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PubMed1989

Transformation of murine fibroblasts by a retrovirus encoding the murine c-fms proto-oncogene.

The c-fms proto-oncogene is the growth factor receptor for the macrophage colony stimulating factor, M-CSF. In this paper we have investigated the inappropriate expression of c-fms within a species as a relevant model for analysing transformation, growth, and differentiation promoting activities of c-fms. A retroviral vector was constructed for the expression of the murine c-fms proto-oncogene in murine cells. Initial characterization of this vector was performed in fibroblasts. Infection of Balb/c 3T3 cells with the murine c-fms retrovirus resulted in high level expression of the gp140c-fms precursor and the gp165c-fms mature receptor protein on the cell surface and both proteins exhibited kinase activity. Up to 3.3 x 10(4) M-CSF receptors per cell were detectable. The c-fms retrovirus induced foci of morphologically transformed Balb/c cells that exhibited anchorage independent growth in soft agar and produced progressively growing tumors in syngeneic animals. The Balb/c cells synthesize and secrete M-CSF and therefore these results suggest an autocrine mechanism of transformation caused solely by the expression of a normal growth factor receptor in an inappropriate, endogenous M-CSF-producing cell.

Animals↗
PubMed2006

Modeling and analysis of dual-output piezoelectric transformer operating at the thickness-shear vibration mode.

In our previous study, the multioutput piezoelectric transformer operating at the thickness-shear vibration mode was proposed and experimentally investigated. By designing a new construction of support and lead wire connection, a power density of 52.7 W/cm3 and a total output power of 169.8 W were achieved at a temperature rise less than 20 degrees C. In this work, a theoretical model was developed for the dual-output piezoelectric transformer operating at the thickness-shear vibration mode. The equivalent circuit parameters of the piezoelectric transformer were derived. Based on this, the impedance characteristics, equivalent inductance, capacitance ratio, voltage gain, and efficiency of the piezoelectric transformer were calculated. The theoretical results were verified by experimental data. Furthermore, the effect of the transformer size on the voltage gain, efficiency, output power and power density, and the effect of the load of one output on the voltage gain of another output were analyzed. Some useful guidelines were achieved by these analyses.

Journal Article↗
PubMed1978

Transformation by viruses: simian virus 40 as a model system.

Simian virus 40 (SV40), a DNA-containing tumor virus in the papovavirus group, represents an ideal model system for the analysis of the mechanism of viral-induced tumorigenesis because of the small size of its genome and its broad range of oncogenic potential. Viral genes persist and are expressed in SV40-transformed cells. Temperature-sensitive (ts) mutants of the virus have proved to be valuable tools for the identification and analysis of viral gene expression in transformed cells. Through the use of such mutants, it has been determined that a specific gene product (A-protein) is required to initiate cellular transformation. The role of virus genes in the maintenance of the transformed state was determined by transformation of the cells of mouse, hamster, and human origin by ts virus containing A-gene mutations. These cells were then examined under permissive and nonpermissive conditions for the presence of a variety of intracellular and surface alterations commonly associated with neoplastic transformation. From the results of such experiments, it has been concluded that an SV40-specific function is also necessary for the maintenance of at least some of the phenotypic properties of the transformed state. Indirect evidence, derived from a comparison of the biological and biochemical properties of the SV40-induced tumor (T) antigen and the gene A-protein, supports the idea that T-antigen is a product of the A-gene. One model devised to explain the mechanism by which the gene A-protein might function as an effector of transformation is presented.

Animals↗
PubMed2002

Enhanced transformation of polycyclic aromatic hydrocarbons using a combined Fenton's reagent, microbial treatment and surfactants.

The potential for using Fenton's reagent (H(2)O(2)+ Fe(2+)) as an advanced oxidation pretreatment process to enhance microbial transformation of two model polycyclic aromatic hydrocarbons, anthracene and benzo[a]pyrene, in an aqueous system was evaluated. Fenton's reagent at a concentration of 0.5% H(2)O(2) and 10 mM Fe(2+) (molar ratio, 15:1) was most effective in transforming anthracene at pH 4. Application of non-ionic surfactants during Fenton's pre-treatment was found to be more effective in the transformation of both anthracene and benzo[a]pyrene. The extent of removal of substrates by a combined Fenton's-biotreatment was 2-4 times higher than with Fenton's treatment or biotreatment alone. In a chemical-biological treatment train, 48 h of Fenton's pre-treatment in the presence of a non-ionic surfactant, followed by 7 days of biological treatment resulted in 80-85% removal of PAHs (100 ppm).

Anthracenes↗
PubMed1989

Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice.

Transgenic mice that overproduce the hepatitis B virus large envelope polypeptide and accumulate toxic quantities of hepatitis B surface antigen (HBsAg) within the hepatocyte develop severe, prolonged hepatocellular injury that initiates a programmed response within the liver, characterized by inflammation, regenerative hyperplasia, transcriptional deregulation, and aneuploidy. This response inexorably progresses to neoplasia. The incidence of hepatocellular carcinoma in this model corresponds to the frequency, severity, and age of onset of liver cell injury, which itself corresponds to the intrahepatic concentration of HBsAg and is influenced by genetic background and sex. Thus, the inappropriate expression of a single structural viral gene is sufficient to cause malignant transformation in this model. These results suggest that severe, prolonged cellular injury induces a preneoplastic proliferative response that fosters secondary genetic events that program the cell for unrestrained growth.

Aging↗
PubMed2026

CodonMoE: DNA language models for codon-dependent mRNA prediction.

MOTIVATION: Genomic language models (gLMs) face a fundamental efficiency challenge: one must either maintain separate specialized models for each biological modality (DNA and RNA) or develop large multimodal architectures. Both approaches impose significant computational burdens-modality-specific models require redundant infrastructure despite inherent biological connections, while multi-modal architectures demand increased parameter counts and extensive cross-modality pretraining. RESULTS: To address this limitation, we introduce CodonMoE (Adaptive Mixture of Codon Reformative Experts), a lightweight adapter that transforms DNA language models into effective RNA analyzers without RNA-specific pretraining. Our theoretical analysis establishes CodonMoE as a universal approximator at the codon level, capable of mapping arbitrary functions from codon sequences to codon-dependent RNA properties given sufficient expert capacity. Across four RNA prediction tasks spanning stability, expression, and regulation, DNA models augmented with CodonMoE significantly outperform their unmodified counterparts, with the HyenaDNA+CodonMoE series achieving state-of-the-art results using 80% fewer parameters than specialized RNA models. By maintaining sub-quadratic complexity while achieving superior performance, our approach provides a principled path toward unifying genomic language modeling, leveraging more abundant DNA data and reducing computational overhead while preserving modality-specific performance advantages. AVAILABILITY AND IMPLEMENTATION: Source code for the method and to reproduce the results is available at https://github.com/Kingsford-Group/CodonMoE.

Codon↗
PubMedDate not supplied

[A model for evaluating internal accuracy].

OBJECTIVE: To provide an evaluation model of internal accuracy illustrating its use in a quality control program of clinical chemistry. METHODS: The model uses data transformed to percentage of assigned value (%AV) that allows the pooling of different controls. Precision is evaluated by the mean of the intracontrol coefficients of variation, and accuracy by the mean of means of the %VAs and its standard deviation. The model was used in 17,280 measurements of 23 analytes assayed in seven pairs of controls (medium and high concentration) during four years in two automated clinical chemistry analyzers. RESULTS: The model established inaccuracy of 5% to 25% in seven analytes, five of them enzymes. It also detected interanalyzer differences in accuracy of five analytes (22%) and an erroneous assigned value in 19 of 304 controls (6%). CONCLUSIONS: The model showed its capacity to dissect the sources of variation of accuracy. There was inaccuracy in 30% of the analytes but further studies are needed to validate these inaccuracies with controls of other sources. The model can be useful for control programs of any quantitative assay system. A summary description of the model's operation is given.

Chemistry, Clinical↗
PubMed1994

Intra-arterial pressure wave parameters modeled using electrical analogs.

An Electrical Model was developed to help identify parameters obtained from dynamic pressure data on the in vitro rat aortic artery. The data was obtained using a Multifunction Pressure Generator (MPG) and recording MPG Input Pressure (Pi) and Intraarterial Pressure (Po). Transfer functions of the form Po/Pi = (A1S+Ao)/(B2S2 + B1S+Bo) were obtained and it is necessary to link A1, Ao, B2, B1 and Bo to the Biological Parameters of Inertance (M), Vascular Resistance (R) and Compliance (C). Using the Electrical Analogs to P, M, R and C which are Voltage (V), Inductance (L), Resistance (Re), and Capacitance (Ce), an Electrical Model was built. The Electrical Model has the form Vo/Vi = (Re1S + 1/Ce)/[LS2 + (Re1 + Re2)S + 1/Ce]. Since Ao = Bo = 1 from our experimental data we multiplied the denominator and numerator by Ce to obtain Vo/Vi = (CeRe1S + 1)/[CeLS2 + Ce(Re1 + Re2)S + 1]. We then transformed our Electrical Model to its Pressure Equivalent and obtained Po/Pi = (CR2S + 1)/[CMS2 + C(R1 + R2)S + 1]. Since R2 is less than R1 + R2 we theorize that total R is composed of two viscoelastic or resistive elements R1 and R2. Using measured values of compliance it should be possible to obtain reasonable values for R1, R2 and Inertance.

Animals↗
PubMed2000

A theoretical study on the effect of surface roughness on mass transport and transformation in biofilms.

This modeling study evaluates the influence of biofilm geometrical characteristics on substrate mass transfer and conversion rates. A spatially two-dimensional model was used to compute laminar fluid flow, substrate mass transport, and conversion in irregularly shaped biofilms. The flow velocity above the biofilm surface was varied over 3 orders of magnitude. Numerical results show that increased biofilm roughness does not necessarily lead to an enhancement of either conversion rates or external mass transfer. The average mass transfer coefficient and Sherwood numbers were found to decrease almost linearly with biofilm area enlargement in the flow regime tested. The influence of flow, biofilm geometry and biofilm activity on external mass transfer could be quantified by Sh-Re correlations. The effect of biofilm surface roughness was incorporated in this correlation via area enlargement. Conversion rates could be best correlated to biofilm compactness. The more compact the biofilm, the higher the global conversion rate of substrate. Although an increase of bulk fluid velocity showed a large effect on mass transfer coefficients, the global substrate conversion rate per carrier area was less affected. If only diffusion occurs in pores and channels, then rough biofilms behave as if they were compact but having less biomass activity. In spite of the fact that the real biofilm area is increased due to roughness, the effective mass transfer area is actually decreased because only biofilm peaks receive substrate. This can be explained by the fact that in the absence of normal convection in the biofilm valleys, the substrate gradients are still largely perpendicular to the carrier. Even in the cases where convective transport dominates the external mass transfer process, roughness could lead to decreased conversion rates. The results of this study clearly indicate that only evaluation of overall conversion rates or mass fluxes can describe the correct biofilm conversion, whereas interpretation of local concentration or flow measurements as such might easily lead to erroneous conclusions.

Biofilms↗
PubMed1993

A new infrared spectroscopoic marker for cochleate phases in phosphatidylserine-containing model membranes.

Fourier transform-infrared (IR) spectroscopic and electron microscopic studies are reported for 1,2-dimyristoylphosphatidylserine (DMPS) and for DMPS/1,2-dimyristoylphosphatidylcholine mixtures in the presence and absence of Ca2+ ion. The frequency of the methyl symmetric deformation mode near 1,378 cm-1, previously assumed insensitive to changes in lipid morphology, has been found to respond to cochleate phase formation by undergoing an approximately 8 cm-1 increase. The new IR spectroscopic marker at 1,386 cm-1 has been used to identify and verify structures suggested from the phase diagram of J. R. Silvius and J. Gagné (1984. Biochemistry. 23:3241-3247) for this system. In addition, the ability of Mg2+ ion to induce cochleate formation has been demonstrated. Higher Mg2+ than Ca2+ levels are required for this process. Finally, IR spectroscopy has been used to monitor dehydration of the lipid surface through changes in the asymmetric PO2- stretching mode. Dehydration precedes cochleate phase formation (i.e., occurs at a lower Ca2+/phosphatidylserine level).

Biophysical Phenomena↗
PubMed1993

Microcomputer BASIC programs for rapid determination of lethal dosages of biocides using logit transformations.

The probit analysis model is generally used for the determination of lethal dosages in bioassay applications. However, the logit models, which use the logistic curve instead of the integrated normal curve, could also be effectively used for the determination of lethal dosages and regression coefficients. In this paper, two types of logit models, namely minimum logit chi square and maximum likelihood, have been described in detail for the estimation of the parameters. The results of these two models are also compared with those of the probit model.

Animals↗
PubMed2006

A novel SV40 TAg transgenic model of asbestos-induced mesothelioma: malignant transformation is dose dependent.

Although it has been clear for >40 years that mesothelioma can be caused by asbestos, not all patients with this disease have a history of asbestos exposure. Other factors, including non-asbestos fibers and ionizing radiation, are known to cause malignant transformation of mesothelial cells. In addition, it is likely that genetics will play some role in susceptibility. Recently, it has been suggested that SV40 viral oncogenes could contribute to the carcinogenicity of asbestos. To better understand the role of SV40, we used the mesothelin promoter to construct MexTAg mice that express SV40 large T antigen (TAg) in the mesothelial compartment. We generated four MexTAg lines that carry high, intermediate, and low copy numbers of the transgene. All of these mice show a relatively low level of spontaneous tumor development. High-copy, 299h mice rapidly developed mesotheliomas when exposed to asbestos, and these tumors were faster growing and more invasive than those developing in wild-type and single-copy (266s) mice. In addition, we found a direct relationship between transgene copy number and survival after exposure to asbestos. A single copy of TAg was sufficient to immortalize mesothelial cells in vitro, but these cells did not show evidence of malignant transformation. In contrast, cell lines developed from mesothelial cells of animals carrying multiple copies of TAg were growth factor independent and could be cloned at limiting dilution in soft agar. These data provide the first in vivo demonstration of co-carcinogenicity between SV40 and asbestos.

Animals↗
PubMed1997

The association between baseline lung function and bronchial responsiveness to methacholine.

It has been reported that females show an increased frequency of bronchial hyperresponsiveness (BHR) compared to males and that this difference is abolished after taking into account differences in baseline FEV1. The aim of our study was to analyse how the distribution of BHR in males and females depends on the definition of BHR. Special emphasis was paid to the question whether the prevalence rates of BHR according to different definitions were related to baseline characteristics of the subjects and baseline lung function in the same manner. We analysed the data obtained within the European Community Respiratory Health Survey (ECRHS) in the Eastern German population sample of Erfurt aged 20-65 years (n = 931). In logistic regression analyses of different definitions of BHR, we used as parameters age, height, gender, smoking habits, baseline forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1 as a percent of FVC (FEV1% FVC). Symptoms and reported diagnosis of asthma did not significantly depend on gender or age. When BHR was defined as the provocative dose causing a 20% fall in FEV1, BHR was more prevalent in females than in males (27.6% vs. 13.2%). Similar gender differences were found when defining BHR via a 10% fall in FEV1 or by using corresponding cut-off values of the linear dose-response slopes of the percent decline in FEV1 (DRS). Multiple linear regression analyses of various transformations of the DRS also indicated a higher degree of BHR in females. Independently of the definition chosen, however, the gender difference in the prevalence of BHR disappeared when height and FEV1 or FEV1% FVC or appropriate combinations were included in the model. The reciprocally transformed DRS showed the best resolution of the spectrum of bronchial responsiveness. These data are compatible with the hypotheses that (1) estimates of the distribution of BHR are distorted by differences in the methacholine dosage per lung size and that (2) airway geometry affects the measurement of BHR. It appears that these factors and not intrinsic differences in BHR between males and females contribute to the gender differences in the prevalence of BHR. Furthermore, our data support the superiority of the dose response slope for the analysis of bronchial responsiveness in epidemiologic surveys.

Adult↗