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At least 1,315 records · Page 73Linked to original sources
PubMed1991

Mechanisms of the tetrahydroaminoacridine effect on action potential and ion currents in myelinated axons.

9-Amino-1,2,3,4-tetrahydroacridine (THA) in the range of 10-300 microM was shown to prolong the action potential in myelinated nerve fibres of Xenopus laevis. Voltage-clamp experiments showed that THA, besides reducing the Na+ and the K+ current, modified the Na+ current inactivation and the K+ current activation. The effects were frequency dependent. Quantitative models were developed and used in computer simulations of the THA effect on the action potential. The computations showed that the observed effects on the ion currents were sufficient to explain the observed prolongation of the action potential. The models further suggest that THA binds to Na+ channels in an open state and from the axoplasmic side while it binds to K+ channels in a closed state. The findings suggest an explanation to some aspects of the clinical effects of THA on Alzheimer patients.

Action Potentials↗
PubMed1996

Introducing spatio-temporal reasoning into the inverse problem in electroencephalography.

Studying the Brain's Electrical and Magnetic Signals (BEMS) requires the contribution of many area of research that include anatomy, neurophysiology and electromagnetic theory. NEUROLAB is a framework dedicated to the study of brain disorders. Upon completion, it should provide users with an intelligent computational environment that incorporates qualitative and quantitative models of the brain and head, and a model for representing and reasoning about time and space. Spatio-temporal knowledge of a given problem is represented as a constraint network where to each node of the network are attached temporal and spatial variables that must satisfy the constraints defined by the arch labels connecting the nodes. In this paper, we show how temporal reasoning can be combined with spatial descriptions to produce different scenarios of possible seizure spread. These scenarios can provide a priori information for the inverse problem the role of which is to localise the sources of the observed BEMS.

Artificial Intelligence↗
PubMed1995

Helix design, prediction and stability.

Recent work revealing that our knowledge is now sufficient to build a reasonable quantitative model for the helix/coil transition in heteropolypeptides represents a watershed in research into alpha-helix stability, prediction and design. The opportunity is presented to design specific alpha-helix propensity patterns that may be used both to modify thermodynamic properties of target proteins and peptides, and for de novo protein design. Despite these advances, the picture is not yet complete and further studies of still poorly characterized factors are required to obtain a more precise understanding of alpha-helix stability.

Amino Acid Sequence↗
PubMed1993

A rich complexity emerges in phototransduction.

Over the past two decades there has been an explosive growth in our understanding of phototransduction, leading to the development of a comprehensive scheme for the process. On the basis of this scheme the finer details of the process are being elucidated. Additional protein components and pathways have been identified, successful quantitative models of parts of the process have been developed, and a detailed understanding of the molecular basis of physiological function has begun to emerge. Here we summarize the most recent developments.

Animals↗
PubMed1993

Pattern generation.

Significant advances have been made in understanding the cellular mechanisms for pattern generation in both invertebrate and vertebrate preparations. In a number of preparations, slow neuromodulators have been shown not only to modify network function, but to be intimately involved in development and/or normal function of the neural network and its associated behavior. The mechanisms underlying coordination between multiple pattern-generating networks, including switching of neurons from one network to another, are now being studied. Several new quantitative models of network function have been developed, and modeling is now an important component of research in this field.

Animals↗
PubMed1995

Work hours and sleepiness.

The present paper finds that shift work is associated with severe sleepiness on the night shift and to some extent on the morning shift. This sleepiness is at least as severe as that seen in hypersomnia and is associated with a strongly increased risk of accidents. The reason for night shift sleepiness is work at the circadian nadir, extended periods of wakefulness, and truncated sleep. Much of the sleepiness in shift work may be predicted using a quantitative model.

Accidents, Occupational↗
PubMed2006

Computerized estimation of the lung volume removed during lung volume reduction surgery.

RATIONALE AND OBJECTIVES: This study was designed to develop an automated method for estimating lung volume removed during lung volume reduction surgery (LVRS) using computed tomography (CT). MATERIALS AND METHODS: The CT examinations of six patients who underwent bilateral LVRS were analyzed in this study. The resected lung tissue (right and left) was weighed during pathologic examination. An automated computer scheme was developed to estimate the lung volume removed using the CT voxel values and lung specimen weight. The computed fraction of lung volume removed was evaluated across a range of simulated surgical planes (ie, other than parallel to the CT image plane) and CT reconstruction kernels, and it was compared with the surgeons' postsurgical estimates. RESULTS: The computed fraction of the lung volume removed during LVRS was linearly correlated with the resected lung tissue weight (Pearson correlation = 0.697, P = .012). The computed fraction of lung volume removed ranged from 12.9% to 51.7% of the total lung volume. The surgeons' postsurgical estimates of lung volume removed ranged from 30% to 33%. The percent difference between the surgeons' estimates and the computed lung volume removed as a percentage of the surgeons' estimates ranged from -72.3% to 57.0% with mean absolute difference of 29.7% (+/-20.7). CONCLUSION: The preliminary findings of this study suggest that the proposed quantitative model should provide an objective measure of lung volume removed during LVRS that may be used to investigate the relationship between lung volume removed and outcome.

Absorptiometry, Photon↗
PubMed2006

Force encoding by human periodontal mechanoreceptors during mastication.

This overview summarises current knowledge on the force-encoding properties of periodontal mechanoreceptors supplying the human postcanine teeth and describe their signalling during chewing. Microneurographic experiments reveal that these receptors adapt slowly to maintained tooth loads. Similar to periodontal receptors at anterior teeth, about half respond to forces applied to more than one tooth and their receptive fields are broadly tuned to direction of force application. However, population analyses demonstrate that periodontal receptors supplying anterior and posterior teeth differ in their capacity to signal horizontal and vertical forces, respectively. Most periodontal receptors exhibit a strongly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in force at forces below 1N for anterior teeth and 4N for posterior teeth. Also the dynamic sensitivity is markedly reduced at high forces. According to a quantitative model of responses in periodontal receptors based on these data, most receptors efficiently encode food contact during chewing, but due to the marked saturation tendencies at higher forces these receptors poorly encode the magnitude of the strong chewing forces and the force changes occurring at these high loads. Information provided by periodontal receptors is critical for the specification of manipulative forces used when food is positioned between the teeth and prepared for chewing. When the strong chewing forces are applied to crush the food, the receptors signal functionally important information about the mechanical properties of food as well as the spatial contact patterns between the food and the dentition.

Humans↗
PubMed2006

Charge compensation during the phagocyte respiratory burst.

The phagocyte NADPH oxidase produces superoxide anion (O(2)(.-)) by the electrogenic process of moving electrons across the cell membrane. This charge translocation must be compensated to prevent self-inhibition by extreme membrane depolarization. Examination of the mechanisms of charge compensation reveals that these mechanisms perform several other vital functions beyond simply supporting oxidase activity. Voltage-gated proton channels compensate most of the charge translocated by the phagocyte NADPH oxidase in human neutrophils and eosinophils. Quantitative modeling of NADPH oxidase in the plasma membrane supports this conclusion and shows that if any other conductance is present, it must be miniscule. In addition to charge compensation, proton flux from the cytoplasm into the phagosome (a) helps prevent large pH excursions both in the cytoplasm and in the phagosome, (b) minimizes osmotic disturbances, and (c) provides essential substrate protons for the conversion of O(2)(*-) to H(2)O(2) and then to HOCl. A small contribution by K+ or Cl- fluxes may offset the acidity of granule contents to keep the phagosome pH near neutral, facilitating release of bactericidal enzymes. In summary, the mechanisms used by phagocytes for charge compensation during the respiratory burst would still be essential to phagocyte function, even if NADPH oxidase were not electrogenic.

Animals↗
PubMed2004

Structural determinants of heparan sulfate interactions with Slit proteins.

We have previously demonstrated that the Slit proteins, which are involved in axonal guidance and related processes, are high-affinity ligands of the heparan sulfate proteoglycan glypican-1. Glypican-Slit protein interactions have now been characterized in greater detail using two approaches. The ability of heparin oligosaccharides of defined structure (ranging in size from disaccharide to tetradeccasaccharide) to inhibit binding of a glypican-Fc fusion protein to recombinant human Slit-2 was determined using an ELISA. Surface plasmon resonance (SPR) spectroscopy, which measures the interactions in real time, was applied for quantitative modeling of heparin-Slit binding on heparin biochips. Heparin was covalently immobilized on these chips through a pre-formed albumin-heparin conjugate, and the inhibition of Slit binding by heparin, LMW heparin, and heparin-derived oligosaccharides (di-, tetra-, hexa-, and octa-) was examined utilizing solution competition SPR. These competition studies demonstrate that the smallest heparin oligosaccharide competing with heparin binding to Slit was a tetrasaccharide, and that in the ELISA maximum inhibition (approximately 60% at 2 microM concentration) was attained with a dodecasaccharide.

Amino Acid Sequence↗
PubMed2004

Identification of two novel markers for alveolar epithelial type I and II cells.

Alveolar epithelial type I and type II cells (AEC I and II) are closely aligned in alveolar surface. There is much interest in the precise identification of AEC I and II in order to separate and evaluate functional and other properties of these two cells. This study aims to identify specific AEC I and AEC II cell markers by DNA microarray using the in vitro trans-differentiation of AEC II into AEC I-like cells as a model. Quantitative real-time PCR confirmed five AEC I genes: fibroblast growth factor receptor-activating protein 1, aquaporin 5, purinergic receptor P2X 7 (P2X7), interferon-induced protein, and Bcl2-associated protein, and one AEC II gene: gamma-aminobutyric acid receptor pi subunit (GABRP). Immunostaining on cultured cells and rat lung tissue indicated that GABRP and P2X7 proteins were specifically expressed in AEC II and AEC I, respectively. In situ hybridization of rat lung tissue confirmed the localization of GABRP mRNA in type II cells. P2X7 and GABRP identified in this study could be used as potential AEC I and AEC II markers for studying lung epithelial cell biology and monitoring lung injury.

Animals↗
PubMed2006

Reaction times in discriminations of varying difficulty: decision modulated by arousal.

Pigeons discriminated the hue of a spot of light that appeared in discrete trials. A green spot always signaled food ("green S+") and so did a red spot of constant hue ("red S+"), but on most trials a different red hue appeared and no food was given for pecks ("red S-"). The hue of red S- stayed the same during blocks of up to twelve sessions, but it changed from block to block. During a final group of sessions red S- was omitted and the percent reinforcement to the two S+ stimuli was varied. Major findings were that (1) percent response (Pct(R)) to S- varied with S+/S- similarity, describing a typical ogival psychometric function; (2) Reaction times (RTs) to both red and green S+s were minimal when the red discrimination was impossible (that is, when red S+ and S- were identical); (3) RTs to red S+ were greatest during discriminations of intermediate difficulty; (4) as Pct(R) declined during the learning of a difficult discrimination, RTs increased to red S+ as well as red S-. Most aspects of the data were reproduced by simulations with a quantitative model that incorporated reinforcement-based decision and arousal processes.

Animals↗
PubMed2006

Temporal generalization accounts for response resurgence in the peak procedure.

The peak interval (PI) procedure is commonly used to evaluate animals' ability to produce timed intervals. It consists of presenting fixed interval (FI) schedules in which some of the trials are replaced by extended non-reinforced trials. Responding will often resume (resurge) at the end of the non-reinforced trials unless precautions are taken to prevent it. Response resurgence was replicated in rats and pigeons. Variation of the durations of the FI and the non-reinforced probe trials showed it to be dependent on the time when reinforcement is expected. Timing of both the normal time to reinforcement, and the subsequent time to reinforcement during the probe trials followed Weber's law. A quantitative model of resurgence is described, suggesting how animals respond to the signaling properties of reinforcement omission. Model results were simulated using a stochastic binary counter.

Animals↗
PubMed2005

Atom, atom-type and total molecular linear indices as a promising approach for bioorganic and medicinal chemistry: theoretical and experimental assessment of a novel method for virtual screening and rational design of new lead anthelmintic.

Helminth infections are a medical problem in the world nowadays. In this paper a novel atom-level chemical descriptor has been applied to estimate the anthelmintic activity. Total and local linear indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The discriminant model has an accuracy of 90.11% in the training set, with a high Matthews' correlation coefficient (MCC=0.80). To assess the robustness and predictive power of the obtained model, internal (leave-n-out) and external validation process was performed. The QSAR model correctly classified 88.55% of compounds in this external prediction set, yielding a MCC of 0.77. Another LDA model was carried out to outline some conclusions about the possible modes of action of anthelmintic drugs. It has an accuracy of 93.50% in the training set, and 80.00% in the external prediction set. After that, the developed model was used in the virtual--in silico--screening and several compounds from the Merck Index, Negwer's Handbook and Goodman and Gilman were identified by the model as anthelmintic. Finally, the experimental assay of an organic chemical (a furylethylene derivative) by an in vivo test permits us to carry out an assessment of the model. An accuracy of 100% with the theoretical predictions was observed. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.

Anthelmintics↗
PubMed2006

Translational and rotational motions of proteins in a protein crowded environment.

Fluorescence correlation spectroscopy (FCS) was used to measure the translational diffusion of labeled apomyoglobin (tracer) in concentrated solutions of ribonuclease A and human serum albumin (crowders), as a quantitative model system of protein diffusive motions in crowded physiological environments. The ratio of the diffusion coefficient of the tracer protein in the protein crowded solutions and its diffusion coefficient in aqueous solution has been interpreted in terms of local apparent viscosities, a molecular parameter characteristic for each tracer-crowder system. In all protein solutions studied in this work, local translational viscosity values were larger than the solution bulk viscosity, and larger than rotational viscosities estimated for apomyoglobin in the same crowding solutions. Here we propose a method to estimate local apparent viscosities for the tracer translational and rotational diffusion directly from the bulk viscosity of the concentrated protein solutions. As a result of this study, the identification of protein species and the study of hydrodynamic changes and interactions in model crowded protein solutions by means of FCS and time-resolved fluorescence depolarization techniques may be expected to be greatly simplified.

Apoproteins↗
PubMed2003

Physical investigations of surface membrane-water relationship of intact and gelatinized wheat-starch systems.

Water mobility in intact and dried gelatinized starch was investigated by gravimetric water sorption, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (NMR). A multi-component exponential model quantitatively measured different spin-spin relaxation times of two water components, namely bound water (Tsi) at 3.16 ms and mobile or free water (Tsii) at 3.23 ms, as a function of water activity (aw). The starch samples were moistened to 30% moisture content. SEM confirmed the disrupted, absorbent microstructure in dried, gelatinized starch powder and revealed starch granules in an incomplete gelatinized state, as compared to the complete membrane surface of the intact starch granule. Starch granules sorbed significantly differently at low aw, but after aw=0.44, sorption leveled similarly with increasing aw. The presence and role of a surface membrane was concluded, in support of the hypothetical "water sink" properties of intact granules, and was considered to influence in part the sorption behavior of incompletely gelatinized starch granules.

Adsorption↗
PubMed2006

Downregulation of PP2A(Cdc55) phosphatase by separase initiates mitotic exit in budding yeast.

After anaphase, the high mitotic cyclin-dependent kinase (Cdk) activity is downregulated to promote exit from mitosis. To this end, in the budding yeast S. cerevisiae, the Cdk counteracting phosphatase Cdc14 is activated. In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. During anaphase, Cdk- and Polo-dependent phosphorylation of Net1 is thought to release active Cdc14. How Net1 is phosphorylated specifically in anaphase, when mitotic kinase activity starts to decline, has remained unexplained. Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase. The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PP2A(Cdc55) downregulation also promotes phosphorylation of Bfa1, contributing to activation of the "mitotic exit network" that sustains Cdc14 as Cdk activity declines. These findings allow us to present a new quantitative model for mitotic exit in budding yeast.

Cell Cycle Proteins↗
PubMed2004

Prediction of gas chromatographic retention indices of a diverse set of toxicologically relevant compounds.

For a set of 846 organic compounds, relevant in forensic analytical chemistry, with highly diverse chemical structures, the gas chromatographic Kovats retention indices have been quantitatively modeled by using a large set of molecular descriptors generated by software Dragon. Best and very similar performances for prediction have been obtained by a partial least squares regression (PLS) model using all considered 529 descriptors, and a multiple linear regression (MLR) model using only 15 descriptors obtained by a stepwise feature selection. The standard deviations of the prediction errors (SEP), were estimated in four experiments with differently distributed training and prediction sets. For the best models SEP is about 80 retention index units, corresponding to 2.1-7.2% of the covered retention index interval of 1110-3870. The molecular properties known to be relevant for GC retention data, such as molecular size, branching and polar functional groups are well covered by the selected 15 descriptors. The developed models support the identification of substances in forensic analytical work by GC-MS in cases the retention data for candidate structures are not available.

Calibration↗