111 research outputs found
The Genesis Solar Wind Concentrator Target: Mass Fractionation Characterised by Neon Isotopes
The concentrator on Genesis provided samples of increased fluences of solar wind ions for precise determination of the oxygen isotopic composition. The concentration process caused mass fractionation as a function of the radial target position. This fractionation was measured using Ne released by UV laser ablation and compared with modelled Ne data, obtained from ion-trajectory simulations. Measured data show that the concentrator performed as expected and indicate a radially symmetric concentration process. Measured concentration factors are up to ∼30 at the target centre. The total range of isotopic fractionation along the target radius is 3.8%/amu, with monotonically decreasing 20Ne/22Ne towards the centre, which differs from model predictions. We discuss potential reasons and propose future attempts to overcome these disagreement
Analysis of lead oxide (PbO) layers for direct conversion X-ray detection
Lead oxide (PbO) is a candidate direct conversion material for medical X-ray applications. We produced various samples and detectors with thick PbO layers. X-ray performance data such as dark current, charge generation yield and temporal behavior were evaluated on small samples. The influence of the metal contacts was studied in detail. We also covered large a-Si thin-film transistor (TFT)-plates with PbO. Imaging results from a large detector with an active area of 18 cm × 20 cm are presented. The detector has 960 × 1080 pixels with a pixel pitch of 184 ?m. The modulation transfer function at the Nyquist frequency of 2.72 linepairs/mm is 50%. Finally, a full size X-ray image is presented
13C labeling experiments at metabolic nonstationary conditions: An exploratory study
<p>Abstract</p> <p>Background</p> <p>Stimulus Response Experiments to unravel the regulatory properties of metabolic networks are becoming more and more popular. However, their ability to determine enzyme kinetic parameters has proven to be limited with the presently available data. In metabolic flux analysis, the use of <sup>13</sup>C labeled substrates together with isotopomer modeling solved the problem of underdetermined networks and increased the accuracy of flux estimations significantly.</p> <p>Results</p> <p>In this contribution, the idea of increasing the information content of the dynamic experiment by adding <sup>13</sup>C labeling is analyzed. For this purpose a small example network is studied by simulation and statistical methods. Different scenarios regarding available measurements are analyzed and compared to a non-labeled reference experiment. Sensitivity analysis revealed a specific influence of the kinetic parameters on the labeling measurements. Statistical methods based on parameter sensitivities and different measurement models are applied to assess the information gain of the labeled stimulus response experiment.</p> <p>Conclusion</p> <p>It was found that the use of a (specifically) labeled substrate will significantly increase the parameter estimation accuracy. An overall information gain of about a factor of six is observed for the example network. The information gain is achieved from the specific influence of the kinetic parameters towards the labeling measurements. This also leads to a significant decrease in correlation of the kinetic parameters compared to an experiment without <sup>13</sup>C-labeled substrate.</p
Development of a kinetic metabolic model: application to Catharanthus roseus hairy root
A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independent pathways. Hairy root specific growth rate was described as a function of intracellular concentration in cell building blocks. Intracellular transport and accumulation kinetics for major nutrients were included. The model uses intracellular nutrients as well as energy shuttles to describe metabolic regulation. Model calibration was performed using experimental data obtained from batch and medium exchange liquid cultures of C. roseus hairy root using a minimal medium in Petri dish. The model is efficient in estimating the growth rate
Recent advances in Pichia pastoris as host for heterologous expression system for lipases : a review
The production of heterologous lipases is one of the most promising strategies to increase the productivity of the bioprocesses and to reduce costs, with the final objective that more industrial lipase applications could be implemented. In this chapter, an overview of the new success in synthetic biology, with traditional molecular genetic techniques and bioprocess engineering in the last 5 years in the cell factory Pichia pastoris, the most promising host system for heterologous lipase production, is presented. The goals get on heterologous Candida antarctica, Rhizopus oryzae, and Candida rugosa lipases, three of the most common lipases used in biocatalysis, are showed. Finally, new cell factories producing heterologous lipases are presented
A design–build–test cycle using modeling and experiments reveals interdependencies between upper glycolysis and xylose uptake in recombinant S. cerevisiae and improves predictive capabilities of large-scale kinetic models
What is the Oxygen Isotope Composition of Venus? The Scientific Case for Sample Return from Earth’s “Sister” Planet
Venus is Earth’s closest planetary neighbour and both bodies are of similar size and mass. As a consequence, Venus is often described as Earth’s sister planet. But the two worlds have followed very different evolutionary paths, with Earth having benign surface conditions, whereas Venus has a surface temperature of 464 °C and a surface pressure of 92 bar. These inhospitable surface conditions may partially explain why there has been such a dearth of space missions to Venus in recent years.The oxygen isotope composition of Venus is currently unknown. However, this single measurement (Δ17O) would have first order implications for our understanding of how large terrestrial planets are built. Recent isotopic studies indicate that the Solar System is bimodal in composition, divided into a carbonaceous chondrite (CC) group and a non-carbonaceous (NC) group. The CC group probably originated in the outer Solar System and the NC group in the inner Solar System. Venus comprises 41% by mass of the inner Solar System compared to 50% for Earth and only 5% for Mars. Models for building large terrestrial planets, such as Earth and Venus, would be significantly improved by a determination of the Δ17O composition of a returned sample from Venus. This measurement would help constrain the extent of early inner Solar System isotopic homogenisation and help to identify whether the feeding zones of the terrestrial planets were narrow or wide.Determining the Δ17O composition of Venus would also have significant implications for our understanding of how the Moon formed. Recent lunar formation models invoke a high energy impact between the proto-Earth and an inner Solar System-derived impactor body, Theia. The close isotopic similarity between the Earth and Moon is explained by these models as being a consequence of high-temperature, post-impact mixing. However, if Earth and Venus proved to be isotopic clones with respect to Δ17O, this would favour the classic, lower energy, giant impact scenario.We review the surface geology of Venus with the aim of identifying potential terrains that could be targeted by a robotic sample return mission. While the potentially ancient tessera terrains would be of great scientific interest, the need to minimise the influence of venusian weathering favours the sampling of young basaltic plains. In terms of a nominal sample mass, 10 g would be sufficient to undertake a full range of geochemical, isotopic and dating studies. However, it is important that additional material is collected as a legacy sample. As a consequence, a returned sample mass of at least 100 g should be recovered.Two scenarios for robotic sample return missions from Venus are presented, based on previous mission proposals. The most cost effective approach involves a “Grab and Go” strategy, either using a lander and separate orbiter, or possibly just a stand-alone lander. Sample return could also be achieved as part of a more ambitious, extended mission to study the venusian atmosphere. In both scenarios it is critical to obtain a surface atmospheric sample to define the extent of atmosphere-lithosphere oxygen isotopic disequilibrium. Surface sampling would be carried out by multiple techniques (drill, scoop, “vacuum-cleaner” device) to ensure success. Surface operations would take no longer than one hour.Analysis of returned samples would provide a firm basis for assessing similarities and differences between the evolution of Venus, Earth, Mars and smaller bodies such as Vesta. The Solar System provides an important case study in how two almost identical bodies, Earth and Venus, could have had such a divergent evolution. Finally, Venus, with its runaway greenhouse atmosphere, may provide data relevant to the understanding of similar less extreme processes on Earth. Venus is Earth’s planetary twin and deserves to be better studied and understood. In a wider context, analysis of returned samples from Venus would provide data relevant to the study of exoplanetary systems
Magnesium isotope evidence that accretional vapour loss shapes planetary compositions
It has long been recognized that Earth and other differentiated planetary bodies are chemically fractionated compared to primitive, chondritic meteorites and, by inference, the primordial disk from which they formed. However, it is not known whether the notable volatile depletions of planetary bodies are a consequence of accretion1 or inherited from prior nebular fractionation2. The isotopic compositions of the main constituents of planetary bodies can contribute to this debate3, 4, 5, 6. Here we develop an analytical approach that corrects a major cause of measurement inaccuracy inherent in conventional methods, and show that all differentiated bodies have isotopically heavier magnesium compositions than chondritic meteorites. We argue that possible magnesium isotope fractionation during condensation of the solar nebula, core formation and silicate differentiation cannot explain these observations. However, isotopic fractionation between liquid and vapour, followed by vapour escape during accretionary growth of planetesimals, generates appropriate residual compositions. Our modelling implies that the isotopic compositions of magnesium, silicon and iron, and the relative abundances of the major elements of Earth and other planetary bodies, are a natural consequence of substantial (about 40 per cent by mass) vapour loss from growing planetesimals by this mechanism
From correlation to causation: analysis of metabolomics data using systems biology approaches
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
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