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PubMed1995

Transformational leadership: qualities and strategies for the CNS.

The model of transformational leadership has been widely applied in the management arena and recently introduced as worthwhile in guiding the practice of nurse executives and managers. The CNS as an expert practitioner and role model can bring about positive change in clinical practice by using transformational strategies. To this end, the CNS can work to develop the qualities of a transformational leader and implement strategies as an integral part of the CNS's diverse role components. In this article, qualities and strategies are presented and methods for implementation are suggested.

Humans↗
PubMed1998

A concept analysis of personal transformation.

Personal transformation, a multidimensional concept, is applicable to nursing practice, education, and research. Using a modified version of Walker and Avant's concept analysis model, personal transformation was analysed relative to Newman's Theory of Health as Expanding Consciousness. By integrating common themes from definitions of several disciplines with Newman's theory, a definition of personal transformation was derived. Personal transformation is a dynamic, uniquely individualized process of expanding consciousness whereby individuals become critically aware of old and new self-views and choose to integrate these views into a new self-definition. A conceptual map depicts the defining attributes, antecedents and consequences of personal transformation. A model case illustrates the applicability of the concept to nursing education. Because the transformation process is revealed through individual patterns, qualitative research for further analysis of the concept is recommended.

Consciousness↗
PubMed1999

A revised arithmetic model of long slender to short stumpy transformation in the African trypanosomes.

An arithmetic model that closely approximates an African trypanosome infection in immunosuppressed mice is presented. The final model was based on an examination of the following parameters: the rate of long slender to short stumpy transition, the maximum percentage of long slender to short stumpy stages that can be induced, the survival time or half life of the short stumpy stage in vivo, and the rate (%) of long slender to short stumpy stage transition following the peak in transformation. The model is based on the assumption that the long slender to short stumpy transition is parasite population dependent and that in mice the long slender to short stumpy transition only begins when the trypanosome population reaches a density of 1 x 10(7) trypanosomes/ml. The model predicts that the parasitemia during the first several days of an infection is controlled solely by the kinetics of the transition of the dividing long slender stage to the nondividing short stumpy stage. It was not necessary to include in the model the host's immune response in order to simulate the early growth kinetics of pleomorphic trypanosomes in infected mice.

Animals↗
PubMed1991

Mutagenesis of the DNA contact site in Fos protein: compatibility with the scissors grip model and requirement for transformation.

To elucidate the mechanisms involved in the transformation by fos we have initiated a study pertaining to the identification of molecular functions of Fos protein that are crucial for transformation. We have previously reported that the presence of an intact leucine zipper in Fos is an absolute requirement for the induction of transformation, but that the autorepression function of Fos is dispensable. We now show that Fos protein also needs an intact DNA (TRE)-binding site to be able to transform. Amino acid substitutions in this domain of Fos which impair DNA binding also destroy the transforming potential of Fos, suggesting that the interaction of Fos-Jun complexes with TREs may be a crucial part of Fos-induced transformation. This hypothesis is further strengthened by our observation that Fos and Jun can cooperate in the induction of transformation. We show that a Fos protein which contains a Jun leucine zipper and is thus capable of dimerization is still dependent on the presence of exogenous Jun to induce transformation. The critical positions in the Fos DNA-binding site include those which the 'scissors grip' model predicts to be crucial, although the DNA-binding site in Fos seems to extend beyond the basic region into an adjacent cluster of acidic amino acids.

Amino Acid Sequence↗
PubMed1989

A single-site allosteric model of intracellular androgen-receptor interaction.

We present a single-site, two-state model for analyzing the effect of time and ligand concentration on the extent and character of 5 alpha-dihydrotestosterone, methyltrienolone or mibolerone binding to the specific androgen receptor within cultured human genital skin fibroblasts. The model has three basic attributes: formation of the initial low-affinity androgen-receptor complex, and its transformation to a higher affinity state are irreversible, first-order processes; and receptors released from complexes in each state not only differ from each other and from their pre-liganded progenitor, but can also reassociate with androgen to yield complexes in their respective parental states. The rate constants of dissociation and apparent equilibrium binding constants of the two affinity states were determined for each of the three androgens within normal cells and those of a transformation-defective mutant. When these values are combined with estimates of the rate constants at which the complexes are formed and transformed, the model accurately simulates time-dependent changes in the slopes and character of experimental Scatchard plots. It can also generate Scatchard plots that are concave, convex or sigmoidal simply by making sequential changes in its formation or transformation constants. Thus, our model can explain complex ligand-receptor binding kinetics that have heretofore been interpreted according to alternate models of transformation and binding-site multiplicity with or without properties of cooperativity, and it supports the notion that receptor recycling involves intermediate receptor states.

Allosteric Regulation↗
PubMed1995

The Syrian hamster embryo (SHE) cell transformation system: a biologically relevant in vitro model--with carcinogen predicting capabilities--of in vivo multistage neoplastic transformation.

Neoplastic transformation is a multistep process that can be modeled in vitro using Syrian hamster embryo (SHE) cells. SHE cells multistage transformation involves several intermediate stages, including morphological transformation, immortality, acquisition of tumorigenicity, and malignant progression. Analysis of the molecular alterations that occur at each stage indicated that morphological transformation results from both carcinogen-induced irreversible chromosomal/genetic mutations and reversible genetic events, including altered DNA methylation. Morphological transformation results from a block in the cellular differentiation of progenitor and determined stem-like cells in the SHE cell population via alternation in the expression of the H19 tumor suppressor gene and other genes. Immortality results from genetic mutations in growth factor responsiveness, including loss of growth suppression by TGF beta and autocrine growth factor production, and genomic stability, resulting in genomic instability and an increased mutation rate. Acquisition of tumorigenicity involves loss of tumor suppressor gene function, altered mitogenic signal transduction, mutation of oncogenes, acquisition of anchorage independent growth, and chromosomal aberrations. Malignant progression is associated with alterations in extracellular matrix growth characteristics, alterations in cytoskeleton structure, elevated fibrinolytic activity, secretion of proteases, and changes in extracellular matrix protein secretion. Together, these changes model the alterations observed during in vivo neoplastic transformation and possibly explain why the SHE assay, as a carcinogen screening tool, is able to identify carcinogens with a 80 to 85% accuracy.

Animals↗
PubMed2002

Hepatitis B virus X protein activates the p38 mitogen-activated protein kinase pathway in dedifferentiated hepatocytes.

Hepatitis B virus X protein (pX) is implicated in hepatocarcinogenesis by an unknown mechanism. Employing a cellular model linked to pX-mediated transformation, we investigated the role of the previously reported Stat3 activation by pX in hepatocyte transformation. Our model is composed of a differentiated hepatocyte (AML12) 3pX-1 cell line that undergoes pX-dependent transformation and a dedifferentiated hepatocyte (AML12) 4pX-1 cell line that does not exhibit transformation by pX. We report that pX-dependent Stat3 activation occurs only in non-pX-transforming 4pX-1 cells and conclude that Stat3 activation is not linked to pX-mediated transformation. Maximum Stat3 transactivation requires Ser727 phosphorylation, mediated by mitogenic pathway activation. Employing dominant negative mutants and inhibitors of mitogenic pathways, we demonstrate that maximum, pX-dependent Stat3 transactivation is inhibited by the p38 mitogen-activated protein kinase (MAPK)-specific inhibitor SB 203580. Using transient-transreporter and in vitro kinase assays, we demonstrate for the first time that pX activates the p38 MAPK pathway only in 4pX-1 cells. pX-mediated Stat3 and p38 MAPK activation is Ca(2+) and c-Src dependent, in agreement with the established cellular action of pX. Importantly, pX-dependent activation of p38 MAPK inactivates Cdc25C by phosphorylation of Ser216, thus initiating activation of the G(2)/M checkpoint, resulting in 4pX-1 cell growth retardation. Interestingly, pX expression in the less differentiated hepatocyte 4pX-1 cells activates signaling pathways known to be active in regenerating hepatocytes. These results suggest that pX expression in the infected liver effects distinct mitogenic pathway activation in less differentiated versus differentiated hepatocytes.

Cell Cycle Proteins↗
PubMed2006

Model based analysis of piezoelectric transformers.

Piezoelectric transformers are increasingly getting popular in the electrical devices owing to several advantages such as small size, high efficiency, no electromagnetic noise and non-flammable. In addition to the conventional applications such as ballast for back light inverter in notebook computers, camera flash, and fuel ignition several new applications have emerged such as AC/DC converter, battery charger and automobile lighting. These new applications demand high power density and wide range of voltage gain. Currently, the transformer power density is limited to 40 W/cm(3) obtained at low voltage gain. The purpose of this study was to investigate a transformer design that has the potential of providing higher power density and wider range of voltage gain. The new transformer design utilizes radial mode both at the input and output port and has the unidirectional polarization in the ceramics. This design was found to provide 30 W power with an efficiency of 98% and 30 degrees C temperature rise from the room temperature. An electro-mechanical equivalent circuit model was developed to describe the characteristics of the piezoelectric transformer. The model was found to successfully predict the characteristics of the transformer. Excellent matching was found between the computed and experimental results. The results of this study will allow to deterministically design unipoled piezoelectric transformers with specified performance. It is expected that in near future the unipoled transformer will gain significant importance in various electrical components.

Journal Article↗
PubMed2000

DNA-liposome versus adenoviral mediated gene transfer of transforming growth factor beta1 in vascularized cardiac allografts: differential sensitivity of CD4+ and CD8+ T cells to transforming growth factor beta1.

We have developed a model of transforming growth factor (TGF)beta1 gene transfer into mouse vascularized cardiac allografts to study the use of gene transfer as an immunosuppressive therapy in transplantation. Donor hearts were perfused with either DNA-liposome complexes or adenoviral vectors that encode the active form of human TGFbeta1. DNA-liposome mediated transfection prolonged allograft survival in approximately two-thirds of transplant recipients, while adenoviral delivery of TGFbeta1 was not protective. Protective TGFbeta1 gene transfer was associated with reduced Th1 responses and an inhibition of the alloantibody isotype switch. The protective effects of TGFbeta1 gene transfer were overridden by exogenous interleukin-12 administration. Interestingly, alloreactive CD4+ and CD8+ cells exhibited distinct sensitivities to TGFbeta1 gene transfer: CD4+ Th1 function was abrogated by this modality, although CD8+ Th1 function was not. Transient depletion of recipient CD8+ cells markedly prolonged the survival of grafts transfected with either DNA-liposome complexes or adenoviral vectors. Transgene expression persisted for at least 60 days, and Th1 responses were not detectable until CD8+ T cells repopulated the periphery. However, long-term transfected allografts appeared to exhibit exacerbated fibrosis and neointimal development. These manifestations of chronic rejection were absent in long-term transfected isografts, suggesting that long-term expression of active TGFbeta1 alone is not sufficient to induce fibrosis of the grafts. Collectively, these data illustrate the utility of immunosuppressive gene therapy as a treatment for transplantation when combined with additional conditioning regimens. Further, they illustrate that alloreactive CD4+ and CD8+ cells may be differentially influenced by cytokine manipulation strategies.

Adenoviridae↗
PubMed2003

Adaptive test for testing the difference in survival distributions.

An adaptive test is proposed for the problem of testing the difference in survival distributions when the shape of the hazard ratio is unknown, hence the efficient test is unknown. The proposed adaptive test selects a test statistic from a finite set of the weighted logrank statistics T on the basis of the estimates of the efficiencies of the tests in T for given data. The efficiency estimator uses the length of the test based nonparametric confidence interval for the shift in a time transformed shift model. The suggested adaptive test is shown to be asymptotically efficient among the tests in T under the time transformed shift model and conditions commonly used in survival analysis. Simulations demonstrate that the adaptive test enjoys good small sample properties and in most situations is more powerful than the test using the maximum of the tests in T.

Computer Simulation↗
PubMed2006

Interruption of cell transformation and cancer formation.

A review of the results of X-ray and chemical carcinogen induction of transformation of mouse cells supports a two-step epigenetic model of transformation. According to this model, exposure induces an epigenetic regulatory alteration that makes the cells hypermutable so that when the cell population inheriting this alteration becomes sufficiently large, the second step, a mutation to the transformant phenotype, becomes increasingly likely. The epigenetic alteration in X-ray-exposed mouse cells has been demonstrated to be reversible by brief exposure to certain protease inhibitors. If the rodent cell experiments constitute a valid system for studying human cancer, then this two-step model may herald rich opportunities for preventing and perhaps even treating cancer in humans.

Animals↗
PubMed1984

Evaluations of wasted mouse fibroblasts and SV-40 transformed human fibroblasts as models of ataxia telangiectasia in vitro.

Fibroblast cultures from wasted mice have been derived and the responses of these cultures to bleomycin treatment or gamma-irradiation have been examined. No differences were observed between wasted fibroblasts and littermate controls in the post-treatment inhibition of DNA replication. In contrast, a human SV-40 transformed ataxia telangiectasia fibroblast line mimicked the abnormal response of primary ataxia telangiectasia fibroblasts to gamma-rays or bleomycin and thus appears to be a useful in vitro model of ataxia telangiectasia.

Animals↗
PubMed2003

Developing quality indicators and auditing protocols from formal guideline models: knowledge representation and transformations.

Automated quality assessment of clinician actions and patient outcomes is a central problem in guideline- or standards-based medical care. In this paper we describe a model representation and algorithm for deriving structured quality indicators and auditing protocols from formalized specifications of guidelines used in decision support systems. We apply the model and algorithm to the assessment of physician concordance with a guideline knowledge model for hypertension used in a decision-support system. The properties of our solution include the ability to derive automatically context-specific and case-mix-adjusted quality indicators that can model global or local levels of detail about the guideline parameterized by defining the reliability of each indicator or element of the guideline.

Algorithms↗
PubMed1996

Similar architectures of native and transformed human alpha2-macroglobulin suggest the transformation mechanism.

The refined three-dimensional structure of native human alpha2-macroglobulin (alpha2M) has been determined by cryoelectron microscopy and three-dimensional reconstruction. New features corresponding to "sigmoid arches," "basal bodies," and "apical connections" were observed in the molecule. Since similar elements are found in the architecture of transformed alpha2M, the 2 volumes were aligned in three dimensions. In their common orientations, they show many similarities except near the openings of the central chamber. In the native conformation, these apertures are fully opened, allowing the proteases to access the central chamber of the molecule, while in the transformed structure, they are partially closed. These structures suggest that alpha2M conformational change involves a strong lateral compression and a vertical stretching of the native particle seen in its four-petaled flower view to produce the H view of the transformed form. A model of structural transformation, in which all the parts of the alpha2M molecule seem involved in the entrapment of the proteinases is proposed.

Cryopreservation↗
PubMed1994

Cointegration of transforming DNAs in Aspergillus nidulans: a model using autonomously-replicating plasmids.

Transforming DNAs form cointegrates in Aspergillus nidulans by homologous and non-homologous recombination as well as by end-to-end ligation of linear fragments. This process has been studied by means of a model in which the linkage of a marker gene to the origin of autonomous replication AMA1 was selected for. Recombinant plasmids were rescued into Escherichia coli and subjected to restriction mapping and sequence analysis. It was shown that circular DNA molecules recombined predominantly within homologous fragments. Linear DNA fragments integrated into circular plasmids by invasion of their ends into random non-homologous sites, but exhibited some bias in choice of a target sequence. Cointegrates of multiple plasmid copies were often observed. In some of the plasmids analysed, short duplications of the target sequence flanking an inserted linear DNA fragment have been revealed.

Aspergillus nidulans↗
PubMed1998

Leukemia inhibitory factor and oncostatin M influence the mineral phases formed in a murine heterotopic calcification model: a Fourier transform-infrared microspectroscopic study.

The study of bone mineralization processes is of considerable interest in understanding bone diseases and developing new therapies for skeletal disorders, particularly since bone homeostasis requires numerous cell types and a large cytokine network. Cell culture models of mineralization have often been used to study the cellular mechanisms of mineralization, but few data have been reported concerning the influence of extracellular matrix components and cytokines on the physicochemical properties of mineral. The purpose of this study was to analyze the effects of two cytokines, leukemia inhibitory factor (LIF) and oncostatin M (OSM), involved in bone metabolism on the physicochemical properties of bone mineral formed in a murine in vivo mineralization model. Murine bone marrow cells implanted under the kidney capsule in the presence or absence of cytokines led to heterotopic ossicle formation. A scanning electron microscopic microprobe revealed that heterotopic calcification had a lower (approximately 20%) Ca/P ratio after cytokine treatment as compared with the control without cytokine. Transmission electron microscopic analysis of cytokine-treated ossicles showed numerous areas with low mineral density, whereas electron diffraction pattern revealed an apatitic phase. These areas were not observed in the absence of cytokine. Moreover, Fourier transform-infrared microspectroscopy showed at the molecular level that the presence of either cytokine induced many microscopic areas in which short-range order organization, such as incorporation of carbonate and crystallinity/maturity of ossicle mineral, were modified. LIF and OSM influenced mineral phase formation in the present model and may thus be key protagonists in bone mineral development and skeletal diseases.

Animals↗