Observation of two-neutrino double-beta decay in 136Xe with the EXO-200 detector.

We report the observation of two-neutrino double-beta decay in (136)Xe with T(1/2) = 2.11 ± 0.04(stat) ± 0.21(syst) × 10(21) yr. This second-order process, predicted by the standard model, has been observed for several nuclei but not for (136)Xe. The observed decay rate provides new input to matrix element calculations and to the search for the more interesting neutrinoless double-beta decay, the most sensitive probe for the existence of Majorana particles and the measurement of the neutrino mass scale.

A magnetically driven piston pump for ultra-clean applications.

A magnetically driven piston pump for xenon gas recirculation is presented. The pump is designed to satisfy extreme purity and containment requirements, as is appropriate for the recirculation of isotopically enriched xenon through the purification system and large liquid xenon time projection chamber of EXO-200. The pump, using sprung polymer gaskets, is capable of pumping more than 16 standard liters per minute of xenon gas with 750 Torr differential pressure.

Observation of plasma focusing of a 28.5 GeV positron beam.

The observation of plasma focusing of a 28.5 GeV positron beam is reported. The plasma was formed by ionizing a nitrogen jet only 3 mm thick. Simultaneous focusing in both transverse dimensions was observed with effective focusing strengths of order tesla per micron. The minimum area of the beam spot was reduced by a factor of 2.0+/-0.3 by the plasma. The longitudinal beam envelope was measured and compared with numerical calculations.

The achievements of William Crawford Gorgas.

From an obscure frontier surgeon George Crawford Gorgas became internationally acclaimed as a preventive medicine genius. By his initiative in translating the known scientific facts made possible during the blossoming of bacteriology, he performed service not only in the United States but in Cuba, Central and South America, South Africa, and Eastern Europe. He fought for 10 years successfully against yellow fever, malaria, and other diseases during the construction of the Panama Canal, and continued triumphs against disease in other world situations. This is a rather concise account emphasizing his continued devotion and dedication as a humanitarian. He fashioned the Army Medical Department into an efficient machine as Surgeon General, and following his amazing military career of over 38 years, made further contributions in preventive medicine with the Rockefeller Foundation.

Leonard Wood: surgeon, soldier, administrator.

Leonard Wood's (1860-1927) 42 years of distinguished service to the United States are covered herein. Wood received the Congressional Medal of Honor for the capture of the Apaches. He was commander of the famous "Rough Riders," and was distinguished for his Cuban labors as Military Governor. As Army Chief of Staff, he and Theodore Roosevelt pursued the problems of military preparedness for America's involvement in World War I. After World War I, Wood quelled disruptive situations caused by growing industrial problems. He became a supporter of veterans' rights, enrolling 27,000 veterans in college and providing them with the necessary education that would help solve the problems of four million veterans. After being operated on successfully for a brain tumor by Harvey Cushing in 1910, he suffered a recurrence while serving his second tour as the Philippines' Military Governor. Returning home, he died in 1927 during the second surgery.

Dietary caffeine reduces the genotoxicity of MeIQx in the host-mediated assay in mice.

The influence of dietary caffeine on the genotoxicity of the cooked food mutagen 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) was evaluated using the host-mediated assay in mice. For four weeks, BALB/c mice were fed a purified diet with or without caffeine (0.01% wt/wt in the diet). In the host-mediated assay, Salmonella typhimurium TA98 was given intravenously immediately before an oral dose of MeIQx (1.5 mg/kg body wt). After one hour, the mice were killed, the Salmonellae were recovered from the liver, and the number of mutants (his+ revertants) were determined. Consumption of caffeine led to a 47% reduction in the number of mutants induced by MeIQx (p < 0.001). Subsequent in vitro experiments using S. typhimurium TA98 revealed that the capacity of hepatic S-9 fractions from the caffeine-fed mice to covert MeIQx to an active mutagen was reduced by approximately 35%. This effect was not attributable to caffeine in the S-9 preparation. These data suggest that consumption of caffeine modifies MeIQx mutagenicity by altering the spectrum of enzymes involved in its activation.

Effect of hepatic cytochrome P-450 inducing agents on mutagen activity in the host-mediated assay.

Intraperitoneal treatment of female BALB/c mice with either phenobarbitone or beta-naphthoflavone led to the induction of various hepatic enzymes associated with xenobiotic metabolism and to increased abilities of hepatic S9 fractions to convert the dietary carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) to an active bacterial mutagen. In the case of another carcinogen, aflatoxin B1 an increase in in vitro hepatic activation was seen only in mice treated with phenobarbitone. In contrast, pretreatment with either phenobarbitone or beta-naphthoflavone reduced the in vivo activity of both aflatoxin B1 and MeIQx in the host mediated bacterial mutation assay. These data indicate that, for some carcinogens at least, the host-mediated assay may be used to predict the carcinogenic consequences of hepatic enzyme induction.

Development changes to gut microflora metabolism in mice.

Developmental changes in the activities of bacterial nitrate reductase, nitroreductase and beta-glucuronidase and their response to fermentable dietary fibre, were investigated in caecal contents from suckling mice (2-week-old) and in mice aged 4-24 weeks fed either a purified fibre-free diet or that diet supplemented with 5% (w/w) pectin. There was no apparent age-related trend common to the three enzymes studied. Nitrate reductase activity in the mice fed the fibre-free diet did not markedly alter with age. Pectin administration, however, was associated with a significant increase in nitrate reductase activity, particularly in 4-week-old mice. Nitroreductase activity exhibited an overall upward trend in mice from 2 to 12 weeks and thereafter decreased. Caecal beta-glucuronidase activity in mice increased sharply between 2 weeks and 4 weeks of age, thereafter not changing significantly until the 24th week. Pectin feeding had no consistent effect on activities either of nitroreductase or beta-glucuronidase. The changes in enzyme activities with age were not related to the concentration of bacteria in the caecum, which was highest in the 2-week-old mice. We conclude that the weaning is a period in which marked changes in caecal bacterial enzyme activities can occur.

Dietary fat modifies the in vivo mutagenicity of some food-borne carcinogens.

Female BALB/c mice were fed a low fat diet (1% safflower oil, by weight) or one supplemented with 25% (by weight) of beef fat or olive oil. The abilities of these diets to modify the in vitro and in vivo hepatic conversion of the dietary carcinogens aflatoxin B1, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to bacterial mutagens was evaluated. Dietary olive oil appeared to increase the metabolism of both MeIQ and Trp-P-2 to bacterial mutagens in vivo using the intrasanguineous host-mediated assay. Feeding mice either of the high-fat diets increased hepatic conversion of these two compounds to bacterial mutagens in vitro. Dietary fat had no effect on the metabolism of aflatoxin B1. Subsequent experiments suggested that the in vivo effects of dietary olive oil on MeIQ and Trp-P-2 mutagenesis were due to the induction of hepatic enzyme activities rather than to increased rates of uptake of the carcinogen from the gut-lumen.

Roles of dietary fat and fibre in the disposition and metabolism of carcinogens associated with foods.

The abilities of dietary fibre (wheat bran) or fat (olive oil) to modify the genotoxicity of radiolabelled MeIQ were evaluated in mice using in vivo and in vitro bacterial mutation assays. Bran reduced genotoxicity by restricting uptake of MeIQ from the gut lumen. In contrast, feeding mice a high fat diet led to increased hepatic conversion of MeIQ to an active genotoxin.

Continuous culture of human faecal bacteria as an in vitro model for the colonic microflora.

To investigate the role of human gut bacteria in the metabolism of potentially reactive compounds we have developed an in vitro model of the human faecal microflora using a two-stage continuous culture inoculated with human faeces. The cultured bacterial population retained many of the bacteriological and biochemical characteristics of the flora present in the faecal sample used for inoculation. Obligate anaerobes were the predominant bacterial types found in vitro and included Bacteroides ovatus and Bifidobacterium adolescentis. A comparison of in vivo (faeces) and in vitro bacterial enzyme activities that are known to be involved in the biotransformation of potentially toxic compounds found the activities of hydrolytic enzymes to be similar but reductive enzymes exhibited higher activities in the continuous culture model. When substrates of the enzymes were added to the culture vessel, the enzymes were induced to varying extents. The short-chain fatty acid profile in the culture was almost identical to that in faeces with the order of abundance being the same in two systems. These results indicate that the continuous culture of faecal bacteria can provide a suitable model for studying bacterial interactions and biotransformation of the human colonic flora.

Developmental changes in hepatic activation of dietary mutagens by mice.

Metabolic activation of the food mutagens 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and aflatoxin B1 by female BALB/c mice of different ages (2-24 weeks) was investigated in vivo and in vitro using Salmonella typhimurium TA98 as the indicator organism. The in vivo activation of the three mutagens was investigated in 4- and 24-week-old mice using an intrasanguineous host-mediated assay. All three compounds showed reduced levels of activation with the older hosts. Hepatic S9 fractions from female mice of varying ages between 2 and 24 weeks were used in the in vitro mutagenicity assay. To achieve optimal activation to bacterial mutagens, 5% S9 was required for aflatoxin B1 and Trp-P-2 and 10% S9 for MeIQ; age of donor generally had little effect on the profile of these protein activation curves. Under these optimal conditions MeIQ and Trp-P-2 both exhibited, as before, age-dependent decreases in activation over a wide range of mutagen concentrations, however the in vitro activation of aflatoxin showed no consistent change with age. Spectrophotometric measurements of S9 cytochrome P-450 content showed a decrease in concentration with increasing age, but this was not sufficient to account for changes observed in hepatic mutagen activation. However, changes in the activities of certain cytochrome P-450 isoenzymes and cytosolic GSH-transferases, which in turn result in changes in the activation and detoxification capacity of the liver, would appear to explain age-dependent changes in the activity of mutagens in vivo.