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A mathematical treatment of AIDS and condom use.

In this paper we examine the impact of condom use on the sexual transmission of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) amongst a homogeneously mixing male homosexual population. We first derive a multi-group SIR-type model of HIV/AIDS transmission where the homosexual population is split into subgroups according to frequency of condom use. Both susceptible and infected individuals can transfer between the different groups. We then discuss in detail an important special case of this model which includes two risk groups and perform an equilibrium and stability analysis for this special case. Our analysis shows that this model can exhibit unusual behaviour. As normal, if the basic reproduction number, R0, is greater than unity then there is a unique disease-free equilibrium which is locally unstable and a unique endemic equilibrium. However, when R0 is less than unity two endemic equilibrium solutions can also co-exist simultaneously with the disease-free solution which is locally stable. Numerical simulations using realistic parameter values confirm this and we find that in certain circumstances the disease-free solution and one of the endemic solutions are both locally asymptotically stable, while the other endemic solution is unstable. This unusual behaviour has important implications for control of the disease as reducing R0 to less than unity no longer guarantees eradication of the disease. For a restricted special case of this two-group model we show that there is only the disease-free equilibrium for R0 < or = 1 which is globally stable. For R0 > 1 the disease-free equilibrium is unstable and there is a unique endemic equilibrium which is locally stable. We then attempt to fit the model to HIV and AIDS incidence data from San Francisco, USA. The paper concludes with a brief discussion.

Acquired Immunodeficiency Syndrome↗

Pattern formation in intracortical neuronal fields.

This paper introduces a neuronal field model for both excitatory and inhibitory connections. A single integro-differential equation with delay is derived and studied at a critical point by stability analysis, which yields conditions for static periodic patterns and wave instabilities. It turns out that waves only occur below a certain threshold of the activity propagation velocity. An additional brief study exhibits increasing phase velocities of waves with decreasing slope subject to increasing activity propagation velocities, which are in accordance with experimental results. Numerical studies near and far from instability onset supplement the work.

Action Potentials↗

[Purification and stability studies of prokaryotic PDCD5 protein].

OBJECTIVE: To set up an effective and simple purification method to obtain highly purified prokaryotic protein of PDCD5 and study its stability. METHODS: Recombinant PDCD5 protein expressed in E. coli. was accumulated as an inclusion body. After washing, the inclusion body was denatured, renatured, digested with thrombine and then purified by two steps of chromatography. The purity of the products was analyzed by capillary electrophoresis and the stability was identified by SDS-PAGE. RESULTS: Capillary electrophoresis showed that the purity of protein was 100%, and molecular weight was 15,800 with pI 5.9. Further bioactivity assay indicated that the purified PDCD5 could enhance the apoptosis of HL-60 cells withdrawing cytokine, which was in a dose-dependent manner. Stability analysis showed that the PDCD5 protein was sensitive to temperature and easy to degrade at 4 degrees C and 25 degrees C. However, it was relatively stable at -20 degrees C or lyophilized. CONCLUSION: Highly purified and stable recombinant PDCD5 protein was obtained, which lays a foundation for the functional study and application investigation of PDCD5.

Apoptosis Regulatory Proteins↗

Validity and reliability of BodyGem for measuring resting metabolic rate on Taiwanese women.

Resting metabolic rate (RMR) accounts for about two thirds of total energy expenditure. The widely used Harris-Benedict equations systematically overestimate RMR. This study assessed overall reliability and validity of a handheld indirect calorimeter, BodyGem, on a sample of women. Thirty healthy nurses participated in this study with an age of 41.9+/-9.0 years old and a body mass index of 24.0+/- 2.8 kg/m2. The Deltatrac Metabolic Monitor was used as the criterion method to validate BodyGem. Reliability was estimated by repeated measures of BodyGem to test internal consistency and stability. Analysis indicated that measurements of Deltatrac and BodyGem are well correlated (r=0.76, P<0.001). The correlation coefficients of two BodyGem RMR measurements were of large statistical significance (r=0.96, P<0.001, mean difference = 15.8+/-55.8 Kcal/d). A significant difference (F =3.81, P=0.04) in repeated measures ANOVA and post hoc revealed a difference between BodyGem and Deltatrac. There was a systematic difference between both methods (mean difference between BodyGem and Deltatrac =36.4 to 52.2 Kcal/d). After adjustment of additional energy demand by holding BodyGem in position, the difference became non-significant (F =1.62, P=0.22). Bland-Altman plots revealed that there was no significant trend in both methods, and repeated measurements of Bodygem. In conclusion, RMR obtained using the BodyGem has a high degree of reproducibility and an acceptable validity compared to the Deltatrac. Further validity research is needed in Taiwanese women.

Adult↗

[Use of DNA polymorphism detected by M13 phage DNA in population studies].

Hypervariable "minisatellite" regions detected in human genome by wild-type phage M13 DNA were found to have high polymorphism and somatic stability. Analysis of individual specific patterns of hybridization of 44 human DNAs from the Kirov province is presented. Molecular weight of fragments varied from 2 to 6 kb. Mean frequency of a fragment in the population under study is p = 0.294 +/- 0.158. The mean number of fragments per individual is 11.6 +/- 1.8. Comparison between the Kirov population and that of Krasnodar studied earlier was carried out. The mean genetic distance between Kirov and Krasnodar populations calculated according to Nei is 0.2082. The possibility of using in population-genetic studies of hypervariable DNA markers having fingerprint type of hybridization is discussed.

Bacteriophages↗

Stacking energies in DNA.

Variations in base mono- and dipoles result in variations in stacking energies for the 10 unique neighbor pairs in DNA. Stacking energies for pair M on N, expressed as TMN, were derived by matrix decomposition of a large set of linear algebraic expressions relating the measured Tm for subtransitions emanating from large polymeric DNAs, and the fractional neighbor frequencies, fMN, for the domains responsible for the transitions, Tm = sigma fMNTMN. Tm were determined for subtransitions that dissociate in approximately all-or-none fashion in high resolution melting profiles of partially deleted and recombinant forms of pBR322 DNA. Three different analytical maneuvers were undertaken to resolve subtransitions: site-specific cleavage of domains; deletion of domains; and addition of domains. Three dozen domains of widely divergent, quasi-random neighbor frequencies were identified and assigned, resulting in a unique set of values for TMN with standard deviation, sigma = +/- 0.23 degree C. The average difference between calculated and experimental Tm for domains is only +/- 0.17 degree C, indicating that the thermodynamic properties of these domains are not in any way unusual. Assuming delta S to be constant for all pairs, the corresponding delta HMN are found to have a precision of +/- 10 calories.mol-1 and an accuracy of +/- 606 calories.mol-1. TMN used to calculate melting curves by statistical mechanical analysis of sequences of the different plasmid specimens in this study were in quantitative agreement with observed curves for most sequences. These TMN differ significantly from those determined previously and also correlate poorly with values determined by quantum chemical analysis. Stabilities of neighbor pairs, expressed as the difference in free energy between that for a given pair (MN) and that for the average of like pairs (M, N), depend on the relationship of stacked purines and pyrimidines as follows. delta delta Gpu-py(-466 cal) greater than delta delta Gpu-pu(+52 cal) greater than delta delta Gpy-pu(+335 cal) Differences between experimental Tm and Tm calculated with TMN for the isolated neighbor pairs in the B-conformation are useful in the identification of altered structures and unusual modes of dissociation of helixes. A significantly higher Tm is observed for the highly biased repeated sequence synthetic helixes dA.dT, d(AGC).d(GCT), and d(GAT).d(ATC), reflecting auxiliary sources of stability such as bifurcated hydrogen bonds and/or altered structures for these helixes.

Amino Acid Sequence↗

[Effect of a fragment of pBR322 plasmid in the region of tetracycline resistance gene on the stability of this plasmid].

A fragment destabilizing the pBR322 plasmid has been localized in the region of pBR322 tet gene promoter. On the basis of stability analysis of pBR322 derivatives comprising the modified region of tet gene, we deduced that it is the DNA sequence localized at the beginning of tet gene in the region of HindIII splitting site that ensures the plasmid destabilization, and not tet gene product or the active transcription of this region. The destabilizing effect of this fragment of the plasmid is manifested both in cis and in trans. Possible molecular mechanisms of the phenomenon are discussed.

DNA, Bacterial↗

May active solute flux control the cell volume in the steady state?

The dynamics of a bioreactor with a variable volume and an active solute flux based on the thermodynamics of irreversible processes and stability analysis was studied. The active solute flux may control both the bioreactor volume and the hydrostatic pressure as well as the concentration of the solute inside the cell in the steady state. The range of the active solute flux is limited by amplitudes (j1(0), J2(0] of the active transport depending on the membrane transport parameters. The dynamic system is stable for j0 greater than jth0.

Body Fluids↗

[Cloning and expression of beta-glucosidase gene in Xanthomonas campestris XA5-5].

A beta-glucosidase gene from Xanthomonas campestris XA5-5 was cloned in Escherichia coli with the broad-host-range plasmid pRK404. The beta-glucosidase encoding plasmid designated pLZS1 contained a 1.1kb PstI DNA fragment deriving from XA5-5. The plasmid pLZS1 was transconjugated by filter mating into XA5-5 producing homologous clones XA5-5(pLZS1). Plasmid stability analysis revealed that pLZS1 was more stable in XA5-5 than in E. coli JM83. The level of beta-glucosidase expressed in XA5-5 (pLZS1) was much higher than in E. coli JM83 (pLZS1) using salicin as the substrate. From the results obtained, it seems that the gene product of this cloned DNA fragment has higher affinity to salicin substrate, and in some sense reduces the affinity between the enzyme and pNPG substrate in XA5-5.

Cloning, Molecular↗

Multiple emulsions.

The purpose of this review is to update the information on multiple emulsions known to be promising delivery systems for both pharmaceuticals and cosmetic materials. The possibility of encapsulating active substances within liquid membranes may lead to interesting opportunities in both fields. Thus the formulation, manufacturing, stabilization, analysis and potential application of multiple emulsions seems to be worth surveying, putting a special emphasis on cosmetic applications.

Chemistry, Pharmaceutical↗

Differential use of protein 4.1 translation initiation sites during erythropoiesis: implications for a mutation-induced stage-specific deficiency of protein 4.1 during erythroid development.

Expression of multiple protein 4.1 isoforms in erythroid progenitors and in a variety of nonerythroid tissues results from alternative pre-mRNA splicing. In 4.1 pre-mRNA, several translation initiation sites are present; synthesis of isoforms larger than 80 kD occurs when an upstream 5' AUG is spliced in, whereas the 80-kD mature erythroid isoform is produced when the upstream AUG is spliced out and translation is initiated at the downstream AUG. During erythropoiesis, this splicing switch is developmentally regulated. We studied this developmental switch in hereditary elliptocytosis 4.1Alg, in which a DNA rearrangement involving the exon containing the downstream AUG results in loss of coding capacity for the 80-kD 4.1, leading to mature red blood cells deficient in 4.1 with decreased membrane mechanical stability. Analysis of erythroblast RNA by reverse transcriptase-polymerase chain reaction showed that, although it retained the upstream AUG, its coding region was approximately 2.2 kb, compared with approximately 2.5 kb of normal 4.1 mRNA, because of the deletion of exons, including the one that codes for the downstream AUG. Immunofluorescent microscopy and Western blot analysis documented protein 4.1 expression in HE 4.1Alg erythroblasts. These studies emphasize the crucial role of differentiation-regulated RNA splicing because, within the same erythroid tissue, the HE 4.1Alg phenotype did not appear until after the differentiation-associated splicing event.

Base Sequence↗

A reaction-diffusion model of cancer invasion.

We present mathematical analyses, experimental data, and clinical observations which support our novel hypothesis that tumor-induced alteration of microenvironmental pH may provide a simple but complete mechanism for cancer invasion. A reaction-diffusion model describing the spatial distribution and temporal development of tumor tissue, normal tissue, and excess H+ ion concentration is presented. The model predicts a pH gradient extending from the tumor-host interface, which is confirmed by reanalysis of existing experimental data. Investigation of the structure and dynamics of the tumor-host interaction within the context of the model demonstrates a transition from benign to malignant growth analogous to the adenoma-carcinoma sequence. The effect of biological parameters critical to controlling this transition are supported by experimental and clinical observations. Tumor wave front velocities determined via a marginal stability analysis of the model equations are consistent with in vivo tumor growth rates. The model predicts a previously unrecognized hypocellular interstitial gap at the tumor-host interface which we demonstrate both in vivo and in vitro. A direct correlation between the interfacial morphology and tumor wave front velocity provides an explicit, testable, clinically important prediction.

Carcinoma, Squamous Cell↗

Stability of the canine shoulder joint: an in vitro analysis.

The stability of the canine shoulder joint was assessed with and without the restraining effects of selected supporting structures. Shoulder joints from medium-sized (15 to 30 kg) canine cadavers were dissected, and all soft tissues were removed except for the 4 cuff muscles (supraspinous, infraspinous, teres minor, subscapular), the biceps muscle (m biceps brachii) and the joint capsule with its associated glenohumeral ligaments. The humerus was fixed in position, and with the shoulder extended, the joint was stressed into abduction, adduction, internal rotation, and external rotation. The range of motion was measured from transverse pins placed above and below the joint. Measurements were made before and after severance of the cuff tendons and joint capsule. In selected joints, medial and lateral luxations were created. The biceps tendon was then transposed medially or laterally, respectively, to aid joint stability. Selected medial luxations were stabilized by transferring a portion of the insertion of the supraspinous tendon to a medial location. All joints were stressed as just described, and the range of motion was measured before and after tendon transfer. The joint capsule with its associated glenohumeral ligaments was an important restraint of joint motion. Lateral transfer of the biceps tendon partially corrected lateral joint instability by imposed marked rotational constraints on the joint. Medial transfer of the biceps tendon or the supraspinous tendon partially corrected medial joint instability, but did not resolve rotational abnormalities.

Animals↗

Stability and cost analysis of clindamycin-gentamicin admixtures given every eight hours.

Stability and costs of a mixture of clindamycin and gentamicin in a single carrier solution for every-eight-hour i.v. administration were analyzed. Duplicate solutions containing clindamycin 900 mg (as the phosphate salt) and gentamicin 100 mg (as the sulfate salt) in 5% dextrose injection 150 mL in flexible plastic containers were prepared. Samples withdrawn at 0-24 hours were visually inspected and assayed for content of both drugs. Clindamycin concentrations were determined by high-performance liquid chromatography and gentamicin concentrations by fluorescence-polarization immunoassay. Preparation and administration times were measured in two trials to determine cost differences between every-eight-hour administration of the two-antibiotic mixture and separate administration of the two drugs (four daily doses of clindamycin and three of gentamicin). No precipitate was seen. Concentrations of both drugs after 24 hours were greater than 90% of initial concentrations. Total daily costs (per patient) for labor, drug, and carrier solution were $3.08 less when the two drugs were mixed and administered every eight hours. At the concentrations studied, clindamycin and gentamicin mixed together in 5% dextrose injection are stable for 24 hours. Administration of this drug mixture every eight hours is safe and less costly than separate administration of the two drugs.

Chromatography, High Pressure Liquid↗

Polymerized ragweed antigen E. IV. The analysis of the stability of molecular size and antigenic reactivity of the polymer.

Ragweed antigen E polymerized by treatment with glutaraldehyde offers a potentially improved method for immunotherapy of human IgE-mediated pollinosis because studies have demonstrated that the polymer retains antigenic reactivity but has decreased ability to release histamine when these functions are compared on a weight basis. The potential clinical usefulness of the polymer is dependent both on stability of the polymer and on retention of antigenic reactivity. The method used for the analysis of the stability of the polymer under conditions of storage was the comparison of gel filtration fractionation profiles. No depolymerization was demonstrated during storage conditions for 2 mo, and only minimal evidence of additional polymerization (less than 8%) or depolymerization (less than 7%) was observed after 6 mo of storage. There was no difference in the per cent of polymerized antigen E precipitated by rabbit antiserum after storage as compared with control samples.

Antigens↗

7-Deaza purine bases offer a higher ion stability in the analysis of DNA by matrix-assisted laser desorption/ionization mass spectrometry.

Oligodeoxynucleotides which contain 7-deaza analogues of the normal purine nucleotides have been synthesized both enzymatically and chemically. When subjected to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis, the modified samples offer both higher stability and increased sensitivity compared to otherwise identical unmodified oligodeoxynucleotides. In view of these observations, models for the fragmentation of oligodeoxynucleotides in MALDI-MS with positive ion detection mode are presented. Additionally, the potential use of 7-deaza purine nucleotides in the MALDI-MS analysis of DNA sequencing reactions is discussed.

Base Sequence↗

Biomechanical analysis of clinical stability in the cervical spine.

This study was undertaken because there is a dearth of objective information in the literature on the clinical instability of the cervical spine below C2. To our knowledge, it is the first biomechanical investigation designed to analyze clinical stability. We have carried out a quantitative analysis of the behavior of the spine as a function of the systematic destruction of various anatomic elements. Under controlled conditions designed to maintain the biological integrity of the specimens, 17 motion segments from 8 cervical spines were analyzed. The spines were studied with either flexion or extension simulated using physiologic loads. Some of the more important findings are: (1) In sectioning the ligaments, one observes small increments of change followed without warning by sudden, complete disruption of the spine; (2) Removal of the facets alters the motion segment such that in flexion, there is less angular displacement and more horizontal displacement; (3) The anterior ligaments contribute more to stability in extension than the posterior ligaments and in flexion, the converse is true; (4) The adult cervical spine is unstable, or on the brink of instability, when any of the following conditions are present: a) All the anterior or all the posterior elements are destroyed or unable to function. b) More than 3.5 mm horizontal displacement of one vertebra in relation to an adjacent vertebra measured on lateral roentgenograms (resting or flexion-extension). c) More than 11 degrees of rotation difference to that of either adjacent vertebra measured on a resting lateral or flexion-extension roentgenogram. These findings can be aptly applied to clinical situations and when instability as determined by the above criteria is present, surgical fusion or some other method to achieve stability should be seriously considered. Work is continuing on this problem as we do not consider this to be altogether complete or definitive. Hopefully, this initial study will stimulate further scientific and clinical investigations.

Adult↗

[Analysis of the stability and local cooperativity of DNA : elements permitting the recognition of promoters by DNA-dependent RNA polymerase].

Analysis of the local stability of promoters processed by E. Coli RNA polymerase shows that they bear a characteristic stability profile: two segments of low stability are located around --35 and --8 bases ahead of the transcription start and are generally bordered by more stable segments. This key profile may act as a recognition signal for both attracting and positioning the RNA polymerase in the promoter site.

Base Sequence↗