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Transient response in a dendritic neuron model for current injected at one branch.

Mathematical expressions are obtained for the response function corresponding to an instantaneous pulse of current injected to a single dendritic branch in a branched dendritic neuron model. The theoretical model assumes passive membrane properties and the equivalent cylinder constraint on branch diameters. The response function when used in a convolution formula enables one to compute the voltage transient at any specified point in the dendritic tree for an arbitrary current injection at a given input location. A particular numerical example, for a brief current injection at a branch terminal, illustrates the attenuation and delay characteristics of the depolarization peak as it spreads throughout the neuron model. In contrast to the severe attenuation of voltage transients from branch input sites to the soma, the fraction of total input charge actually delivered to the soma and other trees is calculated to be about one-half. This fraction is independent of the input time course. Other numerical examples, which compare a branch terminal input site with a soma input site, demonstrate that, for a given transient current injection, the peak depolarization is not proportional to the input resistance at the injection site and, for a given synaptic conductance transient, the effective synaptic driving potential can be significantly reduced, resulting in less synaptic current flow and charge, for a branch input site. Also, for the synaptic case, the two inputs are compared on the basis of the excitatory post-synaptic potential (EPSP) seen at the soma and the total charge delivered to the soma.

Animals↗

Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration.

Continuous deformation and entry flow of single blood granulocytes into small caliber micropipets at various suction pressures have been studied to determine an apparent viscosity for the cell contents and to estimate the extent that dissipation in a cortical layer adjacent to the cell surface contributes to the total viscous flow resistance. Experiments were carried out with a wide range of pipet sizes (2.0-7.5 microns) and suction pressures (10(2)-10(4) dyn/cm2) to examine the details of the entry flow. The results show that the outer cortex of the cell maintains a small persistent tension of approximately 0.035 dyn/cm. The tension creates a threshold pressure below which the cell will not enter the pipet. The superficial plasma membrane of these cells appears to establish an upper limit to surface dilation which is reached after microscopic "ruffles" and "folds" have been pulled smooth. With aspiration of cells by small pipets (less than 2.7 microns), the limit to surface expansion was derived from the maximal extension of the cell into the pipet; final areas were measured to be 2.1 to 2.2 times the area of the initial spherical shape. For suctions in excess of a threshold, the response to constant pressure was continuous flow in proportion to excess pressure above the threshold with only a small nonlinearity over time until the cell completely entered the pipet (for pipet calibers greater than 2.7 microns). With a theoretical model introduced in a companion paper, (Yeung, A., and E. Evans., 1989, Biophys. J. 56:139-149) the entry flow response versus pipet size and suction pressure was analyzed to estimate the apparent viscosity of the cell interior and the ratio of cortical flow resistance to flow resistance from the cell interior. The apparent viscosity was found to depend strongly on temperature with values on the order of 2 x 10(3) poise at 23 degrees C, lower values of 1 x 10(3) poise at 37 degrees C, but extremely large values in excess of 10(4) poise below 10 degrees C. Because of scatter in cell response, it was not possible to accurately establish the characteristic ratio for flow resistance in the cortex to that inside the cell; however, the data showed that the cortex does not contribute significantly to the total flow resistance.

Granulocytes↗

Cation radius effects on the helix-coil transition of DNA. Cryptates and other large cations.

Most polyelectrolyte theories of the effect of ions on the thermal melting of DNA assume that the predominant influence of the cations comes through their charge. Ion size and structure are treated, for analytic convenience, as negligible variables. We have examined the validity of this assumption by measuring the melting temperature of calf thymus DNA as a function of salt concentration with four univalent cations of different hydrated radii. These are K+ (3.3 A), (n-Pr)4N+ (4.5 A), (EtOH)4N+ (4.5 A), and C222-K+ (5 A). C222-K+ is a complex of cryptand C222 with K+. With K+ as the sole cation, Tm varies linearly with the log of ionic strength over the range 0.001-0.1 M. With all the K+ sequestered by an equimolar amount of C222, Tm is depressed by 10-20 degrees C and the slope of Tm vs. ionic strength is lower. At low ionic strength, an even greater reduction in Tm is achieved with (n-Pr)4N+; but the similar-sized (EtOH)4N+ gives a curve more similar to K+. Theoretical modeling, taking into account cation size through the Poisson-Boltzmann equation for cylindrical polyelectrolytes, predicts that larger cations should be less effective in stabilizing the double helix; but the calculated effect is less than observed experimentally. These results show that valence, cation size, and specific solvation effects are all important in determining the stability of the double-helical form of DNA.

Bridged Bicyclo Compounds↗

Increased vesicle endocytosis due to an increase in the plasma membrane phosphatidylserine concentration.

Endocytosis vesiculation consists of local membrane invaginations, continuously generated on the plasma membrane surface of living cells. This vesiculation process was found to be activated in vivo by the generation of a transmembrane surface area asymmetry in the plasma membrane bilayer, after enhancement of transbilayer phospholipid translocation. The observed enhancement was shown to be in good quantitative agreement with a theoretical model of elastic equilibrium describing stabilization of 100-nm vesicles in response to phospholipid redistribution. Very rapid dynamic vesiculation and direct re-fusion of the vesicles, both dependent on the phospholipid translocation activity, were found on a time scale of seconds. Both vesiculation and re-fusion were shown to result in a steady-state population of internal vesicles at long time points. The plasma membrane appears to be a dynamic structure, oscillating between two distinct curvature states, the 10 microns-1 "vesicle" and the 0.1 micron-1 "plasma membrane" curvature states. This dynamic behavior is discussed in terms of an elastic control of the membranes curvature state by the phospholipid translocation activity.

Cell Line↗

Hydration of nucleic acid fragments: comparison of theory and experiment for high-resolution crystal structures of RNA, DNA, and DNA-drug complexes.

A computationally efficient method to describe the organization of water around solvated biomolecules is presented. It is based on a statistical mechanical expression for the water-density distribution in terms of particle correlation functions. The method is applied to analyze the hydration of small nucleic acid molecules in the crystal environment, for which high-resolution x-ray crystal structures have been reported. Results for RNA [r(ApU).r(ApU)] and DNA [d(CpG).d(CpG) in Z form and with parallel strand orientation] and for DNA-drug complexes [d(CpG).d(CpG) with the drug proflavine intercalated] are described. A detailed comparison of theoretical and experimental data shows positional agreement for the experimentally observed water sites. The presented method can be used for refinement of the water structure in x-ray crystallography, hydration analysis of nuclear magnetic resonance structures, and theoretical modeling of biological macromolecules such as molecular docking studies. The speed of the computations allows hydration analyses of molecules of almost arbitrary size (tRNA, protein-nucleic acid complexes, etc.) in the crystal environment and in aqueous solution.

Crystallography, X-Ray↗

Structure of gel phase saturated lecithin bilayers: temperature and chain length dependence.

Systematic low-angle and wide-angle x-ray scattering studies have been performed on fully hydrated unoriented multilamamellar vesicles of saturated lecithins with even chain lengths N = 16, 18, 20, 22, and 24 as a function of temperature T in the normal gel (L beta') phase. For all N, the area per chain Ac increases linearly with T with an average slope dAc/dT = 0.027 A2/degree C, and the lamellar D-spacings also increase linearly with an average slope dD/dT = 0.040 A/degree C. At the same T, longer chain length lecithins have more densely packed chains, i.e., smaller Ac's, than shorter chain lengths. The chain packing of longer chain lengths is found to be more distorted from hexagonal packing than that of smaller N, and the distortion epsilon of all N approaches the same value at the respective transition temperatures. The thermal volume expansion of these lipids is accounted for by the expansion in the hydrocarbon chain region. Electron density profiles are constructed using four orders of low-angle lamellar peaks. These show that most of the increase in D with increasing T is due to thickening of the bilayers that is consistent with a decrease in tilt angle theta and with little change in water spacing with either T or N. Because of the opposing effects of temperature on area per chain Ac and tilt angle 0, the area expansivity alpha A is quite small. A qualitative theoretical model based on competing head and chain interactions accounts for our results.

Gels↗

Introducing dielectrophoresis as a new force field for field-flow fractionation.

We present the principle of cell characterization and separation by dielectrophoretic field-flow fractionation and show preliminary experimental results. The operational device takes the form of a thin chamber in which the bottom wall supports an array of microelectrodes. By applying appropriate AC voltage signals to these electrodes, dielectrophoretic forces are generated to levitate cells suspended in the chamber and to affect their equilibrium heights. A laminar flow profile is established in the chamber so that fluid flows faster with increasing distance from the chamber walls. A cell carried in the flow stream will attain an equilibrium height, and a corresponding velocity, based on the balance of dielectrophoretic, gravitational, and hydrodynamic lift forces it experiences. We describe a theoretical model for this system and show that the cell velocity is a function of the mean fluid velocity, the voltage and frequency of the signals applied to the electrodes, and, most significantly, the cell dielectric properties. The validity of the model is demonstrated with human leukemia (HL-60) cells subjected to a parallel electrode array, and application of the device to separating HL-60 cells from peripheral blood mononuclear cells is shown.

Cell Separation↗

Condensed complexes of cholesterol and phospholipids.

Mixtures of dihydrocholesterol and phospholipids form immiscible liquids in monolayer membranes at the air-water interface under specified conditions of temperature and 2-dimensional pressure. In recent work it has been discovered that a number of these mixtures exhibit two upper miscibility critical points. Pairs of upper critical points can be accounted for by a theoretical model that implies the cooperative formation of molecular complexes of dihydrocholesterol and phospholipid molecules. These complexes are calculated to be present in the membranes both above and below the critical points. Below the critical points the complexes form a separate phase, whereas above the critical points the complexes are completely miscible with the other lipid components. The cooperativity of complex formation prompts the use of the terminology condensed complex.

Cholestanol↗

[Ethical foundations of institutional psychotherapy].

HISTORICAL ASPECTS: The idea behind this work is to have an ethical examination of the institutional psychotherapy movement which has long influenced French public psychiatry and which has progressively, since the 80s, been subject to growing doubts. In the first part, institutional psychotherapy is presented. It is a model for theoretical development and practice in psychiatric care. It came into being just following the end of the Second World War at the same time as modern medical ethics. Its principles come on the one hand, from recognition of asylums' pathogenic effects--which led to the crushing of the patient's being--and on the other, through recognition of the uniqueness of each person and the subjectivity of mental suffering. These elements gave rise to creativity within the world of medicine and, in the sector, generated the science of psychiatry which advocated for continuity in care (both inpatient and outpatient) and preventive work directed at the population. This movement called for the use of the institution in its dynamic aspect which promotes exchanges and allows patients to situate or resituate themselves in historic and symbolic dimensions. It privileges a high level of transversality, maximum communication, favouring speaking out loud and responsibility. It requires a permanent analysis of the institutional counter transference (emotional reactions of the caregivers involved, their interrelations and the social and material organization of the institution) which determines the therapeutic action itself. THEORICAL BASIS: In a second part, its theoretical foundations and its practice shall be investigated in light of the guiding concepts of medical ethics (justice, autonomy, beneficence, non-malfeasance). Institutional psychotherapy responds to the need for justice by considering the patient as a whole and by conceiving each patient as being like oneself despite the differences (associated with the mode of hospitalization, the social or diagnostic category). The principle of autonomy lies always at care's horizon, made concrete in practice by notions of habitability, orientation to place and time, references, by activities and by meetings. The principle of beneficence was the basis for round-the-clock intakes, the use of an established theoretical model and clinical practice centred on the patient's words. Institutional analysis attempts not to repeat the alienation felt by the patient, alienation being associated with the treatment environment, and draws from the principle of non-malfeasance. It therefore appears that the approach of institutional psychotherapy conforms with ethical requirements, given its major interest in the subject who aspires to find meaning in life. CURRENT SITUATION: The third part discusses current orientations in care related to the explosion in neuroscience and technology, the promotion of the citizen as an individual, and legal doctrine, budgetary constraints, and new demands made on psychiatry from the social and political domains. The widespread trend towards simplification, swollen with hypotheses from neuroscientific research, is progressively reducing mental illness to target symptoms. The recovery of the notion of citizenship through technological capture and ideological strains in contemporary culture have also affected a suspension of the subject as a thinking and desiring being, and exempted caregivers from considering transferral phenomena, indicated with the appearance of new signifiers: user, stress, plague, network. The new medical-technical jargon of scales, tables, and management participates in the same process of patient objectification and care compartmentalization. In this context, under the cover of science and generally good actions, psychiatry has become biologisized, whilst being diluted from its social aspect, even as it becomes more repressive for patients. CONCLUSION: This observation leads to the conclusion, in the fourth part, that there is a need for psychiatry, which within its own discipline has a hard time finding sufficient resources, to refocus itself ethically. This enlightenment could come within a multi-disciplinary ethical space, uniting practitioners and psychiatric caregivers, psychoanalysts, philosophers, sociologists, neurobiologists etc. The research should concern the legitimacy of the principles that underlie psychiatric action in its care and preventive aspects.

Ethics, Clinical↗

Impact of a cryopreservation program on the multiple pregnancy rate associated with assisted reproductive technologies.

OBJECTIVE: To determine the impact of a cryopreservation program on pregnancy rates and multiple-pregnancy rates in ART cycles. DESIGN: Retrospective study. SETTING: University teaching hospital. PATIENT(S): Women who underwent stimulation for in vitro fertilization at the Jones Institute for Reproductive Medicine between October 1987 and June 1999. INTERVENTION(S): Analysis of pregnancy and multiple-pregnancy rates based on the number of embryos transferred. MAIN OUTCOME MEASURE(S): Implantation; pregnancy and multiple-pregnancy rates. RESULT(S): Pregnancy rates per transfer increased from 9% when one embryo was transferred to 20% with two embryos, 35% with three embryos, 40% with four embryos, and 41% with five embryos. The rate of twin pregnancies increased to 21% with two embryos, 23% with three embryos, 21% with four embryos, and 22% with five embryos. The triplet pregnancy rates were 8% with three embryos, 9% with four embryos, and 2% with five embryos. A theoretical model limiting the number of embryos transferred to two with cryopreservation and subsequent transfer yields a cumulative pregnancy rate of 77%, a twin rate of less than 20%, and no triplet or higher-order pregnancies. CONCLUSION(S): The use of a cryopreservation program can help maximize pregnancy rates while minimizing multiple-pregnancy rates. Cryopreservation should be considered in all assisted reproductive technology cycles.

Adult↗

A critical parameter for transcapillary exchange of small solutes in countercurrent systems.

Small solute transport by a countercurrent capillary loop was studied using a theoretical model. In the model, the afferent and the efferent limbs of the loop share a common interstitial space, with which exchange of solute occurs. Sources of solute, epithelial cells, exist near capillaries and secret solute into the interstitial fluid. Parameters based on experimental measurements on young Sprague-Dawley rats were used in the model, and asymptotic solutions were derived. Comparison of the solute distribution in the interstitium between a capillary loop and a single capillary reveals that the ratio of the product of permeability (P(1)) and surface area (A(1)) to flow (F(1)) of the afferent limb, gamma(1)=P(1)A(1)/F(1) is a critical parameter for the countercurrent exchange system. It alone determines whether the countercurrent arrangement of capillaries facilitates clearance of solute from the interstitial fluid, a greater axial gradient of solute in the interstitium from the base to the tip of the capillary loop and a greater effect of flow, F, upon this gradient. The properties of the efferent limb affect the results, but it is gamma(1) that determines the characteristic difference between a capillary loop and a single capillary.

Animals↗

Analysis of contraceptive behavior of sexually active female adolescents in the United States.

Drawing on a theoretical model of adolescent contraceptive behavior, we examined the relationships between various social and behavioral variables and contraceptive use by sexually active female adolescents. Hypotheses were tested with the use of a national random sample of sexually active female adolescents (n = 1426), aged 15 to 20 years, from Cycle III of the National Survey of Family Growth. The data were analyzed with Pearson correlation coefficients and multiple regression analysis. Noncompliance with the initial birth control method was the strongest predictor of the adolescents' contraceptive behavior at the time of the interview. Not acquiring birth control at the initial family planning visit and the frequency of family planning visits during the previous 12 months were the second and third best predictors of subjects' contraceptive use. Coital frequency and the length of time between first coitus and the initiation of birth control each explained a small amount of additional variation in the regression model. When combined, these five variables explained 40% of the variation in the contraceptive behavior of this representative sample of sexually active female adolescents. The findings could be useful for clinicians in providing more effective birth control counseling to adolescent patients.

Adolescent↗

A diffusion limited reaction theory for a solid-phase immunoassay.

Theoretical calculations are presented, describing the kinetics of a solid-phase immunoassay where reactants are allowed to diffuse through a gel wedge in the bottom of a circular basin. The analysis is based on the assumption of a diffusion rate limited reaction at the underlaying surface. The influence of initial concentration, incubation time, temperature and the effect of stirring are predicted by the theoretical model. Experimental data are found to follow the theoretical model with parameters consistent with previous values.

Diffusion↗

Diagnostic ultrasound artifacts during imaging of two-body interfaces: part 2--beam thickness artifact.

A diagnostic ultrasound method is being developed for measuring surface contact areas at the tibio-femoral interface of a total knee replacement in a non-clinical industrial setting as an engineering design tool. As an initial step towards this, a previous study mathematically predicted the effect of ultrasound beam thickness on contact area measurements at a two-body interface. In the current study, a novel metal-on-polymer acoustic test object was constructed to create circular two-body interfaces of known geometry. The object was ultrasonically imaged, contact areas measured, and the results compared with the theoretical model previously developed.

Aluminum↗

Atmospheric particulate mercury concentration and its dry deposition flux in Changchun City, China.

From July 1999 to January 2000, we determined the particulate mercury [Hg(p)] concentration in the atmosphere of five function sites and one contrast site in the city of Changchun, China. During non-heating season, the Hg(p) concentration in air in urban areas ranged from 0.022 to 0.398 ng m(-3) with an average of 0.145 ng m(-3), and at the contrast site with an average of 0.084 ng m(-3). During the heating season, the Hg(p) concentration in urban areas was in the range of 0.148-1.984 ng m(-3) with an average of 0.461 ng m(-3) and with an average of 0.211 ng m(-3) at the contrast site. The Hg(p) concentration during heating season is two times higher than that during non-heating time. Coal burning and wind-blown soil material are the two important sources of Hg(p). Wind-blown soil material contributes 7.9-38.5% to the Hg(p) with an average of 24.1% in urban area. A theoretical model was used to estimate the dry deposition flux, with results of 43.06 microg m(-2) a(-1) in the urban area and 21.28 microg m(-2) a(-1) at the contrast site.

Air Movements↗

Responding to symptoms and signs of acute myocardial infarction--how do you educate the public?: a social-psychologic approach to intervention.

In an era of highly time-dependent therapies for acute myocardial infarction-namely thrombolytic therapy and cardiopulmonary resuscitation-it is imperative that public education programs facilitate expeditious care-seeking. However, community intervention studies to reduce the interval of time-from the onset of an acute myocardial infarction to arrival at a hospital emergency department-have shown ambiguous results. To understand and reduce this time interval, a theoretic model is proposed that draws from self-regulation theory. The combined model focuses on three issues: first, information for systematic sign-and-symptom recognition and labeling; second, behavioral information as to what to do in the event of an acute myocardial infarction; and third, information on how to control affective and emotional responses that may interfere with effective coping. Seven recommendations are made for guiding community intervention with use of the proposed model.

Cognition↗

Nonlinear regression using spreadsheets.

Pharmacologists are often required to analyse nonlinear experimental effects by fitting the data to defined theoretical models. This may require a specialized computer program capable of performing nonlinear regression analysis, which can prove costly given the variety of pharmacological research. Here, Wayne Bowen and Jeff Jerman describe a generic method of performing nonlinear regression using spreadsheet applications, and demonstrate how this approach can be used to create automated systems of data analysis.

Algorithms↗

Theoretical and experimental evidence of extinction and coexistence of killer and sensitive strains of yeast grown as a mixed culture in water.

Theoretical and experimental evidences of extinction and coexistence during batch interaction of killer and sensitive strains of Saccharomyces cerevisiae grown as a mixed culture in pure water are provided. The experimental results show that in the limited nutrient conditions of growth in pure water, the killer yeast is subject to extinction when the initial concentration ratio of killer to sensitive yeast is 1:100. However, if the initial concentration ratio of killer to sensitive yeast is 1:1, both strains coexist. Substantial damped oscillations are associated with the growth process in the mixed culture. A new theoretical model that was originally developed for recovering the growth of single species in isolation is extended and applied to two species competing over a common ecological niche. The solutions of the model are shown to recover all the qualitative features captured in the experiments.

Coculture Techniques↗