Production test IP-614-A: Irradiation of thorium target elements

Limited irradiations of thorium target elements have been conducted at HAPO during the past ten years but large-scale irradiations have not been attempted. An obstacle encountered in thorium irradiation programs has been the formation of U-232, which is undesirable because of intense gamma radiation. Further study of the problem indicates that by employing certain restrictions during irradiation of the thorium a relatively ``clean``, free of U-232,,product U-233 may be obtained. The objectives of this production test described in this report are to: irradiate small quantities of metallic thorium elements to confirm physics predictions; provide small quantities of irradiated thorium for laboratory evaluation of problems associated with chemical processing of the irradiated metallic thorium; and provide preliminary information for study of large-scale irradiations of thorium at HAPO

Reversibility of Defective Hematopoiesis Caused by Telomere Shortening in Telomerase Knockout Mice.

Telomere shortening is common in bone marrow failure syndromes such as dyskeratosis congenita (DC), aplastic anemia (AA) and myelodysplastic syndromes (MDS). However, improved knowledge of the lineage-specific consequences of telomere erosion and restoration of telomere length in hematopoietic progenitors is required to advance therapeutic approaches. We have employed a reversible murine model of telomerase deficiency to compare the dependence of erythroid and myeloid lineage differentiation on telomerase activity. Fifth generation Tert-/- (G5 Tert-/-) mice with shortened telomeres have significant anemia, decreased erythroblasts and reduced hematopoietic stem cell (HSC) populations associated with neutrophilia and increased myelopoiesis. Intracellular multiparameter analysis by mass cytometry showed significantly reduced cell proliferation and increased sensitivity to activation of DNA damage checkpoints in erythroid progenitors and in erythroid-biased CD150hi HSC, but not in myeloid progenitors. Strikingly, Cre-inducible reactivation of telomerase activity restored hematopoietic stem and progenitor cell (HSPC) proliferation, normalized the DNA damage response, and improved red cell production and hemoglobin levels. These data establish a direct link between the loss of TERT activity, telomere shortening and defective erythropoiesis and suggest that novel strategies to restore telomerase function may have an important role in the treatment of the resulting anemia

Partnerships for Affordable and Equitable Disaster Insurance

Extreme events are becoming more frequent and intense, inflating the economic damages and social hardship set-off by natural catastrophes. Amidst budgetary cuts, there is a growing concern on societies' ability to design solvent disaster recovery strategies, while addressing equity and affordability concerns. The participation of private sector along with public one through Public-Private Partnerships (PPPs) has gained on importance as a means to address these seemingly conflicting objectives through the provision of (catastrophic) natural hazard insurance. This is the case of many OECD countries, notably some EU Member States such as the United Kingdom and Spain. The EU legislator has adapted to this new scenario and recently produced major reforms in the legislation and regulation that govern the framework in which PPPs for (catastrophic) natural hazard insurance develop. This paper has a dual objective: 1) review the complex legal background that rules the provision of insurance against natural catastrophes in the EU after these major reforms; 2) assess the implications of the reforms and offer concise Policy Guiding Principles

Comparison of HSC and MPP numbers between G0 <i>Tert</i>+/- and G5 <i>Tert</i>-/- mice.

<p>(A) Representative FACS profiles of lineage-, c-Kit+ and Sca1+ cells separated based on CD34 and CD150 expression, showing absolute numbers of HSC (Lin-c-Kit+Sca1+CD34-CD150+), MPP-A (Lin-c-Kit+Sca1+CD34+CD150+) and MPP-B (Lin-c-Kit+Sca1+CD34+CD150-) populations in G0 <i>Tert</i>+/- and G5 <i>Tert</i>-/- BM. (B-D) Comparison of absolute numbers of (B) HSC, (C) MPP-A and (D) MPP-B in the femurs of G0 <i>Tert</i>+/- (n = 17) and G5 <i>Tert</i>-/- (n = 11) mice aged 11–20 months. The ends of the whiskers represent minimum and maximum values while the bar indicates the median value (50^th percentile). p values are based on a 2-tailed <i>t</i> test. (E) Representative FACS profile of CD34-LKS cells subdivided into CD150hi, CD150lo and CD150negative fractions in G0 <i>Tert</i>+/- and G5 <i>Tert</i>-/- BM cells. (F) Ratios of the three CD150 fractions within CD34-LKS cells from G0 <i>Tert</i>+/- (n = 6) and G5 <i>Tert</i>-/- (n = 9) mice aged 11–20 months, as calculated from the absolute numbers of total HSC population. p value < 0.01(two-way ANOVA) demonstrating that the differences between the three CD150 fractions in G0 <i>Tert</i>+/- and G5 <i>Tert</i>-/- mice are statistically significant.</p