SV40-transformed hamster prostatic tissue: a model of human prostatic malignancy.
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Acid Phosphatase↗
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A comparison of models used as alternative magnetic resonance image reconstruction methods.
In magnetic resonance (MR) imaging, excellent reconstructions are obtained on large data sets using the inverse discrete Fourier transform (IDFT). Modeling procedures have been proposed to overcome the image artifacts from the truncation of small data sets. In this paper, a relationship between image reconstruction using modeling and the standard IDFT is presented. A comparison of the assumptions behind the Smith and Haacke models is given and an experimental evaluation of the validity of the models provided. Various methods of evaluating model coefficients are discussed. Images are reconstructed from both models using the Transient Error reconstruction approach (TERA) algorithm. TERA is an algorithm that reintroduces data information components that cannot be modeled: useful when the assumed model characteristics do not completely match all portions of the image. Although very different in their basic assumptions, both the Smith and Haacke models were found to reduce truncation artifacts and improve resolution when used with the TERA algorithm.
Algorithms↗
Predictors of a normal chest x-ray in respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) accounts for the majority of lower respiratory tract infections (LRTI) in infants and young children. A chest x-ray is frequently performed in infants with LRTI caused by RSV. The aim of this study was to develop and validate a prediction model to estimate the probability for a normal chest x-ray in children with RSV infection. For this purpose, easy obtainable diagnostic parameters were used. This prediction model may be applied to decide which patients do not require a chest x-ray. The data of 287 children admitted with RSV infection or diagnosed as such in the outpatient department of the Sophia Children's Hospital between 1992-1996 were studied. The derivation set comprised 232 patients (1992-1995), and the validation set contained 55 patients (1995-1996). A chest x-ray was designated as normal when atelectasis, hyperinflation, or pulmonary infiltrates were absent. In order to develop a prediction model, patient history and clinical and laboratory variables were consecutively entered into a logistic regression model according to the diagnostic workup that was practiced at the time. Variables with P < or = 0.10 were retained in the model. The predictive accuracy of the multivariable models was examined using the area under receiver operating curve (ROC-area). In 202 (87%) patients from the derivation set, a chest x-ray was performed. A normal chest x-ray could be predicted by increasing age, increasing birth weight, presence of rhinitis, absence of retractions, and increasing arterial oxygen saturation. The ROC-area was 0.80 in the derivation and validation sets. This prediction model was transformed into a score chart. In conclusion, a normal chest x-ray can accurately be predicted, using a model including easily obtainable patient characteristics, and clinical and laboratory variables. This model may be a useful tool in deciding whether or not to perform a chest x-ray in patients with RSV infections.
Diagnosis, Differential↗
Fast burst firing and short-term synaptic plasticity: a model of neocortical chattering neurons.
We present an ionic conductance model of chattering neurons in the neocortex, which fire fast rhythmic bursts in the gamma frequency range (approximately 40 Hz) in response to stimulation [Gray C. M. and McCormick D. A. (1996) Science 274, 109-113]. The bursting mechanism involves a "ping-pong" interplay between soma-to-dendrite back propagation of action potentials and an afterdepolarization generated by a persistent dendritic Na+ current and a somatic Na+ window current. The oscillation period is primarily determined by a slowly inactivating K+ channel and passive membrane properties. The model behavior is compared quantitatively with the experimental data. It is shown that the cholinergic muscarinic receptor activation can transform the model cell's firing pattern from tonic spiking to rapid bursting, as a possible pathway for acetylcholine to promote 40-Hz oscillations in the visual cortex. To explore possible functions of fast burst firing in the neocortex, a hypothetical neural pair is simulated, where a chattering cell is presynaptic to an inhibitory interneuron via stochastic synapses. For this purpose, we use a synapse model endowed with a low release probability, short-term facilitation and vesicle depletion. This synapse model reproduces the behavior of certain neocortical pyramid-to-interneuron synapses [Thomson A. M. et al. (1993) Neuroscience 54, 347-360]. We showed that the burstiness of cell firing is required for the rhythmicity to be reliably transmitted to the postsynaptic cell via unreliable synapses, and that fast burst firing of chattering neurons can provide an exceptionally powerful drive for recruiting feedback inhibition in cortical circuits. From these results, we propose that the fast rhythmic burst firing of neocortical chattering neurons is generated by a calcium-independent ionic mechanism. Our simulation results on the neural pair highlight the importance of characterizing the short-term plasticity of the synaptic connections made by chattering cells, in order to understand their putative pacemaker role in synchronized gamma oscillations of the visual cortex.
Animals↗
A stochastic model of oncogene expression and the relevance of this model to cancer therapy.
BACKGROUND: Ablation of an oncogene or of the activity of the protein it encodes can result in apoptosis and/or inhibit tumor cell proliferation. Therefore, if the oncogene or set of oncogenes contributing maximally to a tumor cell's survival can be identified, such oncogene(s) are the most appropriate target(s) for maximizing tumor cell kill. METHODS AND RESULTS: A mathematical model is presented that describes cellular phenotypic entropy as a function of cellular proliferation and/or survival, and states of transformation and differentiation. Oncogenes become part of the cellular machinery, block apoptosis and differentiation or promote proliferation and give rise to new states of cellular transformation. Our model gives a quantitative assessment of the amount of cellular death or growth inhibition that result from the ablation of an oncogene's protein product. We review data from studies of chronic myelogenous leukemia and K562 cells to illustrate these principles. CONCLUSION: The model discussed in this paper has implications for oncogene-directed therapies and their use in combination with other therapeutic modalities.
Antineoplastic Agents↗
H-2z homozygous New Zealand mice as a model for B-cell chronic lymphocytic leukemia: elevated bcl-2 expression in CD5 B cells at premalignant and malignant stages.
In New Zealand mice, the major histocompatibility complex (MHC) controls the development of both autoimmune disease and B cell chronic lymphocytic leukemia (B-CLL). While H-2d/H-2z heterozygosity acts as one major predisposing genetic element for autoimmune disease, H-2z/H-2z homozygosity acts as an element for B-CLL. In the H-2z/H-2z homozygotes, there was an age-dependent increase in frequencies of CD5 B cells in the blood and spleen, and such CD5 B cells showed oligoclonal to monoclonal expansion, giving rise to B-CLL. B-CLL cells from these mice had surface phenotypes typical of CD5 B lineage cells, and expressed high levels of proto-oncogene bcl-2. Elevated bcl-2 expression was also observed in premalignant B cells in the aged mice, thereby suggesting that apoptosis-resistant, long-surviving CD5 B cells with a self-renewal capacity form the basis of malignant transformation. This model not only provides clues for analyzing multiple steps of genetic alterations involved in the generation of B-CLL, but also sheds light on the correlation between B-CLL and autoimmune disease.
Animals↗
Evaluation of data transformations and validation of a model for the effect of temperature on bacterial growth.
The temperature of chilled foods is an important variable for controlling microbial growth in a production and distribution chain. Therefore, it is essential to model growth as a function of temperature in order to predict the number of organisms as a function of temperature and time. This article deals with the correct variance-stabilizing transformation of the growth parameters A (asymptotic level), mu (specific growth rate), and lambda (lag time). This is of importance for the regression analysis of the data. A previously gathered data set and model for the effect of temperature on the growth of Lactobacillus plantarum (M. H. Zwietering, J. T. de Koos, B. E. Hasenack, J. C. de Wit, and K. van 't Riet, Appl. Environ. Microbiol. 57:1094-1101, 1991) is extended with new data. With the total data set (original and new data), a variance-stabilizing transformation is selected in order to determine which transformation should precede fitting. No transformation for the asymptote data, a square root for the growth rate, and a logarithmic transformation for the lag time were found to be appropriate. After these transformations, no significant correlation was found between the variance and the magnitude of the variable. Model corrections were made and model parameters were estimated by using the original data. With the new data, the models were validated by comparing the lack of fit of the models with the measurement error, using an F test. The predictions of the models for mu and lambda were adequate. The model for A showed a systematic deviation, and therefore a new model for A is proposed.
Journal Article↗
Behavioral responses to novelty in mice: a reanalysis.
A recently proposed searching procedure for scale transformations and models was applied to previously obtained data on rearing responses and locomotor activity in mice from two inbred selection lines (SRH and SRL) and four hybrid generations. Logarithmic transformation provided the most appropriate scale of measurement for both behaviors. For rearing, the simple additive model was adequate, thus validating the earlier findings. However, contrary to the previous conclusions, an additivity-dominance model fitted the locomotion data best. These results demonstrate the usefulness of the procedure described.
Animals↗
Transforming an MFT program: a model for enhancing diversity.
Marriage and family therapy programs need to go beyond the typical practices of recruiting and retaining students of color. Marriage and family therapy educators must assume positions of leadership by transforming graduate programs to reflect a deep, active, systemic commitment to both diversity and social justice. In this article, we argue that it is through this type of transformation that programs become truly ready to support students of color and to prepare all therapists to advocate for equity in a diverse, often unfair society. This article offers a model that addresses readiness, recruitment, retention, assessment, and professional development from this perspective.
Cultural Diversity↗
Fibrous dysplasia of the face: utility of three-dimensional modeling and ex situ malar recontouring.
A 20-year-old male with fibrous dysplasia involving the right fronto-orbital and malar regions showed no significant progression of disease by serial computed tomography (CT) scans over 6 years. Two prior attempts to recontour the right maxilla and zygoma in situ and to increase the right orbital volume had been unsatisfactory. To solve the problem of persistent right-sided proptosis and facial asymmetry, a three-dimensional model of the midface and orbits was made on the basis of a pre-operative CT scan. Removable components transformed the model of the affected right side of the midface into a mirror image of the unaffected side, giving a precise indication of where and how much bone needed to be removed. Surgical correction was performed using a right malar osteotomy in which the zygoma was mobilized in continuity with the lateral and inferior orbital rims. This approach gave direct access to the orbit, through which the lateral and medial orbital walls were re-contoured to increase intraorbital volume. The freely mobilized zygoma was then shaped to match the prefabricated model. The zygoma was repositioned, and the affected maxilla was recontoured to blend with the remodeled zygoma. Follow-up CT scan and physical examinations postoperatively demonstrate excellent facial symmetry and correction of right-sided proptosis. When there is no documented progression of fibrous dysplasia in the face over several years, three-dimensional modeling as a guide to ex situ malar recontouring can improve the accuracy of facial reconstruction. This approach also provides direct access to the orbit for the correction of bony orbital volume.
Adolescent↗
Structure and transformation: Large molecular clusters as models of condensed matter.
This paper reviews investigations of homogeneous nucleation in phase transitions in large molecular clusters. The principal techniques brought to bear are electron diffraction analyses of transformations in clusters formed by condensation of vapor in supersonic expansions and computer simulations of spontaneous phase changes in clusters. Results obtained to date are contrasted with those of larger systems and interpreted in terms of nucleation theory. The review also refers to some unresolved aspects of nucleation theory.
Journal Article↗
Complete displacement of somatic histones during transformation of spermatid chromatin: a model experiment.
Displacement of histones from calf thymus chromatin has been studied in an attempt to postulate the mechanisms involved in the total removal of somatic-type histones during transformation of spermatid chromatin. When chromatin is saturated with protamine (protamine/DNA, 0.5), histone I becomes displaceable at 0.15-0.3 M NaCl, suggesting that direct replacement by highly basic sperm histone could be a mechanism for its removal. While histone I is the only histone which is extensively degraded upon incubation of chromatin and, therefore, proteolysis might provide an additional mechanism for the removal of this histone, acetylation of chromatin by acetic anhydride greatly increases suscpetibility of histones IIb1, IIb2, and III to the chromosomally associated protease. These histones are extensively degraded and displaced from the DNA upon incubation of the acetylated chromatin. Although histone IV is not appreciably degraded, the proteolytic removal of acetylated histone III from chromatin weakens the interaction of acetylated histone IV to the DNA, and this histone becomes dissociable at 0.3 M NaCl. A comparison of the extent of chemical acetylation of individual histones observed in this investigation with that of enzymatic acetylation which can be achieved in vivo suggests that acetylation and proteolysis could be a mechanism for the removal of histone IIb2 and III. The displacement of histones IIb1 and IV could be explained on the basis of decreased binding to DNA as a result of their acetylation together with the proteolytic removal of their respective partner histones, IIb2 and III.
Acetylation↗
Differential response to transforming growth factors-beta(1) and beta(2): connective tissue deposition in animal models.
The ability of transforming growth factor (TGF)-beta(1) and TGF-beta(2) to promote connective tissue deposition were compared in different animal models. A single subcutaneous injection of TGF-beta(2) in collagen/heparin gel carrier promoted markedly more extensive development of connective tissue than TGF-beta(1) at the site of injection in both neonatal and adult mice. Both TGF-beta(1) and TGF-beta(2) promoted deposition of dense and well-vascularized connective tissue matrix infiltrated with macrophages and fibroblasts. However, the results of immunohistochemical analyses suggested that TGF-beta(2) promoted an accumulation of more macrophages in the connective tissue than TGF-beta(1). Similar differences in the extent of connective tissue development were observed in neonatal mice when these factors were administered as a solution, without the collagen/heparin gel carrier. TGF-beta(2) was also more potent than TGF-beta(1) in domestic pigs. However, in guinea pigs, TGF-beta(1) promoted more extensive connective tissue development than TGF-beta(2). These results suggest that the differential connective tissue response to TGF-beta(1) and TGF-beta(2) is species dependent. However, the differences in the physical and chemical properties of these factors may account in part for the differential response as well.
Journal Article↗
CCD noise removal in digital images.
In this work, we propose a denoising scheme to restore images degraded by CCD noise. The CCD noise model, measured in the space of incident light values (light space), is a combination of signal-independent and signal-dependent noise terms. This model becomes more complex in image brightness space (normal camera output) due to the nonlinearity of the camera response function that transforms incoming data from light space to image space. We develop two adaptive restoration techniques, both accounting for this nonlinearity. One operates in light space, where the relationship between the incident light and light space values is linear, while the second method uses the transformed noise model to operate in image space. Both techniques apply multiple adaptive filters and merge their outputs to give the final restored image. Experimental results suggest that light space denoising is more efficient, since it enables the design of a simpler filter implementation. Results are given for real images with synthetic noise added, and for images with real noise.
Algorithms↗
In vitro transformation of rat tracheal epithelial cells: a model for the study of multistage carcinogenesis.
A multistage transformation assay has been developed using normal primary rat tracheal epithelial cells as targets for measuring the transforming activity of a variety of test substances. The assay is suited for quantitation of cell transformation and allows the study of effects of promoters as well as inhibitors of transformation at various stages of this multiphasic process. Studies with TPA and retinoic acid have shown that the first stage of neoplastic transformation of RTE cells cannot be enhanced by TPA but is inhibited by retinoic acid. However, TPA can enhance a later stage of transformation, the conversion of the ag- to the ag+ phenotype. The cellular and biochemical mechanism of the inhibitory effects of RA are under investigation.
Animals↗
A transformation cross-talk technique for simultaneous dual radionuclide imaging: a myocardial perfusion 201Tl/99Tcm sestamibi dog SPECT study.
We have developed a novel transformation method for the correction of cross-talk in simultaneous dual radionuclide single photon emission CT (SPECT) imaging. It is based on the assumption that the transformations, which transform the primary energy window images into the scatter images as viewed in the other energy windows, are known. The method was tested on a dog model. These transformations were found by measuring the point response functions (prf) in different energy windows for both radionuclides in water. The dual radionuclide correction method described takes into account the different spatial distributions of the primary and scatter cross-talk photons in different energy windows. This method also includes the sequential application of restoration filters to the resulting cross-talk corrected images. We used a dog model in three separate studies: two single radionuclide studies used as references and one dual radionuclide study. Contrast between the left ventricular cavity (LVC) and the myocardium was used in horizontal long axis (HLA) slices as a parameter to evaluate the results of the dual radionuclide correction method with restoration. The increase of the contrast in the dual radionuclide corrected images in both energy windows, i.e. 201Tl primary window (70 keV) and 99Tcm primary window (140 keV), was significant. The cross-talk corrected 70 keV dual radionuclide HLA slice had a contrast of 0.62 compared with 0.35, which was the value in the non-corrected dual radionuclide HLA slice. Restoration improved the contrast to 0.68. In the single radionuclide 201Tl image, the same contrast was 0.59, improving to 0.70 after restoration. For the dual radionuclide 140 keV HLA slice, the contrast increased from 0.69 to 0.76 after cross-talk correction. Additional increase of the contrast to 0.83 resulted from restoration filtering. In the single radionuclide 99Tcm sestamibi 140 keV HLA slice the improvement of contrast was from 0.63 to 0.86 as a result of the restoration. The transformation three-window, dual radionuclide correction method with restoration improves the quality of the simultaneous rest 201Tl/stress 99Tcm sestamibi SPECT imaging.
Animals↗
Analysis of two-component signal transduction by mathematical modeling using the KdpD/KdpE system of Escherichia coli.
A mathematical model for the KdpD/KdpE two-component system is presented and its dynamical behavior is analyzed. KdpD and KdpE regulate expression of the kdpFABC operon encoding the high affinity K+ uptake system KdpFABC of Escherichia coli. The model is validated in a two step procedure: (i) the elements of the signal transduction part are reconstructed in vitro. Experiments with the purified sensor kinase and response regulator in presence or absence of DNA fragments comprising the response regulator binding-site are performed. (ii) The mRNA and molecule number of KdpFABC are determined in vivo at various extracellular K+ concentrations. Based on the identified parameters for the in vitro system it is shown, that different time hierarchies appear which are used for model reduction. Then the model is transformed in such a way that a singular perturbation problem is formulated. The analysis of the in vivo system shows that the model can be separated into two parts (submodels which are called functional units) that are connected only in a unidirectional way. Hereby one submodel represents signal transduction while the second submodel describes the gene expression.
Base Sequence↗
Internal models of limb dynamics and the encoding of limb state.
Studies of reaching suggest that humans adapt to novel arm dynamics by building internal models that transform planned sensory states of the limb, e.g., desired limb position and its derivatives, into motor commands, e.g., joint torques. Earlier work modeled this computation via a population of basis elements and used system identification techniques to estimate the tuning properties of the bases from the patterns of generalization. Here we hypothesized that the neural representation of planned sensory states in the internal model might resemble the signals from the peripheral sensors. These sensors normally encode the limb's actual sensory state in which movement errors occurred. We developed a set of equations based on properties of muscle spindles that estimated spindle discharge as a function of the limb's state during reaching and drawing of circles. We then implemented a simulation of a two-link arm that learned to move in various force fields using these spindle-like bases. The system produced a pattern of adaptation and generalization that accounted for a wide range of previously reported behavioral results. In particular, the bases showed gain-field interactions between encoding of limb position and velocity, very similar to the gain fields inferred from behavioral studies. The poor sensitivity of the bases to limb acceleration predicted behavioral results that were confirmed by experiment. We suggest that the internal model of limb dynamics is computed by the brain with neurons that encode the state of the limb in a manner similar to that expected of muscle spindle afferents.
Arm↗