Project Progress

The proposed study investigates the effect of low dose and low dose rate radiation exposure (X-rays) on induced genomic instability and the adaptive response, including the molecular mechanisms for these phenomena. The proposed studies will utilize human cell lines containing a stably integrated plasmid that can be caused by certain kinds of mutational insults to recombine to express the green fluorescent proteins, GFP. The study will use this cell line with the fluorescent plasmid recombination reporter system in a direct study of the effects of 1, 2.5, 5, 7.5, 10, 100 and 500 rads acute X-irradiation and the same doses delivered by protraction at 1 rad or 0.01 rad per minute. This system will be used to provide a quantitative measure of the kinetics of genomic instability in colonies of cells exposed to low dose/dose rate, as well as to examine the adaptive response. The study will also apply micro array technology to investigate the molecular mechanisms underlying induced instability and adaptive effects

Final Technical Report for the grant entitled "Genetic Factors Affecting Susceptibility to Low-Dose Radiation"

The goal of this proposal was to test the hypothesis that mice heterozygous for the Nijmegen Breakage Syndrome (NBS1) gene are genetically susceptible to low doses of ionizing radiation. The rationale for this is that patients with NBS are radiation sensitive, because of defects in cellular responses to radiation induced genetic damage and haploinsufficiency at this genetic locus provides the potential for genetic susceptibility to low doses of ionizing radiation. Wild type and heterozygous NBS1 mice were irradiated and followed over their lifetime for radiation induced genomic instability, carcinogenesis and non-specific life shortening. No differences in cytogenetic damage, cancer induction or life span were observed between the hypomorphic mice indicating that genetic imbalance at the NBS1 loci does not modulate low dose radiation sensitivity

Air-Cooled Turbine Blades with Tip Cap For Improved Leading-Edge Cooling

An investigation was conducted in a modified turbojet engine to determine the cooling characteristics of the semistrut corrugated air- cooled turbine blade and to compare and evaluate a leading-edge tip cap as a means for improving the leading-edge cooling characteristics of cooled turbine blades. Temperature data were obtained from uncapped air-cooled blades (blade A), cooled blades with the leading-edge tip area capped (blade B), and blades with slanted corrugations in addition to leading-edge tip caps (blade C). All data are for rated engine speed and turbine-inlet temperature (1660 F). A comparison of temperature data from blades A and B showed a leading-edge temperature reduction of about 130 F that could be attributed to the use of tip caps. Even better leading-edge cooling was obtained with blade C. Blade C also operated with the smallest chordwise temperature gradients of the blades tested, but tip-capped blade B operated with the lowest average chordwise temperature. According to a correlation of the experimental data, all three blade types 0 could operate satisfactorily with a turbine-inlet temperature of 2000 F and a coolant flow of 3 percent of engine mass flow or less, with an average chordwise temperature limit of 1400 F. Within the range of coolant flows investigated, however, only blade C could maintain a leading-edge temperature of 1400 F for a turbine-inlet temperature of 2000 F

Insulinlike Growth Factor 1- and 2-Augmented Collagen Gel Repair of Facial Osseous Defects

BACKGROUND: Defects of the facial bone structure are common problems for the facial plastic surgeon. Native type 1 collagen gels (T1CGs) have been shown to mediate repair of facial critical-size defects in rat models. OBJECTIVE: To evaluate the efficacy of T1CG augmented with insulinlike growth factor (IGF) 1, IGF-2, and a combination of IGF-1 and IGF-2 on the repair of facial critical-size defects in a rodent model. METHODS: Twenty-four retired male breeder Sprague-Dawley rats were divided into 4 groups of 6 animals. Facial critical-size defects were created by removing the nasalis bones with a bone-cutting drill. Defects were treated with 300 pg of type 1 collagen gel (T1CG), T1CG augmented with 3 microg of IGF-1, T1CG augmented with 3 microg of IGF-2, or T1CG augmented with a combination of 3 microg of IGF-1 and 3 microg of IGF-2. After 30 days the animals were examined at necropsy with precise planimetry, histological analysis of new bone growth, and radiodensitometric analysis of bone thickness. RESULTS: Radiodensitometric measurements showed that IGF-2 augmentation resulted in greatest osseous healing, with measurements being statistically significant over those of all other groups (P\u3c or = .03). Combination IGF-1 and IGF-2 had osseous healing that was intermediate between IGF-1 augmentation and IGF-2 augmentation alone, with measurements being statistically significant over those of unaugmented gels (P CONCLUSION: Collagen gels augmented with IGF significantly enhance the osteoconductive repair of nasal critical-size defects in a rodent model, with IGF-2 showing highest efficacy

Ophidiomycosis in a Timber Rattlesnake, Crotalus horridus (Linnaeus 1758), with behavioral and thermal observations: A case report from Georgia, USA

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Morally Respectful Listening and its Epistemic Consequences

What does it mean to listen to someone respectfully, that is, insofar as they are due recognition respect? This paper addresses that question and gives the following answer: it is to listen in such a way that you are open to being surprised. A specific interpretation of this openness to surprise is then defended

Comparative Anticancer Activity in Human Tumor Xenograft Models, Preclinical Pharmacology and Toxicology for 4- Hydroperoxyifosfamide (HOOI): A Potential Neuro-Alkylating Agent for Primary and Metastatic Cancers Involving the Central Nervous System

Background: 4-Hydropeoxyifosfamide (HOOI) is a hydroperoxy derivative of ifosfamide that was developed as an anticancer agent that can penetrate the blood-brain barrier (BBB), which can be potentially useful in the management of brain tumors