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PubMed1979

Functional homology of chemotaxis genes in Escherichia coli and Salmonella typhimurium.

Generally nonchemotactic mutants of Escherichia coli and Salmonella typhimurium were analyzed by interspecies complementation tests to determine the functional correspondence between the che genes of these two organisms. The E. coli che region was introduced into Salmonella recipients by means of a series of F-prime elements. Wild-type che genes of E. coli F'420 complemented all che mutants of Salmonella except cheS, cheV, and a subclass of cheU. A series of tester episomes carrying E. coli che mutations were then used to determine which E. coli che function was responsible for the complementation of each Salmonella che defect. By this method, the following correspondences were determined: cheAE and chePS,cheWE, and cheWS, cheXE and cheRS, cheYE and cheQS, cheCE and cheUS, cheBE and cheXS, and cheZE and cheTS. (The subscripts E and S refer to E. coli and S. typhimurium genes, respectively.) In some tests, especially those involving the last two pairs of genes, poor complementation was observed between noncorresponding genes. A model explaining these observations in terms of subunit interactions is proposed.

Chemotaxis↗

PubMed1987

Radiographic quantification of alveolar bone level changes. Predictors of longitudinal bone loss.

The purpose of the present study was to determine the relative importance of a set of predictors for the radiographic change in alveolar bone level over 2 years in a group of 180 subjects and to assess the fit of the applied multivariate model. The included predictors were age, sex, initial bone level, type of initial lesion, tooth type, proximal tooth surface, calculus, and the presence of metal crowns or proximal fillings. The multivariate method of choice was multiple classification analysis. The results indicated that in descending order tooth type, initial bone level, and age were the most important predictors. Sex, calculus, and crown and filling margins also showed significant direct effects (beta) on longitudinal bone loss (p less than 0.05). However, their relative importance was far less than that of tooth type, initial bone level, and age. Proximal side showed no significant direct effect. Using seven predictors, the applied multivariate model explained 20% of the variance in longitudinal bone loss.

Adolescent↗

PubMed1995

Drug progression model: a social control test.

A social control drug progression model was delineated and tested using a sample of 2,626 high school students from the southwestern United States. Along with the social control constructs of parental attachment, educational attachment, religious attachment, and conventional values, we incorporated alcohol, cigarette, and marijuana use into the model as intervening variables. The model explains 39% of the variation in the self-reported amphetamine use and 24% of the variation in "hard drug" use (cocaine, heroin, LSD, and PCP). The findings suggest that the integration of social control theory and drug progression improves the predictive power of the model of adolescent drug use.

Adolescent↗

PubMed2007

Mild head injury--a close relationship between motor function at 1 week post-injury and overall recovery at 3 and 6 months.

Based on previous findings of impaired eye and arm motor control after mild closed head injury (CHI), this study examined whether early eye and arm motor function, and the level of post-injury cerebral dysfunction manifested in motor control, relates systematically to recovery at 3 and 6 months after mild CHI. At 1 week post-injury, we assessed oculomotor function, upper-limb visuomotor performance, and cognitive status in 37 mild CHI patients. Re-examination at 3 and 6 months determined outcome in terms of postconcussional symptoms and performance of everyday tasks, as assessed by the Rivermead Postconcussion Symptoms Questionnaire, the Rivermead Head Injury Follow-up Questionnaire and the SF-36 Health Survey. We then examined the association of early motor function, cognitive status and self-reported health condition with outcome using linear regression. Motor-based regression models explained a high proportion of the variance in outcome (70-89%), with motor function at 1 week being more closely related to outcome at 3 and 6 months than early psychometric assessment (13-32%) or self-reported health status (54-79%). These motor-based models incorporated subcortical/subconscious motor functions alongside motor functions that are subject to volitional control and are primarily mediated by frontal, parietal and temporal cortical brain regions. Early assessment of eye and arm motor function may help in improving accuracy of outcome prediction after mild CHI. Such assessment may assist in the better targeting of early health care intervention and help decrease head-trauma-related morbidity and rehabilitation costs.

Adolescent↗

PubMed2004

Electron-phonon interaction in the t-J model.

We derive a t-J model with electron-phonon coupling from the three-band model, considering modulation of both hopping and Coulomb integrals by phonons. While the modulation of the hopping integrals dominates, the modulation of the Coulomb integrals cannot be neglected. The model explains the experimentally observed anomalous softening of the half-breathing mode upon doping and a weaker softening of the breathing mode. It is shown that other phonons are not strongly influenced, and, in particular, the coupling to a buckling mode is not strong in this model.

Journal Article↗

PubMed1984

Socioeconomic ramifications of changing cohort size: an analysis of U.S. postwar suicide rates by age and sex.

This paper presents a relative cohort size model of suicide. The model states that as relative cohort size (the ratio of younger to older workers) rises, income and income aspirations diverge for the young. One possible extreme reaction to this disequilibrium is suicide. The model explains the variation in age- and sex-specific suicide rates for the United States over the period 1948 to 1976. It identifies the direct effect of changes in cohort size on suicide rates as well as the indirect effect operating through other demographic variables. The model predicts the suicide rates for males above 45 years of age to rise and those for all other groups to decline. For most groups this is a reversal of recent movements in their suicide rates.

Adolescent↗

PubMed1999

Neurobiology of the structure of personality: dopamine, facilitation of incentive motivation, and extraversion.

Extraversion has two central characteristics: (1) interpersonal engagement, which consists of affiliation (enjoying and valuing close interpersonal bonds, being warm and affectionate) and agency (being socially dominant, enjoying leadership roles, being assertive, being exhibitionistic, and having a sense of potency in accomplishing goals) and (2) impulsivity, which emerges from the interaction of extraversion and a second, independent trait (constraint). Agency is a more general motivational disposition that includes dominance, ambition, mastery, efficacy, and achievement. Positive affect (a combination of positive feelings and motivation) is closely associated with extraversion. Extraversion is accordingly based on positive incentive motivation. Parallels between extraversion (particularly its agency component) and a mammalian behavioral approach system based on positive incentive motivation implicate a neuroanatomical network and modulatory neurotransmitters in the processing of incentive motivation. A corticolimbic-striatal-thalamic network (1) integrates the salient incentive context in the medial orbital cortex, amygdala, and hippocampus; (2) encodes the intensity of incentive stimuli in a motive circuit composed of the nucleus accumbens, ventral pallidum, and ventral tegmental area dopamine projection system; and (3) creates an incentive motivational state that can be transmitted to the motor system. Individual differences in the functioning of this network arise from functional variation in the ventral tegmental area dopamine projections, which are directly involved in coding the intensity of incentive motivation. The animal evidence suggests that there are three neurodevelopmental sources of individual differences in dopamine: genetic, "experience-expectant," and "experience-dependent." Individual differences in dopamine promote variation in the heterosynaptic plasticity that enhances the connection between incentive context and incentive motivation and behavior. Our psychobiological threshold model explains the effects of individual differences in dopamine transmission on behavior, and their relation to personality traits is discussed.

Animals↗

PubMed2003

The solitary wave of asexual evolution.

Using a previously undescribed approach, we develop an analytic model that predicts whether an asexual population accumulates advantageous or deleterious mutations over time and the rate at which either process occurs. The model considers a large number of linked identical loci, or nucleotide sites; assumes that the selection coefficient per site is much less than the mutation rate per genome; and includes back and compensating mutations. Using analysis and Monte Carlo simulations, we demonstrate the accuracy of our results over almost the entire range of population sizes. Two limiting cases of our results, when either deleterious or advantageous mutations can be neglected, correspond to the Fisher-Muller effect and Muller's ratchet, respectively. By comparing predictions of our model (no recombination) to those of simple single-locus models (strong recombination), we show that the accumulation of advantageous mutations is slowed by linkage over a broad, finite range of population size. This supports the view of Fisher and Muller, who argued in the 1930s that progressive evolution of organisms is slowed because loci at which beneficial mutations can occur are often linked together on the same chromosome. These results follow from our main finding, that distribution of sequences over the mutation number evolves as a traveling wave whose speed and width depend on population size and other parameters. The model explains a logarithmic dependence of steady-state fitness on the population size reported recently for an RNA virus.

Biological Evolution↗

PubMed2004

Disability measures in stroke: relationship among the Barthel Index, the Functional Independence Measure, and the Modified Rankin Scale.

BACKGROUND AND PURPOSE: Residual disability after stroke presents a major economic and humanistic burden. To quantify disability in patients, activities of daily living (ADL; Barthel Index [BI], and motor component of Functional Independence Measure [M-FIM]) and categorical disability measures (Modified Rankin Scale [MRS]) are used. The purpose of this study is to examine the predicting ability of ADL measures to global disability scale. METHODS: Kansas City Stroke Study data were used for the present study. Correlation coefficient, Kruskal-Wallis test, and polytomous logistic regression analysis were applied to examine the relationship between the ADL measure and global disability scale. Model fit statistics were examined to verify logistic regression appropriateness. A categorization scheme, which minimized the false-positive response rate, was selected as the optimal categorizing system. RESULTS: The 3 measures were highly correlated. Both BI and M-FIM differentiated disability better in lower than higher disability. In logistic regression, BI differentiated 4 disability levels; M-FIM differentiated 3 levels in MRS. However, on the basis of results of the Kruskal-Wallis and multiple comparison tests, we suspect that M-FIM may have the potential to predict MRS categories better with a different model. CONCLUSIONS: The proposed categorization scheme can serve as a translation between measures. However, because of the ceiling effect of BI and M-FIM, the translation could not be completed for all 6 levels of MRS. No apparent variation over time in the categorization scheme was observed. Further research needs to be conducted to develop better prediction models explaining the relationship between M-FIM and MRS.

Activities of Daily Living↗

PubMed1983

Tertiary structures, receptor binding, and antigenicity of insulinlike growth factors.

Three-dimensional models for human insulinlike growth factors (IGF-I and IGF-II) have been constructed by using interactive molecular graphics. It is suggested that the two growth factors have structures in which the A and B chains and the hydrophobic cores are identical to those of insulin. The conformations of the connecting peptides and COOH-terminal extensions are predicted by statistical methods but the structures are limited by the constraints implied by the insulinlike part. The models explain the nonsuppressibility by anti-insulin antibodies of the IGFs and show that part of the insulin receptor-binding region is conserved, which explains the growth factors' ability to bind insulin receptors.

Amino Acid Sequence↗

PubMed2004

A biochemical oscillator explains several aspects of Myxococcus xanthus behavior during development.

During development, Myxococcus xanthus cells produce a series of spatial patterns by coordinating their motion through a contact-dependent signal, the C-signal. C-signaling modulates the frequency at which cells reverse their gliding direction. It does this by interacting with the Frz system (a homolog of the Escherichia coli chemosensory system) via a cascade of covalent modifications. Here we show that introducing a negative feedback into this cascade results in oscillatory behavior of the signaling circuit. The model explains several aspects of M. xanthus behavior during development, including the nonrandom distribution of reversal times, and the differences in response of the reversal frequency to both moderate and high levels of C-signaling at different developmental stages. We also propose experiments to test the model.

Bacterial Proteins↗

PubMed2005

Central visual function and the NEI-VFQ-25 near and distance activities subscale scores in people with type 1 and 2 diabetes.

PURPOSE: To investigate relationships between clinical measures of central visual function and NEI-VFQ-25 Near and Distance Activities subscales in patients with diabetic retinopathy. DESIGN: Clinic-based, cross-sectional, observational study. METHODS: The NEI-VFQ-25 was administered to 170 people with type 1 or 2 diabetes before an ocular examination that included visual acuity, contrast sensitivity, and central visual fields. Multiple linear regression and exact multiple logistic regression were used to assess the relationship between poor acuity (<69 letters), poor contrast sensitivity (<1.5 log units), and abnormal visual fields (mean deviation < or = -5dB) and NEI-VFQ-25 subscale scores. RESULTS: Final multivariable linear models explained a beta = 4.7 letter difference (P < or = .001) for each 25-point Near Activities subscale score difference. Similar effects were observed for the Distance Activities subscale, although the magnitudes of regression and partial correlation coefficients were lower (beta = 3.3 letters, P < or = .01). Final logistic regression models on abnormal clinical categories of central visual function demonstrated relationships only with the Near Activities subscale. For a 1-point change in Near Activities subscale score, the odds of obtaining a poor score for visual acuity, central visual fields, and contrast sensitivity changed by 0.08 (P < or = .001), 0.07 (P < or = .05), and 0.12 (P < or = .001), respectively. CONCLUSIONS: NEI-VFQ-25 Near and Distance Activities subscales demonstrate utility as measures of central visual function in persons with type 1 or 2 diabetes. Low scores on the NEI-VFQ-25 may reflect poor central visual fields and contrast sensitivity in addition to poor visual acuity.

Adult↗

PubMed2005

Do theories of the glass transition, in which the structural relaxation time does not define the dispersion of the structural relaxation, need revision?

Upon decreasing temperature or increasing pressure, a noncrystallizing liquid will vitrify; that is, the structural relaxation time, taualpha, becomes so long that the system cannot attain an equilibrium configuration in the available time. Theories, including the well-known free volume and configurational entropy models, explain the glass transition by invoking a single quantity that governs the structural relaxation time. The dispersion of the structural relaxation (i.e., the structural relaxation function) is either not addressed or is derived as a parallel consequence (or afterthought) and thus is independent of taualpha. In these models the time dependence of the relaxation bears no fundamental relationship to the value of taualpha or other dynamic properties. Such approaches appear to be incompatible with a general experimental fact recently discovered in glass-formers: for a given material at a fixed value of taualpha, the dispersion is constant, independent of thermodynamic conditions (T and P); that is, the shape of the alpha-relaxation function depends only on the relaxation time. If derived independently of taualpha, it is an unlikely result that the dispersion of the structural relaxation would be uniquely defined by taualpha.

Journal Article↗

PubMed1997

Pharmacology of 21-day oral etoposide given in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer: a cancer and leukemia group B study (CALGB 9062).

This was a pharmacological companion study to a randomized Phase III trial comparing 21-day oral versus 3-day i.v. etoposide in combination with i.v. cisplatin in patients with extensive-stage small cell lung cancer. Etoposide plasma concentrations were measured in patients randomized to the 21-day schedule and correlated with toxicity and tumor response. Patients were treated with etoposide (50 mg/m2/day) orally for 21 days and cisplatin (33 mg/m2/day) i.v. for 3 consecutive days every 28 days for 6 courses. Plasma samples before the daily etoposide dose (trough concentrations) and complete blood counts were obtained weekly during treatment. The average of three etoposide concentrations (EC) per course was calculated. Of 158 patients registered to this schedule of the study, 150 were eligible. In 106 patients, etoposide samples were obtained at least in the first course in which the mean EC was 0.39 microgram/ml (SD = 0.29). In 102 patients (missing albumin values in 4 of 106 patients), the concentration of etoposide not bound to protein (Efree) was estimated based on the following equation: percentage unbound = (1.4 x total bilirubin) - (6.8 x albumin) + 34.4. Regression analysis revealed that increasing age was correlated with higher EC (r = 0.27; two-tailed P < 0.01) and Efree (r = 0.31; two-tailed P < 0.01). Higher EC and Efree values were associated with lower WBC counts and absolute neutrophil counts after the first treatment course in 83 patients with nadir counts. Using multiple linear regression, a pharmacodynamic model was developed that included EC or Efree, age, and alkaline phosphatase. An interaction with bone marrow results at diagnosis was found, indicating a sharper decline in nadir counts with increasing EC or Efree when the marrow was involved with small cell lung cancer. This model explained 29% of the variation for WBC nadirs (P < 0.001) and 31% of the variation for absolute neutrophil count nadirs (P < 0. 001). Neither EC nor Efree showed a significant correlation with tumor response. A pharmacokinetic relationship between EC or Efree and age was found. A pharmacodynamic model could be developed for toxicity but not for tumor response.

Administration, Oral↗

PubMed2005

Band-broadening in capillary zone electrophoresis with axial temperature gradients.

It is widely accepted that Joule heating effects yield radial temperature gradients in capillary zone electrophoresis (CZE). The resultant parabolic profile of electrophoretic velocity of analyte molecules is believed to increase the band-broadening via Taylor-Aris dispersion. This typically insignificant contribution, however, cannot explain the decrease in separation efficiency at high electric fields. We show that the additional band-broadening due to axial temperature gradients may provide the answer. These axial temperature variations result from the change of heat transfer condition along the capillary, which is often present in CZE with thermostating. In this case, the electric field becomes nonuniform due to the temperature dependence of fluid conductivity, and hence the induced pressure gradient is brought about to meet the mass continuity. This modification of the electroosmotic flow pattern can cause significant band-broadening. An analytical model is developed to predict the band-broadening in CZE with axial temperature gradients in terms of the theoretical plate height. We find that the resultant thermal plate height can be very high and even comparable to that due to molecular diffusion. This thermal plate height is much higher than that due to radial temperature gradients alone. The analytical model explains successfully the phenomena observed in previous experiments.

Electrophoresis, Capillary↗

PubMed1995

Coordinated hydrolysis explains the mechanical behavior of kinesin.

The two-headed motor protein kinesin hydrolyzes nucleotide to move unidirectionally along its microtubule track at speeds up to 1000 nm/s (Saxton et al., 1988) and develops forces in excess of 5 pN (Hunt et al., 1994; Svoboda et al., 1994a). Individual kinesin molecules have been studied recently in vitro, and their behavior has been characterized in terms of force-velocity curves and variance measurements (Svoboda and Block, 1994a; Svoboda et al., 1994b). We present a model for force generation in kinesin in which the ATP hydrolysis reactions are coordinated with the relative positions of the two heads. The model explains the experimental data and permits us to study the relative roles of Brownian motion and elastic deformation in the motor mechanism of kinesin.

Animals↗

PubMed1981

Spermatogenesis in Sciara coprophila. I. Chromosome orientation on the monopolar spindle of meiosis I.

Meiosis I of spermatogenesis in the fungus fly, Sciara coprophila, has a monopolar spindle which collects the maternal and supernumerary L chromosome sets, while the paternal chromosomes migrate away from the single pole to be excluded in a bud. By inspection, the metacentric paternal chromosome IV moves with its centromere lagging rather than leading the direction of motion. Therefore, we wondered if all paternal homologues move in such a reverse orientation. To determine the orientation of the other homologues which are acrocentrics (chromosomes II, III, X), their centromeres were localized by use of the DAPI C-bonding technique. In addition, we characterized centromeric heterochromatin on polytene chromosomes by C-banding and in situ hybridization of satellite DNA isolated by Ag+-Cs2SO4 (rho CsC1 satellite I=1.698 g/ml; rho CsC1 satellite II=1.705 g/ml). The two satellite fractions were localized to the centromeric heterochromatin of all the chromosomes, and to a varying degree to all chromosome telomeres. By DAPI C-banding we could precisely locate each centromere band on polytene chromosomes, and these results agreed with those of satellite cRNA in situ hybridization. We then applied the DAPI C-banding technique to primary spermatocyte preparations, and determined that all paternal chromosomes migrate at anaphase I with their centromeres lagging rather than leading movement to the cell periphery. Since in polytene chromosomes the X chromosome contains a moderately fluorescent band on its noncentromeric end as well, in order to clarify its DAPI C-banding result in primary spermatocytes, we did in situ hybridization of (3)H nick-translated cloned rDNA, since rDNA is a convenient marker for the centromeric heterochromatin of the X. These data and the DAPI C-banding results indicate that the X as well as all th other paternal homologues display a reverse orientation (centromeres lag) as they migrate away from the single spindle pole to the cell periphery. - One model explaining this unusual paternal chromosome orientation is that there may be unique neocentromeric-like attachments to the non-centromeric free ends of these chromosomes. These attachments could serve to pull the paternal chromosomes to the cellular periphery as anaphase I progresses. In order to test this model, we analyzed anaphase I spermatocytes after a terminal block of heterochromatin had been removed from metacentric paternal chromosome IV by X-irradiation. We observed that when metacentric paternal chromosome IV is broken, it maintains its inverted "V" orientation rather than assuming a rod-like configuration. These data imply that there are no unique, terminal neocentromeric attachments to paternal chromosome IV as it progresses to the cellular periphery.

Animals↗

PubMed1991

Color opponent coding in the visual system of the honeybee.

A model is presented for the color vision system of the honeybee, which takes the nonlinear phototransduction process in the photoreceptors into account and assumes linear computations of the excitations of the photoreceptors. The model parameters are derived by a least squares fit of the scale values determined by multidimensional scaling analysis of the results of color choice experiments to the excitation values of two hypothetical spectral antagonistic coding cells. The psychophysical scale values are interpreted physiologically. Furthermore, a color difference formula is presented which is based on the color opponent coding (COC) model. The model explains quantitatively (1) the sensitivity of spectral antagonistic neurons measured by Kien and Menzel (1977; Journal of Comparative Physiology, 113, 17-34, 35-53), (2) the color discrimination function measured by von Helversen (1972; Journal of Comparative Physiology, 80, 439-472). The following predictions are derived from the model: (1) excitation/log (I) curves of the spectral antagonistic neurons; and from the model in conjunction with the color difference formula: (2) intensity dependent color shifts (Bezold-Brücke effect); (3) the intensity dependence of wavelength discrimination.

Animals↗