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Adolescent onset of the gender difference in lifetime rates of major depression: a theoretical model.

Prepubescent boys are, if anything, more likely than girls to be depressed. During adolescence, however, a dramatic shift occurs: between the ages of 11 and 13 years, this trend in depression rates is reversed. By 15 years of age, females are approximately twice as likely as males to have experienced an episode of depression, and this gender gap persists for the next 35 to 40 years. We offer a theoretical framework that addresses the timing of this phenomenon. First, we discuss the social and hormonal mechanisms that stimulate affiliative needs for females at puberty. Next, we describe how heightened affiliative need can interact with adolescent transition difficulties to create a depressogenic diathesis as at-risk females reach puberty. This gender-linked vulnerability explains why adolescent females are more likely than males to become depressed when faced with negative life events and, particularly, life events with interpersonal consequences.

Adolescent↗

Theoretical modeling of micro-scale biological phenomena in human coronary arteries.

This paper presents a mathematical model of biological structures in relation to coronary arteries with atherosclerosis. A set of equations has been derived to compute blood flow through these transport vessels with variable axial and radial geometries. Three-dimensional reconstructions of diseased arteries from cadavers have shown that atherosclerotic lesions spiral through the artery. The theoretical framework is able to explain the phenomenon of lesion distribution in a helical pattern by examining the structural parameters that affect the flow resistance and wall shear stress. The study is useful for connecting the relationship between the arterial wall geometries and hemodynamics of blood. It provides a simple, elegant and non-invasive method to predict flow properties for geometrically complex pathology at micro-scale levels and with low computational cost.

Biomechanical Phenomena↗

Measurement of the net production of acidity by a sulphate-reducing bacterium: experimental checking of theoretical models of microbially influenced corrosion.

The net production and consumption of acidity by Desulfovibrio fructosovorans, growing with lactate as the carbon and energy source, were measured in an unbuffered medium in a pH-controlled bioreactor. At alkaline pH (7.2 and 8.5), net acidity production was measured. At pH 6.0, acidity consumption was obtained, although bacterial growth was not observed. These observations are in good agreement with theoretical predictions emphasizing the key role of H+ ions in the relationship between the metabolism of sulphate-reducing bacteria and microbially influenced corrosion.

Acetates↗

Stress mediation in caregivers of cognitively impaired adults: theoretical model testing.

The purpose of the study was to test a midrange model of caregiver stress mediation based on Modeling and Role-Modeling theory. Perceived support and self-worth were examined to determine if these self-care resources had a mediating effect between stress and well-being in caregivers of cognitively impaired adults. The sample of 117 caregivers completed measures of basic need status, perceived support, self-worth, stress, and well-being. There were significant correlations among the study variables in the expected directions. Resources mediated the relationship between stress and well-being, providing tentative support for theoretically proposed linkages.

Adaptation, Psychological↗

Development of a theoretical model for chromatographic-based competitive binding immunoassays with simultaneous injection of sample and label.

This study examined the theory and behavior of an HPLC-based chromatographic competitive binding immunoassay with the simultaneous injection of sample and a labeled analyte analogue. Equations based on nonlinear chromatographic theory were derived to describe the calibration curve for this assay in a system with adsorption-limited kinetics and homogeneous binding sites. These equations related the assay response (B/Bo) to the column's binding capacity, the moles of injected analyte or labeled analogue, and the flow rate/adsorption kinetics of the system. There was good agreement between the predicted theoretical response and experimental data obtained for the binding of human serum albumin (HSA) to an immobilized anti-HSA antibody column. This theory was also successful in describing the changes that occurred in the calibration curve when the flow rate or amount of labeled analogue applied to the column was varied. A comparison was made between the results of this study and previous theoretical work that examined the behavior of a related, sequential injection competitive binding method. On the basis of the results reported in this work, several general guidelines were developed for the design and optimization of simultaneous injection methods for use in such areas as clinical testing, pharmaceutical analysis, and environmental monitoring.

Adsorption↗

A theoretical model for pulsatile blood flow with applications to cerebrovascular diseases.

A solution for fully developed pulsatile flow of a couple stress fluid through a circular, rigid tube of infinite length has been obtained in the form of a Bessel-Fourier series. The velocity profiles and flow rates for different values of flow parameters have been shown graphically. It has been observed that velocity and flow rate are almost in phase with pressure gradient for low values of pulsatile Reynolds number alpha (alpha 2 = 0.1). For higher values of alpha(= 2) a phase difference of approximately 30 degrees between the velocity profile and pressure gradient has been observed. The obtained results are in good agreement with other theoretical and experimental results. The present analysis is valid for both values of alpha , i.e., alpha greater than or equal to 1 and alpha less than 1, whereas the existing analysis for pulsatile flow of couple stress fluid is valid for only alpha less than 1. The first, second, and third approximate solutions have been obtained and it is found that the convergence of the solutions is quite fast and the series could be terminated after the second term. This theoretical work could be useful in the measurement of blood flow rates, its apparent viscosity, and peripheral resistance of the circulatory system which, at present, are thought to be some of the main causes of many cerebrovascular diseases and stroke problems.U

Cerebrovascular Circulation↗

A new theoretical model for noninvasive quantification of mitral regurgitation.

The most common objective assessments of mitral regurgitation are limited by their invasive or semiquantitative nature. Recent attempts at correlation with jet size from Doppler flow maps have failed to produce a direct measure of regurgitant volume and are fundamentally limited by the dependence of jet dimensions on factors other than flow volume. The purpose of this paper was to develop an equation, based on the physics of turbulent regurgitant jets, for calculating regurgitant volume from quantities that can be measured by Doppler ultrasound. The result is an equation forw flow rate Q as a function of orifice velocity Uo, a downstream centerline velocity Um and the intervening distance chi: Q = pi U2m chi 2/160Uo. This equation can also be modified to obtain total regurgitant volume in clinical pulsatile flow. The assumptions made demand a free turbulent jet for which momentum is conserved, but should otherwise be physiologically applicable. The advantage of this technique compared to correlations with jet size are its theoretical justification and ability to quantify regurgitant volume directly.

Blood Flow Velocity↗

A graph-theoretic modeling on GO space for biological interpretation of gene clusters.

MOTIVATION: With the advent of DNA microarray technologies, the parallel quantification of genome-wide transcriptions has been a great opportunity to systematically understand the complicated biological phenomena. Amidst the enthusiastic investigations into the intricate gene expression data, clustering methods have been the useful tools to uncover the meaningful patterns hidden in those data. The mathematical techniques, however, entirely based on the numerical expression data, do not show biologically relevant information on the clustering results. RESULTS: We present a novel methodology for biological interpretation of gene clusters. Our graph theoretic algorithm extracts common biological attributes of the genes within a cluster or a group of interest through the modified structure of gene ontology (GO) called GO tree. After genes are annotated with GO terms, the hierarchical nature of GO terms is used to find the representative biological meanings of the gene clusters. In addition, the biological significance of gene clusters can be assessed quantitatively by defining a distance function on the GO tree. Our approach has a complementary meaning to many statistical clustering techniques; we can see clustering problems from a different viewpoint by use of biological ontology. We applied this algorithm to the well-known data set and successfully obtained the biological features of the gene clusters with the quantitative biological assessment of clustering quality through GO Biological Process.

Algorithms↗

Individual differences in the coming out process for gay men: implications for theoretical models.

One hundred ninety-nine self-defined homosexual males were asked about the ages at which milestone events occurred in the coming out process (i.e., initial awareness of same-sex attractions, same-sex acts, self-designation as homosexual, initial involvement in a long-term relationship, self-disclosures to significant others, and acquiring a positive gay identity). Overall findings indicated that an orderly developmental sequence underlies the coming out process; however, not all subjects progressed in a predictable fashion from an awareness of same-sex feelings through behavior to eventual self-labelling, self-disclosure, and final stabilization of a positive gay identity. A number of individual differences emerged: 18% of the sample labelled themselves "homosexual" in the absence of any overt same-sex sexual experience; 22% arrived at homosexual self-definitions while participating in a long-term relationship with another man; 23% adopted homosexual self-definitions only after involvement in such a relationship. Fifteen percent of the respondents indicated that they had not acquired a positive gay identity (i.e., were not glad to be gay). These individuals differed from the remainder of the sample on a number of significant measures reflective of psychological health. Significant differences were also found among three cohort groups with respect to age at occurrence of particular milestone events. Findings from the present investigation were explored in relation to both the theoretical conceptions and available empirical data concerned with homosexual identity formation.

Adult↗

Migration of 99mTc-labelled syngeneic lymphocytes in the rat. Biological and theoretical models predict radiation damage and poor scintigraphic detectability.

The possibility of obtaining useful scintigrams of secondary lymphoid organs after infusion of syngeneic lymphocytes labelled with technetium-99m (99mTc) was explored in a rat model. Thoracic duct lymphocyte (TDL) accumulation in various organs was measured with both 99mTc and 51Cr labelled cells, the latter processed with a method that has been shown not to damage lymphocytes. 99mTc labelled TDL did not localize properly in the lymph nodes and spleen. We could not visualize lymph nodes in scintigrams, neither could we demonstrate any difference between normal and hyperplastic spleens. Our conclusion is that radiation from the 99mTc label readily influences lymphocyte migration so that useful scintigraphy in rats and other small experimental animals becomes impossible. This was supported by results from culture experiments with 99mTc labelled, radiosensitive mouse haemopoietic progenitor cells. Theoretical considerations, including the calculations of lymphocyte self-irradiation and signal/noise ratios during scintigraphy of rat tissues, supported our conclusion that scintigraphy in small animals, to disclose the physiological migration of lymphocytes, may be impossible with the present sensitivity of gamma cameras.

Animals↗

Theoretical model of the ionic mechanism of 1/f noise in nerve membrane.

A model is presented for the ionic mechanism of low frequency 1/f electrical noise which has been observed in axonal membranes. The model consists of narrow channels which open randomly throughout the membrane and remain open for only a short time compared with f-1max where fmax approximately 2 kHz is the maximum frequency for which 1/f noise is observed. The fluctuation in channel formation is coupled to low frequency normal mode vibrations in liquid crystals which have properties similar to nerve membranes. Ionic current flow through the channels is assumed to occur via single file diffusion. The diffusion process is regarded as a non-Markovian random walk on a one-dimensional lattice which is mathematically decomposed into its spatial and temporal components. This technique allows calculation of the mean and variance of the number of ions which flow through any single short-lived channel. The final result for the current noise power spectrum, S, is S(f) = (A + k/I/2)/f, where I is the mean membrane current and A and k are parameters which are independent of membrane voltage. The theoretical result is consistent with observations of 1/f noise in lobster axon by Poussart (1971, Biophys. J. 11:212.) on the dependence of S(f) on the mean steady-state current and the external potassium concentration. We also calculate the mean channel density and the Frank elastic constant of the membrane. This work is an extension of a macroscopic model of Lundström and McQueen (1974, J. Theor. Biol. 45:405.) who obtain a spectral density of the form S approximately /I/2/f.

Animals↗

Assembly of three major subclasses of mouse immunoglobulin G: a theoretical model for covalent assembly in vivo.

A mathematical model, based on second-order reaction kinetics, has been used to describe the covalent assembly of immunoglobulin G(IgG) in vitro from its heavy (H) and light (L) chains (Percy, M.E., Baumal, R., Dorrington, K.J. & Percy, J. (1976) Can. J. Biochem. 54, 675-687). In the present paper, the same model has now been applied to the steady-state assembly of IgG in vivo. This mathematical approach permits a quantitative comparison of the pathways of covalent assembly used by given immunoglobulins in vivo and in vitro. The assumptions in the model are: the species L, H, HL, HH, HHL and LHHL belong to a common pool; incompleted IgG intermediates may freely assemble to form HL, HH, HHL and LHHL; the reaction rate for covalent linkage between any two reacting species is proportional to the products of the number densities of the reactants and to a parameter P which takes the value PHH if the reaction joins two H chains, and PHL if it joins an H and L chain. In vivo values of PHH/PHL were determined for the 18 mouse myeloma tumours and cell lines studied by Baumal et al. (Baumal, R., Potter, M. & Scharff, M. (1971) J. Exp. Med. 134, 1316-1334). From these analyses, we have arrived at the following conclusions: (1) the three major IgG subclasses have distinctive values of PHH/PHL (mean value 53 for IgG1, 12 for IgG2a and 2.8 for IgG2b); (2) for IgGs of the same subclass, the values of PHH/PHL are similar; (3) the mean in vivo values of PHH/PHL are very close to those determined from in vitro assembly experiments. Finally, the individual values of PHH/PHL have been used to simulate pulse-chase experiments in the various tumours and cell lines. Considering the sources and magnitude of experimental error, the theoretical pathways of assembly agree with those determined qualitatively from the pulse-chase experiments.

Cell Line↗

A theoretical model for the noninvasive assessment of the transmitral pressure-flow relation.

The purpose of this paper is to formulate from the equations of fluid mechanics an equation which describes the transmitral pressure-flow relationship. According to the linear momentum equation applied to the atrioventricular coupling, the left-atrium-left-ventricle pressure difference (Pa-Pv) can be written as Pa-P v = A delta v/delta t + B v 2 + C v, where v is the transmitral blood velocity and A, B, and C are variables related to the geometry of the atrium, ventricle and mitral orifice, respectively. Based on this theory, Pa-Pv is calculated noninvasively in a patient with a nonobstructive mitral valve. Mitral flow and cardiac dimensions recorded by Doppler echocardiography are digitized and analyzed. Calculation shows that Pa-Pv reaches its peak value at the time of flow peak acceleration and has already considerably decreased at the time of peak velocity. The time course of calculated Pa-Pv is in close agreement with the published experimental catherization data. Numerical computation of early diastolic left atrium and left ventricle pressure curves based on the experimental data of others for the time constant of left ventricular relaxation, left atrial and ventricular chambers stiffness constants, combined with sine-waveform-simulated mitral flow, verifies the time course and the magnitude of Pa-Pv as predicted from flow equations. This paper provides a theoretical method for the noninvasive assessment of the transmitral pressure-flow relationship using ultrasound technique and might help to achieve a better understanding of the diastolic function as assessed by Doppler echocardiography.

Computer Simulation↗

Schizophrenic deficits in the processing of context. A test of a theoretical model.

BACKGROUND: Schizophrenic patients show various deficits in cognitive functions that have been difficult to understand in terms of a common unifying hypothesis. Previously described neural network models of cognitive tasks suggest that several schizophrenic performance deficits may be related to a single function-an impairment in maintaining contextual information over time and in using that information to inhibit inappropriate responses. METHODS: We tested first-episode schizophrenic patients and patients later in the course of their illness on a new variant of the Continuous Performance Test designed specifically to elicit deficits in the processing of contextual information. RESULTS: Unmedicated schizophrenic patients showed a deterioration of their signal detection performance that followed the pattern predicted by the context hypothesis, ie, they responded inappropriately when correct responding required the maintenance of context information over time to inhibit the expression of a habitual response. This deficit correlated with positive symptoms. The results also suggested that the deficit may be worse in unmedicated patients who have had a longer course of illness. Medicated patients showed a more diffuse performance deficit. CONCLUSIONS: These results support the view that a single deficit in the processing of context information may underlie various cognitive impairments observed in schizophrenia. They also suggest that such an impairment is associated with positive rather than negative symptoms, and that it may worsen with the course of the illness as in the kraepelinian view of schizophrenia.

Adult↗

The nicotinic cholinergic receptor: a theoretical model.

Based on published affinity-labeling and mutagenesis experiments describing the effect of changes in specific amino acids in molecular biological studies on the nicotinic acetylcholinergic receptor (nAChR), we have identified 12 amino acids which are important in functioning at the nicotinic cholinergic receptor. The work presented here provides an atomistic model of this important receptor based on our molecular modeling studies. We found five of these amino acids (TRP86, ASP89, TYR93, ASP138, and THR191) to be associated with the cationic end of acetylcholine (ACh), which is electron-deficient. Three other amino acids (ARG209, TYR190, and TYR198) are associated with the ester end, where an enhanced electron density is present. After hydrogen bonding between the two oxygen atoms at the ester end, and two of the guanidinium hydrogen atoms in ARG209. ASP200 hydrogen bonds to the other two hydrogen atoms of the guanidinium group, thus forming a pseudo-ring. Two aromatic amino acids (TRP149 and TYR151) then enhance the binding at the pseudo-ring through additional hydrogen bonding and charge-transfer complexation, with THR150 functioning to further stabilize this evolving charge-transfer complex. We postulate that this latter process allows the ion channel to twist, thus opening it. From the published amino acid sequence in the polypeptides at the 5HT-3, GABA, and glycine receptors (Maricq et al.: Science 254:432-437, 1991), we also speculate on which amino acids are involved in these three receptors.

Acetylcholine↗

Restricted diffusion and exchange of intracellular water: theoretical modelling and diffusion time dependence of 1H NMR measurements on perfused glial cells.

Intracellular diffusion properties of water in F98 glioma cells immobilized in basement membrane gel threads, are investigated with a pulsed-field-gradient spin-echo NMR technique at diffusion times from 6 to 2000 ms and at different temperatures. In extended model calculations the concept of 'restricted intracellular diffusion at permeable boundaries' is described by a combined Tanner-Kärger formula. Signal components in a series of ct experiments (constant diffusion time) are separated due to different diffusion properties (Gaussian and restricted diffusion), and physiological as well as morphological cell parameters are extracted from the experimental data. The intracellular apparent diffusion coefficients strongly depend on the diffusion time and are up to two orders of magnitude smaller than the self diffusion constant of water. Propagation lengths are found to be in the range of 4-7 microns. Hereby intracellular signals of compartments with a characteristic diameter could be selected by an appropriate gradient strength. With cg experiments (constant gradient) a mean intracellular residence time for water is determined to be about 50 ms, and the intrinsic intracellular diffusion constant is estimated to 1 x 10(-3)mm2/s. Studying the water diffusion in glial cells provides basic understanding of the intracellular situation in brain tissue and may elucidate possible influences on the changes in the diffusion contrast during ischemic conditions.

Animals↗