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Results for “Fluctuating selection”

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PubMed2006

[Compliance and persistence].

PURPOSE: 1) To summarize the literature on compliance (the extent to which the patient's behaviors correspond with the provider's recommendations) and persistence (total time on therapy) in patients with open-angle glaucoma or ocular hypertension. 2) To suggest guidelines to improve these two parameters, which are both essential and integral elements of optimizing patient care. METHODS: Compliance-related research published between 1980 and March 2005. RESULTS: Medication compliance has mostly been investigated and measured using patient self-reports, electronic monitoring, and medication possession ratio. Noncompliance-related problems are underestimated, complex, unpredictable and frequent. Noncompliance rates of at least 25% have been reported. The main obstacles to medication compliance are situational/environmental or related to the side effects or complexity of the medication regimen. Persistence with glaucoma medications has also been proven to be poor. Based on retrospective studies using survival analyses, fewer than 25% of patients may be persistent over 12 months. Persistence rates differ from one treatment to another and may fluctuate with time in the same patient. CONCLUSIONS: Improving the quality of information, the patient-physician relationship, and educating patients are all crucial. Simplification of the treatment regimen and selection of medications with the fewest systemic and ocular side effects must be a priority. Accurately assessing patient compliance and persistence are indispensable to reducing mistakes from either medication noncompliance or lack of persistence with poor efficacy and to avoid unnecessary changes in a patient's therapeutic regimen or surgery.

Glaucoma, Open-Angle↗
PubMed2006

Molecular engineering and measurements to test hypothesized mechanisms in single molecule conductance switching.

Six customized phenylene-ethynylene-based oligomers have been studied for their electronic properties using scanning tunneling microscopy to test hypothesized mechanisms of stochastic conductance switching. Previously suggested mechanisms include functional group reduction, functional group rotation, backbone ring rotation, neighboring molecule interactions, bond fluctuations, and hybridization changes. Here, we test these hypotheses experimentally by varying the molecular designs of the switches; the ability of the molecules to switch via each hypothetical mechanism is selectively engineered into or out of each molecule. We conclude that hybridization changes at the molecule-surface interface are responsible for the switching we observe.

Journal Article↗
PubMed2002

Evolution of microbial genomes: sequence acquisition and loss.

We present models describing the acquisition and deletion of novel sequences in populations of microorganisms. We infer that most novel sequences are neutral. Thus, sequence duplications and gene transfer between organisms sharing the same environment are rarely expected to generate adaptive functions. Two classes of models are considered: (1) a homogeneous population with constant size, and (2) an island model in which the population is subdivided into patches that are in contact through slow migration. Distributions of gene frequencies are derived in a Moran model with overlapping generations. We find that novel, neutral or near-neutral coding sequences in microorganisms will not be fixed globally because they offer large target sizes for mutations and because the populations are so large. At most, such genes may have a transient presence in only a small fraction of the population. Consequently, a microbial population is expected to have a very large diversity of transient neutral gene content. Only sequences that are under strong selection, globally or in individual patches, can be expected to persist. We suggest that genome size is maintained in microorganisms by a quasi-steady state mechanism in which random fluctuations in the effective acquisition and deletion rates result in genome sizes that vary from patch to patch. We assign the genomic identity of a global population to those genes that are required for the participation of patches in the genetic sweeps that maintain the genomic coherence of the population. In contrast, we stress the influence of sequence loss on the isolation and the divergence (speciation) of novel patches from a global population.

Biological Evolution↗
PubMed1991

Genomic diversity and antigenic variation of HIV-1: links between pathogenesis, epidemiology and vaccine development.

Recent analysis of primate lentivirus genomes indicates that lentiviruses have infected primates for hundreds of years. The pathogenicity of such viruses may fluctuate due to the high evolution rate of some parts of the viral genome. Fixed nucleic acid substitutions in the gag gene appear to be caused by random fixation of selectively neutral mutants, whereas nonrandom fixation of selectively advantageous mutants, as has been observed for MHC molecules and serine protease inhibitors, appears to be operational for some hypervariable env gene regions. The former is characterized by an excess of silent mutations independent of the rate of change, the latter by an excess of nonsilent mutations. This latter type of selection may especially characterize the third variable region of the external HIV envelope (V3), which contains the principal neutralization domain.

Acquired Immunodeficiency Syndrome↗
PubMed1975

Potential-dependent conductances in lipid membranes containing alamethicin.

This article is concerned primarily with the mechanism of the potential-dependent conductance induced in artificial lipid membranes by the cyclic polypeptide andibiotic alamethicin. It has already been shown from studies of the fluctuations that can be detected in very small membrane currents that alamethicin forms transient pores of some 0.6 nm in diameter and that, for small inorganic ions, these are poorly selective. The origin of these pores, their spatial distribution and interaction are discussed. It is demonstrated that the sensitivity of the membrane conductance to the applied potential arises only to a slight extent from the current-voltage relations for the individual pores, and that the main effect stems from the influence of the potential on the frequency of opening of the pores. From the properties of lipid membranes containing alamethicin in a wide variety of electrolytes, and from other evidence, it is concluded that the polypeptide reacts to the electric field more probably because it has dipole moment than because it binds ions. It is proposed that the conducting complex is capable of functioning in either of two orientations, and that it is these two possibilities that give rise to certain differences in the single channel characteristics for the two directions of the field.

Alamethicin↗
PubMed2002

Surface-related phase noise in SAW resonators.

With the advent of nanotechnologies, electronic devices are shrinking in thickness and width to reduce mass and, thereby, increase frequency and spe Lithographic approaches are capable of creating metal connections with thickness and lateral dimensions down to about 20 nm, approaching the molecular scale. As a result, the dimensions of outer particles are comparable with, or even larger than, those of active or passive regions in electronics devices. Therefore, directing our attention toward the effect of surface fluctuations is of practical significance. In fact, electronic device surface-related phenomena have already received more and more attention as device size decreases. In connection with surface phase noise, selection of a suitable device with high surface sensitivity is important. In this paper, high Q-value surface acoustic wave resonators were employed because of their strong sensitivity to surface perturbation. Phase noise in SAW resonators related to surface particle motion has been examined both theoretically and experimentally. This kind of noise has been studied from the point of view of a stochastic process resulting from particle molecular adsorption and desorption. Experimental results suggest that some volatile vapors can change flicker noise 1/f and random walk noise 1/f2. An analysis has been made indicating that these effects are not associated with Q value variation, but are generated by the change in the dynamic rate of adsorption and desorption of surface particles. Research on particle motion above the device substrate might explain the differences observed from the model based only on the substrate itself. Results might lead to a better understanding of the phase noise mechanism in micro-electronic devices and help us to build oscillators with improved performance.

Acoustics↗
PubMed1988

Theophylline-terbutaline, a steady state study on possible pharmacokinetic interactions with special reference to chronopharmacokinetic aspects.

1. The pharmacokinetic interaction of terbutaline and theophylline and chronopharmacokinetics of both drugs were studied in a three-way crossover study with repeated administration of terbutaline (Bricanyl Depot) 7.5 mg twice daily, theophylline (Theo-Dur) 300 mg twice daily alone or the combination of both for 7 days to 12 healthy volunteers (six male and six female). 2. After the morning dose on day 7, blood and urine were sampled for 12 h, and after the evening dose on day 7, blood and urine were sampled for 48 h. Theophylline concentrations in plasma and concentrations of unchanged drug and metabolites in urine were determined by two selective high performance liquid chromatography methods. Terbutaline concentrations in plasma and urine were measured with a gas chromatography-mass spectrometry method. Area under the plasma concentration-time curve, fluctuations in plasma concentration, mean residence time, elimination half-life, renal clearance as well as maximal, minimal and average plasma concentration at steady state were evaluated. 3. The addition of terbutaline to the repeated administration of theophylline lowered the relative bioavailability of theophylline by approximately 11% during the night interval. The rate of elimination of theophylline and mean residence time were influenced accordingly. No significant changes in excretion of the theophylline metabolites were observed, but the excretion of 3-methylxanthine was slightly reduced by the concomitant terbutaline administration. None of the observed changes should be of any clinical importance. 4. The addition of theophylline did not influence any of the calculated pharmacokinetic parameters of terbutaline. 5. It can be concluded that no dosage adjustment is necessary when terbutaline and theophylline are given together.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Linearity of summation of synaptic potentials underlying direction selectivity in simple cells of the cat visual cortex.

Intracellular recordings from simple cells of the cat visual cortex were used to test linear models for the generation of selectivity for the direction of visual motion. Direction selectivity has been thought to arise in part from nonlinear processes, as suggested by previous experiments that were based on extracellular recordings of action potentials. In intracellular recordings, however, the fluctuations in membrane potential evoked by moving stimuli were accurately predicted by the linear summation of responses to stationary stimuli. Nonlinear mechanisms were not required.

Animals↗
PubMed1999

Antioxidant defense in the follicular fluid of water buffalo.

Oxidative damages to the oocyte or follicular cells were suggested to trigger atresia. In water buffalo, loss of the blood-follicle barrier sieving effect on the diffusion of plasma haptoglobin was previously found to be associated with atretic oocytes. The redox status of water buffalo follicles was evaluated by measuring in follicular fluid both the total antioxidant capacity (TAC), expressed as Trolox equivalents, and the concentration of specific free radical scavengers, determined by high-performance liquid chromatography. Among follicles at random stages of the reproductive cycle (n = 74), a number (n = 32) were analyzed also for the cumulus-oocyte morphology or plasma haptoglobin penetration. The haptoglobin follicular concentration compatible with the barrier selectivity function was calculated to be less than 53% of the concentration in plasma. The data on TAC, retinol, alpha-tocopherol, gamma-tocopherol, ascorbic acid, and uric acid fluctuated in a wide range. The relative (follicular vs. plasmatic) levels of alpha-tocopherol were found to be negatively correlated with those of retinol (p < 0.01). In the follicles, the alpha-tocopherol levels were 1.25 +/- 0.35 or 1.99 +/- 0.72 microM when the haptoglobin concentration was <53 or >53% of the concentration in plasma, respectively. The concentration of ascorbic acid or uric acid was higher (up to 10- or 30-fold, respectively) in follicular fluid than in plasma. Fluids containing haptoglobin >53% or associated with cumulus-oocyte complexes of bad quality displayed levels of uric acid about 20-fold higher than in plasma. The results suggest that a high penetration of haptoglobin in the follicle and cumulus-oocyte degradation is associated with alterations of the level of the major antioxidants, particularly with enhancement of the uric acid concentration.

Animals↗
PubMed2005

[Study on analytic precision of laser microemission spectral analysis in argon atmosphere at reduced pressure].

According to mathematic statistics, data for laser microemission spectroscopic analysis were selected, which were collected with the use of CCD (charge-coupled device) in arg on atmosphere at reduced pressure. By selection, the effects of some factors, such as the difference of bore ablated on the sample surface by the laser, the distribution nonuniformity of element in the sample, and the fluctuation of output energy of the laser, etc. were reduced. The method that improves analytic precision of laser microemission spectroscopic analysis was studied. And quantitative analysis of Cu, Zn and Mg in aluminum alloy standard samples was performed, using the Cu (I) line at 324.7 nm, the Zn (I) line at 334.5 nm, and the Mg (I) line at 383.8 nm. The results show that the RSDs of relative intensity of the spectral lines of Cu, Zn, Mg are 1.80%, 4.35% and 6.29% respectively, and the RSDs of quantitative analysis of them are 10.1%, 6.98% and 8.17% respectively. The relative errors of the average of analysis of them are -3.76%, 3.62% and -1.62% respectively.

Algorithms↗
PubMed2005

Cycle dependent expression of endometrial metallothionein.

OBJECTIVES: Molecular changes observed in endometrium with respect to menstrual cycle changes seem to be crucial for the reproductive function. Accumulation of cytotoxic cells increases the exposure of endometrial cells to apoptosis. Protection against apoptosis may be reached by endometrial cells by self molecular regulation. Metallothionein was suggested to participate in this process. The aim of our study was to evaluate endometrial MT immunoreactivity with respect to the menstrual cycle phases. MATERIALS AND METHODS: MT expression was assessed using immunohistochemistry method in 47 endometrial tissue samples derived from randomly selected patients with respect to the menstrual cycle phases--proliferative and secretory with distinguishing early, mid and late subphases in each. RESULTS: MT expression changes were observed respectively to hormonal fluctuations with the highest level during mid secretory phase and its respective decrease during the early, late secretory and mid proliferative menstrual cycle phases. The lowest MT immunoreactivity level was disclosed during early proliferative phase. CONCLUSION: Significant differences in MT expression observed in endometrium with respect to menstrual cycle changes might suggest MT participation in endometrial cells protection against apoptosis.

Adult↗
PubMedDate not supplied

[Oscillating mechanism of chromosome conjugation].

The macroscopic theory of selective interaction of large molecules suspended in liquid medium is developed. The structure of such molecules permits them to maintain their excited oscilation at the expense of the medium thermal fluctuations. Interaction is realized through the oscillatory energy transfer from one macromolecule to another in the type of beatings. The resonant attraction forces, appearing in the second order of the bond constant, are proportional to the third degree of inverce distance between the oscilators.

Chemical Phenomena↗
PubMed1992

Leukemia inhibitory factor is expressed by the preimplantation uterus and selectively blocks primitive ectoderm formation in vitro.

Among its many activities, leukemia inhibitory factor (LIF) can maintain embryonic stem cell monolayers in a pluripotent undifferentiated state. Presuming that this might reflect its physiologic role during embryogenesis, we have examined LIF expression in the embryonic environment by RNase protection assays and have determined its in vitro effect on differentiating embryonic stem cell embryoid bodies. Of all adult tissues analyzed, LIF transcripts appear only in the uterus, where their level fluctuates with the estrous cycle, peaking after ovulation. LIF expression continues in the uteri of pregnant and pseudopregnant females, with a relative peak when blastocysts are normally present. As for its effects on in vitro differentiation, we have found that LIF blocks embryoid body differentiation only partially, yet in a precise manner. Using molecular markers to follow the differentiation of defined cell types, we demonstrate that LIF selectively inhibits the formation of primitive ectoderm, while permitting the differentiation of primitive endoderm. These results suggest a specific role for LIF in preimplantation mouse development.

Animals↗
PubMed1998

Hypervariability generated by natural selection in an extracellular complement-inhibiting protein of serotype M1 strains of group A Streptococcus.

In many countries, M1 strains of the human pathogenic bacterium group A Streptococcus are the most common serotype recovered from patients with invasive disease episodes. Strains of this serotype express an extracellular protein that inhibits complement [streptococcal inhibitor of complement (Sic)] and is therefore believed to be a virulence factor. Comparative sequence analysis of the 915-bp sic gene in 165 M1 organisms recovered from diverse localities and infection types identified 62 alleles. Inasmuch as multilocus enzyme electrophoresis and pulsed-field gel electrophoresis previously showed that most M1 organisms represent a distinct streptococcal clone, the extent of sic gene polymorphism was unexpected. The level of polymorphism greatly exceeds that recorded for all other genes examined in serotype M1 strains. All insertions and deletions are in frame, and virtually all nucleotide substitutions alter the amino acid sequence of the Sic protein. These molecular features indicate that structural change in Sic is mediated by natural selection. Study of 70 strains recovered from two temporally distinct epidemics of streptococcal infections in the former East Germany found little sharing of Sic variants among strains recovered in the different time periods. Taken together, the data indicate that sic is a uniquely variable gene and provide insight into a potential molecular mechanism contributing to fluctuations in streptococcal disease frequency and severity.

Antigens, Bacterial↗
PubMed2006

CORSICA: correction of structured noise in fMRI by automatic identification of ICA components.

When applied to functional magnetic resonance imaging (fMRI) data, spatial independent component analysis (sICA), a data-driven technique that addresses the blind source separation problem, seems able to extract components specifically related to physiological noise and brain movements. These components should be removed from the data to achieve structured noise reduction and improve any subsequent detection and analysis of signal fluctuations related to neural activity. We propose a new automatic method called CORSICA (CORrection of Structured noise using spatial Independent Component Analysis) to identify the components related to physiological noise, using prior information on the spatial localization of the main physiological fluctuations in fMRI data. As opposed to existing spectral priors, which may be subject to aliasing effects for long-TR data sets (typically acquired with TR >1 s), such spatial priors can be applied to fMRI data, regardless of the TR of the acquisitions. By comparing the proposed automatic selection to a manual selection performed visually by a human operator, we first show that CORSICA is able to identify the noise-related components for long-TR data with a high sensitivity and a specificity of 1. On short-TR data sets, we validate that the proposed method of noise reduction allows a substantial improvement of the signal-to-noise ratio evaluated at the cardiac and respiratory frequencies, even in the gray matter, while preserving the main fluctuations related to neural activity.

Biometry↗
PubMed1999

Dominant frequency uncertainty analysis of EEG alpha activity in pilots with transient ischemic attacks.

Objective. To study the characteristics of EEG after transient ischemic attack and to offer reference for screening procedure of aircrew and astronaut selection. Method. The dominant frequency uncertainty of alpha band EEG in 12 pilots (males; age 30 +/- 5) with transient ischemic episodes in middle cerebral artery (MCA) territories and in 20 normal healthy pilots was analyzed with frequency-fluctuation analysis. Result. The dominant probability of the main frequency coinciding with sites affected by transient ischemic attack (TIA) in patient pilots was higher than that in healthy pilots (P<0.01), and the dominant probability ratio logarithmic index I >or= 0 in all patient pilots with normal EEG, but I<0 in all healthy pilots. It was also found that not only I >or= 0, but the second component shifted to lower frequency (8 Hz) in patients with slight focal EEG alterations, i.e. slowing of frequency. The relative entropy values (percentage) were decreased significantly in pilots with TIA as compared with healthy pilots (P<0.05). Conclusion. The dominant frequency uncertainty analysis of alpha band showed clear superiority of computerized evaluation over routine visual assessment for the diagnosis of minor cerebral ischemia. It offers not only a possibility of studying pathophysiological functional parameter, but also the reference for screening procedure in aircrew and astronaut selection.

Acceleration↗
PubMed2006

Hybrid molecular probe for nucleic acid analysis in biological samples.

The ability to detect changes in gene expression, especially in real-time and with sensitivity sufficient enough to monitor small variations in a single-cell, will have considerable value in biomedical research and applications. Out of the many available molecular probes for intracellular monitoring of nucleic acids, molecular beacon (MB) is the most frequently used probe with the advantages of high sensitivity and selectivity. However, any processes in which the MB stem-loop structure is broken will result in a restoration of the fluorescence in MB. This brings in a few possibilities for false positive signal such as nuclease degradation, protein binding, thermodynamic fluctuation, solution composition variations (such as pH, salt concentration) and sticky-end pairing. These unwanted processes do exist inside living cells, making nucleic acid monitoring inside living cells difficult. We have designed and synthesized a hybrid molecular probe (HMP) for intracellular nucleic acid monitoring to overcome these problems. HMP has two DNA probes, one labeled with a donor and the other an acceptor. The two DNA probes are linked by a poly(ethylene glycol) (PEG) linker, with each DNA being complementary to adjacent areas of a target sequence. Target binding event brings the donor and acceptor in proximity, resulting in quenching of the donor fluorescence and enhancement of the acceptor emission. The newly designed HMP has high sensitivity, selectivity, and fast hybridization kinetics. The probe is easy to design and synthesize. HMP does not generate any false positive signal upon digestion by nuclease, binding by proteins, forming complexes by sticky-end pairing, or by other molecular interaction processes. HMP is capable of selectively detecting nucleic acid targets from cellular samples.

Animals↗
PubMed2006

Duplication, balancing selection and trans-species evolution explain the high levels of polymorphism of the DQA MHC class II gene in voles (Arvicolinae).

Major histocompatibility complex (MHC) genes play important role in host-parasite interactions and parasites are crucial factors influencing the population dynamics of hosts. We described the structure and diversity of exon 2 of the MHC class II DQA gene in three species of voles (Arvicolinae) exhibiting regular multi-annual fluctuations of population density and analysed the processes leading to the observed MHC polymorphism. By using cloning-sequencing methodology and capillary electrophoresis-single strand conformation polymorphism, we described seven sequences in the water, eight in the common, and seven in the bank voles coming from an area of 70 km(2) around the Nozeroy canton in the Jura Mountains (Franche Comté, France). All exon 2 sequences translate to give unique amino acid sequences and positive selection was found to act very intensively on antigen binding sites. We documented the presence of recombination at vole DQA region but its importance in generating allelic polymorphism seems to be relatively limited. For the first time within rodents, we documented the duplication of the DQA gene in all three species with both copies being transcriptionally active. Phylogenetic analysis of allelic sequences revealed extensive trans-species polymorphism within the subfamily although no alleles were shared between species in our data set. We discuss possible role of parasites in forming the recent polymorphism pattern of the DQA locus in voles.

Alleles↗