82 research outputs found
Effect of dexamethasone on fetal hepatic glutamine-glutamate exchange
Intravenous infusion of dexamethasone (Dex) in the fetal lamb causes a
two- to threefold increase in plasma glutamine and other glucogenic amino
acids and a decrease of plasma glutamate to approximately one-third of
normal. To explore the underlying mechanisms, hepatic amino acid uptake
and conversion of L-[1-(13)C]glutamine to L-[1-(13)C]glutamate and
(13)CO(2) were measured in six sheep fetuses before and in the last 2 h of
a 26-h Dex infusion. Dex decreased hepatic glutamine and alanine uptakes
(P < 0.01) and hepatic glutamate output (P < 0.001). Hepatic outputs of
the glutamate (R(Glu,Gln)) and CO(2) formed from plasma glutamine
decreased to 21 (P < 0.001) and 53% (P = 0.009) of control, respectively.
R(Glu,Gln), expressed as a fraction of both outputs, decreased (P < 0.001)
from 0.36 +/- 0.02 to 0.18 +/- 0.04. Hepatic glucose output remained
virtually zero throughout the experiment. We conclude that Dex decreases
fetal hepatic glutamate output by increasing the routing of glutamate
carbon into the citric acid cycle and by decreasing the hepatic uptake of
glucogenic amino acids
Changes in fetal mannose and other carbohydrates induced by a maternal insulin infusion in pregnant sheep
BACKGROUND: The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short (2-wk) and long (8-wk) durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions (1-wk hyperinsulinemic-isoglycemic clamp) to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. RESULTS: A maternal insulin infusion resulted in lower maternal (50%, P < 0.01) and fetal (35-45%, P < 0.01) mannose concentrations, which were highly correlated (r(2) = 0.69, P < 0.01). A fetal insulin infusion resulted in a 50% reduction of fetal mannose (P < 0.05). Neither maternal nor fetal plasma inositol changed with exogenous insulin infusions. Additionally, maternal insulin infusion resulted in lower fetal sorbitol and fructose (P < 0.01). CONCLUSIONS: Chronically decreased glucose supply to the fetus as well as fetal hyperinsulinemia both reduce fetal non-glucose carbohydrates. Given the role of these carbohydrates in protein glycosylation and lipid production, more research on their metabolism in pregnancies complicated by abnormal glucose metabolism is clearly warranted
Umbilical uptakes and transplacental concentration ratios of amino acids in severe fetal growth restriction
Background: This study examines the relationship between placental amino acid (AA) transport and fetal AA demand in an ovine fetal growth restriction (FGR) model in which placental underdevelopment induces fetal hypoxemia and hypoglycemia. Methods: Umbilical uptakes of AA, oxygen, glucose, and lactate were measured near term in eight experimental ewes (FGR group) and in eight controls (C group). Results: The FGR group demonstrated significantly reduced umbilical uptakes of oxygen, glucose, lactate, and 11 AAs per kg fetus. The combined uptake of glucose, lactate, and AAs, expressed as nutrient/oxygen quotients, was reduced almost to 1.00 (FGR: 1.05 vs. C: 1.32, P ≤ 0.02). In contrast to a decrease in umbilical glucose concentration, all but one of the AAs that were transported from placenta to fetus demonstrated normal or elevated fetal concentrations, and five of the essential AAs were transported against a significantly higher feto/maternal (F/M) concentration ratio. This ratio peaked at the lowest fetal oxygen levels. Conclusion: We conclude that, in the hypoxic FGR fetus, the reduction in AA uptake is not due to a disproportionally small placental AA transport capacity. It is the consequence of decreased fetal oxidative metabolism and growth rate, which together reduce fetal AA demand. © 2013 International Pediatric Research Foundation, Inc
CMB-S4: Forecasting Constraints on Primordial Gravitational Waves
CMB-S4---the next-generation ground-based cosmic microwave background (CMB)
experiment---is set to significantly advance the sensitivity of CMB
measurements and enhance our understanding of the origin and evolution of the
Universe, from the highest energies at the dawn of time through the growth of
structure to the present day. Among the science cases pursued with CMB-S4, the
quest for detecting primordial gravitational waves is a central driver of the
experimental design. This work details the development of a forecasting
framework that includes a power-spectrum-based semi-analytic projection tool,
targeted explicitly towards optimizing constraints on the tensor-to-scalar
ratio, , in the presence of Galactic foregrounds and gravitational lensing
of the CMB. This framework is unique in its direct use of information from the
achieved performance of current Stage 2--3 CMB experiments to robustly forecast
the science reach of upcoming CMB-polarization endeavors. The methodology
allows for rapid iteration over experimental configurations and offers a
flexible way to optimize the design of future experiments given a desired
scientific goal. To form a closed-loop process, we couple this semi-analytic
tool with map-based validation studies, which allow for the injection of
additional complexity and verification of our forecasts with several
independent analysis methods. We document multiple rounds of forecasts for
CMB-S4 using this process and the resulting establishment of the current
reference design of the primordial gravitational-wave component of the Stage-4
experiment, optimized to achieve our science goals of detecting primordial
gravitational waves for at greater than , or, in the
absence of a detection, of reaching an upper limit of at CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note:
text overlap with arXiv:1907.0447
Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
CMB-S4
We describe the stage 4 cosmic microwave background ground-based experiment CMB-S4
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