High mortality associated with tapeworm parasitism in geladas (Theropithecus gelada) in the Simien Mountains National Park, Ethiopia

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138266/1/ajp22684.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138266/2/ajp22684_am.pd

Reversal of oncogene transformation and suppression of tumor growth by the novel IGF1R kinase inhibitor A-928605

BACKGROUND: The insulin-like growth factor (IGF) axis is an important signaling pathway in the growth and survival of many cell and tissue types. This pathway has also been implicated in many aspects of cancer progression from tumorigenesis to metastasis. The multiple roles of IGF signaling in cancer suggest that inhibition of the pathway might yield clinically effective therapeutics. METHODS: We describe A-928605, a novel pyrazolo [3,4-d]pyrimidine small molecule inhibitor of the receptor tyrosine kinases (IGF1R and IR) responsible for IGF signal transduction. This compound was first tested for its activity and selectivity via conventional in vitro kinome profiling and cellular IGF1R autophosphorylation. Additionally, cellular selectivity and efficacy of A-928605 were analyzed in an IGF1R oncogene-addicted cell line by proliferation, signaling and microarray studies. Finally, in vivo efficacy of A-928605 was assessed in the oncogene-addicted cell line and in a neuroblastoma model as a single agent as well as in combination with clinically approved therapeutics targeting EGFR in models of pancreatic and non-small cell lung cancers. RESULTS: A-928605 is a selective IGF1R inhibitor that is able to abrogate activation of the pathway both in vitro and in vivo. This novel compound dosed as a single agent is able to produce significant growth inhibition of neuroblastoma xenografts in vivo. A-928605 is also able to provide additive effects when used in combination with clinically approved agents directed against EGFR in non-small cell lung and human pancreatic tumor models. CONCLUSION: These results suggest that a selective IGF1R inhibitor such as A-928605 may provide a useful clinical therapeutic for IGF pathway affected tumors and warrants further investigation

Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)

This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior

Pre-Conceptual Design of a Fluoride-Salt-Cooled Small Modular Advanced High Temperature Reactor (SmAHTR)

This document presents the results of a study conducted at Oak Ridge National Laboratory during 2010 to explore the feasibility of small modular fluoride salt-cooled high temperature reactors (FHRs). A preliminary reactor system concept, SmATHR (for Small modular Advanced High Temperature Reactor) is described, along with an integrated high-temperature thermal energy storage or salt vault system. The SmAHTR is a 125 MWt, integral primary, liquid salt cooled, coated particle-graphite fueled, low-pressure system operating at 700 C. The system employs passive decay heat removal and two-out-of-three , 50% capacity, subsystem redundancy for critical functions. The reactor vessel is sufficiently small to be transportable on standard commercial tractor-trailer transport vehicles. Initial transient analyses indicated the transition from normal reactor operations to passive decay heat removal is accomplished in a manner that preserves robust safety margins at all times during the transient. Numerous trade studies and trade-space considerations are discussed, along with the resultant initial system concept. The current concept is not optimized. Work remains to more completely define the overall system with particular emphasis on refining the final fuel/core configuration, salt vault configuration, and integrated system dynamics and safety behavior

Manipulation of Cell:Cell Contacts and Mesoderm Suppressing Activity Direct Lineage Choice from Pluripotent Primitive Ectoderm-Like Cells in Culture

In the mammal, the pluripotent cells of embryo differentiate and commit to either the mesoderm/endoderm lineages or the ectoderm lineage during gastrulation. In culture, the ability to direct lineage choice from pluripotent cells into the mesoderm/endoderm or ectoderm lineages will enable the development of technologies for the formation of highly enriched or homogenous populations of cells. Here we show that manipulation of cell:cell contact and a mesoderm suppressing activity in culture affects the outcome of pluripotent cell differentiation and when both variables are manipulated appropriately they can direct differentiation to either the mesoderm or ectoderm lineage. The disruption of cell:cell contacts and removal of a mesoderm suppressor activity results in the differentiation of pluripotent, primitive ectoderm-like cells to the mesoderm lineage, while maintenance of cell:cell contacts and inclusion, within the culture medium, of a mesoderm suppressing activity results in the formation of near homogenous populations of ectoderm. Understanding the contribution of these variables in lineage choice provides a framework for the development of directed differentiation protocols that result in the formation of specific cell populations from pluripotent cells in culture

Digital culture clash: “massive” education in the E-learning and Digital Cultures MOOC

While education has been both open and online, the sizeable enrolment numbers associated with massive open online courses (MOOCs) are somewhat unprecedented. In order to gauge the significance of education at scale, this article analyses specific examples of massive participation derived from E-learning and Digital Cultures, a MOOC from the University of Edinburgh in partnership with Coursera. Student-created content, user statistics, and survey data are illustrated to examine the experiences and repercussions of engaging with educational activity where participants number in the tens of thousands. This activity is shown to mirror established instructionist or constructivist approaches to pedagogy. However, rather than working with “massiveness,” these positions are suggested to oppose large participant numbers. Concluding remarks propose an irreducible diversity of participation, rather than a generalised categorisation of “student,” and call for future considerations of the MOOC to move beyond individualism and self-interest

Biological maturation and β-adrenergic effectors: development of β-adrenergic receptors in rabbit heart

The β-adrenergic receptor, transduction processes and catalytic activity of the adenylate cyclase enzyme complex have been investigated in rabbit heart at different stages of biological maturation. The binding of [ 3 H]-dihydroalprenolol to a washed membrane preparation isolated from rabbit ventricular muscle was used to characterize β-adrenergic receptors. Significant age-related differences were noted in β-receptor affinity (K d ) and density (RD) of neonatal and adult animals; the adult K d was 3.7-fold greater and the RD 2-fold higher than the neonates. No significant differences in these parameters were detected among the 27-day old fetus and the 1- and 7-day old neonates. Age-dependent differences in agonist isoproterenol affinity for the receptor were not observed in contrast to the significant changes in antagonist (DHA) affinity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45349/1/11010_2004_Article_BF00240617.pd