Fuel choice and aggregate energy demand in the residential and commercial sectors

The energy demand response of the residential and commercial sectors to fuel price changes is of increasing importance to public policy makers. In this paper, the demands for energy in both sectors are examined separately using a refined data base. For each sector, a multinomial logit formulation is utilized, along with an aggregate demand equation to determine analytically short- and long-run fuel price elasticities of demand for the major fuels consumed. It is found that increases in energy prices have a greater effect on energy demand in the commercial sector. Furthermore, in both sectors, raising electricity prices has a greater effect for conserving energy (both end-use and primary) than do equal price rises for natural gas or heating oils.     

Using yeast RNA as a probe for generation of hydroxyl radicals by earth materials

Inhalation of certain types of particulate matter can lead to lung disease. The reactivity of these particles and, in part, the pathologic responses that result are dictated by their physicochemical properties. The ability of particles to induce the generation of reactive oxygen species (ROS), especially hydroxyl radicals in vivo, is one property that has been correlated to the development of lung disease. Several minerals, such as quartz and asbestos, are known to generate hydroxyl radicals and cause lung disease, but many other minerals have never been tested. Here, we describe a technique employing yeast RNA as a probe to screen for mineral-generated hydroxyl radicals. The stability of RNA in the presence of hydrogen peroxide, ferrous iron, hydroxyl radicals, and several common minerals (quartz, albite, forsterite, fayalite, hematite, magnetite, coal, and pyrite) was examined. 3'-(p-Aminophenyl) fluorescein (APF) was used to verify mineral generation of ROS. RNA is stable in the presence of hydrogen peroxide, quartz, and albite; while it degrades in the presence of ferrous iron, hydroxyl radicals, and the other minerals. Coal and pyrite are the most reactive both in RNA degradation and hydroxyl radical generation. This noncellular technique provides a straightforward way to compare many different particles simultaneously. Those particles showing reactivity toward RNA using this method are high-priority candidates for further in vitro and possibly in vivo tests.     

Mutation of serine-46 to aspartate in the histidine-containing protein of Escherichia coli mimics the inactivation by phosphorylation of serine-46 in HPrs from gram-positive bacteria

Histidine-containing protein (HPr) is a phosphocarrier protein of the bacterial phosphoenolpyruvate:sugar phosphotransferase system. HPr is phosphorylated at the active site residue, His15, by phosphoenolpyruvate-dependent enzyme I in the first enzyme reaction in the process of phosphoryl transfer to sugar. In many Gram-positive bacterial species HPr may also be phosphorylated at Ser46 by an ATP-dependent protein kinase but not in the Gram-negative Escherichia coli and Salmonella typhimurium. One effect of the phosphorylation at Ser46 is to make HPr a poor acceptor for phosphorylation at His15. In Bacillus subtilis HPr, the mutation Ser46Asp mimics the effects of phosphorylation. A series of mutations were made at Ser46 in E. coli HPr: Ala, Arg, Asn, Asp, Glu, and Gly. The two acidic replacements mimic the effects of phosphorylation of Ser46 in HPrs from Gram-positive bacteria. In particular, when mutated to Asp46, the His 15 phosphoacceptor activity (enzyme I Km/Kcat) decreases by about 2000-fold (enzyme I Km, 4 mM HPr; Kcat, approximately 30%). The alanine and glycine mutations had near-wild-type properties, and the asparagine and arginine mutations yielded small changes to the Km values. The crystallographic tertiary structure of Ser46Asp HPr has been determined at 1.5 A resolution, and several changes have been observed which appear to be the effect of the mutation. There is a tightening of helix B, which is demonstrated by a consistent shortening of hydrogen bond lengths throughout the helix as compared to the wild-type structure. There is a repositioning of the Gly54 residue to adopt a 3(10) helical pattern which is not present in the wild-type HPr. In addition, the higher resolution of the mutant structure allows for a more definitive placement of the carbonyl of Pro11. The consequence of this change is that there is no torsion angle strain at residue 16. This result suggests that there is no active site torsion angle strain in wild-type E. coli HPr. The lack of substantial change at the active center of E. coli HPr Ser46Asp HPr suggests that the effect of the Ser46 phosphorylation in HPrs from Gram-positive bacteria is due to an electrostatic interference with enzyme I binding.     

Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes

In children and adolescents with type 1 diabetes, we have reported an association between duration of puberty and the prevalence of nephromegaly and microalbuminuria (MA), which are early markers of diabetic nephropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationship of these hormonal factors to kidney volume (KV) and MA in 155 subjects (78 males, age 13.2 +/- 3.5 years [mean +/- SD]) with similar diabetes duration (6.83 +/- 1.6 years) but varying pubertal experience (0-10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, and NaLi countertransport, and urinary albumin, urinary GH, and urinary IGF-I from three 24-h collections were measured. Multiple regression analysis showed that BSA (P < 0.0001) and urinary IGF-I (P = 0.001) were significantly associated with KV. MA subjects (albumin excretion rate 15-200 microg/min) had higher urinary IGF-I (P = 0.005) and urinary GH (P = 0.05) compared with normoalbuminuric subjects. Only 9% of the variance in urinary IGF-I could be attributed to plasma IGF-I (r = 0.30, P < 0.0001). Testosterone and prorenin were not associated with MA, but they were associated with KV in univariate analyses. The strong association of urinary IGF-I with KV, a marker for glomerular hypertrophy, and of both urinary IGF-I and urinary GH with MA suggests a role for these growth factors in the development of human diabetic nephropathy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis of early diabetic nephropathy.     

Demonstration of protein-protein interaction specificity by NMR chemical shift mapping

Chemical shift mapping is becoming a popular method for studying protein-protein interactions in solution. The technique is used to identify putative sites of interaction on a protein surface by detecting chemical shift perturbations in simple (1H, 15N)-HSQC NMR spectra of a uniformly labeled protein as a function of added (unlabeled) target protein. The high concentrations required for these experiments raise questions concerning the possibility for non-specific interactions being detected, thereby compromising the information obtained. We demonstrate here that the simple chemical shift mapping approach faithfully reproduces the known functional specificities among pairs of closely related proteins from the phosphoenolpyruvate:sugar phosphotransferase systems of Escherichia coli and Bacillus subtilis.     

A novel cyclic adenosine monophosphate analog induces hypercalcemia via production of 1,25-dihydroxyvitamin D in patients with solid tumors

The treatment of cancer patients with conventional chemotherapy is sometimes associated with severe systemic toxicity and only a minimal survival benefit. Because of this, new less toxic and more efficacious treatments have been sought. 8-Chloro-cAMP (8-Cl-cAMP) is one of a new generation of anticancer drugs that act at the level of signal transduction. In preclinical models, 8-Cl-cAMP modulates protein kinase A (PKA) leading to growth inhibition and increased differentiation of cancer cells. 8-Cl-cAMP was given to 16 patients with advanced cancer as an infusion via an indwelling subclavian venous catheter. We showed that 8-Cl-cAMP had a parathyroid hormone-like effect leading to increased synthesis of renal 1,25-dihydroxyvitamin D [up to 14 times the baseline value, median 3.6 times; P = 0.00001 (Student's paired t test)]. This produced the dose-limiting toxicity of reversible hypercalcemia that could not be controlled by the administration of either pamidronate or dexamethasone. The treatment was otherwise well tolerated, and other cAMP-dependent pathways (cortisol and TSH) were not affected, emphasizing the marked differences between organs in their sensitivity to this cAMP analog. Our results have shown that 8-Cl-cAMP is biologically active, and it is feasible that if the hypercalcemia can be controlled, then this drug may have a role as a single agent, or as a short infusion between cycles of chemotherapy.     

Metal-catalyzed oxidation in the presence of water in foods

Methyl linoleate was oxidized in model systems consisting of either cellulose or casein with which the lipid was dispersed with water containing cobalt salts. The dispersion was extruded into Warburg flasks, frozen and freeze-dried at 100 μ Hg and with platen temperatures of 80 F. The samples were then humidified over saturated salt solutions to give moisture contents from less than 1 g H₂O/100 g solids up to 30 g H₂O/100 g solids. The higher moisture contents were obtained by addition of glycerol to the model system during preparation and humidification at 60–75% RH. Chelating agents including EDTA and citric acid in concentrations of 1 to 10 moles per mole of cobalt ion were used in some experiments. Oxidation was followed manometrically and by peroxide analysis. At low water contents, water acts as an antioxidant through hydration of metallic catalysts. As the moisture content increases, water promotes oxidation through its solvent activity. In the region of capillary condensation, antioxidant effect of metal hydration is overshadowed by the prooxidant effect of metal solubilization. The water soluble chelating agents such as EDTA act on metals in aqueous solution and their activity is promoted by increased moisture content. One of 28 papers presented at the Symposium, “Metal-Catalyzed Lipid Oxidation,” ISF-AOCS World Congress, Chicago, September 1970.