Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transformer model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,279 records · Page 71Linked to original sources
PubMed2001

Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo.

The dorsal ectoderm of the vertebrate gastrula was proposed by Nieuwkoop to be specified towards an anterior neural fate by an activation signal, with its subsequent regionalization along the anteroposterior (AP) axis regulated by a graded transforming activity, leading to a properly patterned forebrain, midbrain, hindbrain and spinal cord. The activation phase involves inhibition of BMP signals by dorsal antagonists, but the later caudalization process is much more poorly characterized. Explant and overexpression studies in chick, Xenopus, mouse and zebrafish implicate lateral/paraxial mesoderm in supplying the transforming influence, which is largely speculated to be a Wnt family member. We have analyzed the requirement for the specific ventrolaterally expressed Wnt8 ligand in the posteriorization of neural tissue in zebrafish wild-type and Nodal-deficient embryos (Antivin overexpressing or cyclops;squint double mutants), which show extensive AP brain patterning in the absence of dorsal mesoderm. In different genetic situations that vary the extent of mesodermal precursor formation, the presence of lateral wnt8-expressing cells correlates with the establishment of AP brain pattern. Cell tracing experiments show that the neuroectoderm of Nodal-deficient embryos undergoes a rapid anterior-to-posterior transformation in vivo during a short period at the end of the gastrula stage. Moreover, in both wild-type and Nodal-deficient embryos, inactivation of Wnt8 function by morpholino (MO(wnt8)) translational interference dose-dependently abrogates formation of spinal cord and posterior brain fates, without blocking ventrolateral mesoderm formation. MO(wnt8) also suppresses the forebrain deficiency in bozozok mutants, in which inactivation of a homeobox gene causes ectopic wnt8 expression. In addition, the bozozok forebrain reduction is suppressed in bozozok;squint;cyclops triple mutants, and is associated with reduced wnt8 expression, as seen in cyclops;squint mutants. Hence, whereas boz and Nodal signaling largely cooperate in gastrula organizer formation, they have opposing roles in regulating wnt8 expression and forebrain specification. Our findings provide strong support for a model of neural transformation in which a planar gastrula-stage Wnt8 signal, promoted by Nodal signaling and dorsally limited by Bozozok, acts on anterior neuroectoderm from the lateral mesoderm to produce the AP regional patterning of the CNS.

Animals↗
PubMed2006

Inference for a family of survival models encompassing the proportional hazards and proportional odds models.

For survival data regression, the Cox proportional hazards model is the most popular model, but in certain situations the Cox model is inappropriate. Various authors have proposed the proportional odds model as an alternative. Yang and Prentice recently presented a number of easily implemented estimators for the proportional odds model. Here we show how to extend the methods of Yang and Prentice to a family of survival models that includes the proportional hazards model and proportional odds model as special cases. The model is defined in terms of a Box-Cox transformation of the survival function, indexed by a transformation parameter rho. This model has been discussed by other authors, and is related to the Harrington-Fleming G(rho) family of tests and to frailty models. We discuss inference for the case where rho is known and the case where rho must be estimated. We present a simulation study of a pseudo-likelihood estimator and a martingale residual estimator. We find that the methods perform reasonably. We apply our model to a real data set.

Chlamydia Infections↗
PubMed2000

Identification of cis-acting promoter elements that support expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) in v-src transformed Madin-Darby canine kidney cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) expressed in tumor cells is believed to be important for the pericellular degradation of extracellular matrices during invasion and metastasis. To analyze the mechanism by which MT1-MMP becomes expressed in cancer cells, we assessed the MT1-MMP promoter region for the presence of cis-acting promoter elements that support transcription in transformed cells. Our tumor model consisted of Madin-Darby canine kidney (MDCK) cells transformed by v-src (src4 cells). MT1-MMP mRNA was only faintly detected in parental cells but was strongly expressed in the src4 cells. In parallel, src4 cells invaded into collagen gels, whereas MDCK cells did not. When MDCK and src4 cells were transiently transfected with a plasmid containing of -3000 to -99 nt from the upstream region of the MT1-MMP gene, the promoter activity was 2.6-fold higher in src4 cells than in MDCK cells. Furthermore, the region between -399 and -356 nt was found to contain the src4-specific enhancer element(s). Tandem Sp1 binding sites were also found to be essential in promoting transcription. An Egr-1 site that partially overlaps with the Sp1 sites was found to cooperate with the src4-specific enhancer and to also contribute weakly to the basal promoter activity. The presence of transcription factors that bind to the src4-specific enhancer site was detected by mobility-shift assays in src4 cell nuclear extracts but only weakly in MDCK extracts. Thus, we have identified a novel enhancer element that acts specifically in the transformed cells to enhance MT1-MMP expression.

Animals↗
PubMedDate not supplied

Measurement of the presampling modulation transfer function of film digitizers using a curve fitting technique.

A curve fitting technique combined with an angulated slit image has been developed for the measurement of the presampling modulation transfer function (MTF) of film digitizers. The noisy line spread functions (LSFs) acquired from an angulated slit image are fitted using a combination of two functions by means of a nonlinear least-square fitting technique. The parameters in the model function for each LSF are obtained by minimizing the residual root mean square (RMS), and then averaged over all the LSF fittings. The resulting analytical function is representative of the continuous presampled LSF. We have found that a combination of Gaussian and exponential functions provides a good fit to the LSFs obtained with film digitizers. The corresponding analytical Fourier transformation of the model function yields the presampling MTF, without Nyquist frequency limitation. Measurements of spatial resolution properties using this method were performed for two laser scanners and an optical drum scanner.

Biophysical Phenomena↗
PubMed1996

What structure and function of avian plasminogen activator and matrix metalloproteinase-2 reveal about their counterpart mammalian enzymes, their regulation and their role in tumor invasion.

Rous sarcoma virus-transformed chick embryo fibroblasts (RSVCEF) constitute a well-characterized model system for oncogenic transformation, matrix degradation, and cancer invasion. As RSVCEF cultures employ both serine protease and metalloprotease cascades in the process of matrix degradation, they have contributed significantly to understanding the nature and regulation of these molecules involved in invasive cell behavior. RSVCEF produce elevated levels of a matrix metalloprotease-2 (MMP-2) whose hemopexin domain differs from mammalian MMP-2. The majority of MMP-2 produced by RSVCEF is present in a TIMP-free form which enhances its activation, catalytic activity and substrate specificity and therefore its matrix-degrading ability. RSVCEFs also exhibit high levels of urokinase-type plasminogen activator (uPA), which is found in active form in their conditioned medium in complete absence of plasminogen. Recombinantly expressed avian uPA is also in active form, while an active-site mutant of the same maintains its zymogen form, indicating the mechanism of activation of chicken uPA is autocatalytic. A domain and sequence comparison between chicken and human uPA attempts to identify motifs potentially responsible for the zymogen instability of avian uPA and its capability to autoactivate.

Amino Acid Sequence↗
PubMed1995

Immunotherapy with low-dose interleukin-2 and interferon-gamma in a murine tumor model.

The aim of this study was to evaluate the therapeutic efficacy of locally administered low-dose interleukin-2 (IL-2) alone or together with interferon-gamma (IFN-gamma) in a herpes simplex virus type 2-transformed murine (H238) fibrosarcoma model. In vitro incubation showed that IL-2, but not IFN-gamma, had a significant inhibitory effect on DNA synthesis in H238 cells. In vivo experiments were performed with BALB/c mice to determine the optimal time of treatment with each cytokine after subcutaneous (sc) tumor implantation. The greatest antitumor effect with IL-2 (1 x 10(5) total international units, sc) was noted when treatment was administered during the first week after tumor injection, whereas with IFN-gamma (500 total units, intraperitoneally) treatment during the second week proved best. Combination of the two agents produced complete tumor regression in 44.4% of mice; regression with single-modality treatment was 0-11%. The presence of H238 tumor induced splenomegaly and enhanced the oxidative burst capacity of phagocytes. Peripheral blood leukocyte counts were low in tumor-bearing groups, regardless of treatment. IL-2 and IFN-gamma were nondetectable in the plasma of tumor-bearing or control mice; however, total TGF-beta 1 was 248% higher with IL-2 treatment compared with tumor-bearing nontreated controls. These results show that IL-2 and IFN-gamma can significantly inhibit the growth of highly aggressive H238 tumors and support further investigations with these agents.

Animals↗
PubMed1998

Models of amino acid substitution and applications to mitochondrial protein evolution.

Models of amino acid substitution were developed and compared using maximum likelihood. Two kinds of models are considered. "Empirical" models do not explicitly consider factors that shape protein evolution, but attempt to summarize the substitution pattern from large quantities of real data. "Mechanistic" models are formulated at the codon level and separate mutational biases at the nucleotide level from selective constraints at the amino acid level. They account for features of sequence evolution, such as transition-transversion bias and base or codon frequency biases, and make use of physicochemical distances between amino acids to specify nonsynonymous substitution rates. A general approach is presented that transforms a Markov model of codon substitution into a model of amino acid replacement. Protein sequences from the entire mitochondrial genomes of 20 mammalian species were analyzed using different models. The mechanistic models were found to fit the data better than empirical models derived from large databases. Both the mutational distance between amino acids (determined by the genetic code and mutational biases such as the transition-transversion bias) and the physicochemical distance are found to have strong effects on amino acid substitution rates. A significant proportion of amino acid substitutions appeared to have involved more than one codon position, indicating that nucleotide substitutions at neighboring sites may be correlated. Rates of amino acid substitution were found to be highly variable among sites.

Amino Acid Substitution↗
PubMed1995

Calculation of unconditional and conditional reference intervals for foetal size and growth from longitudinal measurements.

Methods for estimating unconditional and conditional reference intervals for foetal size and growth based on longitudinal observations are presented. The methods are based on simple random-effects regression models and involve transforming both the response and the covariate (timepoint). A dataset from a designed longitudinal study of foetal size is analysed in detail as a motivating example.

Anthropometry↗
PubMed1999

Concerning the ultrastructural origin of large-scale swelling in articular cartilage.

The swelling behaviour of the general matrix of both normal and abnormally softened articular cartilage was investigated in the context of its relationship to the underlying subchondral bone, the articular surface, and with respect to the primary structural directions represented in its strongly anisotropic collagenous architecture. Swelling behaviours were compared by subjecting tissue specimens under different modes of constraint to a high swelling bathing solution of distilled water and comparing structural changes imaged at the macroscopic, microscopic and ultrastructural levels of resolution. Near zero swelling was observed in the isolated normal general matrix with minimal structural change. By contrast the similarly isolated softened general matrix exhibited large-scale swelling in both the transverse and radial directions. This difference in dimensional stability was attributed to fundamentally different levels of fibril interconnectivity between the 2 matrices. A model of structural transformation is proposed to accommodate fibrillar rearrangements associated with the large-scale swelling in the radial and transverse directions in the softened general matrix.

Animals↗
PubMed2006

Solid-state NMR study of the transformation of octacalcium phosphate to hydroxyapatite: a mechanistic model for central dark line formation.

For many years, octacalcium phosphate (OCP) has been postulated as the precursor phase of biological apatite in bones and teeth. In this work, we study the molecular mechanism of OCP to hydroxyapatite (HAp) transformation in vitro by several physical techniques, with particular emphasis on solid-state (31)P homonuclear double-quantum (DQ) NMR spectroscopy. The in vitro system is prepared by mixing urea, sodium phosphate monobasic dehydrate, and calcium nitrate tetrahydrate at 100 degrees C. The images obtained by scanning electron microscopy and transmission electron microscopy show that the bladelike OCP crystals will transform into hexagonal rod-shaped HAp crystals as the pH of the reaction mixture increases slowly from 4.35 to 6.69 in 12 h. Powder X-ray diffraction patterns indicate that a trace amount of monetite was also precipitated when the pH was around 5. Together with computer-assisted lattice matching, our DQ NMR data reveal that OCP crystals transform to HAp topotaxially, where the [000](HAp) and [20](HAp) axes are along the same directions as the [001](OCP) and [010](OCP) axes, respectively. On the basis of our in vitro results, the formation of the central dark line commonly found in biological hard tissues could be explained by the inherent lattice mismatch between OCP and HAp. Furthermore, the data of the (31)P{(1)H} cross-polarization NMR suggest that water molecules enter the hydration layers of OCP crystals via the hydrolysis reaction HPO(4)(2)(-) + OH(-) = PO(4)(3)(-) + H(2)O, which also accounts for the deprotonation of the HPO(4)(2)(-) ions during the transformation.

Calcium Compounds↗
PubMed2005

Tackling calibration problems of spectroscopic analysis in high-throughput experimentation.

High-throughput experimentation and screening methods are changing work flows and creating new possibilities in biochemistry, organometallic chemistry, and catalysis. However, many high-throughput systems rely on off-line chromatography methods that shift the bottleneck to the analysis stage. On-line or at-line spectroscopic analysis is an attractive alternative. It is fast, noninvasive, and nondestructive and requires no sample handling. The disadvantage is that spectroscopic calibration is time-consuming and complex. Ideally, the calibration model should give reliable predictions while keeping the number of calibration samples to a minimum. In this paper, we employ the net analyte signal approach to build a calibration model for Fourier transform near-infrared measurements, using a minimum number of calibration samples based on blank samples. This approach fits very well to high-throughput setups. With this approach, we can reduce the number of calibration samples to the number of chemical components in the system. Thus, the question is no longer how many but which type of calibration samples should one include in the model to obtain reliable predictions. Various calibration models are tested using Monte Carlo simulations, and the results are compared with experimental data for palladium-catalyzed Heck cross-coupling.

Journal Article↗
PubMed1980

[Towards the end of Kraepelin era?].

The kraepelinian conception which still prevails in contemporary psychiatry no longer allows us to express all the diversity of observed mental disorders. Moreover, some classical resistances and innovations had foreshadowed the necessity of its renewal. Nowadays the quantitative studies using statistics and the computer, as well as the application of scientific theories to the qualitative aspect of disorders have until now failed in improving the situation. However the theory of communication, cybernetic, the general system theory have shown the possibility of seeing mental disorders as dysfunction of systems. Likewise a new method of operatory observation has permitted to result in an integrated system of permanently open functional models. Moreover the transformations of the disorders among some patients lead to evoke the abstract notion of psychopathologic continuum. The latter allows to view mental pathology, no longer as syndromes and entities, but as functional disorders of a same psychodynamic whole. Consequently, the disorders are the evidence of dysregulations of various mental organizations and the result of a dysfunction in the integration of the latter. Their expression in terms of integrated functional models better shows their diversity, polymorphism, and mobility. What is at stake in such a debate is not only theoretic but also practical and therapeutical.

Adult↗
PubMed1991

Inducibility of neoplastic transformation by Fujinami sarcoma virus in an in vitro chick embryo model for osteosarcoma: (i) effect of differentiation and (ii) investigation for in vivo growth potential in athymic mice.

We have described previously a novel in vitro model for the study of osteosarcoma. In this system, chick periosteal explants (CEP) transformed by the P140gag-fps oncoprotein of Fujinami avian sarcoma virus (FSV) exhibit biochemical and histological manifestations characteristic of osteosarcoma. In the present study, a hypothesis suggesting that more differentiated bone cells may resist FSV-induced oncogene changes was tested. In one set of experiments, CEP cultures were pretreated with a high dose of dexamethasone (10(-7) M), a bone cell differentiating agent, prior to FSV infection. In another experiment, CEP explants were allowed to grow and thus differentiate for various lengths of time in culture prior to infection with FSV. Another goal of this study was to show that FSV-transformed cultures were tumorigenic in nude mice. In experiments focusing on differentiation and FSV-transformation, it was found that groups that had been infected at stages where osteogenic differentiation had been induced or allowed to occur, exhibited significantly decreased values for biochemical parameters associated with osteosarcomatous transformation. Specifically, these parameters were alkaline and acid phosphatase activity, protein content, [3H]thymidine incorporation, mineral profile, and acidification of culture media. Furthermore, osteosarcomatous histopathological features were more prominent in cultures subjected to FSV infection prior to differentiation. These findings indicate that differentiated osteogenic cells are less susceptible to oncogene-mediated transformation than their progenitors. The tumorigenic potential of some CEP cultures transformed in vitro with FSV was examined by transplantation into athymic mice. FSV-transformed CEP cultures xenografted subcutaneously exhibited tumor formation, whereas xenografts of uninfected cultures did not grow or were completely resorbed. This demonstrates that FSV-transformed cultures are tumorigenic, and confirms that this model system is useful for the investigation of the mechanisms governing the development of osteosarcoma in vitro.

Animals↗
PubMed1988

Experimental design strategy for the Weibull dose response model.

The objective of this research was to determine optimum design point allocation for estimation of relative yield losses from ozone pollution when the true and fitted yield-ozone dose response relationship follows the Weibull. The optimum design is dependent on the values of the Weibull model parameters. A transformation was developed which allowed the optimum design (by the determinant criterion) for one parametric situation to be translated to any other, and permitted the search for optimum designs to be restricted to one set of Weibull parameters. Optimum designs were determined for the case where the Weibull parameters are assumed known, and effects of deviating from the optimum designs were investigated. Several alternative design strategies were considered for protecting against incorrectly guessing the Weibull model parameters when their true values are not known.

Journal Article↗
PubMed2001

Cadmium adsorption by sediment in a turbulence tank.

The mechanism sediment motion that affects cadmium (Cd) adsorption on sediment particles was studied in a turbulence tank in the presence (and absence) of bed mud. The experimental results were verified by a mathematical model for heavy metal transport-transformation developed for the turbulence tank. The mathematical model includes the equations of water flow, sediment motion, heavy metal transport-transformation, heavy-metal reaction kinematics and equations for prescribing the initial conditions and boundary conditions for the experiment. The model conforms the transport-transformation of heavy-metal pollutants in surface waters to following the law of convective-diffusive of common tracers and the characteristics of fate and transport of sediment motion. Variations of dissolved Cd concentrations and suspended particulate Cd concentrations with time and in the water column were measured and computed. The experimental measurements correspond with the computed results. Both the experimental measurements and computed results show that it takes about 6 h to reach equilibrium condition for cadmium adsorption by sediment particles. This is different from the result obtained from experiments conducted in continuously stirred tank reactors (or batch reactors) in which adsorption equilibrium can be achieved in about 20 min. Determination of the model parameters for sediment adsorption-desorption of metals in the tank is discussed. The experimental and computed results obtained in this study are useful to solve practical engineering problems in surface waters.

Adsorption↗
PubMed2006

Thermodynamics of entropy-driven phase transformations.

Thermodynamic properties of one-dimensional lattice models exhibiting entropy-driven phase transformations are discussed in quantum and classical regimes. Motivated by the multistability of compounds exhibiting photoinduced phase transitions, we consider systems with asymmetric, double, and triple well on-site potential. One finds that among a variety of regimes, quantum versus classical, discrete versus continuum, a key feature is asymmetry distinguished as a "shift" type and "shape" type in limiting cases. The behavior of the specific heat indicates one phase transformation in a "shift" type and a sequence of two phase transformations in "shape"-type systems. Future analysis in higher dimensions should allow us to identify which of these entropy-driven phase transformations would evolve into phase transitions of the first order.

Journal Article↗
PubMed1987

Induction of glucagon sensitivity in a transformed kidney cell line by prostaglandin E2 and its inhibition by epidermal growth factor.

A model system using a transformed dog kidney cell line (Madin-Darby canine kidney), has been established for studying the process of differentiation. Glucagon responsiveness can be restored to these transformed cells by various differentiation inducers, including prostaglandin E2. Glucagon response was measured in terms of the ability of glucagon to stimulate cAMP production. Induction of glucagon sensitivity seems to be mediated by cAMP. The ability of various prostaglandin analogs to elevate the cAMP level correlates closely with their ability to induce glucagon sensitivity. In fact, 8-Br-cAMP is also a potent inducer. To define the nature of this cAMP-mediated process, we identified several inhibitors of this induction process. These differentiation inhibitors include serum, phorbol ester, and epidermal growth factor. These inhibitors do not have a direct effect on cAMP production by cells in the presence or absence of hormones. Furthermore, induction by 8-Br-cAMP is also inhibited by these agents. Therefore, the site of inhibition is located beyond the point of cAMP production. Possible interaction between cAMP- and epidermal growth factor-dependent phosphorylations is discussed.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2005

Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas.

Indolent non-Hodgkin lymphomas are characterized by a prolonged phase that is typically followed by a clinical progression associated with an accelerated clinical course and short survival time. Previous studies have not identified a consistent cytogenetic or molecular abnormality associated with transformation. The development of a transformed phenotype, evolving from the original low-grade component, most likely depends on multiple genetic events, including the activation of synergistic dominant oncogenes and a loss of tumor suppressor gene functions. Complex karyotypes and relatively bad chromosome morphology are typical of transformed non-Hodgkin lymphomas, rendering complete cytogenetic analysis difficult. Here, we report the use of transformed non-Hodgkin lymphoma cell lines and primary samples to identify the involvement of the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) gene that maps at chromosome 12q24 in transformed non-Hodgkin lymphomas. We also show that down-regulation of SMRT in the immortalized "Weinberg's model" cell lines induces transformation of the cells. Assessment of cDNA array profiles should further help us to design a working model for SMRT involvement in non-Hodgkin lymphoma transformation as a novel, nonclassical tumor suppressor.

Apoptosis↗