Unbalanced translocations as well as interstitial deletions of the short arm of chromosome 12 del(12p) are found as recurring chromosomal changes in a broad spectrum of hematopoietic malignancies. ...These changes result in the hemizygous deletion of genetic material from 12p. We mapped a yeast artificial chromosome containing the TEL gene, a cosmid contig containing part of TEL and a P1 contig containing the KIP1 gene to 12p13. These probes were used for fluorescence in situ hybridization to analyze samples from 47 patients with various hematologic malignancies who had unbalanced translocations (25 patients) leading to loss of 12p or deletions (22 patients) involving 12p13. The patients had acute lymphoblastic leukemia (8 cases), myelodysplastic syndrome (MDS; 11 cases), acute myeloid leukemia (AML; 10 cases), myeloproliferative disorders (4 cases), therapy-related MDS or AML (7 cases), non-Hodgkin's lymphoma (2 cases), and other hematopoietic malignancies (5 cases). All three probes were hemizygously deleted in 26 cases and were completely retained in only 9 cases. In 12 cases probes for one of the two genes were deleted, allowing us to map the smallest region of overlap of these deletions to a small genomic region that is bordered on the telomeric side by the TEL gene and on the centromeric side by KIP1. The genomic distance between TEL and KIP1 is estimated to be about 1 to 2 Mbp.
The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers ...completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established.
A Vigorous Explorer Program Martin, Elvis; Beasley, Matthew; Brissenden, Roger ...
arXiv.org,
11/2009
Paper, Journal Article
Odprti dostop
Explorers have made breakthroughs in many fields of astrophysics. The science from both these missions contributed to three Nobel Prizes - Giacconi (2002), Mather, and Smoot (2006). Explorers have: ...marked the definitive beginning of precision cosmology, discovered that short gamma-ray bursts are caused by compact star mergers and have measured metalicity to redshifts z>6. NASA Explorers do cutting-edge science that cannot be done by facility-class instruments. The Explorer program provides a rapid response to changing science and technology, to enable cutting-edge science at moderate cost. Explorers also enable innovation, and engage & train scientists, managers and engineers, adding human capital to NASA and the nation. The astrophysics Explorer launch rate now being achieved is 1 per 3 years, and budget projections are in the $150M/year range for the next five years. A newly Vigorous Explorer Program should be created to: 1. Reach the long-stated goal of annual astrophysics launches; 2. Find additional launch options for Explorers and actively encourage cost savings in launchers and spacecraft, such as new commercial vehicles and innovative partnerships. 3. Mitigate risk via stronger technical development and sub-orbital programs, and through longer, more thorough, Phase A programs, potentially reducing the need for a 30% contingency; 4. Strive to protect the funding for missions that have reached Phase B, to prevent significant launch slips and cancellations, with a goal of 4 to 5 years from Phase B to launch; 5. Review the project management procedures and requirements to seek cost reductions, including the risk management strategy and the review and reporting process; 6. Review and possibly modify the cost caps for all Explorer classes to optimize scientific returns per dollar. ABRIDGED
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