Additional media studies for site suitability criteria

Site suitability studies have been made previously at LLL on bedded salt and shale. In the present study domed salt, basalt, and crystalline rock are compared with bedded salt and shale and with each other as possible repositories. The level of effort required to develop models for these media that are similar in quality to those available for bedded salt and shale is evaluated. The effort necessary to develop data bases on the physical and chemical properties comparable to that available for bedded salt and shale is also estimated. Each medium is evaluated as a suitable repository environment. The funding necessary for model and data base development is estimated. (JSR

Technical Report 1701

This report describes two separate High-Data-Rate (HDR), Ultra-High-Frequency (UHF), Line-ofSight (LOS) digital radio communication experiments and demonstrations conducted during FY 95 and the instruments used to support these demonstrations. The development of the HDR UHF LOS capabilities is sponsored by what was formerly the Office of Naval Technology, now the Office of Naval Research (ONR), Arlington, Virginia, under a communication block program at the Naval Command, Control and Ocean Surveillance Center (NCCOSC), RDT&E Division (NRaD) in San Diego, California. It began in FY 93 with the goal of exploring the possibilities of providing for T1 (1.544 Mbps) digital communications between ships in the 225- to 400-MHz, UHF band. The instruments used to support the demonstrations in this report represent Phase 1 of a planned three phases of instrument evolution. The Phase 1 instruments are based around the use of the AN/WSC--3 external modem interface and existing shipboard antenna couplers, RF cabling, and omnidirectional antennas. This system is proven by these demonstrations to provide reliable communications at fractional T1 data rates (256 kbps to 576 kbps) to a maximum range of about 18 nmi between ships at sea. RESULTS Commander, Destroyer Squadron 33 and Commander, Naval Surface Forces Pacific (CNSP) sponsored a series of experiments and demonstrations with the USS Rentz and the USS Abraham Lincoln Battle Group with funding from the Aegis Program Manager, PMS 400ED3 (described in section 4) and the Naval Medical Information Management Center (NMIMC) (described in Appendix A). Their goal was to provide technical, medical, and administrative support to the fleet more efficiently through voice, ethernet, and video teleconferencing. This report describes experimen..

Oxidized mC modulates synthetic lethality to PARP inhibitors for the treatment of leukemia

TET2 haploinsufficiency is a driving event in myeloid cancers and is associated with a worse prognosis in patients with acute myeloid leukemia (AML). Enhancing residual TET2 activity using vitamin C increases oxidized 5-methylcytosine (mC) formation and promotes active DNA demethylation via base excision repair (BER), which slows leukemia progression. We utilize genetic and compound library screening approaches to identify rational combination treatment strategies to improve use of vitamin C as an adjuvant therapy for AML. In addition to increasing the efficacy of several US Food and Drug Administration (FDA)-approved drugs, vitamin C treatment with poly-ADP-ribosyl polymerase inhibitors (PARPis) elicits a strong synergistic effect to block AML self-renewal in murine and human AML models. Vitamin-C-mediated TET activation combined with PARPis causes enrichment of chromatin-bound PARP1 at oxidized mCs and γH2AX accumulation during mid-S phase, leading to cell cycle stalling and differentiation. Given that most AML subtypes maintain residual TET2 expression, vitamin C could elicit broad efficacy as a PARPi therapeutic adjuvant. [Display omitted] •Vitamin C synergizes with PARPis, causing S phase stalling and AML differentiation•Combination treatment efficacy is dependent on TET2 expression in AML•PARPi treatment with vitamin C causes 5fC accumulation in the genome of AML cells•PARPi treatment with vitamin C enriches for PARP1 binding and γH2AX at 5fC sites Vitamin C treatment can slow the progression of AML by enhancing TET2 activity but is not curative as a single agent therapy. Using genetic and compound screening approaches, Brabson et al. identify a rational combination treatment strategy where vitamin C enhances the therapeutic efficacy of PARPis for AML treatment