IntroductionHematopoiesis is the regulated development of distinct cellular lineages from a common precursor, the hematopoietic stem cell. Fundamental changes in gene expression result in each cell type expressing a characteristic complement of genes necessary for its function. This is achieved through the action of transcriptional regulators with general and restricted expression patterns in the hematopoietic system. 1 The ets domain transcription factor PU.1 is preferentially expressed in myeloid and B cells. 2,3 Inactivation of the PU.1 gene in mice causes defects in the development of multiple hematopoietic lineages, including B and T lymphocytes, monocytes, and granulocytes. 4,5 PU.1 regulates the expression of almost all characterized myeloid genes, including growth factor receptors. In particular, it directs the monocyte-specific expression of the macrophage colony-stimulating factor receptor. 6,7 PU.1 probably plays an important role at several stages in the differentiation process, and there is evidence that it is active at an early stage, mediating commitment of multipotential progenitor cells to the myeloid lineage. 8 CCAAT/enhancer-binding protein alpha (C/EBP␣) was initially identified in liver and adipose tissue, where it was found to be important for terminal differentiation. 9-14 C/EBP␣ expression is prominent in immature myeloid cells. 15-17 C/EBP␣-null mice lack the entire granulocyte lineage but develop normal monocytes. 18 Recently, we identified dominant-negative mutations of C/EBP␣ in acute myeloid leukemia 19 and a down-regulation of C/EBP␣ expression by the leukemic fusion protein AML1/ETO, 20 suggesting an important role of C/EBP␣ in leukemogenesis. Ectopic expression of C/EBP␣ in U937 monocyte leukemia cells induces granulocytic differentiation over a 2-week period and inhibits monocyte differentiation. 16 These hematopoietic progenitors require PU.1 to initiate monocyte differentiation and C/EBP␣ to initiate granulopoiesis. PU.1 has been shown to interact with a C/EBP family member, C/EBP␦. 21 However, the interaction of these transcription factors in differentiating to a specific lineage is still unclear.We propose here that the granulocyte factor C/EBP␣ interacts with the myeloid master regulator PU.1 and inactivates PU.1. c-Jun belongs to the b-ZIP group of DNA-binding proteins and is a component of AP-1 transcription complexes. 22 c-Jun has been shown to be a coactivator of PU.1, resulting in increased macrophage-colony-stimulating factor (M-CSF) receptor expression, and it is involved in the development of the monocyte lineage. 23 Here we show that C/EBP␣ blocks PU.1 function by displacing c-Jun, the coactivator of PU.1. Furthermore, C/EBP␣ specifies the fate of myeloid progenitor cells to the granulocyte lineage by inactivating PU.1 through protein-protein interactions. Materials and methods Cell lines and cell cultureFibroblast F9 and 293T cells were cultured in Dulbecco Modified Eagle Medium (PAN Biotech GmbH, Karlsruhe, Germany) containing 10% fetal bovine serum (FBS; Gibco BR...

Semicrystalline polymers have been classified into crystal-mobile and crystal-fixed polymers, depending on the existence or absence of intracrystalline chain dynamics. Although it was claimed that polymers with intracrystalline chain dynamics generally have a higher crystallinity, its effect on the semicrystalline morphology is not known in detail. Using a new approach for the quantitative analysis of small-angle X-ray scattering data, we compare the structural characteristics of fully crystallized samples for two model polymers with and without chain motion in the crystallites. Whereas for crystal-fixed polymers the semicrystalline morphology is characterized by lamellar crystals of well-defined thickness and marginal stability, the intracrystalline dynamics leads to additional stabilization of the crystals during growth and a minimization of the amorphous layers characterized by a well-defined thickness. Results of 1H solid-state NMR experiments enable us to determine the time scale of intracrystalline chain dynamics in the relevant temperature range and to relate it to the time scale of crystal growth. If both processes act on the same time scale, the crystallization process is an interplay between crystal growth and stabilization by reorganization enabled by intracrystalline mobility. Viewing this competition as fundamental for the formation of the semicrystalline morphology, seemingly contradictory models suggested in the past to describe polymer crystallization can at least be partially reconciled.

Abstract:The dimethyldioxirane oxida-served. Even for these alkenes, which are proposed radical mechanism. The selection of a-methylstyrene, rruns-cyclo-prone to radical reactions, the previously tive hydroxylation of ( -)-2-phenylbutane octene, and 1 -vinyl-2,2-diphenylcycloestablished electrophilic concerted mech-by dimethyldioxirane gave only ( -)-2-propane gave, under all reaction condi-anism applies, rather than the recently phenylbutan-2-01 with complete retention tions employed, the corresponding epoxof configuration and no loss of optical ides in high yields. No radical products purity. Thus, a radical-chain oxidation is also discounted in the oxygen insertion infrom allylic oxidation, from translcis isoto hydrocarbon C-H bonds for dioximerization, or from cyclopropylcarbinyl ranes. rearrangement (radical clock) were ob-

This work focuses on the influence of amorphous-phase entanglements on the semicrystalline morphology of poly­(ϵ-caprolactone). This polyester is classified as crystal-fixed; i.e., it displays no translational chain dynamics in the crystals. We study a wide range of well-entangled samples with molecular weights up to several million using polarization microscopy to assess the lamellar growth rate, small-angle X-ray scattering and proton time-domain NMR to characterize the morphology, and proton multiple-quantum NMR, auxiliary carbon-13 NMR, rheology, and tensile deformation to assess the entangled chain dynamics in the melt and semicrystalline states. We demonstrate a significant increase in the density of entanglements in the amorphous phase relative to the melt. The dependencies of our observables on crystallization temperature and molecular weight suggest that entanglements control the thickness of the amorphous layers. This is rationalized by an only slowly relaxing exclusion zone with enhanced entanglement density acting as an entropically repulsive layer between adjacent lamellae.