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1
Cobelli, C., G. Toffolo, D. M. Bier, and R. Nosadini. "Models to interpret kinetic data in stable isotope tracer studies." American Journal of Physiology-Endocrinology and Metabolism 253, no. 5 (November 1, 1987): E551—E564. http://dx.doi.org/10.1152/ajpendo.1987.253.5.e551.
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In contrast to "weightless" radioactive tracers, stable isotope tracers have nonnegligible mass and are naturally present in the system, and the measured variable is a ratio of two isotopic species. These features do not allow stable isotopic tracer data analysis using straightforward analogy with radioactive tracer approaches, even though this practice is common. In this study, we present kinetic variables, models, and measurements for the analysis and interpretation of stable isotope tracer data. Assumptions and mathematical techniques for modeling the data when perturbation is both nonnegligible and negligible are discussed. Emphasis is placed on the rich information content of the dynamic portion of a stable isotope tracer curve and on the role of compartmental and noncompartmental modeling approaches for its interpretation. A presumed and commonly used analogy between the radioactive specific activity and stable isotopic enrichment is shown to be incorrect. We show that the proper analogue of specific activity is the tracer-to-tracee molar ratio. This variable is not a directly measurable one, but a formula is derived that allows its computation from the data. A method for reconstructing the time course in blood of the concentration component due to endogenous synthesis is presented. This allows measurement of the extent of the perturbation in the case where a nonweightless tracer is used. Special attention is given to data analysis originating from a multiple tracer experiment, a configuration necessary for studying more complex systems, e.g., the kinetics of interacting substrates.
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Rosenblatt, J., and R. R. Wolfe. "Calculation of substrate flux using stable isotopes." American Journal of Physiology-Endocrinology and Metabolism 254, no. 4 (April 1, 1988): E526—E531. http://dx.doi.org/10.1152/ajpendo.1988.254.4.e526.
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The use of stable isotope tracers to calculate substrate kinetics in humans is favored over the use of radioactive isotopes because of their greater safety and versatility. However, potential complications not met when dealing with radioactive tracers are caused by 1) the natural occurrence of the stable isotope used as a tracer and 2) the necessity to administer the tracer in an amount that cannot be treated as "massless." We therefore found it desirable to derive a theoretically valid equation for calculating the rate of appearance, Ra, of a substrate under steady-state conditions using a stable isotope tracer. This theoretically valid equation yields results that differ from those of the equations conventionally used to calculate (endogenous) Ra in steady state. Quantitative determination of the error in one of these equations revealed that for tracers commonly used in metabolic studies the error is negligible, whereas the error made in the other equation is likely to be quite high in commonly encountered situations. Finally, to allow for proper use of different definitions of isotopic enrichment that have arisen from practical considerations, we use the results derived above to determine valid equations for Ra appropriate to the two prevalent definitions.
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Patterson, Kristine Y., and Claude Veillon. "Stable Isotopes of Minerals as Metabolic Tracers in Human Nutrition Research." Experimental Biology and Medicine 226, no. 4 (April 2001): 271–82. http://dx.doi.org/10.1177/153537020122600403.
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Enriched stable isotopes used as tracers have proven to be valuable in studies of the absorption and metabolism of minerals. Unlike radioisotopes, they can be used in high-risk population groups such as infants, children, and pregnant or lactating women. Estimates of mineral absorption can be made from the oral administration of a single tracer or from two tracers, one given orally and the other intravenously (IV). It is possible to determine the metabolism of the mineral with modeling based on the amount of the tracer or tracers in different biological samples. One of the key decisions in studies of this type is determining which enriched isotope and what amount to use. An example is given of calculations to estimate and compare the amounts of tracers needed for an absorption study. Methods for calculating the amounts of tracer in oral and IV doses are presented, and limits of detection and quantitation are discussed in terms of percent of enrichment and related to isotope ratio measurement precision. A general review of the use of mass spectrometric instruments for quantifying various stable isotopes is given.
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Argoud, G. M., D. S. Schade, and R. P. Eaton. "Underestimation of hepatic glucose production by radioactive and stable tracers." American Journal of Physiology-Endocrinology and Metabolism 252, no. 5 (May 1, 1987): E606—E615. http://dx.doi.org/10.1152/ajpendo.1987.252.5.e606.
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Although negative hepatic glucose production rates are physiologically impossible, they have been observed when hepatic glucose production is measured with the tracer-dilution technique during the hyperinsulinemic, euglycemic glucose clamp. Because hepatic glucose production is determined from the difference between tracer-derived glucose disposal and the known exogenous glucose infusion rate, the negative values for hepatic glucose production must result from an underestimation of glucose disposal by the tracer technique. In the current investigation, tracer-derived glucose disposal was measured in 25 subjects undergoing hyperinsulinemic, euglycemic clamps. Glucose disposal was measured with both radioactive and stable isotopes that utilize different methodologies, to determine whether discriminant metabolism of the isotopes versus methodological error leads to underestimation of tracer-derived glucose disposal. Both the radioactive and stable methodologies underestimated the exogenous glucose infusion rate during the hyperinsulinemic euglycemic clamp by 27 and 17%, respectively. Mean hepatic glucose production was -2.1 +/- 0.2 and -1.3 +/- 0.2 mg X kg-1 X min-1 as determined by the radioactive and stable isotope methodologies, respectively. Methodological error was an unlikely cause of this underestimation because it occurred with two different methodologies. The most likely explanation for underestimated rates of glucose disposal determined by the two types of isotope methodologies is discrepant metabolism of glucose tracers in comparison with unlabeled glucose.
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Jeong, Heesoo, Yan Yu, Henrik J. Johansson, Frank C. Schroeder, Janne Lehtiö, and Nathaniel M. Vacanti. "Correcting for Naturally Occurring Mass Isotopologue Abundances in Stable-Isotope Tracing Experiments with PolyMID." Metabolites 11, no. 5 (May 12, 2021): 310. http://dx.doi.org/10.3390/metabo11050310.
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Stable-isotope tracing is a method to measure intracellular metabolic pathway utilization by feeding a cellular system a stable-isotope-labeled tracer nutrient. The power of the method to resolve differential pathway utilization is derived from the enrichment of metabolites in heavy isotopes that are synthesized from the tracer nutrient. However, the readout is complicated by the presence of naturally occurring heavy isotopes that are not derived from the tracer nutrient. Herein we present an algorithm, and a tool that applies it (PolyMID-Correct, part of the PolyMID software package), to computationally remove the influence of naturally occurring heavy isotopes. The algorithm is applicable to stable-isotope tracing data collected on low- and high- mass resolution mass spectrometers. PolyMID-Correct is open source and available under an MIT license.
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Preston, Tom. "Existing and Emerging Technologies for Measuring Stable Isotope Labelled Retinol in Biological Samples: Isotope Dilution Analysis of Body Retinol Stores." International Journal for Vitamin and Nutrition Research 84, Supplement 1 (December 1, 2014): 30–39. http://dx.doi.org/10.1024/0300-9831/a000186.
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This paper discusses some of the recent improvements in instrumentation used for stable isotope tracer measurements in the context of measuring retinol stores, in vivo. Tracer costs, together with concerns that larger tracer doses may perturb the parameter under study, demand that ever more sensitive mass spectrometric techniques are developed. GCMS is the most widely used technique. It has high sensitivity in terms of sample amount and uses high resolution GC, yet its ability to detect low isotope ratios is limited by background noise. LCMSMS may become more accessible for tracer studies. Its ability to measure low level stable isotope tracers may prove superior to GCMS, but it is isotope ratio MS (IRMS) that has been designed specifically for low level stable isotope analysis through accurate analysis of tracer:tracee ratios (the tracee being the unlabelled species). Compound-specific isotope analysis, where GC is interfaced to IRMS, is gaining popularity. Here, individual 13C-labelled compounds are separated by GC, combusted to CO2 and transferred on-line for ratiometric analysis by IRMS at the ppm level. However, commercially-available 13C-labelled retinol tracers are 2 - 4 times more expensive than deuterated tracers. For 2H-labelled compounds, GC-pyrolysis-IRMS has now become more generally available as an operating mode on the same IRMS instrument. Here, individual compounds are separated by GC and pyrolysed to H2 at high temperature for analysis by IRMS. It is predicted that GC-pyrolysis-IRMS will facilitate low level tracer procedures to measure body retinol stores, as has been accomplished in the case of fatty acids and amino acids. Sample size requirements for GC-P-IRMS may exceed those of GCMS, but this paper discusses sample preparation procedures and predicts improvements, particularly in the efficiency of sample introduction.
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Cobelli, C., G. Toffolo, and D. M. Foster. "Tracer-to-tracee ratio for analysis of stable isotope tracer data: link with radioactive kinetic formalism." American Journal of Physiology-Endocrinology and Metabolism 262, no. 6 (June 1, 1992): E968—E975. http://dx.doi.org/10.1152/ajpendo.1992.262.6.e968.
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A kinetic formalism for the analysis of stable isotope transient tracer data is developed by establishing the link with the formalism available for radioactive tracer data. The crucial variable is the tracer-to-tracee ratio. By expressing the measurements in terms of this ratio, the conventional kinetic formalism used for radioactive data can be applied to estimate noncompartmental parameters using stable isotope tracer data. The tracer-to-tracee ratio also plays an important role in compartmental modeling. By considering the tracer masses in the compartments as state variables the system-experiment model can be written in a format analogous to that usually adopted for the radioactive tracer. Finally, it is shown that the tracer-to-tracee ratio also plays a role in a test of the endogenous steady-state assumption.
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Jahn, A., K. Lindsay, X. Giraud, N. Gruber, B. L. Otto-Bliesner, Z. Liu, and E. C. Brady. "Carbon isotopes in the ocean model of the Community Earth System Model (CESM1)." Geoscientific Model Development 8, no. 8 (August 5, 2015): 2419–34. http://dx.doi.org/10.5194/gmd-8-2419-2015.
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Abstract. Carbon isotopes in the ocean are frequently used as paleoclimate proxies and as present-day geochemical ocean tracers. In order to allow a more direct comparison of climate model results with this large and currently underutilized data set, we added a carbon isotope module to the ocean model of the Community Earth System Model (CESM), containing the cycling of the stable isotope 13C and the radioactive isotope 14C. We implemented the 14C tracer in two ways: in the "abiotic" case, the 14C tracer is only subject to air–sea gas exchange, physical transport, and radioactive decay, while in the "biotic" version, the 14C additionally follows the 13C tracer through all biogeochemical and ecological processes. Thus, the abiotic 14C tracer can be run without the ecosystem module, requiring significantly fewer computational resources. The carbon isotope module calculates the carbon isotopic fractionation during gas exchange, photosynthesis, and calcium carbonate formation, while any subsequent biological process such as remineralization as well as any external inputs are assumed to occur without fractionation. Given the uncertainty associated with the biological fractionation during photosynthesis, we implemented and tested three parameterizations of different complexity. Compared to present-day observations, the model is able to simulate the oceanic 14C bomb uptake and the 13C Suess effect reasonably well compared to observations and other model studies. At the same time, the carbon isotopes reveal biases in the physical model, for example, too sluggish ventilation of the deep Pacific Ocean.
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Jahn, A., K. Lindsay, X. Giraud, N. Gruber, B. L. Otto-Bliesner, Z. Liu, and E. C. Brady. "Carbon isotopes in the ocean model of the Community Earth System Model (CESM1)." Geoscientific Model Development Discussions 7, no. 6 (November 6, 2014): 7461–503. http://dx.doi.org/10.5194/gmdd-7-7461-2014.
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Abstract. Carbon isotopes in the ocean are frequently used as paleo climate proxies and as present-day geochemical ocean tracers. In order to allow a more direct comparison of climate model results with this large and currently underutilized dataset, we added a carbon isotope module to the ocean model of the Community Earth System Model (CESM), containing the cycling of the stable isotope 13C and the radioactive isotope 14C. We implemented the 14C tracer in two ways: in the "abiotic" case, the 14C tracer is only subject to air–sea gas exchange, physical transport, and radioactive decay, while in the "biotic" version, the 14C additionally follows the 13C tracer through all biogeochemical and ecological processes. Thus, the abiotic 14C tracer can be run without the ecosystem module, requiring significantly less computational resources. The carbon isotope module calculates the carbon isotopic fractionation during gas exchange, photosynthesis, and calcium carbonate formation, while any subsequent biological process such as remineralization as well as any external inputs are assumed to occur without fractionation. Given the uncertainty associated with the biological fractionation during photosynthesis, we implemented and tested three parameterizations of different complexity. Compared to present-day observations, the model is able to simulate the oceanic 14C bomb uptake and the 13C Suess effect reasonably well compared to observations and other model studies. At the same time, the carbon isotopes reveal biases in the physical model, for example a too sluggish ventilation of the deep Pacific Ocean.
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Hungate, Bruce A., Rebecca L. Mau, Egbert Schwartz, J. Gregory Caporaso, Paul Dijkstra, Natasja van Gestel, Benjamin J. Koch, et al. "Quantitative Microbial Ecology through Stable Isotope Probing." Applied and Environmental Microbiology 81, no. 21 (August 21, 2015): 7570–81. http://dx.doi.org/10.1128/aem.02280-15.
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ABSTRACTBacteria grow and transform elements at different rates, and as yet, quantifying this variation in the environment is difficult. Determining isotope enrichment with fine taxonomic resolution after exposure to isotope tracers could help, but there are few suitable techniques. We propose a modification tostableisotopeprobing (SIP) that enables the isotopic composition of DNA from individual bacterial taxa after exposure to isotope tracers to be determined. In our modification, after isopycnic centrifugation, DNA is collected in multiple density fractions, and each fraction is sequenced separately. Taxon-specific density curves are produced for labeled and nonlabeled treatments, from which the shift in density for each individual taxon in response to isotope labeling is calculated. Expressing each taxon's density shift relative to that taxon's density measured without isotope enrichment accounts for the influence of nucleic acid composition on density and isolates the influence of isotope tracer assimilation. The shift in density translates quantitatively to isotopic enrichment. Because this revision to SIP allows quantitative measurements of isotope enrichment, we propose to call it quantitative stable isotope probing (qSIP). We demonstrated qSIP using soil incubations, in which soil bacteria exhibited strong taxonomic variations in18O and13C composition after exposure to [18O]water or [13C]glucose. The addition of glucose increased the assimilation of18O into DNA from [18O]water. However, the increase in18O assimilation was greater than expected based on utilization of glucose-derived carbon alone, because the addition of glucose indirectly stimulated bacteria to utilize other substrates for growth. This example illustrates the benefit of a quantitative approach to stable isotope probing.
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Kelleher, J. K., and T. M. Masterson. "Model equations for condensation biosynthesis using stable isotopes and radioisotopes." American Journal of Physiology-Endocrinology and Metabolism 262, no. 1 (January 1, 1992): E118—E125. http://dx.doi.org/10.1152/ajpendo.1992.262.1.e118.
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Important syntheses in living systems occur by condensation reactions of the type nA----1B (where n is the number of A molecules needed to synthesize 1 molecule of B). Quantitative relationships for estimating the rate of synthesis of B from radioactive and stable isotope tracers are compared. With radioisotope tracers, only a single quantity is detected, the amount of radioactivity in B. In contrast, isotopes of varying mass produce multiple mass isotopomers B that are detected using mass spectrometry. The analysis demonstrates that the rate of synthesis of B is identifiable from stable isotope data but not from radioisotope data. This results because the isotopomer distribution of B at any time after tracer addition is a function of only the multinomial distribution representing the synthesis of B from n molecules of A and two parameters representing the fractional fluxes of isotopically enriched molecules to the sampled compartment of B. The model considers the possibility that the sampled compartment of B may not reach isotopic steady state during the experiment. A graphical method for obtaining initial estimates of the two parameters is presented.
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Ibañez-Mejia, Mauricio, and François L. H. Tissot. "Extreme Zr stable isotope fractionation during magmatic fractional crystallization." Science Advances 5, no. 12 (December 2019): eaax8648. http://dx.doi.org/10.1126/sciadv.aax8648.
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Zirconium is a commonly used elemental tracer of silicate differentiation, yet its stable isotope systematics remain poorly known. Accessory phases rich in Zr4+ such as zircon and baddeleyite may preserve a unique record of Zr isotope behavior in magmatic environments, acting both as potential drivers of isotopic fractionation and recorders of melt compositional evolution. To test this potential, we measured the stable Zr isotope composition of 70 single zircon and baddeleyite crystals from a well-characterized gabbroic igneous cumulate. We show that (i) closed-system magmatic crystallization can fractionate Zr stable isotopes at the >0.5% level, and (ii) zircon and baddeleyite are isotopically heavy relative to the melt from which they crystallize, thus driving chemically differentiated liquids toward isotopically light compositions. Because these effects are contrary to first-order expectations based on mineral-melt bonding environment differences, Zr stable isotope fractionation during zircon crystallization may not solely be a result of closed-system thermodynamic equilibrium.
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Rosenblatt, J., D. Chinkes, M. Wolfe, and R. R. Wolfe. "Stable isotope tracer analysis by GC-MS, including quantification of isotopomer effects." American Journal of Physiology-Endocrinology and Metabolism 263, no. 3 (September 1, 1992): E584—E596. http://dx.doi.org/10.1152/ajpendo.1992.263.3.e584.
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In metabolic tracer studies it is frequently useful to infuse tracers that are differently labeled variants of the same molecule. These tracers are known as isotopomers. Analysis of the enrichment of each isotopic analogue can be accomplished by gas chromatography-mass spectrometry (GC-MS). However, the raw GC-MS data must be corrected to give the information required. This paper addresses how to transform the raw GC-MS data, consisting of relative abundance ratios at specific ion masses, into relative molar ratios of tracer and tracee molecules. Several correction factors are necessary. First, the background must be measured and corrected for, since it is always present in the sample. Second, the abundances in the spectrum of the labeled molecule are different from those in the unlabeled molecule, and this proportionality "skew" is corrected. A third correction factor accounts for the overlapping spectra of two or more isotopomers that cannot be measured independently. The final correction removes the "double vision" effect that may appear in some spectra due to the presence of (M - H)+ species.
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Ala-aho, Pertti, Doerthe Tetzlaff, James P. McNamara, Hjalmar Laudon, and Chris Soulsby. "Using isotopes to constrain water flux and age estimates in snow-influenced catchments using the STARR (Spatially distributed Tracer-Aided Rainfall–Runoff) model." Hydrology and Earth System Sciences 21, no. 10 (October 9, 2017): 5089–110. http://dx.doi.org/10.5194/hess-21-5089-2017.
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Abstract. Tracer-aided hydrological models are increasingly used to reveal fundamentals of runoff generation processes and water travel times in catchments. Modelling studies integrating stable water isotopes as tracers are mostly based in temperate and warm climates, leaving catchments with strong snow influences underrepresented in the literature. Such catchments are challenging, as the isotopic tracer signals in water entering the catchments as snowmelt are typically distorted from incoming precipitation due to fractionation processes in seasonal snowpack. We used the Spatially distributed Tracer-Aided Rainfall–Runoff (STARR) model to simulate fluxes, storage, and mixing of water and tracers, as well as estimating water ages in three long-term experimental catchments with varying degrees of snow influence and contrasting landscape characteristics. In the context of northern catchments the sites have exceptionally long and rich data sets of hydrometric data and – most importantly – stable water isotopes for both rain and snow conditions. To adapt the STARR model for sites with strong snow influence, we used a novel parsimonious calculation scheme that takes into account the isotopic fractionation through snow sublimation and snowmelt. The modified STARR setup simulated the streamflows, isotope ratios, and snow pack dynamics quite well in all three catchments. From this, our simulations indicated contrasting median water ages and water age distributions between catchments brought about mainly by differences in topography and soil characteristics. However, the variable degree of snow influence in catchments also had a major influence on the stream hydrograph, storage dynamics, and water age distributions, which was captured by the model. Our study suggested that snow sublimation fractionation processes can be important to include in tracer-aided modelling for catchments with seasonal snowpack, while the influence of fractionation during snowmelt could not be unequivocally shown. Our work showed the utility of isotopes to provide a proof of concept for our modelling framework in snow-influenced catchments.
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Sanborn, P. T., R. P. Brockley, and B. Mayer. "Stable isotope tracing of fertilizer sulphur uptake by lodgepole pine: foliar responses." Canadian Journal of Forest Research 41, no. 3 (March 2011): 493–500. http://dx.doi.org/10.1139/x10-222.
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A plot-scale fertilizer sulphur (S) stable isotope tracer study was established in 2001 in the Sub-Boreal Spruce biogeoclimatic zone in central interior British Columbia where S deficiencies are common in lodgepole pine ( Pinus contorta var. latifolia Engelm. ex S. Wats.) stands. Treatments used operationally realistic applications of 300 kg N·ha–1 as urea and 100 kg S·ha–1 as either sulphate (SO4) or elemental S (S0). δ34S values of fertilizer S differed by >9‰ from pretreatment δ34S values of total S in foliage at the two study sites (5.2‰ and 8.2‰). These differences enabled quantification of fertilizer uptake using isotopic analysis of post-treatment foliar S. Addition of K2SO4 with δ34S of +17.5‰ increased foliar δ34S by 3.5‰ and 6.6‰ at the two sites, respectively, in the year after treatment, indicating fertilizer contributions >40% to foliar total S. For a S0 fertilizer application with a δ34S value of +19.3‰, foliar δ34S increases were smaller but steadily increased, resulting in an average tracer S uptake of ~20% over three years. These results confirmed the more rapid availability of S from SO4-based fertilizers and demonstrated the feasibility of field tracer experiments using stable S isotopes at natural abundance levels.
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Brkić, Željka, Mladen Kuhta, Tamara Hunjak, and Ozren Larva. "Regional Isotopic Signatures of Groundwater in Croatia." Water 12, no. 7 (July 13, 2020): 1983. http://dx.doi.org/10.3390/w12071983.
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Tracer methods are useful for investigating groundwater travel times and recharge rates and analysing impacts on groundwater quality. The most frequently used tracers are stable isotopes and tritium. Stable isotopes of oxygen (δ18O) and hydrogen (δ2H) are mainly used as indicators of the recharge condition. Tritium (3H) is used to estimate an approximate mean groundwater age. This paper presents the results of an analysis of stable isotope data and tritium activity in Croatian groundwater samples that were collected between 1997 and 2014 at approximately 100 sites. The composition of the stable isotopes of groundwater in Croatia originates from recent precipitation and is described using two regional groundwater lines. One of them is applied to groundwater accumulated in the aquifers in the Pannonian part of Croatia and the other is for groundwater accumulated in the Dinaric karst of Croatia. The isotope content shows that the studied groundwater is mainly modern water. A mix of sub-modern and modern water is mostly accumulated in semi-confined porous aquifers in northern Croatia, deep carbonate aquifers, and (sub)thermal springs.
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Jones, Peter J. H., and Stanley T. Leatherdale. "Stable isotopes in clinical research: safety reaffirmed." Clinical Science 80, no. 4 (April 1, 1991): 277–80. http://dx.doi.org/10.1042/cs0800277.
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Approaching half a century of stable-isotope usage in human metabolic studies has been without documented significant adverse effect. Side-effects with acute D dosing are transitory with no demonstrated evidence of permanent deleterious action. The threshold of D toxicity has been defined in animals and is far in excess of concentrations conceivably used in human studies. The possibility that D may have additional beneficial pharmacological applications cannot be excluded. For isotopes other than D, evidence of observed toxicity remains to be produced even at dosages far in excess of the range used in metabolic studies. Absence of adverse effect may be attributable to small mass differences and the similar properties of tracer and predominantly abundant isotope. Absolute determination of stable isotope toxicity in humans is rendered impossible by ethical considerations. Also, the precision of extrapolating toxicity thresholds from animal studies remains unknown. However, should perturbation of the delicate homoeostatic characteristic of living organisms occur with use of stable isotopes, it is almost undoubtedly at some level of administration greatly in excess of those administered currently in biomedical research.
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Coggan, Andrew R. "Use of stable isotopes to study carbohydrate and fat metabolism at the whole-body level." Proceedings of the Nutrition Society 58, no. 4 (November 1999): 953–61. http://dx.doi.org/10.1017/s0029665199001263.
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The present review discusses the advantages and limitations of using stable-isotope tracers to assess carbohydrate and fat metabolism at the whole-body level. One advantage of stable-(v. radioactive-) isotope tracers is the relative ease with which the location of a label within a molecule can be determined using selected-ion-monitoring GC-mass spectrometry (SIM-GC- MS). This technique minimizes potential problems due to label recycling, allows the use of multiple-labelled compounds simultaneously (e.g. to quantify glucose cycling), and perhaps most importantly, has led to the development of unique stable-isotope methods for, for example, quantifying gluconeogenesis. However, the limited sensitivity of SIM-GC-MS sometimes requires that relatively large amounts of a stable-isotope tracer be used, thus increasing cost and potentially altering metabolism. At least theoretically, stable- (or radioactive-) isotope tracers can also be used in conjunction with indirect calorimetry to estimate utilization of muscle glycogen or triacylglycerol stores, thus potentially circumventing the need to obtain muscle biopsies. These calculations, however, require certain critical assumptions, which if incorrect could lead to major errors in the values obtained. Despite such limitations, stable-isotope tracers provide a powerful and sometimes unique tool for investigating carbohydrate and fat metabolism at the whole-body level. With continuing advances in availability, instrumentation and methods, it is likely that stable-isotope tracers will become increasingly important in the immediate future.
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Hohl, Simon V., Shao-Yong Jiang, Sebastian Viehmann, Wei Wei, Qian Liu, Hai-Zhen Wei, and Stephen J. G. Galer. "Trace Metal and Cd Isotope Systematics of the Basal Datangpo Formation, Yangtze Platform (South China) Indicate Restrained (Bio)Geochemical Metal Cycling in Cryogenian Seawater." Geosciences 10, no. 1 (January 19, 2020): 36. http://dx.doi.org/10.3390/geosciences10010036.
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The behaviour of bioavailable trace metals and their stable isotopes in the modern oceans is controlled by uptake into phototrophic organisms and adsorption on and incorporation into marine authigenic minerals. Among other bioessential metals, Cd and its stable isotopes have recently been used in carbonate lithologies as novel tracer for changes in the paleo primary productivity and (bio)geochemical cycling. However, many marine sediments that were deposited during geologically highly relevant episodes and which, thus, urgently require study for a better understanding of the paleo environment are rather composed of a mixture of organic matter (OM), and detrital and authigenic minerals. In this study, we present Cd concentrations and their isotopic compositions as well as trace metal concentrations from sequential leachates of OM-rich shales of the Cryogenian basal Datangpo Formation, Yangtze Platform (South China). Our study shows variable distribution of conservative and bioavailable trace metals as well as Cd isotope compositions between sequential leachates of carbonate, OM, sulphide, and silicate phases. We show that the Cd isotope compositions obtained from OM leachates can be used to calculate the ambient Cryogenian surface seawater of the restricted Nanhua Basin by applying mass balance calculations. By contrast, early diagenetic Mn carbonates and sulphides incorporated the residual Cd from dissolved organic matter that was in isotopic equilibrium with deep/pore waters of the Nanhua Basin. Our model suggests that the Cd isotopic composition of surface seawater at that time reached values of modern oxygenated surface oceans. However, the deep water Cd isotope composition was substantially heavier than that of modern fully oxygenated oceans and rather resembles deep waters with abundant sulphide precipitation typical for modern oxygen minimum zones. This argues for incomplete recycling of Cd and other bioavailable metals shortly after the Sturtian glaciation in the redox stratified Cryogenian Nanhua Basin. Our study highlights the importance of sequential leaching procedures when dealing with impure authigenic sediments such as OM-rich carbonates, mudstones, or shales to achieve reliable trace metal concentrations and Cd isotope compositions as proxies for (bio)geochemical metal cycling in past aquatic systems.
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James, W. D., A. T. Showler, J. K. Westbrook, and J. S. Armstrong. "Stable isotope tracer marking of individual boll weevils." Journal of Radioanalytical and Nuclear Chemistry 269, no. 2 (August 2006): 267–70. http://dx.doi.org/10.1007/s10967-006-0377-1.
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Mennekes, David, Michael Rinderer, Stefan Seeger, and Natalie Orlowski. "Ecohydrological travel times derived from in situ stable water isotope measurements in trees during a semi-controlled pot experiment." Hydrology and Earth System Sciences 25, no. 8 (August 23, 2021): 4513–30. http://dx.doi.org/10.5194/hess-25-4513-2021.
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Abstract. Tree water uptake processes and ecohydrological travel times have gained more attention in recent ecohydrological studies. In situ measurement techniques for stable water isotopes offer great potential to investigate these processes but have not been applied much to tree xylem and soils so far. Here, we used in situ probes for stable water isotope measurements to monitor the isotopic signatures of soil and tree xylem water before and after two deuterium-labeled irrigation experiments. To show the potential of the method, we tested our measurement approach with 20-year-old trees of three different species (Pinus pinea, Alnus incana and Quercus suber). They were planted in large pots with homogeneous soil in order to have semi-controlled experimental conditions. Additional destructive sampling of soil and plant material allowed for a comparison between destructive (cryogenic vacuum extraction and direct water vapor equilibration) and in situ isotope measurements. Furthermore, isotope-tracer-based ecohydrological travel times were compared to travel times derived from sap flow measurements. The time to first arrival of the isotope tracer signals at 15 cm stem hight were ca. 17 h for all tree species and matched well with sap-flow-based travel times. However, at 150 cm stem height tracer-based travel times differed between tree species and ranged between 2.4 and 3.3 d. Sap-flow-based travel times at 150 cm stem hight were ca. 1.3 d longer than tracer-based travel times. The isotope signature of destructive and in situ isotope measurements differed notably, which suggests that the two types of techniques sampled water from different pools. In situ measurements of soil and xylem water were much more consistent between the three tree pots (on average standard deviations were smaller by 8.4 ‰ for δ2H and by 1.6 ‰ for δ18O for the in situ measurements) and also among the measurements from the same tree pot in comparison to the destructive methods (on average standard deviations were smaller by 7.8 ‰ and 1.6 ‰ for δ2H and δ18O, respectively). Our study demonstrates the potential of semi-controlled large-scale pot experiments and very frequent in situ isotope measurements for monitoring tree water uptake and ecohydrological travel times. It also shows that differences in sampling techniques or sensor types need to be considered when comparing results of different studies and within one study using different methods.
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Li, Shilei, Weiqiang Li, Brian L. Beard, Maureen E. Raymo, Xiaomin Wang, Yang Chen, and Jun Chen. "K isotopes as a tracer for continental weathering and geological K cycling." Proceedings of the National Academy of Sciences 116, no. 18 (April 15, 2019): 8740–45. http://dx.doi.org/10.1073/pnas.1811282116.
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The causal effects among uplift, climate, and continental weathering cannot be fully addressed using presently available geochemical proxies. However, stable potassium (K) isotopes can potentially overcome the limitations of existing isotopic proxies. Here we report on a systematic investigation of K isotopes in dissolved load and sediments from major rivers and their tributaries in China, which have drainage basins with varied climate, lithology, and topography. Our results show that during silicate weathering, heavy K isotopes are preferentially partitioned into aqueous solutions. Moreover, δ41K values of riverine dissolved load vary remarkably and correlate negatively with the chemical weathering intensity of the drainage basin. This correlation allows an estimate of the average K isotope composition of global riverine runoff (δ41K = −0.22‰), as well as modeling of the global K cycle based on mass balance calculations. Modeling incorporating K isotope mass balance better constrains estimated K fluxes for modern global K cycling, and the results show that the δ41K value of seawater is sensitive to continental weathering intensity changes. Thus, it is possible to use the δ41K record of paleo-seawater to infer continental weathering intensity through Earth’s history.
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Knapp, Julia L. A., Colin Neal, Alessandro Schlumpf, Margaret Neal, and James W. Kirchner. "New water fractions and transit time distributions at Plynlimon, Wales, estimated from stable water isotopes in precipitation and streamflow." Hydrology and Earth System Sciences 23, no. 10 (October 28, 2019): 4367–88. http://dx.doi.org/10.5194/hess-23-4367-2019.
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Abstract. Long-term, high-frequency time series of passive tracers in precipitation and streamflow are essential for quantifying catchment transport and storage processes, but few such data sets are publicly available. Here we describe, present, and make available to the public two extensive data sets of stable water isotopes in streamflow and precipitation at the Plynlimon experimental catchments in central Wales. Stable isotope data are available at 7-hourly intervals for 17 months, and at weekly intervals for 4.25 years. Precipitation isotope values were highly variable in both data sets, and the high temporal resolution of the 7-hourly streamwater samples revealed rich isotopic dynamics that were not captured by the weekly sampling. We used ensemble hydrograph separation to calculate new water fractions and transit time distributions from both data sets. Transit time distributions estimated by ensemble hydrograph separation were broadly consistent with those estimated by spectral fitting methods, suggesting that they can reliably quantify the contributions of recent precipitation to streamflow. We found that on average, roughly 3 % of streamwater was made up of precipitation that fell within the previous 7 h, and 13 %–15 % of streamwater was made up of precipitation that fell within the previous week. The contributions of recent precipitation to streamflow were highest during large events, as illustrated by comparing new water fractions for different discharges and precipitation rates. This dependence of new water fractions on water fluxes was also reflected in their seasonal variations, with lower new water fractions and more damped catchment transit time distributions in spring and summer compared to fall and winter. We also compared new water fractions obtained from stable water isotopes against those obtained from concentrations of chloride, a solute frequently used as a passive tracer of catchment transport processes. After filtering the chloride data for dry deposition effects, we found broadly similar new water fractions using chloride and stable water isotopes, indicating that these different tracers may yield similar inferences about catchment storage and transport, if potentially confounding factors are eliminated. These stable isotope time series comprise some of the longest and most detailed publicly available catchment isotope data sets. They complement extensive solute data sets that are already publicly available for Plynlimon, enabling a wide range of future analyses of catchment behavior.
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Preston, T., and D. C. McMillan. "Rapid sample throughput for biomedical stable isotope tracer studies." Biological Mass Spectrometry 16, no. 1-12 (October 1988): 229–35. http://dx.doi.org/10.1002/bms.1200160142.
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Buckley, Wayne T., Stuart N. Huckin, and Guenter K. Eigendorf. "Calculation of stable isotope enrichment for tracer kinetic procedures." Biological Mass Spectrometry 12, no. 1 (January 1985): 1–5. http://dx.doi.org/10.1002/bms.1200120102.
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Schmidt, Harald, Günter Borchardt, S. Weber, and Hubert Scherrer. "Diffusion in Transition Metal Diborides - An Overview." Defect and Diffusion Forum 263 (March 2007): 219–24. http://dx.doi.org/10.4028/www.scientific.net/ddf.263.219.
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Literature data on (self-)diffusion in transition metal borides are extremely sparse due to the low atomic mobility of the constituents and due to the fact that for B there exist no suitable radioactive tracers and only two stable isotopes with a high natural abundance of 19 % (10B) and 81 % (11B), respectively. The present paper reviews our experiments on the tracer diffusion of transition metals and boron in TiB2, WB2+x, and (TixWyCrz)B2 which were carried out using stable isotopes and secondary ion mass spectrometry (SIMS). For tracer deposition, ion implantation and magnetron sputtering were used. In order to measure boron diffusion, a specially designed experiment was build up where a TiB2 layer was sputtered on an isotope-enriched Ti11B2 bulk ceramic sample. In addition, first results on chemical interdiffusion in the system (TixWyCrz)B2 will be presented. Here, a method based on magnetron sputtered layers and secondary neutral mass spectrometry (SNMS) was used which allows to determine much lower diffusivities (down to 10-19 m2/s) than the conventional EDX line-scan method on cross-sectional samples.
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Toffolo, G., and C. Cobelli. "Modeling Stable Isotope Tracer Data: The Effect of a Nonnegligible Mass of Tracer." IFAC Proceedings Volumes 27, no. 1 (March 1994): 301–2. http://dx.doi.org/10.1016/s1474-6670(17)46246-x.
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Wang, Pei, Yujing Deng, and Zhongwang Wei. "Modeling Investigation of Diurnal Variations in Water Flux and Its Components with Stable Isotopic Tracers." Atmosphere 10, no. 7 (July 16, 2019): 403. http://dx.doi.org/10.3390/atmos10070403.
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The isotopic compositions of water fluxes provide valuable insights into the hydrological cycle and are widely used to quantify biosphere–atmosphere exchange processes. However, the combination of water isotope approaches with water flux components remains challenging. The Iso-SPAC (coupled heat, water with isotopic tracer in soil–plant–atmosphere-continuum) model is a useful framework for simulating the dynamics of water flux and its components, and for coupling with isotopic fractionation and mixing processes. Here, we traced the isotopic fractionation processes with separate soil evaporation (Ev) and transpiration (Tr), as well as their mixing in evapotranspiration (E) for simulating diurnal variations of isotope compositions in E flux (δE). Three sub modules, namely isotopic steady state (ISS), non-steady-state (NSS), and NSS Péclet, were tested to determine the true value for the isotope compositions of plant transpiration (δTr) and δE. In situ measurements of isotopic water vapor with the Keeling-plot approach for δE and robust eddy covariance data for E agreed with the model output (R2 = 0.52 and 0.98, RMSD = 2.72‰, and 39 W m−2), illustrating the robustness of the Iso-SPAC model. The results illustrate that NSS is a better approximation for estimating diurnal variations in δTr and δE, specifically during the alternating periods of day and night. Leaf stomata conductance regulated by solar radiation controlled the diurnal variations in transpiration fraction (Tr/E). The study emphasized that transpiration and evaporation, respectively, acted to increase and decrease the δ18O of water vapor that was affected by the diurnal trade-off between them.
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CHAN, Dick C., P. Hugh R. BARRETT, and Gerald F. WATTS. "Lipoprotein transport in the metabolic syndrome: methodological aspects of stable isotope kinetic studies." Clinical Science 107, no. 3 (August 24, 2004): 221–32. http://dx.doi.org/10.1042/cs20040108.
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The metabolic syndrome encapsulates visceral obesity, insulin resistance, diabetes, hypertension and dyslipidaemia. Dyslipidaemia is a cardinal feature of the metabolic syndrome that accelerates the risk of cardiovascular disease. It is usually characterized by high plasma concentrations of triacylglycerol (triglyceride)-rich and apoB (apolipoprotein B)-containing lipoproteins, with depressed concentrations of HDL (high-density lipoprotein). However, lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of these lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in the metabolic syndrome has been achieved chiefly by ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological aspects of stable isotope kinetic studies. The design of in vivo turnover studies requires considerations related to stable isotope tracer administration, duration of sampling protocol and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such models provide novel insight that further understanding of metabolic disorders and effects of treatments. Future investigations of the pathophysiology and therapy of the dyslipoproteinaemia of the metabolic syndrome will require the development of novel kinetic methodologies. Specifically, new stable isotope techniques are required for investigating in vivo the turnover of the HDL subpopulation of particles, as well as the cellular efflux of cholesterol into the extracellular space and its subsequent transport in plasma and metabolic fate in the liver.
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Piovano, Thea I., Doerthe Tetzlaff, Sean K. Carey, Nadine J. Shatilla, Aaron Smith, and Chris Soulsby. "Spatially distributed tracer-aided runoff modelling and dynamics of storage and water ages in a permafrost-influenced catchment." Hydrology and Earth System Sciences 23, no. 6 (June 3, 2019): 2507–23. http://dx.doi.org/10.5194/hess-23-2507-2019.
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Abstract. Permafrost strongly controls hydrological processes in cold regions. Our understanding of how changes in seasonal and perennial frozen ground disposition and linked storage dynamics affect runoff generation processes remains limited. Storage dynamics and water redistribution are influenced by the seasonal variability and spatial heterogeneity of frozen ground, snow accumulation and melt. Stable isotopes are potentially useful for quantifying the dynamics of water sources, flow paths and ages, yet few studies have employed isotope data in permafrost-influenced catchments. Here, we applied the conceptual model STARR (the Spatially distributed Tracer-Aided Rainfall–Runoff model), which facilitates fully distributed simulations of hydrological storage dynamics and runoff processes, isotopic composition and water ages. We adapted this model for a subarctic catchment in Yukon Territory, Canada, with a time-variable implementation of field capacity to include the influence of thaw dynamics. A multi-criteria calibration based on stream flow, snow water equivalent and isotopes was applied to 3 years of data. The integration of isotope data in the spatially distributed model provided the basis for quantifying spatio-temporal dynamics of water storage and ages, emphasizing the importance of thaw layer dynamics in mixing and damping the melt signal. By using the model conceptualization of spatially and temporally variable storage, this study demonstrates the ability of tracer-aided modelling to capture thaw layer dynamics that cause mixing and damping of the isotopic melt signal.
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Andrei, Francesca, Maurizio Barbieri, and Giuseppe Sappa. "Application of 2H and 18O Isotopes for Tracing Municipal Solid Waste Landfill Contamination of Groundwater: Two Italian Case Histories." Water 13, no. 8 (April 13, 2021): 1065. http://dx.doi.org/10.3390/w13081065.
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Groundwater contamination due to municipal solid waste landfills leachate is a serious environmental threat. During recent years, the use of stable isotopes as environmental tracers to identify groundwater contamination phenomena has found application to environmental engineering. Deuterium (2H) and oxygen (18O) isotopes have successfully used to identify groundwater contamination phenomena if submitted to interactions with municipal solid waste landfills leachate, with a significant organic amount. The paper shows two case studies, in central and southern Italy, where potential contamination phenomenon of groundwater under municipal solid waste landfills occurred. In both cases, isotope compositions referred to 2H and 18O highlight a δ2H enrichment for some groundwater samples taken in wells, located near leachate storage wells. The δ2H enrichment is probably caused by methanogenesis phenomena, during which the bacteria use preferentially the hydrogen “lighter” isotope (1H), and the remaining enriched the “heavier” isotope (2H). The study of the isotope composition variation, combined with the spatial trend of some analytes (Fe, Mn, Ni) concentrations, allowed to identify interaction phenomena between the municipal solid waste landfills leachate and groundwater in both case histories. Therefore, these results confirm the effectiveness of 2H isotopes application as environmental tracer of groundwater contamination phenomena due to mixing with municipal solid waste landfills leachate.
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Williams, Holden C., Margaret A. Piron, Grant K. Nation, Adeline E. Walsh, Lyndsay E. A. Young, Ramon C. Sun, and Lance A. Johnson. "Oral Gavage Delivery of Stable Isotope Tracer for In Vivo Metabolomics." Metabolites 10, no. 12 (December 8, 2020): 501. http://dx.doi.org/10.3390/metabo10120501.
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Stable isotope-resolved metabolomics (SIRM) is a powerful tool for understanding disease. Advances in SIRM techniques have improved isotopic delivery and expanded the workflow from exclusively in vitro applications to in vivo methodologies to study systemic metabolism. Here, we report a simple, minimally-invasive and cost-effective method of tracer delivery to study SIRM in vivo in laboratory mice. Following a brief fasting period, we orally administered a solution of [U-13C] glucose through a blunt gavage needle without anesthesia, at a physiological dose commonly used for glucose tolerance tests (2 g/kg bodyweight). We defined isotopic enrichment in plasma and tissue at 15, 30, 120, and 240 min post-gavage. 13C-labeled glucose peaked in plasma around 15 min post-gavage, followed by period of metabolic decay and clearance until 4 h. We demonstrate robust enrichment of a variety of central carbon metabolites in the plasma, brain and liver of C57/BL6 mice, including amino acids, neurotransmitters, and glycolytic and tricarboxylic acid (TCA) cycle intermediates. We then applied this method to study in vivo metabolism in two distinct mouse models of diseases known to involve dysregulation of glucose metabolism: Alzheimer’s disease and type II diabetes. By delivering [U-13C] glucose via oral gavage to the 5XFAD Alzheimer’s disease model and the Lepob/ob type II diabetes model, we were able to resolve significant differences in multiple central carbon pathways in both model systems, thus providing evidence of the utility of this method to study diseases with metabolic components. Together, these data clearly demonstrate the efficacy and efficiency of an oral gavage delivery method, and present a clear time course for 13C enrichment in plasma, liver and brain of mice following oral gavage of [U-13C] glucose—data we hope will aid other researchers in their own 13C-glucose metabolomics study design.
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Van Engeland, T., A. De Kluijver, K. Soetaert, F. J. R. Meysman, and J. J. Middelburg. "Isotope data improve the predictive capabilities of a marine biogeochemical model." Biogeosciences Discussions 9, no. 7 (July 27, 2012): 9453–86. http://dx.doi.org/10.5194/bgd-9-9453-2012.
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Abstract. Mesocosm experiments combined with biogeochemical modeling provide a powerful research tool to better understand marine ecosystem processes. Using an extended Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) model, we investigated the added value of stable isotope tracer additions to constrain biogeochemical transformations within a mesocosm experiment that was designed to study ocean acidification effects on the marine ecosystem. Markov-Chain Monte-Carlo simulations revealed that even when isotope data were available for the majority of the components, not all parameters in the model could be constrained by calibration. However, when isotope tracer data were deliberately excluded from the calibration, the overparameterisation was even stronger. More specifically, it led to unconstrained fluxes through the zooplankton and detritus compartment, and different relative contributions of these two compartments to phytoplankton biomass loss produced equally plausible results. It is concluded that model uncertainty due to overparameterisation can be considerably reduced by explicitly resolving stable isotope dynamics. Therefore, this mesocosm experiment has benefitted substantially from isotope tracer additions to unravel carbon cycling under varying CO2 regimes.
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Wang, Yujue, Fredric E. Wondisford, Chi Song, Teng Zhang, and Xiaoyang Su. "Metabolic Flux Analysis—Linking Isotope Labeling and Metabolic Fluxes." Metabolites 10, no. 11 (November 6, 2020): 447. http://dx.doi.org/10.3390/metabo10110447.
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Metabolic flux analysis (MFA) is an increasingly important tool to study metabolism quantitatively. Unlike the concentrations of metabolites, the fluxes, which are the rates at which intracellular metabolites interconvert, are not directly measurable. MFA uses stable isotope labeled tracers to reveal information related to the fluxes. The conceptual idea of MFA is that in tracer experiments the isotope labeling patterns of intracellular metabolites are determined by the fluxes, therefore by measuring the labeling patterns we can infer the fluxes in the network. In this review, we will discuss the basic concept of MFA using a simplified upper glycolysis network as an example. We will show how the fluxes are reflected in the isotope labeling patterns. The central idea we wish to deliver is that under metabolic and isotopic steady-state the labeling pattern of a metabolite is the flux-weighted average of the substrates’ labeling patterns. As a result, MFA can tell the relative contributions of converging metabolic pathways only when these pathways make substrates in different labeling patterns for the shared product. This is the fundamental principle guiding the design of isotope labeling experiment for MFA including tracer selection. In addition, we will also discuss the basic biochemical assumptions of MFA, and we will show the flux-solving procedure and result evaluation. Finally, we will highlight the link between isotopically stationary and nonstationary flux analysis.
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Koenig, K. M., J. A. Shelford, and W. T. Buckley. "True absorption of selenium in dairy cows: Stable isotope tracer methodology and effect of dietary copper." Canadian Journal of Animal Science 71, no. 1 (March 1, 1991): 175–83. http://dx.doi.org/10.4141/cjas91-019.
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True absorption of Se in dairy cows was determined using a method combining balance techniques with isotopic enrichment of body Se pools. Oral and intravenous routes of isotope administration and tracer enrichment in serum and liver were evaluated for determining endogenous fecal Se. The effect of supplemental dietary Cu on Se absorption was also determined. In two trials, five and six nonlactating Holstein cows were supplemented with 0 or 16 mg Cu kg−1 feed dry matter. The basal diet was cubed orchardgrass hay that contained 0.19 mg Se kg−1 (0.18 mg kg−1 as added selenite) and 14 mg Cu kg−1. Each cow received Se-77 orally and Se-82 intravenously on day 1. Feces, urine and serum samples were collected during two 5-d balance periods (days 16–20 and days 21–25). Liver biopsies were taken on day 27. Endogenous fecal Se determined from tracer enrichment in serum and liver with oral isotope administration and from enrichment in serum with intravenous isotope administration were not different (P > 0.05). It was concluded that any one of these approaches could be used to estimate endogenous fecal Se and true Se absorption. There was no effect of Cu on Se absorption (P > 0.05). True absorption of Se was 11 ± 1.5% of the Se intake. Key words: Selenium, copper, stable isotope, endogenous excretion, absorption, dairy cows
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Schricker, Thomas, Almut Berroth, Uta Pfeiffer, Markus Schreiber, Wolfgang Geisser, Axel Goertz, and Michael Georgieff. "Assessment of perioperative glycerol metabolism by stable isotope tracer technique." Nutrition 13, no. 3 (March 1997): v—195. http://dx.doi.org/10.1016/s0899-9007(96)00400-5.
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Gravel, Simon-Pierre, Sylvia Andrzejewski, Daina Avizonis, and Julie St-Pierre. "Stable Isotope Tracer Analysis in Isolated Mitochondria from Mammalian Systems." Metabolites 4, no. 2 (April 10, 2014): 166–83. http://dx.doi.org/10.3390/metabo4020166.
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Janghorbani, Morteza, Bill T. G. Ting, and Nora E. Lynch. "Inductively coupled plasma mass spectrometry for stable isotope tracer investigations." Mikrochimica Acta 99, no. 3-6 (May 1989): 315–28. http://dx.doi.org/10.1007/bf01244687.
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Diniz Behn, Cecilia, Eunsook S. Jin, Kate Bubar, Craig Malloy, Elizabeth J. Parks, and Melanie Cree-Green. "Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling." Journal of Investigative Medicine 68, no. 1 (September 24, 2019): 3–10. http://dx.doi.org/10.1136/jim-2019-001109.
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Stable isotope tracers have been used to gain an understanding of integrative animal and human physiology. More commonly studied organ systems include hepatic glucose metabolism, lipolysis from adipose tissue, and whole body protein metabolism. Recent improvements in isotope methodology have included the use of novel physiologic methods/models and mathematical modeling of data during different physiologic states. Here we review some of the latest advancements in this field and highlight future research needs. First we discuss the use of an oral [U-13C3]-glycerol tracer to determine the relative contribution of glycerol carbons to hepatic glucose production after first cycling through the tricarboxylic acid cycle, entry of glycerol into the pentose phosphate pathway or direct conversion of glycerol into the glucose. Second, we describe an adaptation of the established oral minimal model used to define postprandial glucose dynamics to include glycerol dynamics in an oral glucose tolerance test with a [2H5]-glycerol tracer to determine dynamic changes in lipolysis. Simulation results were optimized when parameters describing glycerol flux were determined with a hybrid approach using both tracer-based calculations and constrained parameter optimization. Both of these methodologies can be used to expand our knowledge of not only human physiology, but also the effects of various nutritional strategies and medications on metabolism.
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Mao, Yu Xiang, Hai Lin Wang, and Mei Wang. "Study on Mercury Methylation in Sediment Using Enriched Stable Isotope Tracer." Applied Mechanics and Materials 71-78 (July 2011): 3201–6. http://dx.doi.org/10.4028/www.scientific.net/amm.71-78.3201.
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Methylmercury (MeHg) production from inorganic mercury in natural environment leads to bioaccumulation in fish, putting human being under the risk of exposure. This study investigated the transformation of enriched stable isotope tracer,199Hg2+, in sediment slurry of the Florida Everglades. Incubation experiments were conducted under four different laboratory conditions. The results suggest that methylation of mercury mainly happened under anaerobic condition, with microbial activity playing the major role. The relative methylation rate was determined to be 1% per day at the first few days, and then this transformation process slowed down. At the end of incubation experiment, totally around 20% of the isotope tracer199Hg2+was transformed to its methylated form, Me199Hg. This high potential of mercury methylation partially accounts for the contamination and bioaccumulation of MeHg in the relatively pristine Florida Everglades ecosystem.
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Roche, D. M. "δ<sup>18</sup>O water isotope in the <i>i</i>LOVECLIM model (version 1.0) – Part 1: Implementation and verification." Geoscientific Model Development 6, no. 5 (September 12, 2013): 1481–91. http://dx.doi.org/10.5194/gmd-6-1481-2013.
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Abstract. A new 18O stable water isotope scheme is developed for three components of the iLOVECLIM coupled climate model: atmospheric, oceanic and land surface. The equations required to reproduce the fractionation of stable water isotopes in the simplified atmospheric model ECBilt are developed consistently with the moisture scheme. Simplifications in the processes are made to account for the simplified vertical structure including only one moist layer. Implementation of these equations together with a passive tracer scheme for the ocean and a equilibrium fractionation scheme for the land surface leads to the closure of the (isotopic-) water budget in our climate system. Following the implementation, verification of the existence of usual δ18O to climatic relationships are performed for the Rayleigh distillation, the Dansgaard relationship and the δ18O –salinity relationship. Advantages and caveats of the approach taken are outlined. The isotopic fields simulated are shown to reproduce most expected oxygen-18–climate relationships with the notable exception of the isotopic composition in Antarctica.
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Demant, T., C. J. Packard, H. Demmelmair, P. Stewart, A. Bedynek, D. Bedford, D. Seidel, and J. Shepherd. "Sensitive methods to study human apolipoprotein B metabolism using stable isotope-labeled amino acids." American Journal of Physiology-Endocrinology and Metabolism 270, no. 6 (June 1, 1996): E1022—E1036. http://dx.doi.org/10.1152/ajpendo.1996.270.6.e1022.
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The objective of the study was to develop a sensitive method using stable isotope-labeled tracers that would permit the determination of apolipoprotein B (apoB) metabolism in very low-density lipoprotein subfractions (VLDL1, Sf 60-400; VLDL2, Sf 20-60), intermediate-density lipoprotein (IDL, Sf 12-20), and low-density lipoprotein (LDL, Sf 0-12). Six normolipidemic subjects were given trideuterated leucine, and its clearance from plasma and appearance in the four apoB-containing lipoprotein fractions were followed by use of a highly sensitive gas chromatography-mass spectrometry technique in which the m + 3-to-m + 2 ion ratio was selectively monitored. This analytic approach permitted the precise measurement of low enrichments in IDL and LDL and extension of the turnover out to 250-300 h. A compartmental model was developed to derive rate constants from the plasma and apoB enrichment curves. The model was uniquely identifiable once parameter dependencies had been introduced to reduce the number of unknowns. Values were obtained for apoB input into all lipoprotein density intervals, together with rates of interconversion and catabolism; these agreed well with results from radioiodinated tracer experiments. An alternative model structure was also explored in which input occurred only into VLDL1. Altering the protocol of tracer administration (bolus vs. primed constant infusion) and dose (over a 10-fold range) had no influence on the results obtained. The analytic and modeling approach described will permit stable isotopes to be used to elucidate key features of apoB metabolism in normal and pathological states.
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Volkmann, T. H. M., and M. Weiler. "Continual in-situ monitoring of pore water stable isotopes in the subsurface." Hydrology and Earth System Sciences Discussions 10, no. 11 (November 5, 2013): 13293–331. http://dx.doi.org/10.5194/hessd-10-13293-2013.
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Abstract. The stable isotope signature of pore water provides an integral fingerprint of water origin, flow path, transport processes, and residence times and can thus serve as a powerful tracer of hydrological processes in the unsaturated and saturated zone. However, the full potential of stable isotopes to quantitatively characterize subsurface water dynamics is yet unfolded due to the difficulty in obtaining extensive detailed and continual measurements of spatiotemporally variable pore water signatures. With the development of field-deployable laser-based isotope analyzers, such measurements are now becoming feasible. This study presents the development and application of a functional, automatable, and cost-efficient system for non-destructive continual in-situ monitoring of pore water stable isotope signatures with high resolution. The monitoring system uses automatic-controllable valve arrays to continuously extract diluted soil air water vapor via a branching network of multiple small microporous probes into a commercial isotope analyzer. Soil temperature observations are used to convert obtained vapor phase into liquid phase water isotope signatures, but these can also be obtained based on vapor concentration measurements. In-situ sampling was conducted at six depths for each of three plots planted with varying vegetation on an experimental site in SW Germany. Two different methods based on advective and diffusive soil water vapor probing were employed suitable under unsaturated and all (including saturated) moisture conditions, respectively. The advective sampling method was applied using multiple permanently installed probes (continual mode) and using a single probe subsequently inserted to sample the various locations (push-in mode), while the diffusive sampling method was applied in push-in mode only. Using a specific identical treatment onsite calibration approach along with basic corrections for instrument bias and temperature dependent free water-vapor isotopic equilibrium fractionation, the monitoring system facilitated inference of normalized liquid pore water isotopic composition with sufficiently high accuracy and precision at sampling intervals of less than four minutes and resolved the isotopic variability along natural depth profiles. Comparison indicated that the presented in-situ approaches may be used interchangeably with each other and with concurrent laboratory-based direct equilibration measurements of destructively collected samples, such that the choice of method will depend upon the task and anticipated conditions of sampling. The introduced sampling techniques provide powerful tools towards a detailed quantitative understanding of dynamic and heterogeneous shallow subsurface and vadose zone processes.
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Moran, Antoinette, Gianna Toffolo, Michele Schiavon, Adrian Vella, Katherine Klaus, Claudio Cobelli, and K. Sreekumaran Nair. "A novel triple-tracer approach to assess postprandial protein turnover." American Journal of Physiology-Endocrinology and Metabolism 315, no. 4 (October 1, 2018): E469—E477. http://dx.doi.org/10.1152/ajpendo.00012.2018.
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Insulin and nutrients have profound effects on proteome homeostasis. Currently no reliable methods are available to measure postprandial protein turnover. A triple-tracer method was developed using phenylalanine stable isotope tracers to estimate appearance rates of ingested (Ra meal) and endogenous phenylalanine and the rate of phenylalanine disposal (Rd). This was compared with the “traditional” dual-tracer method, using one (1-CM)- and two (2-CM)-compartment models. For both methods, [13C6]phenylalanine was given orally, and [15N]phenylalanine was constantly infused; the triple-tracer method added [2H5]phenylalanine, infused at rates to mimic meal [13C6]phenylalanine appearance. Additionally, incorporation of meal-derived phenylalanine into specific proteins was measured after purification by two-dimensional electrophoresis. The triple-tracer approach reduced modeling errors, allowing improved reconstruction of Ra meal with a tracer-to-tracee ratio that was more constant and better estimated Rd. The 2-CM better described phenylalanine kinetics and Rd than 1-CM. Thus, the triple-tracer approach using 2-CM is superior for measuring non-steady-state postprandial protein turnover. This novel approach also allows measurement of postprandial synthesis rates of specific plasma proteins. We offer a valid non-steady-state model to measure postprandial protein turnover and synthesis of plasma proteins that can safely be applied in adults, children, and pregnant women.
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Banda, Limbikani C., Michael O. Rivett, Robert M. Kalin, Anold S. K. Zavison, Peaches Phiri, Laura Kelly, Geoffrey Chavula, et al. "Water–Isotope Capacity Building and Demonstration in a Developing World Context: Isotopic Baseline and Conceptualization of a Lake Malawi Catchment." Water 11, no. 12 (December 10, 2019): 2600. http://dx.doi.org/10.3390/w11122600.
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Developing countries such as Malawi require improved access to isotope tracer tools to better characterize and manage water resources threatened by land development, deforestation and climate change. This is the first published study to use an isotope facility developed in Malawi for this purpose, instead of relying upon sample analyses from abroad. Results from this new facility are used to evaluate an important Lake Malawi catchment in the Rift Valley. This work successfully established a stable-isotope baseline, hydrochemical signatures, and system conceptualization against which future policy change and management strategies may be measured. Precipitation isotopic composition was consistent with the Global Meteoric Water Line, but varied, confirming different precipitation systems nationally. Groundwater largely followed a Local Meteoric Water Line, with limited isotopic variation indicating predominant areal groundwater recharge, but with dry-season evaporative enrichment of groundwater near Lake Malawi. Surface-water isotopes widely varied with local precipitation, suggesting the latter accounted for wet-season river flows, but upstream dambo (complex wetlands occupying a shallow, seasonal waterlogged depression) helped sustain dry-season flows. Isotope capacity reinforced water-resource conceptualization and provenance in a hydrologically complex, but not atypical, Rift Valley system, exhibiting a noted complexity of groundwater–surface-water interactions. The latter, critical to integrated water resource management, requires more focused study, to which an expanded array of isotopes will contribute to tracking Sustainable Development Goal 6 targets. This study and future catchment studies should help underpin Malawian water-resource policy implementation on several identified fronts.
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Roche, D. M. "δ<sup>18</sup>O water isotope in the <i>i</i>LOVECLIM model (version 1.0) – Part 1: Implementation and verification." Geoscientific Model Development Discussions 6, no. 1 (March 4, 2013): 1467–94. http://dx.doi.org/10.5194/gmdd-6-1467-2013.
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Abstract. A new 18O stable water isotope scheme is developed for three components of the iLOVECLIM coupled climate model: atmospheric, oceanic and land surface. The equations required to reproduce the fractionation of stable water isotopes in the simplified atmospheric model ECBilt are developed consistently with the moisture scheme. Simplifications in the processes are made to account for the simplified vertical structure including only one moist layer. Implementation of these equations together with a passive tracer scheme for the ocean and a equilibrium fractionation scheme for the land surface leads to the closure of the (isotopic-)water budget in our climate system. Following the implementation, verification of the existence of usual δ18O to climatic relationships are performed for the Rayleigh distillation, the Dansgaard relationship and the δ18O–salinity relationship. Advantages and caveats of the approach taken are outlined.
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Ganot, Yonatan, Ran Holtzman, Noam Weisbrod, Anat Bernstein, Hagar Siebner, Yoram Katz, and Daniel Kurtzman. "Managed aquifer recharge with reverse-osmosis desalinated seawater: modeling the spreading in groundwater using stable water isotopes." Hydrology and Earth System Sciences 22, no. 12 (December 6, 2018): 6323–33. http://dx.doi.org/10.5194/hess-22-6323-2018.
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Abstract. The spreading of reverse-osmosis desalinated seawater (DSW) in the Israeli coastal aquifer was studied using groundwater modeling and stable water isotopes as tracers. The DSW produced at the Hadera seawater reverse-osmosis (SWRO) desalination plant is recharged into the aquifer through an infiltration pond at the managed aquifer recharge (MAR) site of Menashe, Israel. The distinct difference in isotope composition between DSW (δ18O = 1.41 ‰; δ2H = 11.34 ‰) and the natural groundwater (δ18O = −4.48 ‰ to −5.43 ‰; δ2H = −18.41 ‰ to −22.68 ‰) makes the water isotopes preferable for use as a tracer compared to widely used chemical tracers, such as chloride. Moreover, this distinct difference can be used to simplify the system to a binary mixture of two end-members: desalinated seawater and groundwater. This approach is validated through a sensitivity analysis, and it is especially robust when spatial data of stable water isotopes in the aquifer are scarce. A calibrated groundwater flow and transport model was used to predict the DSW plume distribution in the aquifer after 50 years of MAR with DSW. The results suggest that after 50 years, 94 % of the recharged DSW was recovered by the production wells at the Menashe MAR site. The presented methodology is useful for predicting the distribution of reverse-osmosis desalinated seawater in various downstream groundwater systems.
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Zhou, Jiaxin, Jinkui Wu, Shiwei Liu, Guoxiong Zeng, Jia Qin, Xiuna Wang, and Qiudong Zhao. "Hydrograph Separation in the Headwaters of the Shule River Basin: Combining Water Chemistry and Stable Isotopes." Advances in Meteorology 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/830306.
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The runoff components were identified in the headwater area of Shule River Basin, using isotopic and chemical tracing with particular focus on the temporal variations of catchment sources. A total of 95 samples, including precipitation, groundwater, and glacial meltwater, were collected and analyzed for stable water isotopes (18O and2H) and major chemical ion parameters (potassium, sodium, calcium, magnesium, sulfate, chloride, and bicarbonate). Based on the isotope and water chemistry data, we applied end member mixing analysis (EMMA) to identify and quantify the major runoff generating sources and their contributions. The contributions of groundwater, precipitation, and glacial meltwater were 66.7%, 19.9%, and 13.4%, respectively. The study indicated that groundwater dominated runoff in the headwater area of Shule River Basin. The roles of glacier meltwater should be remarkable in water resource management in this basin. The uncertainties of the EMMA method were summarized and estimated via a classical Gaussian error propagation technique. Analyses suggested that the uncertainty in the measurement method was less important than that in the temporal and spatial variations of tracer concentrations. The uncertainty was sensitive when the difference between mixing components was small. Therefore, the variation of tracers and the difference of mixing components should be considered when hydrograph separation was applied in the basin.
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Hamilton, Stephen K., and Nathaniel E. Ostrom. "Measurement of the stable isotope ratio of dissolved N2in15N tracer experiments." Limnology and Oceanography: Methods 5, no. 7 (July 2007): 233–40. http://dx.doi.org/10.4319/lom.2007.5.233.
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Schreiber, Th, U. Pfeiffer, A. Berroth, M. Schreiber, W. Geisser, A. Goertz, and M. Georgieff. "O.5 Assessment of perioperative glycerol metabolismby stable isotope tracer technique." Clinical Nutrition 15 (August 1996): 2. http://dx.doi.org/10.1016/s0261-5614(96)80052-5.
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