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PubMed2005

Orientation congruency effects for familiar objects: coordinate transformations in object recognition.

How do observers recognize objects after spatial transformations? Recent neurocomputational models have proposed that object recognition is based on coordinate transformations that align memory and stimulus representations. If the recognition of a misoriented object is achieved by adjusting a coordinate system (or reference frame), then recognition should be facilitated when the object is preceded by a different object in the same orientation. In the two experiments reported here, two objects were presented in brief masked displays that were in close temporal contiguity; the objects were in either congruent or incongruent picture-plane orientations. Results showed that naming accuracy was higher for congruent than for incongruent orientations. The congruency effect was independent of superordinate category membership (Experiment 1) and was found for objects with different main axes of elongation (Experiment 2). The results indicate congruency effects for common familiar objects even when they have dissimilar shapes. These findings are compatible with models in which object recognition is achieved by an adjustment of a perceptual coordinate system.

Adult↗
PubMed1988

A method for determining the optimum transform for covariates of the Cox model with application to 3680 cases of intraocular melanoma.

For most applications of the Cox Model, a simple exponential relationship is assumed between covariates of this model and relative force of mortality (lambda). A method has been developed to examine this relationship in detail for data sets that contain a sufficient number of deaths. This method was applied to 3680 cases of intraocular melanoma with 1178 deaths over 20 years of follow-up, using largest tumor dimension (LTD) as a predictor of tumor-related death. Results indicated that the transform lambda = exp[beta log LTD] provides a closer approximation to observed mortality for this data set than the more traditional lambda = exp [beta LTD]. Additional applications to mathematically generated data sets revealed a close correspondence between lambda estimated by this method and the lambda programmed into each data set.

Epidemiologic Methods↗
PubMed2002

Effects of delayed treatment with transforming growth factor-beta soluble receptor in a three-dose bleomycin model of lung fibrosis in hamsters.

Transforming growth factor-beta (TGF-beta) plays a pivotal role in an exaggerated synthesis and accumulation of collagen in fibrotic disorders of many organs. We have previously demonstrated that repeated intratracheal (IT) instillation of TGF-beta soluble receptor (TR) in hamsters markedly decreased the bleomycin (BL)-induced lung fibrosis in response to a single dose. The present study was carried out in a 3-dose BL-hamster model of lung fibrosis to better evaluate the therapeutic potential of TR. Three doses of BL (2.5, 2.0, and 1.5 U/4 mL/kg) or an equivalent volume of isotonic saline was administered IT consecutively at weekly intervals, and phosphate-buffered saline (PBS) or TR (4 nmol/0.3 mL/hamster) by the same route twice a week, starting after the 2nd BL or 3rd BL dose. Twenty-one days after the 3rd dose of BL instillation, the hamsters were killed for bronchoalveolar lavage (BAL) and biochemical and histopathological analyses. The results showed that treatment with TR starting after either the 2nd or 3rd dose of BL caused significant reduction in BL-induced lung fibrosis, as demonstrated by marked decreases in the hydroxyproline level and prolyl hydroxylase activity of the lungs. Histopathological evaluation of the lungs also revealed that the hamsters in both BL+TR groups had markedly fewer fibrotic lesions than hamsters in BL+PBS group. These results demonstrate the beneficial effects of delayed treatment with TR in attenuating the progression of ongoing fibrotic process and suggest its potential therapeutic uses in the management of lung fibrosis in humans.

Animals↗
PubMed1997

Effect of endotoxin administration on the severity of acute pancreatitis in two experimental models.

CONCLUSIONS: Endotoxemia can transform acute pancreatitis (AP) into a more severe form of the disease in models of AP provoked by common pancreatico-biliary duct ligation or L-arginine injection. BACKGROUND: It has been shown that systemic endotoxemia is a common feature in severe AP. The effect of endotoxemia on the course of experimental pancreatitis is unknown. METHODS: AP was induced by common pancreatico-biliary duct ligation (experiment 1) and i.p. injection of 250 mg/100 g body wt of L-arginine (experiment 2). Test animals of both experiments received i.p. injections of 0.5 and 1.0 mg/100 g body wt of endotoxin at the induction of AP. Saline-treated and only endotoxin-dosed animals served as controls for both experiments. Mortality rates and pancreatic histology were investigated at 48 h. RESULTS: The mortality rate was significantly elevated (60%, p < 0.05) in experiment 1 when 1.0 mg/100 g of endotoxin was given. In experiment 2, the mortality rate was also increased (30%) at this dose of endotoxin without reaching significance. Histologic changes were more severe in both groups of AP treated by the two doses of endotoxin than without it. Acinar necrosis and hemorrhage were highly elevated (p < 0.01) in both experiments when AP was combined with 1.0 mg/100 g body wt of endotoxin. The animals receiving only endotoxin showed only slight inflammatory and necrotic changes.

Acute Disease↗
PubMed1992

Evaluation of data transformations used with the square root and schoolfield models for predicting bacterial growth rate.

A comparison was made between mathematical variations of the square root and Schoolfield models for predicting growth rate as a function of temperature. The statistical consequences of square root and natural logarithm transformations of growth rate use in several variations of the Schoolfield and square root models were examined. Growth rate variances of Yersinia enterocolitica in brain heart infusion broth increased as a function of temperature. The ability of the two data transformations to correct for the heterogeneity of variance was evaluated. A natural logarithm transformation of growth rate was more effective than a square root transformation at correcting for the heterogeneity of variance. The square root model was more accurate than the Schoolfield model when both models used natural logarithm transformation.

Colony Count, Microbial↗
PubMed2003

Comparison of eigenvector methods with classical and model-based methods in analysis of internal carotid arterial Doppler signals.

Doppler ultrasound is known as a reliable technique, which demonstrates the flow characteristics and resistance of arteries in various vascular disease. In this study, internal carotid arterial Doppler signals recorded from 105 subjects were processed by PC-computer using classical, model-based, and eigenvector methods. The classical method (fast Fourier transform), two model-based methods (Burg autoregressive, least-squares modified Yule-Walker autoregressive moving average methods), and three eigenvector methods (Pisarenko, multiple signal classification, and Minimum-Norm methods) were selected for processing internal carotid arterial Doppler signals. Doppler power spectra of internal carotid arterial Doppler signals were obtained using these spectrum analysis techniques. The variations in the shape of the Doppler power spectra were examined in order to obtain medical information. These power spectra were then used to compare the applied methods in terms of their frequency resolution and the effects in determination of stenosis and occlusion in internal carotid arteries.

Arterial Occlusive Diseases↗
PubMed2003

Enhancement of carcinogen-induced malignant cell transformation by prostaglandin F(2 alpha).

The enhancement of carcinogen-induced malignant transformation of C3H/M2 mouse fibroblasts by the tumor promoters 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with the induction of cyclooxygenase expression and the stimulation of prostaglandin (PG) formation. Therefore, the potential of PGs, i.e., PGF(2alpha) and PGE(2), for tumor promotion was studied in the two-step C3H/M2 cell transformation assay, a model of the multi-step process of carcinogenesis. The transformation of fibroblasts was clearly enhanced by the addition of PGF(2alpha) in the promotion phase after pretreatment with a subthreshold dose of a carcinogen (3-methylcholanthrene or N-methyl-N'-nitro-N-nitrosoguanidine). No enhancement of cell transformation was observed in cells without carcinogen-pretreatment, i.e., PGF(2alpha) had no tumor initiating potential. The promotional effect was dose-dependent with a maximum at 16 nM PGF(2alpha). PGE(2) had no significant effect in this assay. Furthermore, PGF(2alpha) (but not PGE(2)) clearly reduced the inhibition of TPA-induced promotion by NS-398, an isozyme-specific inhibitor of cyclooxygenase-2. The inhibition of TPA- or TCDD-induced promotion by the non-specific cyclooxygenase inhibitor indomethacin was not affected by co-treatment with PGF(2alpha) and PGE(2). Our data suggest that PGF(2alpha) acts as an endogenous promoter of cell transformation implying that it may also be critically involved in tumor promoter-induced signalling transfer cascades ultimately triggering the process of carcinogenesis.

Animals↗
PubMed1985

Multiphasic kinetics for transformation of methyl parathion by flavobacterium species.

Transformation rates of an insecticide, methyl parathion, in pure cultures of Flavobacterium sp. followed multiphasic kinetics involving at least two systems (I and II). System I was a high-affinity, low-capacity system, and system II was a low-affinity, high-capacity system. Data from rate experiments suggested that metabolites formed via system II inhibited system I such that only one system operated at a time. System I operated at approximately 20 mug liter and less; system II operated at approximately 4 mg liter and less. These results show that xenobiotic chemicals, like naturally occurring substrates, can be transformed via multiple uptake and transformation systems even by a pure culture. Furthermore, computer simulation models of pollutant transformation rates based on kinetic constants determined in this study show that large errors can occur in predicted rates when the multiphasicity of kinetics is neglected.

Journal Article↗
PubMedDate not supplied

[Causality, systems, and dynamic models. Three approaches of the explanation in demography].

The authors compare three methods of demographic analysis: "causal analysis, the transition models and the dynamic models. The purpose of these three approaches is not the same: transition models examine the transformation of a system during a given period; the dynamic model outlines the evolution of a social process through time; the causal analysis describes the mechanism through which the causes produce its effects. The three approaches differ also in the way they take time into account...[In particular,] causal static models are not pertinent in demographic research." (SUMMARY IN ENG)

Demography↗
PubMed2006

Bringing primary cells to mainstream drug development and drug testing.

Although cell-based screening is already an essential tool in drug discovery, the cell models currently available are fast becoming inadequate. The use of transformed cells as models in almost every step of the discovery pipeline needs to be substituted with more relevant, disease-oriented models, and the use of patient-derived primary cells should logically become the next best strategy. In the past the use of such cells has been restricted by their scarcity and difficulty in manipulation and general handling; however, recent advances in isolation and growth, as well as assay miniaturization, transfection efficiency and assay sensitivity, have enabled their use in the mainstream of drug discovery. This review explores some of these enabling technologies, as well as some of the most critical uses of primary cells that may dramatically alter the landscape of drug discovery and drug testing.

Adipocytes↗
PubMed2006

[Visualization and real-time tracking of the instruments in surgical navigation system].

In order to realize the visualization and real-time tracking of the instruments in surgical navigation system, we use the CAD solid model of the instruments directly or by reverse engineering, and transform the solid model to surface model. Then, the instruments, which are fixed with locator, are characterized and tested their precision. After registration between the CT model and the patient site in intra-operation, the system accurately displays the STL model of the instruments according to the tracked site and orientations. The model construction of the instruments is the base of the surgical navigation and is important to improve the security and precision of operation.

Computer Simulation↗
PubMed1996

Stepwise transformation of astrocytes by simian virus 40 large T antigen and epidermal growth factor receptor overexpression.

We have investigated the transformed phenotype of neonatal mouse cortical astrocytes immortalized by retrovirus-mediated transfer of the SV40 large T antigen gene. Expression of T antigen was driven by the Moloney murine leukemia virus long terminal repeat. Cell lines were selected based on coexpression of neomycin resistance, which provides a selection method believed to be unbiased for transformation state. Astrocyte cell lines derived in this manner express T antigen over a relatively narrow range (approximately 4-fold), are contact inhibited, are able to enter a quiescent state in the presence of growth factors, and do not readily form colonies in soft agar. Compared to mortal astrocytes, the population growth rate is increased 3-fold, saturation densities are 4-fold higher, and the genome is relatively unstable as measured by the presence of DNA-aneuploid stem lines and by changes in DNA ploidy over time. However, changes in transformation phenotype occur at a low rate, making the cell lines amenable to experimentation. Most often, the growth phenotype remained unchanged during months of culture. Transfection of an epidermal growth factor receptor (EGFR) gene was used to generate a subline that was conditionally transformed (colony formation in soft agar was dependent on transforming growth factor alpha). v-raf transfection was used to generate constitutive transformation. Thus, these cell lines appear to be excellent experimental models for progressive transformation. With them, untested hypotheses of brain tumor progression derived from human genetic studies may be tested experimentally.

Animals↗
PubMed1999

DNA uptake in bacteria.

Natural competence is widespread among bacterial species. The mechanism of DNA uptake in both gram-positive and gram-negative bacteria is reviewed. The transformation pathways are discussed, with attention to the fate of donor DNA as it is processed by the competent cell. The proteins involved in mediating various steps in these pathways are described, and models for the transformation mechanisms are presented. Uptake of DNA across the inner membrane is probably similar in gram-positive and gram-negative bacteria, and at least some of the required proteins are orthologs. The initial transformation steps differ, as expected, from the presence of an outer membrane only in the gram-negative organisms. The similarity of certain essential competence proteins to those required for the assembly of type-4 pili and for type-2 protein secretion is discussed. Finally several hypotheses for the biological role of transformation are presented and evaluated.

Adenosine Triphosphate↗
PubMed1983

Abnormal behavior of cultured fibroblasts from nodule and nonaffected aponeurosis of Dupuytren's disease.

Vimentin-positive, desmin-negative cells were established in culture from the nodule and from apparently normal palmar aponeurosis of a patient with Dupuytren's disease and compared with normal human embryonic and adult fibroblasts or sarcomatous cells. Cells from the nodule display in vitro biological properties that are intermediate between those expressed by normal fibroblasts and sarcoma cells or cells from the nodule transformed with SV40 virus. Thus, they represent an interesting in vitro model of partially transformed human cells. This behavior is not evolutive and justifies the classification of Dupuytren's disease among the benign mesenchymal tumors. The production of high level of plasminogen activator probably explains the local reactive pathology, and could act as a mitogenic stimulus for the proliferation of the nodule itself. Cultures derived from the apparently normal palmar aponeurosis show some but not all the abnormal growth properties of cells from nodules; this may help to explain the onset of local recurrences. Our results suggest that Dupuytren's disease is not strictly local and limited to the nodules, but affects, at least partially, the whole aponeurosis. Dupuytren's nodules could be considered as a model of tumor progression in a benign situation.

Blood↗
PubMedDate not supplied

View-based models of 3D object recognition: invariance to imaging transformations.

This report describes the main features of a view-based model of object recognition. The model does not attempt to account for specific cortical structures; it tries to capture general properties to be expected in a biological architecture for object recognition. The basic module is a regularization network (RBF-like; see Poggio and Girosi, 1989; Poggio, 1990) in which each of the hidden units is broadly tuned to a specific view of the object to be recognized. The network output, which may be largely view independent, is first described in terms of some simple simulations. The following refinements and details of the basic module are then discussed: (1) some of the units may represent only components of views of the object--the optimal stimulus for the unit, its "center," is effectively a complex feature; (2) the units' properties are consistent with the usual description of cortical neurons as tuned to multidimensional optimal stimuli and may be realized in terms of plausible biophysical mechanisms; (3) in learning to recognize new objects, preexisting centers may be used and modified, but also new centers may be created incrementally so as to provide maximal view invariance; (4) modules are part of a hierarchical structure--the output of a network may be used as one of the inputs to another, in this way synthesizing increasingly complex features and templates; (5) in several recognition tasks, in particular at the basic level, a single center using view-invariant features may be sufficient.

Depth Perception↗
PubMed2005

Riemannian elasticity: a statistical regularization framework for non-linear registration.

In inter-subject registration, one often lacks a good model of the transformation variability to choose the optimal regularization. Some works attempt to model the variability in a statistical way, but the re-introduction in a registration algorithm is not easy. In this paper, we interpret the elastic energy as the distance of the Green-St Venant strain tensor to the identity, which reflects the deviation of the local deformation from a rigid transformation. By changing the Euclidean metric for a more suitable Riemannian one, we define a consistent statistical framework to quantify the amount of deformation. In particular, the mean and the covariance matrix of the strain tensor can be consistently and efficiently computed from a population of non-linear transformations. These statistics are then used as parameters in a Mahalanobis distance to measure the statistical deviation from the observed variability, giving a new regularization criterion that we called the statistical Riemannian elasticity. This new criterion is able to handle anisotropic deformations and is inverse-consistent. Preliminary results show that it can be quite easily implemented in a non-rigid registration algorithms.

Algorithms↗
PubMed1984

A general model for the light and electron microscopic morphometry/stereology (M & S) of precancerous epithelial transformation using clinical biopsies.

A morphometric model is presented which has proved valuable in the analysis of precancerous lesions at the light and electron microscopic level. The material consisted of biopsies of nasal mucosa embedded in plastic and sectioned perpendicular to the luminal surface. Sampling was restricted to the basal layer in order to compare in the different metaplastic and dysplastic stages a common cell type which is easy to identify in all stages and to reduce the workload. The application of digitizers, classical point counting procedures and linear parameters all allow a good separation between the different types of epithelium. The latter method is especially advisable in diagnostic pathology since the workload becomes drastically reduced as a consequence of linear instead of area parameters (e.g. cell width, i.e. contract zone with basement membrane, instead of cell size) and classifying instead of counting points. A 3-class ruler served for the estimation of the transverse diameters of nuclei, cell width and the sum of the longitudinal and transverse nucleolar axes. The use of a weighted index is more sensitive than simple measurements. The reliability of the method was also tested in a prospective study in which the biopsies were first analyzed by morphometry. The agreement between the prior morphometric classification and the subsequent histologic classification was 91%. The results demonstrate that basal cells alone carry the information for grading metaplastic and dysplastic changes in epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Epithelium↗
PubMed2004

Intrastriatal transforming growth factor alpha delivery to a model of Parkinson's disease induces proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neurons.

We examined the cell proliferative, neurogenic, and behavioral effects of transforming growth factor alpha (TGFalpha) in a 6-OHDA Parkinson's disease model when compared with naive rats. Intrastriatal TGFalpha infusion induced significant proliferation, hyperplastic nodules, and substantial migratory waves of nestin-positive progenitor cells from the adult subventricular zone (SVZ) of dopamine-denervated rats. Interestingly, SVZ cells in naive rats displayed proliferation but minimal migration in response to the TGFalpha infusion. The cells in the expanded SVZ accumulated cytoplasmic beta-catenin, indicating activation of classical Wnt signaling. However, no evidence of any neuronal differentiation was found of these recruited progenitor cells anywhere examined in the brain. Consequently, no evidence of dopaminergic (DA) neurogenesis was found in the striatum or substantia nigra in any experimental group, and amphetamine-induced behavioral rotations did not improve. In summary, the cells in the TGFalpha-induced migratory cellular wave remain undifferentiated and do not differentiate into midbrain-like DA neurons.

Animals↗