POPULARITY
Policy Impact Skills for Historians Workshop 2: Public policy engagement – practice and actors 2.40-3.30pm: Session 4 Learning from Action Planning History and Policy in Practice (HPIP) in 2012/13 was the precursor course to Policy Impact Skills. King's College London PhD students Julie, Naomi and Ben won the HPIP prizes for best Action Plans (which were made available at workshop 1). They will discuss how the action-planning process helped consider a realistic target audience, how best to reach those audiences and their engagement activities since HPIP.
Policy Impact Skills for Historians Workshop 2: Public policy engagement – practice and actors 2.40-3.30pm: Session 4 Learning from Action Planning History and Policy in Practice (HPIP) in 2012/13 was the precursor course to Policy Impact Skills. King's College London PhD students Julie, Naomi and Ben won the HPIP prizes for best Action Plans (which were made available at workshop 1). They will discuss how the action-planning process helped consider a realistic target audience, how best to reach those audiences and their engagement activities since HPIP.
Policy Impact Skills for Historians Workshop 2: Public policy engagement – practice and actors 2.40-3.30pm: Session 4 Learning from Action Planning History and Policy in Practice (HPIP) in 2012/13 was the precursor course to Policy Impact Skills. King's College London PhD students Julie, Naomi and Ben won the HPIP prizes for best Action Plans (which were made available at workshop 1). They will discuss how the action-planning process helped consider a realistic target audience, how best to reach those audiences and their engagement activities since HPIP.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 11/19
Wed, 10 Feb 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13061/ https://edoc.ub.uni-muenchen.de/13061/1/Kaur_Pawandeep.pdf Kaur, Pawandeep
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 05/19
The hallmark of hematopoietic stem cells (HSC) is their ability of self-renewal and differentiation into multiple hematopoietic cell lineages. Although the molecular network controlling stem cell fate decisions is largely unknown, multiple studies have attributed a key role to transcription factors in this developmental process. In this context the family of homeobox genes was characterized as ‘master genes’ of this early hematopoietic development. The identification of new genes involved in normal and leukemic hematopoiesis and the development of therapies against deregulated processes in hematopoiesis are the major goals in experimental and clinical hematology. . The identification of new genes involved in normal and leukemic hematopoiesis and the development of therapies against deregulated processes in hematopoiesis are the major goals in experimental and clinical hematology. Therefore, the focus of this thesis was the characterization of two novel putative regulatory proteins of early human hematopoiesis, the hematopoietic PBX-interacting protein (HPIP) and the human Vent-like Homeobox gene (VENTX2) and to investigate to the activity of the FLT3 protein kinase inhibitor SU5614 on leukemic blast from AML patient samples. Using complex in vitro assays we analyzed the impact of constitutive expression of HPIP and VENTX2 on stem cell and early human hematopoietic development. To detect clonal progenitor cells primary and secondary colony-forming-unit (CFC) assays were performed. In addition the in vitro equivalent of HSC long-term culture initiating cells were detected with the (LTC-IC) assay. We were able to show that the constitutive expression of HPIP can rapidly lead to increased numbers of cells detected on the level of committed clonogenic progenitor cells and LTC-ICs. In addition, the production of CFC per LTC-IC is markedly enhanced when cord blood (CB) cells are transduced with HPIP as compared to the control. Notably, besides its effect on maintenance of primitive hematopoietic progenitor cells, constitutive expression of HPIP did not block terminal hematopoietic differentiation. Additional we could show that the constitutive expression of HPIP leads to an increase of myeloid cells in transplanted NOD/SCID mice. These data characterize HPIP as a novel regulator of the early human hematopoietic stem cell, demonstrating that its constitutive expression has a notable impact on self renewal and differentiation of human hematopoietic stem cells. In vitro and in vivo analyses shed light on the understanding to the function of the homeobox gene VENTX2. On the level of the most primitive hematopoietic progenitors we could not observe a significant increase in the frequency of HSCs. Furthermore, the number of colonies generated per LTC-IC did not significantly differ between the VENTX2 arm and the control arm. A strong effect was obtained on the level of clonogenic progenitor cells. VENTX2 increased the production of myeloid cells 1.7-fold in comparison to the control. Secondary replating assay confirmed the amplificatory effect of VENTX2 transduced cells in the number of secondary G-CFU indicating that VENTX2 promote myeloid lineage differentiation. Interestingly, on the level of clonogenic progenitors VENTX2 expression resulted in a significantly decreased growth of erythroid colonies by 4.2-fold compared to the control suggesting that constitutive expression of VENTX2 may inhibit early erythroid differentiation. This inhibition did not occur on the level of primitive hematopoietic cells detected by Limiting Dilution LTC-IC assay where VENTX2 increased within a 2.2 fold compared to the control. The observation that VENTX2 overexpression drives CD34+ to differentiate into myeloid lineage was additional proved by in vivo experiments. In NOD/SCID mice VENTX2 induced a 3-fold increase in the proportion of CD15+ mature myeloid cells within the GFP-positive compartment compared to the control. A 7-fold increase was observed in the total of CD38+ GFP+ cells in comparison to the MIG mice control (p