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Biomedical subjects

R J Prill

Publications and source records attributed to R J Prill.

7 recordsLinked to original sources

Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction.

Several nonmammalian members of the RNase A superfamily exhibit anticancer activity that appears to correlate with resistance to the cytosolic ribonuclease inhibitor (RI). We mutated two human ribonucleases-pancreatic RNase (hRNAse) and eosinophil-derived neurotoxin (EDN)-to incorporate cysteine residues at putative sites of close contact to RI, but distant from the catalytic sites. Coupling of Cys89 of RNase and Cys87 of EDN to proteins at these sites via a thioether bond produced enzymatically active conjugates that were resistant to RI. To elicit cellular targeting as well as to block RI binding, transferrin was conjugated to a mutant human RNase, rhRNase(Gly89)-->Cys) and a mutant EDN (Thr87-->Cys). The transferrin-rhRNase(Gly89-->Cys) thioether conjugate was 5000-fold more toxic to U251 cells than recombinant wild-type hRNase. In addition, transferrin-targeted EDN exhibited tumor cell toxicities similar to those of hRNase. Thus, we endowed two human RI-sensitive RNases with greater cytotoxicity by increasing their resistance to RI. This strategy has the potential to generate a novel set of recombinant human proteins useful for targeted therapy of cancer.

Animals↗

New methods of energy efficient radon mitigation.

Two new radon mitigation techniques are introduced and their evaluation in a field study complemented by numerical model predictions is described. Based on numerical predictions, installation of a sub gravel membrane at the study site resulted in a factor of 2 reduction in indoor radon concentrations. Experimental data indicated that installation of "short-circuit" pipes extending between the subslab gravel and outdoors caused an additional factor of 2 decrease in the radon concentration. Consequently, the combination of these two passive radon mitigation features, called the membrane and short-circuit (MASC) technique, was associated with a factor of 4 reduction in indoor radon concentration. The energy-efficient active radon mitigation method, called efficient active subslab pressurization (EASP), required only 20% of the fan energy of conventional active subslab depressurization and reduced the indoor radon concentration by approximately a factor of 15, including the numerically-predicted impact of the sub-gravel membrane.

Air Pollution, Indoor↗

Effectiveness of radon control techniques in fifteen homes.

Radon control systems were installed and evaluated in fourteen homes in the Spokane River Valley/Rathdrum Prairie and in one home in Vancouver, Washington. Because of local soil conditions, subsurface ventilation (SSV) by pressurization was always more effective in these houses than SSV by depressurization in reducing indoor radon levels to below guidelines. Basement overpressurization was successfully applied in five houses with airtight basements where practical-sized fans could develop an overpressure of 1 to 3 Pascals. Crawlspace ventilation was more effective than crawlspace isolation in reducing radon entry from the crawlspace, but had to be used in conjunction with other mitigation techniques, since the houses also had basements. Indoor radon concentrations in two houses with air-to-air heat exchangers (AAHX) were reduced to levels inversely dependent on the new total ventilation rates and were lowered even further in one house where the air distribution system was modified. Sealing penetrations in the below-grade surfaces of substructures was relatively ineffective in controlling radon. Operation of the radon control systems (except for the AAHX's) made no measureable change in ventilation rates or indoor concentrations of other measured pollutants. Installation costs by treated floor area ranged from approximately $4/m2 for sealing to $28/m2 for the AAHX's. Based on the low electric rates for the region, annual operating costs for the active systems were estimated to be approximately $60 to $170.

Air Pollution, Radioactive↗

Characterizing the occurrence, sources, and variability of radon in Pacific Northwest homes.

A compilation of data from earlier studies of 172 homes in the Pacific Northwest indicated that approximately 65 percent of the 46 homes tested in the Spokane River Valley/Rathdrum Prairie region of eastern Washington/northern Idaho had heating season indoor radon (222Rn) concentrations above the U. S. EPA guideline of 148 Bq m-3 (4 pCi L-1). A subset of 35 homes was selected for additional study. The primary source of indoor radon in the Spokane River Valley/Rathdrum Prairie was pressure-driven flow of soil gas containing moderate radon concentrations (geometric mean concentration of 16,000 Bq m-3) from the highly permeable soils (geometric mean permeability of 5 x 10(-11) m2) surrounding the house substructures. Estimated soil gas entry rates ranged from 0.4 to 39 m3h-1 and 1 percent to 21 percent of total building air infiltration. Radon from other sources, including domestic water supplies and building materials was negligible. In high radon homes, winter indoor levels averaged 13 times higher than summer concentrations, while in low radon homes winter levels averaged only 2.5 times higher. Short-term variations in indoor radon were observed to be dependent upon indoor-outdoor temperature differences, wind speed, and operation of forced-air furnace fans. Forced-air furnace operation, along with leaky return ducts and plenums, and openings between the substructure and upper floors enhanced mixing of radon-laden substructure air throughout the rest of the building.

Air Pollutants↗

Evaluation of radon mitigation systems in 14 houses over a two-year period.

Fourteen single-family detached houses in Spokane, Washington, and Coeur D'Alene, Idaho, were monitored for two years after high concentrations of indoor radon had been mitigated. Each house was monitored quarterly using mailed alpha-track radon detectors deployed in each zone of the structure. To assess performance of mitigation systems during the second heating season after mitigation, radon concentrations in seven houses were monitored continuously for several weeks, mitigation systems in all houses were inspected, and selected other measurements were taken. In addition, occupants were also interviewed regarding their maintenance, operation, and subjective evaluation of the radon mitigation systems. Quarterly alpha-track measurements showed that radon levels had increased in most of the homes during many follow-up measurement periods when compared with concentrations measured immediately after mitigation. Mitigation-system performance was adversely affected by (1) accumulated outdoor debris blocking the outlets of subsurface pressurization pipes; (2) fans being turned off (e.g., because of excessive noise or vibration); (3) air-to-air heat exchanger, basement pressurization, and subsurface ventilation fans being turned off and fan speeds reduced; and (4) crawl-space vents being closed or sealed.

Air Pollution, Radioactive↗

Developing soil gas and 222Rn entry potentials for substructure surfaces and assessing 222Rn control diagnostic techniques.

Research-based procedures for characterizing the causes of elevated indoor 222Rn levels and guiding the selection of an appropriate control technique were evaluated at seven New Jersey houses. Procedures such as thorough visual inspections, blower door air leakage tests, pressure field mapping, subsurface vacuum extension tests, sampling of 222Rn concentrations throughout the substructure, and measurements of the additional depressurization caused by various appliances all were found to furnish important information to the mitigation contractor or researcher. An analysis of data from these and other diagnostic techniques performed at the seven houses also indicated: (1) regions of very high permeability existed directly adjacent to the exterior of substructure walls and floors; (2) the additional substructure depressurization caused by operation of forced-air furnaces and attic exhaust fans could exceed 1 Pascal; (3) 222Rn concentrations below basement slabs and slabs-on-grade adjoining below grade basement walls were approximately seven times higher than those within block wall cavities; and (4) air leakage areas of crawlspace and basement ceilings were quite large, ranging up to 0.15 m2. The pressure field mapping tests identified the areas surrounding the substructure that were well coupled to the indoors. Using flow, pressure difference, and 222Rn concentration data, indices of soil gas entry potential and 222Rn entry potential were developed to indicate the areas of the substructure that may have high entry rates of soil gas and 222Rn, respectively. These indices could be helpful for quantifying the relative resistance to soil gas movement of substructure surfaces and surrounding soils and for determining the placement of 222Rn control systems.

Air Pollutants↗