Transcriptional dysregulation during myeloid transformation in AML

The current paradigm on leukemogenesis indicates that leukemias are propagated by leukemic stem cells. The genomic events and pathways involved in the transformation of hematopoietic precursors into leukemic stem cells are increasingly understood. This concept is based on genomic mutations or functional dysregulation of transcription factors in malignant cells of patients with acute myeloid leukemia (AML). Loss of the CCAAT/enhancer binding protein-alpha (CEBPA) function in myeloid cells in vitro and in vivo leads to a differentiation block, similar to that observed in blasts from AML patients. CEBPA alterations in specific subgroups of AML comprise genomic mutations leading to dominant-negative mutant proteins, transcriptional suppression by leukemic fusion proteins, translational inhibition by activated RNA-binding proteins, and functional inhibition by phosphorylation or increased proteasomal-dependent degradation. The PU.1 gene can be mutated or its expression or function can be blocked by leukemogenic fusion proteins in AML. Point mutations in the RUNX1/AML1 gene are also observed in specific subtypes of AML, in addition to RUNX1 being the most frequent target for chromosomal translocation in AML. These data are persuasive evidence that impaired function of particular transcription factors contributes directly to the development of human AML, and restoring their function represents a promising target for novel therapeutic strategies in AML.

Efficient transformation of Lactococcus lactis IL1403 and generation of knock-out mutants by homologous recombination

Lactococcus lactis IL1403 is a Gram-positive bacterium of great biotechnological interest for food grade applications. Its use is however hampered by the difficulty to efficiently transform this strain. We here describe a detailed, optimized electrotransformation protocol which yields a transformation efficiency of 10(6) cfu/microg of DNA with the two E. coli Gram-positive shuttle vectors pC3 and pVA838. The utility of the protocol was demonstrated by the generation of single- and double-knock-out mutants by homologous recombination.

Lymphocyte transformation by insulin and insulin-zinc suspensions

The lymphocyte transformation response to the mitogen phytohaemagglutinin (PHA) was determined in 15 well controlled insulin-dependent diabetics (IDD) with a history of insulin allergy or an acute insulin allergy. There was no significant difference in the PHA response of IDD and normal subjects matched in respect of age and sex. The response of peripheral blood lymphocytes to insulin (Actrapid) and an insulin zinc suspension (Monotard) was also determined. Fifty-three percent of IDD gave a positive reaction to Actrapid. Monotard produced positive reactions both in IDD and normal subjects. In normal subjects, a close correlation between the stimulation indices of Monotard and PHA was found (r = 0 . 966) suggesting that these stimulations depend on a common parameter namely, the reactivity to mitogens.

Invitational rhetoric : alternative rhetorical strategy for transformation of perception and use of energy in the residential built environment from the Keweenaw to Kerala

This dissertation explores the viability of invitational rhetoric as a mode of advocacy for sustainable energy use in the residential built environment. The theoretical foundations for this study join ecofeminist concepts and commitments with the conditions and resources of invitational rhetoric, developing in particular the rhetorical potency of the concepts of re-sourcement and enfoldment. The methodological approach is autoethnography using narrative reflection and journaling, both adapted to and developed within the autoethnographic project. Through narrative reflection, the author explores her lived experiences in advocating for energy-responsible residential construction in the Keweenaw Peninsula of Michigan. The analysis reveals the opportunities for cooperative, collaborative advocacy and the struggle against traditional conventions of persuasive advocacy, particularly the centrality of the rhetor. The author also conducted two field trips to India, primarily the state of Kerala. Drawing on autoethnographic journaling, the analysis highlights the importance of sensory relations in lived advocacy and the resonance of everyday Indian culture to invitational principles. Based on field research, the dissertation proposes autoethnography as a critical development in encouraging invitational rhetoric as an alternative mode of effecting change. The invitational force of autoethnography is evidenced in portraying the material advocacy of the built environment itself, specifically the sensual experience of material arrangements and ambience, as well as revealing the corporeality of advocacy, that is, the body as the site of invitational engagement, emotional encounter, and sensory experience. This study concludes that vulnerability of self in autoethnographic work and the vulnerability of rhetoric as invitational constitute the basis for transformation. The dissertation confirms the potential of an ecofeminist invitational advocacy conveyed autoethnographically for transforming perceptions and use of energy in a smaller-scale residential environment appropriate for culture, climate, and ultimately part of the challenge of sustaining life on this planet.

A Study of the Transformation of a Twenty-Eight Per Cent Tin Bronze

In this investigation, attention is directed to the phases covered by a 28 per cent tin alloy. When the investigation was started, consideration was given to the possibility of making a Time - Temperature - Transformation curve for this parti­cular alloy. As the work progressed and further research was carried on, this phase of the work was abandoned.

The Isothermal Transformation Curve for S.A.E. 6150

More than 3000 years ago, men began quenching and tem­pering tools to improve their physical properties. The an­cient people found that iron was easier to shape and form in a heated condition. Charcoal was used as the fuel, and when the shaping process was completed, the smiths cooled the piece in the most obvious way, quenching in water. Quite un­intentionally, these people stumbled on the process for im­proving the properties of iron, and the art of blacksmithing began.

A regioselective palladium-free protocol for accessing unsymmetrical biaryls through ring transformation of 6-aryl-~-pyrones

A regioselective synthesis of unsymmetrical biaryls with electron withdrawing or donating substituents is described and illustrated by carbanion-induced ring transfonnation of 6-aryl-a-pyrones with methoxyacetone in excellent yield. Our methodology is an alternative to classical organometal-catalyzed aryl-aryl coupling reactions and can be applied to the synthesis of functionally demanding naphthyl biaryls for the development of new ligands for asymetric synthesis

Regioselective Synthesis of 2-Amino-isophthalonitriles through a Ring Transformation Strategy

An expeditious synthesis of several 2-amino-isophthalonitriles and their biaryl compounds is described and illustrated by carbanion-induced ring transformation of functionalized 2H-pyran-2-ones with malononitrile in excellent yields. The strength of the reaction lies in the creation of an aromatic ring at room temperature from six membered-lactones under mild reaction conditions. This approach is an alternative to Diels-Alder reactions of 2H-pyran-2-ones with dienophiles, which require forcing thermal conditions to obtain benzene derivatives.

Neighboring group effect: DBU-promoted ring transformation of substituted isoxazoles to substituted pyrroles

A novel DBU-promoted ring transformation of substituted isoxazoles to substituted pyrroles is described

Regioselective Synthesis of Functionally Crowded Benzenes at Room Temperature through Ring Transformation of 2H-Pyran-2-ones

An expeditious synthesis of highly substituted benzenes with electron withdrawing or donating substituents is described and illustrated by carbanion-induced ring transformation of 2H-pyran-2-one with malononitrile in excellent yield. The novelty of the reaction lies in the creation of an aromatic ring at room temperature from six membered-lactones under mild reaction conditions.