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Results for “Generation mean analysis”

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PubMed1993

POU-domain proteins: structure and function of developmental regulators.

POU-domain proteins are a group of developmental regulators found in organisms as distant as worm and man. The sequence conservation of the POU-domain has allowed the characterization of increasing numbers of proteins containing the domain, many of which act to control the generation and maintenance of differentiated cell phenotypes in organs as diverse as skin and brain. Analysis of the means by which POU-domain proteins regulate transcription has led to a further understanding of how this group initiates specific developmental programs.

Animals↗

PubMed1981

Response of epidermal cell proliferation to orally administered aromatic retinoid.

Hairless albino mice were fed aromatic retinoid in daily doses ranging from 1 to 50 mg/kg body weight. In animals receiving 1, 5, and 10 mg/kg, the thickness of the epidermis (vertical epidermal cross sectional areas) and the 3H-thymidine labeling indices were determined throughout a 3-week observation period. The following additional parameters were determined for animals fed 5 mg/kg; individual and cumulative cross sectional areas of epidermal cell nuclei and cytoplasms, nuclear-cytoplasm ratios, mean epidermal cell volume and mean number of epidermal cells. In animals fed 5 mg/kg for 7 days, an analysis of the cell kinetic parameters was performed including determination of duration of S and G2 phases, mean generation time and the proportion of noncycling (Go) cells. The changes induced by the aromatic retinoid were found to be dose dependent and consisted of a transitory cellular hypertrophy and a persistent numerical hyperplasia linked to increased labeling indices. The mean basal cell generation time was found to be greatly accelerated owing to a shortening of all cell cycle phases investigated.

Administration, Oral↗

PubMed2000

Rhythmic activity of uptake hydrogenase in the prokaryote Rhodospirillum rubrum.

Growth of Rhodospirillum rubrum was followed in cultures kept under anoxic conditions at constant temperature in either continuous light (LL, 32 degrees C) or continuous darkness (DD, 32 degrees C and 16 degrees C). In DD, only small modifications of the turbidity were detected; linear regression analysis nevertheless gives a very significant slope (t(34) = 13.07, p < 10(-14), with R2 of 0.834). Mean generation times reflected these differences of growth with 11.9+/-0.5 h in LL and 43.2+/-1.1 h in DD at 32 degrees C and 37.4+/-1.0 h at 16 degrees C cultures. The uptake hydrogenase (Hup) activity has been followed in situ in whole cells of R. rubrum grown in the same conditions, and a clear ultradian rhythm of activity has been observed. Indeed, after about 12 h in the new media, a rapid rise of hydrogenase activity was observed in both LL and DD cultures after which it decreased again to very low values. The activity of Hup continued to show such fluctuations during the rest of the experiment, both in DD and in LL, during the growth and stationary phases. The Lomb-Scargle power periodogram method demonstrates the presence of a clear rhythmic Hup activity both in LL and DD. In the LL-grown cultures, the oscillating activity is faster and continues throughout the growth and the stationary phases, with an ultradian period of 12.1+/-0.5 h. In DD, the slow-growing bacteria showed an ultradian oscillatory pattern of Hup activity with periods of 15.2+/-0.5 h at 32 degrees C and 23.4+/-2.0 h at 16 degrees C. The different periods obtained for LL- and DD-grown bacteria are significantly different.

Activity Cycles↗

PubMed1995

Nerve growth factor promotes the differentiation of pituitary mammotroph cells in vitro.

It is well known that the differentiation of somatotroph cells is dependent on GRF. The extracellular signals that direct the initial proliferation and differentiation of mammotroph cells during pituitary development, however, have remained elusive. In the present study we first report that somatomammotroph and mammotroph cells present in early postnatal rat pituitary cultures express the receptor for nerve growth factor (NGF) and contain NGF. In addition, we demonstrate that endogenous NGF supports the proliferation and terminal differentiation of mammotroph cells during postnatal in vitro maturation. Early postnatal rat pituitary cells were cultured for 1-12 days, double stained with antibodies to PRL and GH, and analyzed by fluorescence-activated cell sorting. Mature mammotroph cells were generated in culture as shown by 1) the increase in PRL production, 2) the spreading of cells secreting only PRL in relation to those producing both PRL and GH, and 3) the expression of D-2 receptors for dopamine. Exposure of cell cultures to NGF produced a remarkable increase in the rate of appearance of mammotroph cells and an increase in their abundance from 20 +/- 0.5% to 44 +/- 1%. Deprivation of secreted NGF by means of a specific antibody completely prevented the generation of mature mamotrophs. The fluorescence-activated cell sorting analysis of cells grown in the presence of the antibody to NGF showed, in fact, that although the proportions of somatotrophs and somatomammotrophs were unchanged, that of mammotrophs was much lower than that in untreated cultures. We, thus, conclude that NGF is critical for generation of the mammotroph phenotype during pituitary maturation.

Animals↗

PubMed2026

Pedagogical Efficacy of LLM-Generated Synthetic Data Versus Real-World Clinical Records: A Randomized Controlled Non-Inferiority Trial.

BACKGROUND: Expert-reviewed clinical cases generated by large language models (LLMs) may supplement case resources in medical education, but their short-term educational performance relative to real-case-derived teaching materials remains uncertain. We compared immediate post-training test performance after teaching with the two types of case materials and assessed non-inferiority against a prespecified margin. METHODS: We conducted a prospective, parallel-group, randomized non-inferiority trial. Through the Wenjuanxing online platform, participants were randomized 1:1 to learn with either real-case-derived teaching cases compiled by clinicians and reviewed by experts or AI-generated clinical cases produced by Gemini 3.0 Pro from fully de-identified matched real cases and reviewed by three senior general surgery specialists with full-professor rank. The primary outcome was the total score on an independent 10-item immediate post-training test (0-10 points), with a prespecified non-inferiority margin of -0.5 points. Secondary outcomes included the training-phase performance score, learning efficiency index, single-item mental effort rating, case realism, and case-source judgment. RESULTS: A total of 403 participants were randomized, of whom 386 were included in the modified intention-to-treat analysis: 192 in the real-case group and 194 in the AI-generated case group. The mean post-training test score was 4.95 (SD, 3.35) in the real-case group and 4.61 (SD, 3.35) in the AI-generated case group. The mean difference (AI-generated minus real-case group) was -0.335 points (95% CI, -1.006 to 0.337). Because the lower bound of the confidence interval was below the prespecified non-inferiority margin of -0.5 points, non-inferiority was not demonstrated (one-sided P = 0.314). No significant between-group differences were observed in the training-phase performance score, learning efficiency index, or single-item mental effort rating. AI-generated cases received lower realism ratings for Level 3 cases. The proportion of participants with at least one high-confidence completely incorrect response was 1.6% in the real-case group and 2.1% in the AI-generated case group. CONCLUSIONS: In this short-term, text-based online case-learning setting, no statistically significant between-group difference was observed in immediate post-training test performance; however, non-inferiority of AI-generated clinical cases relative to real-case-derived teaching materials was not demonstrated.

Humans↗

PubMed2000

Comparison of 99mTc-methoxyisobutyl isonitrile and 201T1 scintigraphy in visualization of suppressed thyroid tissue.

UNLABELLED: Both (201)TI and (99m)Tc-methoxyisobutyl isonitrile (MIBI) have been used in the visualization of suppressed thyroid tissue in patients with autonomously functioning thyroid nodules (AFTNs). It has been suggested that thyroid-stimulating hormone (TSH) control is not a major determinant of both tracers. However, the mechanism of thyroid uptake of these agents is controversial. In this study, we compared (201)TI and MIBI in the visualization of suppressed thyroid tissue in patients with a solitary toxic AFTN. METHODS: Thirty-two patients (13 triiodothyronine [T3] and 19 T3 + levorotatory thyroxine [T4] hyperthyroid patients) with toxic AFTNs visualized on (99m)Tc-pertechnetate scanning were included in the study. All patients underwent MIBI and (201)TI thyroid scintigraphy within a 3-d interval. The scintigrams were analyzed both visually and semiquantitatively. For the semiquantitative analysis, regions of interest (ROIs) were generated over the nodule (N) and contralateral normal lobe (E), and the mean counts in each ROI were calculated. RESULTS: The N/E uptakes (mean +/- SD) for pertechnetate, MIBI, and (201)TI were 11.37 +/- 4.53, 4.76 +/- 1.38, and 1.63 +/- 0.15, respectively, in T3 + T4 hyperthyroid patients and 9.46 +/- 3.64, 2.73 +/- 0.63, and 1.57 +/- 0.23, respectively, in T3 hyperthyroid patients. Our results showed that (201)TI uptake of suppressed thyroid tissue compared with AFTN was more prominent and significantly higher than that of MIBI for both groups of patients (P = 1.08E-05 for T3 and 6.15E-09 for T3 + T4 hyperthyroidism). There was no significant difference for either pertechnetate or (201)TI (P > 0.05) when the N/E uptakes of both groups of patients were compared. However, the N/E uptake of MIBI in T3 + T4 hyperthyroid patients was significantly higher than that in T3 hyperthyroid patients (P = 6.69E-06). CONCLUSION: Clear visualization of suppressed thyroid tissue with both (201)TI and MIBI in patients with low serum concentrations of TSH suggests that TSH is not a major factor in the thyroid uptake of either agent. (201)TI is superior to MIBI in the visualization of suppressed thyroid tissue in patients with a toxic thyroid nodule. An increased rate of metabolism in the follicular cells of AFTNs in T3 + T4 hyperthyroid patients compared with that in T3 hyperthyroid patients might be responsible for the higher N/E for MIBI compared with that for (201)TI.

Adult↗

PubMed2002

Histomorphometric analysis: comparative study of manual and digital image analysis using reproductive organ as a model.

A preliminary analysis of the histological features of testes was carried out on vertical serial sections stained with hematoxylin and eosin techniques. The total spermatogonia per view and areas of seminiferous tubules by means of digitizing the tissue followed by morphometric analysis using software run on a personal computer. The data generated was then compared with traditional manual determinations made by using the ocular scale as well as the x and y coordinated on the light microscope. The data obtained showed that the modified Image Pro system for digitizing and data analysis allowed for high-resolution acquisition of the images as well as relatively high sensitivity of image integration. The results also show more accuracy and repeatability of sampling and a decrease in sampling error between repeated measures compared with the conventional manual measurements. Overall, the use of modified Image Pro digital technology will offer a more accurate and quantitative method to perform routine histomorphometric analysis, as well as allow for repeated measurements of the same sample from several reviewers in a blinded fashion with substantially less error.

Animals↗

PubMed1986

[The origin of the eukaryotic cell. I. Historical sources and current state of the concept of symbiotic and autogenic origins of the cell].

The exogenous (symbiotic) conception of the eukaryotic origin is now widely spread. It is based on the recognition of the principle of combination (addition or enclosing) of diverse prokaryotic organisms; so the complicated unicellular eukaryotic organism (eukaryotic cell) was resulted. the principle of combination takes its historical scientific sources from the ideas of Buffon. With reference to the cell this principle was claimed for the first time. In our time the exogenous conception is characterized as a "symbiotic boom", because it is widely used in attempts to explain the origin of all the main organelles of the cell (right up to the micro-bodies). The autogenetic (endogenous) conception is based on the principle of straight phyliation, on the recognition of a successive evolutionary transformation of prokaryotic forms into eukaryotic ones. In this way all the cell organelles may have an endogenous origin. This principle springing from Lamarck has got a contemporary meaning in the doctrine of Darwin. In the next papers the author will present his own analysis and generation of the present day relevant facts to find out which of these two conceptions based on quite different scientific methodological principles may be correct.

Animals↗

PubMedDate not supplied

[Development and contribution to the validation of a brief French version of the Yesavage Geriatric Depression Scale].

Depression in old age is underdiagnosed. In order to help detection, Yesavage et al. (1983) developed the Geriatric Depression Scale in a 30 items original version, with good reliability and validity. To abbreviate duration of examination, a shortened 15 items version was proposed (Sheikh et al., 1986) and a 4 items GDS for primary care attenders was also developed (D'Ath et al., 1994) with satisfactory metrological characteristics. The aim of this study is to develop a short French version and to contribute to its validation. French elderly depressives (181) and controls (66) were asked to complete the 30 items GDS (french version) and an other french self-rating scale, the QD2A (Pichot, 1986). In an attempt to devise the short scale, data were subjected to logistic regression analysis, multiple regression analysis, item-total Spearman's rank correlation coefficients and finally to mean choice ranks combination method. The generated 4 items version (mini-GDS) was found to be highly correlated with GDS 30 (r = 0.84, p < 0.0001) and with QD2A (r = 0.64, p < 0.0001) and had a high level of internal consistency (KR20 = 0.66). The sensitivity and specificity of the GDS 4 were 69% and 80% (cut-off 0/1) and against QD2A were 75% and 75% (cut-off 0/1). Out of the four items, two were common with the D'Ath's 4 items version. Method with its different statistical developments was discussed and the 4 selected items of the mini-GDS were compared with data from several authors who evaluated, discussed or examined factor structures of the 30 items GDS. Conclusion is that mini-GDS is reliable to easily detect a depressive symptomatology in the elderly, in different circumstances.

Aged↗

PubMed1997

[The study of patient survival in cerebral hemorrhagic and ischemic accident].

The aim of this study was to study stroke survival in Chile in a historic cohort from a random sample of 333 inpatients. All alive selected patients were visited and examined. All the death certificates were reviewed. The diagnosis was done by a neurologist, 35% had a CT scan. Survival was measured in days using lifetest procedure to generate survival curves, Cox's proportional hazards models in Stata 3.1 statistic package and logistic regression analysis. The mean age was 70.5 for the group of died and 62.3 years old for alive patients (p = 0.01). Infectious disease (p = 0.05), localization of stroke (p = 0.01) and rehabilitation (p = 0.005) were significant at univariate analysis. The cumulative probability of survival was 38 days, after one year and after five years, 48.1, 39.0 and 19.8%, respectively. The probability of survival by age, localization, heart disease and rehabilitation was statistically significant. Analysis of survival by sex, and previous stroke risk factors was not significant. Using Cox's proportional hazards regression we found that survival after 5 years depends on age (p = 0.03), rehabilitation (p = 0.008), infection (p = 0.05) and heart disease (p = 0.04). Stroke survival function is close to a decreasing exponential curve with high death probability at one month after the stroke. Survival is conditioned by stroke localization, age, heart disease and rehabilitation.

Age Distribution↗

PubMed2003

Multi-detector row CT of left ventricular function with dedicated analysis software versus MR imaging: initial experience.

PURPOSE: To determine left ventricular (LV) volumetric and functional parameters from retrospectively electrocardiographically gated multi-detector row computed tomography (CT) by using semiautomated analysis software and to correlate results with those of magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 30 patients (mean age, 59.2 years +/- 7.1 [SD]) known to have or suspected of having coronary artery disease, four-channel multi-detector row CT was performed with standard technique, and diastolic and systolic image reconstructions were generated. With commercially available analysis software capable of semiautomated contour detection, end diastolic and end systolic LV volumes were determined from short-axis secondary CT reformations. Steady-state free-precession cine MR images were acquired in short-axis orientation within 48 hours and analyzed by using dedicated software. Bland-Altman analysis was performed to calculate limits of agreement and systematic errors between CT and MR imaging. RESULTS: Mean end diastolic (138.8 mL +/- 31.9) and end systolic (53.9 mL +/- 21.2) LV volumes as determined with CT correlated well with MR imaging measurements (142.0 mL +/- 32.5 [r = 0.93] and 54.9 mL +/- 22.8 [r = 0.94], respectively [P <.001]). LV ejection fraction (61.6% +/- 10.6 for CT vs 62.3% +/- 10.1 for MR imaging; r = 0.89) and stroke volume (84.6 mL +/- 20.9 for CT vs 86.9 mL +/- 21.5 for MR imaging; r = 0.88) also showed good correlation (P <.001). Bland-Altman analysis showed acceptable limits of agreement (+/-9.8% for ejection fraction) without systematic errors. CONCLUSION: In selected patients, semiautomated analysis software enables LV volumetric and functional analysis based on multi-detector row CT data sets, the results of which correlate well with MR imaging findings.

Aged↗

PubMed1997

Ca2+ homeostasis in the endoplasmic reticulum: coexistence of high and low [Ca2+] subcompartments in intact HeLa cells.

Two recombinant aequorin isoforms with different Ca2+ affinities, specifically targeted to the endoplasmic reticulum (ER), were used in parallel to investigate free Ca2+ homeostasis in the lumen of this organelle. Here we show that, although identically and homogeneously distributed in the ER system, as revealed by both immunocytochemical and functional evidence, the two aequorins measured apparently very different concentrations of divalent cations ([Ca2+]er or [Sr2+]er). Our data demonstrate that this contradiction is due to the heterogeneity of the [Ca2+] of the aequorin-enclosing endomembrane system. Because of the characteristics of the calibration procedure used to convert aequorin luminescence into Ca2+ concentration, the [Ca2+]er values obtained at steady state tend, in fact, to reflect not the average ER values, but those of one or more subcompartments with lower [Ca2+]. These subcompartments are not generated artefactually during the experiments, as revealed by the dynamic analysis of the ER structure in living cells carried out by means of an ER-targeted green fluorescent protein. When the problem of ER heterogeneity was taken into account (and when Sr2+ was used as a Ca2+ surrogate), the bulk of the organelle was shown to accumulate free [cation2+]er up to a steady state in the millimolar range. A theoretical model, based on the existence of multiple ER subcompartments of high and low [Ca2+], that closely mimics the experimental data obtained in HeLa cells during accumulation of either Ca2+ or Sr2+, is presented. Moreover, a few other key problems concerning the ER Ca2+ homeostasis have been addressed with the following conclusions: (a) the changes induced in the ER subcompartments by receptor generation of InsP3 vary depending on their initial [Ca2+]. In the bulk of the system there is a rapid release whereas in the small subcompartments with low [Ca2+] the cation is simultaneously accumulated; (b) stimulation of Ca2+ release by receptor-generated InsP3 is inhibited when the lumenal level is below a threshold, suggesting a regulation by [cation2+]er of the InsP3 receptor activity (such a phenomenon had already been reported, however, but only in subcellular fractions analyzed in vitro); and (c) the maintenance of a relatively constant level of cytosolic [Ca2+], observed when the cells are incubated in Ca2+-free medium, depends on the continuous release of the cation from the ER, with ensuing activation in the plasma membrane of the channels thereby regulated (capacitative influx).

Aequorin↗

PubMedDate not supplied

Aberrant photon responses in rods of the macaque monkey.

Recovery from bright light was studied in macaque rods by measuring the membrane current of single outer segments. The recovery phase of some responses displayed a plateau current of about one picoampere lasting for several seconds. The following evidence suggests these "steps" are single photon responses of abnormally long duration. (1) Over a limited range of intensities, step amplitude remained constant and summed linearly with intensity. The collecting area for step generation was about 2.6 x 10(-3) microns2. (2) Step duration varied exponentially with a mean duration of about 6.5 s. (3) Fluctuation analysis of the tail currents was consistent with the idea that a step is evoked by isomerization of a single rhodopsin molecule, and that only 1 in 400 isomerizations leads to a responses with a step-like waveform. (4) With only the distal portion of the outer segment in the electrode, the polarity of the step response reversed when the proximal portion of the outer segment was illuminated, indicating that step generation results from a local change in outer segment conductance near the site of photon absorption. (5) The probability of eliciting a step varied with the wavelength of light in the manner expected from the absorption spectrum of rhodopsin.

Animals↗

PubMed2003

Effects of resolution reduction on data analysis.

BACKGROUND: There is often a need in flow cytometry to display and analyze histograms at resolutions lower than those native to the data. It is common, for example, to analyze DNA histograms at 256-channel resolution, even though the data were acquired at 1,024 channels or more. The most common method for reducing resolution, referred to as the consecutive summation (CS) method, can introduce distortions into the shape of histograms. Peaks that were symmetric in the original data can become skewed in the reduced-resolution histogram. Data analysis can be negatively affected by the distortions produced by reducing the histogram resolution. An alternative technique for reducing histogram resolution, the unbiased summation (US) method, minimizes shape distortion. This paper describes the US method and examines the benefits it provides in the analysis of DNA histograms. METHODS: Reduced chi-square (RCS) was used to measure the response to three experimental variables in the least-squares analysis of simulated DNA histograms. For each variable (the percentage of coefficient of variation [%CV], number of events, and mean position of the G1 distribution), a test data set of 1,000 histograms was generated at 1,024-channel resolution. Histogram resolutions were reduced with each method and then analyzed with ModFit LT cell-cycle analysis software (Verity Software House, Topsham, ME). S-phase error and processor computation time of each method also were evaluated. A Monte Carlo experiment was performed to compare CS and US methods to theoretically correct reductions. RESULTS: CS method analysis results were negatively affected by changes in %CV, number of events, and G1 peak position. The US method produced consistently lower RCS values (more accurate results) within the tested ranges. The US method eliminated bias in S-phase error and had negligible impact on analysis processing speed. It improved RCS values 44.50% on average (P < 0.0002) with actual DNA histograms. Whereas the CS method became less accurate (chi-square test) as the amount of reduction increased, the US method was unaffected, producing consistently better results. CONCLUSIONS: The US method is recommended for reducing histogram resolution in modeling applications such as DNA cell-cycle analysis. It may have implications in other areas of flow cytometric data analysis.

Algorithms↗

PubMed1995

Influence of cohesive properties of micronized drug powders on particle size analysis.

Particle size analysis results with respect to micronized, mean particle size below 10 microns, furosemide, chloramphenicol palmitate and acetaminophen particles are dealt with in this paper. Special consideration was given to the effect of the agglomeration of particles on data generated by three size measurement techniques. The physicochemical basis for preparing sufficiently well dispersed and stable suspensions for analysis by employing mechanical methods of pretreatment are shown. Furthermore, methods to determine the state of dispersion and methods to assess the individual particle size before size analysis are described. An attempt was also made to establish the statistical confidence that can be assigned to a particular instrument and the confidence level that may be placed on comparative data obtained with the different particle size analysers. Results especially showed the impact of the agglomeration of very small furosemide particles, mean size 3 microns, on particle size analysis and the importance of controlling the cohesive properties of this drug. To overcome the problems associated with agglomeration more attention must be paid to the physical properties of the drug substance. Combining particle size analysis with bulk density, surface area and microscopical studies also helped to identify potential problems.

Acetaminophen↗

PubMed1994

A comparison of methods for testing homogeneity of proportions in teratologic studies.

We consider teratologic studies in which the aim is to compare the survival rate of animals in a treatment group to the corresponding rate in a control group. The design of such studies often involves the allocation of intact litters of animals to treatment, invalidating the application of standard statistical methods. We review the strengths and weaknesses of several approaches for dealing with this problem including methodology recently developed for the analysis of clustered binary data. A simulation study is conducted in which litter sizes are generated from a distribution having specified mean and degree of imbalance. It is recommended on the basis of this study and on theoretical considerations that the choice of method should depend on whether the comparison of interest is experimental or observational. For experimental comparisons, involving the random assignment of litters to different treatment groups, methods based on the adjustment of standard chi-square statistics are recommended unless the number of litters in each group is very large.

Animals↗

PubMed1995

Expression of LTP by AMPA and/or NMDA receptors is determined by the extent of NMDA receptors activation during the tetanus.

1. We have tested, in CA1 hippocampal slices, the hypothesis that the expression of long-term potentiation (LTP) by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and/or N-methyl-D-aspartate (NMDA) receptors depends on the degree of NMDA receptors activation during the tetanus. 2. Slices were perfused in an artificial cerebrospinal fluid (ACSF) containing glycine (1 microM), bicuculline (5 microM) and a low Mg2+ concentration (0.3 mM). To measure the AMPA and NMDA receptor-mediated field excitatory postsynaptic potential (fEPSPA and fEPSPN, respectively), we have used the following procedure: control fEPSPA was first measured, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) was then added, and fEPSPN was evoked. CNQX was washed, and once control fEPSPA was recorded, the Schaffer collaterals were tetanized at a weak or a strong intensity. The slope of fEPSPA was measured for 30-45 min followed by that of fEPSPN after the application of CNQX. 3. At a weak intensity (TW, which corresponds to a fEPSPA of approximately 0.3 mV of amplitude and no fEPSPN), the tetanic stimulation generated LTP of fEPSPA (58.7 +/- 8.1% mean +/- SE, n = 9) but no significant potentiation of the fEPSPN (11.2 +/- 2.2%, n = 9). These values were significantly different (P < 0.05, analysis of variance, Fisher test). 4. In 9 of 13 slices, tetanic stimulation of strong intensity (Ts, intensity corresponding to a fEPSPN of approximately 0.3 mV of amplitude) generated LTP of fEPSPN (89.1 +/- 17.2%) but not of fEPSPA (9.44 +/- 2.8%). In the four remaining slices the tetani induce LTP of both fEPSPA and fEPSPN (81.7 +/- 14.7% and 101 +/- 35.6%, respectively, both values were not significantly different). 5. We then examined the effects of decreasing fEPSPN by 50% in LTP generated by Ts and Tw. In the presence of 7-Chlorokynurenate (7Cl(-)-Kyn; 6 microM; n = 6), an antagonist of the allosteric glycine site of the NMDA receptors, Ts generated LTP of fEPSPA (63.2 +/- 8.2%) but not of fEPSPN (12.6 +/- 4.0%). Both values were significantly different. Tw still evoked LTP of fEPSPA but of smaller magnitude (29.8 +/- 6.3%, n = 8) than the one obtained in the absence of the antagonist (58.7 +/- 8.1%). Both values were significantly different. 6. The present observation suggests that l) LTP of fEPSPA has a lower threshold than that of fEPSPN, i.e., stronger activation of NMDA receptors during the tetani is required to induce LTP of fEPSPN than the one required for inducing LTP of fEPSPA; and 2) there is a bell-shaped relationship between the degree of activation of NMDA receptors during the tetani and the magnitude of LTP of the fEPSPA: tetani that generate LTP of fEPSPN have a low probability to induce LTP of fEPSPA. We suggest that AMPA and NMDA components are potentiated through two different presumably postsynaptic processes.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1993

Transition modes in Ising networks: an approximate theory for macromolecular recognition.

For a statistical lattice, or Ising network, composed of N identical units existing in two possible states, 0 and 1, and interacting according to a given geometry, a set of values can be found for the mean free energy of the 0-->1 transition of a single unit. Each value defines a transition mode in an ensemble of nu N = 3N - 2N possible values and reflects the role played by intermediate states in shaping the energetics of the system as a whole. The distribution of transition modes has a number of intriguing properties. Some of them apply quite generally to any Ising network, regardless of its dimension, while others are specific for each interaction geometry and dimensional embedding and bear on fundamental aspects of analytical number theory. The landscape of transition modes encapsulates all of the important thermodynamic properties of the network. The free energy terms defining the partition function of the system can be derived from the modes by simple transformations. Classical mean-field expressions can be obtained from consideration of the properties of transition modes in a rather straightforward way. The results obtained in the analysis of the transition mode distributions have been used to develop an approximate treatment of the problem of macromolecular recognition. This phenomenon is modeled as a cooperative process that involves a number of recognition subsites across an interface generated by the binding of two macromolecular components. The distribution of allowed binding free energies for the system is shown to be a superposition of Gaussian terms with mean and variance determined a priori by the theory. Application to the analysis of the biologically interaction of thrombin with hirudin has provided some useful information on basic aspects of the interaction, such as the number of recognition subsites involved and the energy balance for binding and cooperative coupling among them. Our results agree quite well with information derived independently from analysis of the crystal structure of the thrombin-hirudin complex.

Binding Sites↗