Applying the realized probability of dying to cancer survival

Age comparisons of survival in cancer cohorts generally utilize relative survival rates, which are based on indicators of the probability of survival for a given number of years after diagnosis. Cancer relative survival rates for the same number of years tend to decline as age at diagnosis increases. However, the same number of years of survival reflects higher relative longevity at older ages than at younger ages. The realized probability of dying (RPD) is a survival measure that expresses individual survival time after diagnosis relative to the survival distribution of an age-, race-, and sex-specific reference population, in effect weighing individual survival time more heavily as age at diagnosis increases. The purpose of this study was to apply the RPD as a survival measure in cancer epidemiology. Two cohorts of cancer patients, white males with prostate cancer and white females with breast cancer, aged 55 years and over at diagnosis, were followed for 15 years. Although older subjects survived less time after diagnosis than younger subjects, they achieved more favorable RPD values. We present survival analysis methods for analyzing the RPD in this population, an approach not previously used with this measure. The implications for use of the RPD in cancer epidemiology are discussed.     

Protein thermostability above 100 degreesC: a key role for ionic interactions

The discovery of hyperthermophilic microorganisms and the analysis of hyperthermostable enzymes has established the fact that multisubunit enzymes can survive for prolonged periods at temperatures above 100 degreesC. We have carried out homology-based modeling and direct structure comparison on the hexameric glutamate dehydrogenases from the hyperthermophiles Pyrococcus furiosus and Thermococcus litoralis whose optimal growth temperatures are 100 degreesC and 88 degreesC, respectively, to determine key stabilizing features. These enzymes, which are 87% homologous, differ 16-fold in thermal stability at 104 degreesC. We observed that an intersubunit ion-pair network was substantially reduced in the less stable enzyme from T. litoralis, and two residues were then altered to restore these interactions. The single mutations both had adverse effects on the thermostability of the protein. However, with both mutations in place, we observed a fourfold improvement of stability at 104 degreesC over the wild-type enzyme. The catalytic properties of the enzymes were unaffected by the mutations. These results suggest that extensive ion-pair networks may provide a general strategy for manipulating enzyme thermostability of multisubunit enzymes. However, this study emphasizes the importance of the exact local environment of a residue in determining its effects on stability.     

EFFICIENT NEW SYNTHESES OF POLYCYCLIC AROMATIC HYDROCARBON ORTHO-QUINONES AND THEIR 2′-DEOXYRIBONUCLEOSIDE ADDUCTS

Three mechanisms have been proposed to explain the carcinogenic activities of polycyclic aromatic hydrocarbons (PAHs). On the basis of the nature of the active metabolites involved, they may be termed: the diol epoxide mechanism, the quinone mechanism, and the radical-cation mechanism. In connection with studies to evaluate the relative importance of these pathways, we required practical methods for the syntheses of the active PAH metabolites involved. We now report efficient new synthesis of the o-quinones of benzo[a]pyrene (BPQ), 7,12-dimethylbenz[a]anthracene (DMBAQ), and benz[a]anthracene (BAQ). These quinones are convenient synthetic precursors of the related o-catechols, trans-dihydrodiols, and diol epoxides, as well as the stable adducts of the o-quinones with 2-deoxyadenosine and 2′-deoxyguanosine.     

Microwave-Hydrothermal Synthesis of Nanophase Ferrites

This paper reports the synthesis of technologically important ferrites such as ZnFe₂O₄, NiFe₂O₄, MnFe₂O₄, and CoFe₂O₄ by using novel microwave-hydrothermal processing. Nanophase ferrites with high surface areas, in the range of 72-247m²/g, have been synthesized in a matter of a few minutes at temperatures as low as 164°C. The rapid synthesis of nanophase ferrites via an acceleration of reaction rates under microwave-hydrothermal conditions is expected to lead to energy savings.     

Sol–Gel Synthesis of Strontium Pyroniobate and Calcium Pyroniobate

Strontium and calcium pyroniobates were prepared by a sol–gel process, using strontium/calcium metal and niobium ethoxide as precursors. The formation of Sr₂Nb₂O₇ occurred at 750°C via an intermediate perovskite phase of composition close to Sr_0.82NbO₃. The crystallization of Ca₂Nb₂O₇ occurred at 600°C directly without any intermediate phases. Sintered Sr₂Nb₂O₇ and Ca₂Nb₂O₇ pellets showed a preferred grain orientation. Microstructural studies revealed an increase in grain growth and associated orientation with sintering temperature.     

Anionic Clays as Potential Slow-Release Fertilizers: Nitrate Ion Exchange

Several nitrate containing anionic clays were synthesized at different temperatures and the kinetics of NO₃ ^– release were determined to test their suitability as slow-release N fertilizers. A sample (Mg:Al = 2:1) synthesized at 60°C with smaller particle size released 75, 86 and 100% of its NO₃ ^– in 1, 3 and 7 days, respectively when equilibrated with a simulated soil solution. On the other hand, the 175°C/2 hrs sample with larger particle size released 65, 77 and 84% of its nitrate in 1, 3 and 7 days, respectively. Another anionic clay (synthesized at 175°C/24 hrs) of higher charge density (Mg:Al = 2:1) containing NO₃ ^– was equilibrated with a 0.012 N NaCl or Na₂CO₃ to test the role of different anions in releasing the NO₃ ^– anion from the interlayers. The results showed that Cl^– released more NO₃ ^– than did CO₃ ^2– from this anionic clay after all the treatment times probably as a result of the CO₃ ^2– anion blocking the release of NO₃ ^– from the interior of the crystals. When a lower charge density (Mg:Al = 3:1) sample (synthesized at 175°C/48 hrs) was equilibrated with 0.02N solution of anions the release of nitrate was as follows: Cl^– < F^– < SO₄ ⁼ CO₃ ^2–. These results suggest that the divalent SO₄ ⁼ and CO₃ ^2– anions are more effective in the release of NO₃ ^– from this lower charge density anionic clay. Time-resolved structural analysis of NO₃ ^– exchange with CO₃ ^2– in the above anionic clay using synchrotron x-ray diffraction showed that ion exchange is rapid because of small crystal size and lower charge density. Thus the release of NO₃ ^– from anionic clays is an interplay among the type of anions present in soil solution, their concentration, pH of soil solution, the charge density and crystal size of anionic clay etc.     

Strombus gigas inspired biomimetic ceramic composites via SHELL—Sequential Hierarchical Engineered Layer Lamination

Nature has produced remarkable structural designs based on many millennia of evolutionary optimization. Biological materials, such as the sea-shell, possess unique microstructures and properties that provide inspiration for the next generation of structural ceramics. Strombus gigas (Queen conch) shells contain a hierarchical, multilayered, crossed-lamellar architecture built with two natural materials (calcium carbonate and protein) with at least three identifiable scales (or orders) of structure. Drawing on Strombus gigas for inspiration, we have developed a new process to realize such complex micro-architectures in macroscopic form. SHELL (Sequential Hierarchical Engineered Layer Lamination) is a thermoplastic forming process that is capable of producing the third order structural complexity over the micron-millimeter length scales. We have fabricated silicon nitride—boron nitride ceramics via SHELL that are endowed with excellent damage tolerance, exhibit graceful failure, and exhibit toughening mechanisms similar to those observed in Strombus gigas.     

Uptake of cadmium,copper, and lead by microporous synthetic Na-birnessite

Removal of cadmium, copper and lead with microporous synthetic Na-birnessite (sodium-birnessite) was investigated by carrying out batch-type sorption experiments with 2 days of equilibration at room temperature. The sorption isotherms indicated that synthetic Na-birnessite showed high affinity for all three heavy metal cations. The Na-birnessite was able to take up Cd, Cu and Pb up to approximately 140, 106 and 60%, respectively of its theoretical cation exchange capacity. The above higher uptakes of Cd and Cu than the theoretical cation exchange capacity of birnessite were probably caused by exchange of not only Cd²⁺ but also CdCl⁺ species with Na⁺ and by exchange of not only Cu²⁺ but also CuCl⁺ species with Na⁺. Some exchange of CdCl⁺ and CuCl⁺ species as well as some pH-dependent specific adsorption of the Cd and Cu cations resulted in higher than theoretical uptakes. The XRD patterns after sorption of Cd with Na-birnessite showed an increase in the d(001)-spacing from 7.144 to 7.244 Å with high Cd²⁺ concentration, which indicated that interlayer Na⁺ ions were replaced by Cd²⁺ ions. After the sorption reactions with high Cu concentrations, the XRD patterns showed that the main d(001)-spacing of the birnessite slightly increased from 7.144 to ~7.179 Å. In the case of Pb sorption, the d(001)-spacing slightly decreased to 7.133 Å from 7.144 Å of the as synthesized Na-birnessite. These results suggest that removal of heavy metal cations by Na-birnessite is likely due to both ion exchange and chemisorption, the latter due to surface complexation at the edges and outer planar surfaces of Na-birnessite. Based on these results, Na-birnessite is proposed as a potential candidate material to remove heavy metal cations from groundwater as well as industrial wastewater.