine tumors. This compound is currently marketed in the European Union for the treatment of patients with glioblastoma multiforme and anaplastic astrocytoma, which are serious and aggressive types of brain cancers. It has been postulated that temozolomide exerts its in vivo activity via the decomposition product MTIC, which is believed to alkylate nucleophiles, and in the process is converted to AIC. A high-performance liquid chromatographic (HPLC) method was developed and validated for the analysis of temozolomide in human plasma. The determination of temozolomide involved extraction with ethyl acetate followed by separation on a reversed phase C-18 column and quantification by UV absorbance at 316 nm. The calibration curve was linear over a concentration range of 0.1-20 microg/ml. The limit of quantitation was 0.1 microg/ml, where the coefficient of variation (CV) was 0% and the bias was 10.0%. The method was precise with a coefficient of variation ranging from 2.5 to 6.9% and accurate with a bias ranging from 5.0 to 10.0%. Temozolomide was unstable at 37 degrees C in human plasma with a degradation t1/2 of 15 min; however, it was stable at 4 degrees C for at least 30 min. Temozolomide was stable in acidified human plasma (pH < 4) for at least 24 h at 25 degrees C, and for at least 30 days at -20 degrees C. Moreover, temozolomide was stable in acidified human plasma after being subjected to three freeze thaw cycles. The assay was shown to be specific, accurate, precise, and reliable for use in pharmacokinetic studies.

Antineoplastic Agents↗
PubMed1993

[The correlation between left ventricular segmental kinesis and a Selvester QRS analysis in stabilized myocardial infarct].

We have studied the relationship between left ventricular segmental wall motion evaluated by means of biplane left ventricular cineangiography and the myocardial infarct size estimated using Selvester's scoring system based on the QRS of the electrocardiogram. Seventy consecutive patients with old myocardial infarction were recruited. All patients underwent diagnostic retrograde left heart catheterization including left ventriculography and selective coronary arteriography. Nineteen patients were excluded from the study due to intraventricular conduction disturbances and left ventricular hypertrophy. Of the remaining 51 patients, aged 33-76 years (mean 56 years), 31 had inferior or postero-inferior myocardial infarction (Group 1); 7 patients had combined anterior and inferior myocardial infarction (Group 2); 13 patients had anterior or antero-septal myocardial infarction (Group 3). The analysis of left ventricular segmental wall motion was performed according to the Collaborative Studies in Coronary Artery Surgery assigning at hypokinesia, akinesia and dyskinesia 1, 2 and 3 points, respectively. The values of statistical correlations between QRS scoring system and ventricular scoring were: r = 0.85 (Group 1); r = 0.78 (Group 2); r = 0.70 (Group 3). Our data indicate that Selvester's scoring system may provide useful information on functional status and on the extent of left ventricular wall motion abnormalities in patients with previous myocardial infarction.

Adult↗
PubMed2001

Spatio-temporal pattern formation on spherical surfaces: numerical simulation and application to solid tumour growth.

In this paper we examine spatio-temporal pattern formation in reaction-diffusion systems on the surface of the unit sphere in 3D. We first generalise the usual linear stability analysis for a two-chemical system to this geometrical context. Noting the limitations of this approach (in terms of rigorous prediction of spatially heterogeneous steady-states) leads us to develop, as an alternative, a novel numerical method which can be applied to systems of any dimension with any reaction kinetics. This numerical method is based on the method of lines with spherical harmonics and uses fast Fourier transforms to expedite the computation of the reaction kinetics. Numerical experiments show that this method efficiently computes the evolution of spatial patterns and yields numerical results which coincide with those predicted by linear stability analysis when the latter is known. Using these tools, we then investigate the rĵle that pre-pattern (Turing) theory may play in the growth and development of solid tumours. The theoretical steady-state distributions of two chemicals (one a growth activating factor, the other a growth inhibitory factor) are compared with the experimentally and clinically observed spatial heterogeneity of cancer cells in small, solid spherical tumours such as multicell spheroids and carcinomas. Moreover, we suggest a number of chemicals which are known to be produced by tumour cells (autocrine growth factors), and are also known to interact with one another, as possible growth promoting and growth inhibiting factors respectively. In order to connect more concretely the numerical method to this application, we compute spatially heterogeneous patterns on the surface of a growing spherical tumour, modelled as a moving-boundary problem. The numerical results strongly support the theoretical expectations in this case. Finally in an appendix we give a brief analysis of the numerical method.

Animals↗