Development of high energy density primary batteries 200 watt hours per pound total battery weight minimum Final report, 10 Jun. 1964 - 9 Jun. 1965

High energy density lithium-anode primary cells developed with energy-to-weight ratios over 200 watt hours per poun

Development of high energy density primary batteries First quarterly report, 22 Jun. - 21 Oct. 1965

Electrode and electrolyte studies for lithium- copper fluoride batterie

Development of high energy density primary batteries Second quarterly report, 22 Sep. - 21 Dec. 1965

Copper fluoride-lithium high energy density battery developmen

Synthesis and characterization of [Fe(BPMEN)-ACC]SbF 6 : a structural and functional mimic of ACC-oxidase †

International audienceA mononuclear Fe(II) complex bearing 1-aminocyclopropane-1-carboxylic acid (ACCH) was synthesized and characterized. X-ray crystallography demonstrated that ACC binds to the Fe(II) ion in a bidentate mode constituting the first structural mimic of the expected binding of ACC to the Fe(II) center of the ethylene forming enzyme ACC-oxidase (ACCO). [Fe(BPMEN)ACC]SbF 6 also constitutes a functional biomimetic complex of ACCO, as it reacts with hydrogen peroxide producing ethylene

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

Background: The carboxylesterase Notum has been shown to act as a key negative regulator of the Wnt signalling pathway by mediating the depalmitoleoylation of Wnt proteins. LP-922056 (1) is an orally active inhibitor of Notum. We are investigating the role of Notum in modulating Wnt signalling in the central nervous system and wished to establish if 1 would serve as a peripherally restricted control. An accessible and improved synthetic route would allow 1 to become more readily available as a chemical tool to explore the fundamental biology of Notum and build target validation to underpin new drug discovery programs. / Results: An improved, scalable synthesis of 1 is reported. Key modifications include: (1) the introduction of the C7-cyclopropyl group was most effectively achieved with a Suzuki–Miyaura cross-coupling reaction with MIDA-boronate 11 (5 → 6); and (2) C6 chlorination was performed with 1-chloro-1,2-benziodoxol-3-one (12) (6 → 7) as a mild selective electrophilic chlorination agent. This 7-step route has been reliably performed on large scale to produce multigram quantities of 1 in good efficiency and high purity. Pharmacokinetic studies in mouse showed CNS penetration of 1 is very low with brain:plasma concentration ratio of just 0.01. A small library of amides 17 were prepared from acid 1 to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. Although significant Notum inhibition activity could be achieved, none of these amides demonstrated the required combination of metabolic stability along with cell permeability without evidence of P-gp mediated efflux. / Conclusion: Mouse pharmacokinetic studies demonstrate that 1 is unsuitable for use in models of disease where brain penetration is an essential requirement of the compound but would be an ideal peripherally restricted control. These data will contribute to the understanding of drug levels of 1 to overlay with appropriate in vivo efficacy endpoints, i.e. the PK-PD relationship. The identification of a suitable analogue of 1 (or 17) which combines Notum inhibition with CNS penetration would be a valuable chemical probe for investigating the role of Notum in disease models

Education and Outreach in the Life Sciences: Qualitative Analysis Report

The DOE's National Nuclear Security Agency (NNSA) asked Pacific Northwest National Laboratory (PNNL) to consider the role of individual scientists in upholding safety and security. The views of scientists were identified as being a critical component of this policy process. Therefore, scientists, managers, and representatives of Institutional Biosafety Committees (IBCs) at the national labs were invited to participate in a brief survey and a set of focus groups. In addition, three focus groups were conducted with scientists, managers, and IBC representatives to discuss some of the questions related to education, outreach, and codes of conduct in further detail and gather additional input on biosecurity and dual-use awareness at the laboratories. The overall purpose of this process was to identify concerns related to these topics and to gather suggestions for creating an environment where both the scientific enterprise and national security are enhanced