Dropout Policies: Research-Based Strategies

Educational research has uncovered proven remedies with the potential to lower dropout rates. Yet Colorado’s dropout problem continues at epidemic rates. Approximately 30 percent of Colorado’s students fail to graduate within four years of starting high school. This dropout crisis is costly to our state and is seriously harming children, families, local communities, and the state as a whole. Students without high school diplomas lack the skills and knowledge needed to maintain a sound economy and healthy democracy for future generations

NEPC Review: Successful, Safe, and Healthy Students

The research summary Successful, Safe, and Healthy Students presents the research background for the Obama administration&rsquo;s proposals for comprehensive, community-wide services in high-poverty neighborhoods, extended learning time, family engagement and safe schools. While these policies have broad and common-sense appeal, the research supporting the particular policies proposed by the administration is weak and poorly presented in the research summary. As promising as community-wide services may be, a broad research base does not yet exist concerning how to make them successful. The research on extended learning time is also inconclusive. Family involvement is crucial to education, but the evidence for a causal link between student achievement and the type of parent involvement discussed is ambiguous and suspect. The proposals for safe schools boil down to increased local flexibility and increased gathering of survey data, neither of which can be expected to improve outcomes. Together, the administration&rsquo;s proposals would require an extensive financial commitment in order to be fully implemented, but the scope and source of these funds is not explained. Overall, the evidence provided is not sufficiently strong to justify the programs they champion. While the research summary adequately documents problems, a wiser course for public policy would be a carefully structured set of pilot studies to sharply and accurately identify solutions.</p

Measuring opportunity: Redirecting education policy through research

While scholars develop research with clear implications for policy and practice, this work has been largely ineffective in influencing thought beyond the academy. In this article, we explore challenges researchers face in designing public scholarship to influence policy. To illustrate, we profile one such effort, the “Opportunity to Learn Index,” a national project designed to compare opportunities to learn in all 50 states, and we detail challenges related to method, analysis and presentation. This type of effort, we conclude, asks researchers to embrace unique challenges and the inescapably political nature of the knowledge enterprise, especially when engaging with non-researcher audiences

Laser-Induced Dissociation of an Energetic Polymer: A Spectroscopic Study of the Gaseous Products

Previous studies of GAP (glycidyl azido polymer) laser-induced decomposition (Propellants, ExplosiVes, Pyrotechnics 1996, 21, 258), revealed that the shock wave produced from a diluted polymer is more energetic than from the neat polymer. In this paper, direct measurement of the energy disposal into molecular products is reported using spectroscopic methods. Chemiluminescence probes electronically excited species, and laserinduced fluorescence, ground-state radicals. It is found that the initial velocity and internal energy content of small diatomic molecules is larger in some diluted polymers than in the neat one. This finding is in line with a simple model based on the assumption of a self-sustained reaction following initial laser excitation

Treatment of Chronic Myelogenous Leukemia by Blocking Cytokine Alterations Found in Normal Stem and Progenitor Cells

SummaryLeukemic cells disrupt normal patterns of blood cell formation, but little is understood about the mechanism. We investigated whether leukemic cells alter functions of normal hematopoietic stem and progenitor cells. Exposure to chronic myelogenous leukemia (CML) caused normal mouse hematopoietic progenitor cells to divide more readily, altered their differentiation, and reduced their reconstitution and self-renewal potential. Interestingly, the normal bystander cells acquired gene expression patterns resembling their malignant counterparts. Therefore, much of the leukemia signature is mediated by extrinsic factors. Indeed, IL-6 was responsible for most of these changes. Compatible results were obtained when human CML were cultured with normal human hematopoietic progenitor cells. Furthermore, neutralization of IL-6 prevented these changes and treated the disease

Acetylation of C/EBP alpha inhibits its granulopoietic function

CCAAT/enhancer-binding protein alpha (C/EBP alpha) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBP alpha at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBP alpha DNA-binding ability and modulates C/EBP alpha transcriptional activity. Acetylated C/EBP alpha is enriched in human myeloid leukaemia cell lines and acute myeloid leukaemia (AML) samples, and downregulated upon granulocyte-colony stimulating factor (G-CSF)-mediated granulocytic differentiation of 32Dcl3 cells. C/EBP alpha mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBP alpha-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBP alpha and demonstrate the importance of C/EBP alpha acetylation in myeloid differentiation

Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance.

Hematopoietic stem cells (HSCs) have the potential to replenish the blood system for the lifetime of the organism. Their 2 defining properties, self-renewal and differentiation, are tightly regulated by the epigenetic machineries. Using conditional gene-knockout models, we demonstrated a critical requirement of lysine acetyltransferase 5 (Kat5, also known as Tip60) for murine HSC maintenance in both the embryonic and adult stages, which depends on its acetyltransferase activity. Genome-wide chromatin and transcriptome profiling in murine hematopoietic stem and progenitor cells revealed that Tip60 colocalizes with c-Myc and that Tip60 deletion suppress the expression of Myc target genes, which are associated with critical biological processes for HSC maintenance, cell cycling, and DNA repair. Notably, acetylated H2A.Z (acH2A.Z) was enriched at the Tip60-bound active chromatin, and Tip60 deletion induced a robust reduction in the acH2A.Z/H2A.Z ratio. These results uncover a critical epigenetic regulatory layer for HSC maintenance, at least in part through Tip60-dependent H2A.Z acetylation to activate Myc target genes.Cancer Research UK, Wellcome Trust, National Institutes of Health, Singapore state fundin

Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage at relapse. Many reports have documented conversions of acute lymphoblastic leukemia to acute myeloid leukemia

Transient Activation of Hematopoietic Stem and Progenitor Cells by IFNγ during Acute Bacterial Infection

How hematopoietic stem cells (HSCs) respond to inflammatory signals during infections is not well understood. Our studies have used a murine model of ehrlichiosis, an emerging tick-born disease, to address how infection impacts hematopoietic function. Infection of C57BL/6 mice with the intracellular bacterium, Ehrlichia muris, results in anemia and thrombocytopenia, similar to what is observed in human ehrlichiosis patients. In the mouse, infection promotes myelopoiesis, a process that is critically dependent on interferon gamma (IFNγ) signaling. In the present study, we demonstrate that E. muris infection also drives the transient proliferation and expansion of bone marrow Lin-negative Sca-1+ cKit+ (LSK) cells, a population of progenitor cells that contains HSCs. Expansion of the LSK population in the bone marrow was associated with a loss of dormant, long-term repopulating HSCs, reduced engraftment, and a bias towards myeloid lineage differentiation within that population. The reduced engraftment and myeloid bias of the infection-induced LSK cells was transient, and was most pronounced on day 8 post-infection. The infection-induced changes were accompanied by an expansion of more differentiated multipotent progenitor cells, and required IFNγ signaling. Thus, in response to inflammatory signals elicited during acute infection, HSCs can undergo a rapid, IFNγ-dependent, transient shift from dormancy to activity, ostensibly, to provide the host with additional or better-armed innate cells for host defense. Similar changes in hematopoietic function likely underlie many different infections of public health importance