Nudge to Nobesity I: Minor Changes in Accessibility Decrease Food Intake

Very small but cumulated decreases in food intake may be sufficient to erase obesity over a period of years. We examine the effect of slight changes in the accessibility of different foods in a pay-by-weight-of-food salad bar in a cafeteria serving adults for the lunch period. Making a food slightly more difficult to reach (by varying its proximity by about 10 inches) or changing the serving utensil (spoon or tongs) modestly but reliably reduces intake, in the range of 8-16%. Given this effect, it is possible that making calorie-dense foods less accessible and low-calorie foods more accessible over an extended period of time would result in significant weight loss

Diffractive triangulation of radiative point sources

We describe a general method to determine the location of a point source of waves relative to a twodimensional single-crystalline active pixel detector. Based on the inherent structural sensitivity of crystalline sensor materials, characteristic detector diffraction patterns can be used to triangulate the location of a wave emitter. The principle described here can be applied to various types of waves, provided that the detector elements are suitably structured. As a prototypical practical application of the general detection principle, a digital hybrid pixel detector is used to localize a source of electrons for Kikuchi diffraction pattern measurements in the scanning electron microscope. This approach provides a promising alternative method to calibrate Kikuchi patterns for accurate measurements of microstructural crystal orientations, strains, and phase distributions

Determination of the Tissue Distribution and Excretion by Accelerator Mass Spectrometry of the Nonadecapeptide 14C-Moli1901 in Beagle dogs after Intratracheal Instillation

Administration of {sup 14}C-Moli1901 (duramycin, 2622U90), a 19 amino acid polycyclic peptide by intratracheal instillation (approximately 100 {micro}g) into the left cranial lobe of the lung of beagle dogs resulted in retention of 64% of the dose in the left cranial lobe for up to 28 days. In this study, we used accelerator mass spectrometry (AMS) to quantify Moli901 following administration of only 0.045 {micro}Ci of {sup 14}C-Moli901 per dog. Limits of quantitation of AMS were 0.03 (urine) to 0.3 (feces) ng equiv. Moli1901/g. Whole blood and plasma concentrations of {sup 14}C were <5ng/ml at all times after the dose. Concentrations of {sup 14}C in whole blood and plasma declined over the first day after the dose and rose thereafter, with the rise in plasma concentrations lagging behind those in whole blood. During the first 3 days after the dose, plasma accounted for the majority of {sup 14}C in whole blood, but after that time, plasma accounted for only 25-30% of the {sup 14}C in whole blood. Tissue (left and right caudal lung lobe, liver, kidney, spleen, brain) and bile concentrations were low, always less than 0.25% the concentrations found in the left cranial lung lobe. Approximately 13% of the dose was eliminated in urine and feces in 28 days, with fecal elimination accounting for about 10% of the dose. The data presented here are consistent with that obtained in other species. Moli1901 is slowly absorbed and excreted from the lung, and it does not accumulate in other tissues. Moli1901 is currently in the clinic and has proven to be safe in single dose studies in human volunteers and cystic fibrosis patients by the inhalation route. No information on the disposition of the compound in humans is available. This study in dogs demonstrates the feasibility of obtaining that information using {sup 14}C-Moli1901 and AMS

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN

Urinary Metabolites of the Dietary Carcinogen PhIP are Predictive of Colon DNA Adducts After a Low Dose Exposure in Humans

Epidemiologic evidence indicates that exposure to heterocyclic amines (HAs) in the diet is an important risk factor for the development of colon cancer. Well-done cooked meats contain significant levels of HAs which have been shown to cause cancer in laboratory animals. To better understand the mechanisms of HA bioactivation in humans, the most mass abundant HA, 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), was used to assess the relationship between PhIP metabolism and DNA adduct formation. Ten human volunteers were administered a dietary relevant dose of [{sup 14}C]PhIP 48-72 h prior to surgery to remove colon tumors. Urine was collected for 24 h after dosing for metabolite analysis, and DNA was extracted from colon tissue and analyzed by accelerator mass spectrometry for DNA adducts. All ten subjects were phenotyped for CYP1A2, NAT2, and SULT1A1 enzyme activity. Twelve PhIP metabolites were detected in the urine samples. The most abundant metabolite in all volunteers was N-hydroxy-PhIP-N{sup 2}-glucuronide. Metabolite levels varied significantly between the volunteers. Interindividual differences in colon DNA adducts levels were observed between each individual. The data showed that individuals with a rapid CYP1A2 phenotype and high levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide, had the lowest level of colon PhIP-DNA adducts. This suggests that glucuronidation plays a significant role in detoxifying N-hydroxy-PhIP. The levels of urinary N-hydroxy-PhIP-N{sup 2}-glucuronide were negatively correlated to colon DNA adduct levels. Although it is difficult to make definite conclusions from a small data set, the results from this pilot study have encouraged further investigations using a much larger study group

A compact tritium AMS system

Tritium ({sup 3}H) is a radioisotope that is extensively utilized in biological and environmental research. For biological research, {sup 3}H is generally quantified by liquid scintillation counting requiring gram-sized samples and counting times of several hours. For environmental research, {sup 3}H is usually quantified by {sup 3}He in-growth which requires gram-sized samples and in-growth times of several months. In contrast, provisional studies at LLNL's Center for Accelerator Mass Spectrometry have demonstrated that Accelerator Mass Spectrometry (AMS) can be used to quantify {sup 3}H in milligram-sized biological samples with a 100 to 1000-fold improvement in detection limits when compared to scintillation counting. This increased sensitivity is expected to have great impact in the biological and environmental research community. However in order to make the {sup 3}H AMS technique more broadly accessible, smaller, simpler, and less expensive AMS instrumentation must be developed. To meet this need, a compact, relatively low cost prototype {sup 3}H AMS system has been designed and built based on a LLNL ion source/sample changer and an AccSys Technology, Inc. Radio Frequency Quadrupole (RFQ) linac. With the prototype system, {sup 3}/{sup 1}H ratios ranging from 1 x 10{sup -10} to 1 x 10{sup -13} have to be measured from milligram sized samples. With improvements in system operation and sample preparation methodology, the sensitivity limit of the system is expected to increase to approximately 1 x 10{sup -15}

A Novel 14C-Postlabeling Assay Using Accelerator Mass Spectrometry For the Detection of O6-Methyldeoxyguanosine Adducts

Accelerator mass spectrometry (AMS) is currently one of the most sensitive methods available for the trace detection of DNA adducts and is particularly valuable for measuring adducts in humans or animal models. However, the standard approach requires administration of a radiolabeled compound. As an alternative, we have developed a preliminary {sup 14}C-postlabeling assay for detection of the highly mutagenic O{sup 6}-MedG, by AMS. Procedures were developed for derivatizing O{sup 6}-MedG using unlabeled acetic anhydride. Using conventional LC-MS analysis, the limit of detection for the major product, triacetylated O{sup 6}-MedG, was 10 fmoles. On reaction with {sup 14}C-acetic anhydride, using a specially designed enclosed system, the predominant product was {sup 14}C-di-acetyl O{sup 6}-MedG. This change in reaction profile was due to a modification of the reaction procedure, introduced as a necessary safety precaution. The limit of detection for {sup 14}C-diacetyl O{sup 6}-MedG by AMS was determined as 79 attomoles, {approx}18,000 fold lower than that achievable by LSC. Although the assay has so far only been carried out with labeled standards, the degree of sensitivity obtained illustrates the potential of this assay for measuring O{sup 6}-MedG levels in humans

Applications and perspectives of ultrasonic multi-gas analysis with simultaneous flowmetry

We have developed ultrasonic instrumentation for simultaneous flow and composition measurement in a variety of gas mixtures. Flow and composition are respectively derived from measurements of the difference and average of sound transit times in opposite directions in a flowing process gas. We have developed a sound velocity-based algorithm to compensate for the effects of additional gases, allowing the concentrations of a pair of gases of primary interest to be acoustically measured on top of a varying baseline from ‘third party’ gases whose concentrations in the multi-gas mixture are measured by other means. Several instruments are used in the CERN ATLAS experiment. Three monitor C3F8, (R218), and CO2 coolant leaks into N2-purged environmental envelopes. Precision in molar concentration of better than 2 × 10−5 is routinely seen in mixtures of C3F8 in N2 in the presence of varying known concentrations of CO2. Further instruments monitor air ingress and C3F8 vapor flow (at high mass flows around 1.1 kg s−1) in the 60 kW thermosiphon C3F8 evaporative cooling recirculator. This instrumentation and analysis technique, targeting binary pairs of gases of interest in multi-gas mixtures, is promising for mixtures of anesthetic gases, particularly in the developing area of xenon anesthesia.</jats:p