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The bedside Exhaled Drug MONitor - EDMON measures exhaled propofol in ppbv every minute based on multi-capillary column - ion mobility spectrometry (MCC-IMS). The MCC pre-separates gas samples, thereby reducing the influence of the high humidity in human breath. However, preliminary analyses identified substantial measurement deviations between dry and humid calibration standards. We therefore performed an analytical validation of the EDMON to evaluate the influence of humidity on measurement performance. A calibration gas generator was used to generate gaseous propofol standards measured by an EDMON device to assess linearity, precision, carry-over, resolution, and the influence of different levels of humidity at 100% and 1.7% (without additional) relative humidity (reference temperature: 37°C). EDMON measurements were roughly half the actual concentration without additional humidity and roughly halved again at 100% relative humidity. Standard concentrations and EDMON values correlated linearly at 100% relative humidity (R²=0.97). The measured values were stable over 100min with a variance ≤ 10% in over 96% of the measurements. Carry-over effects were low with 5% at 100% relative humidity after 5min of equilibration. EDMON measurement resolution at 100% relative humidity was 0.4 and 0.6 ppbv for standard concentrations of 3 ppbv and 41 ppbv. The influence of humidity on measurement performance was best described by a second-order polynomial function (R²≥0.99) with influence reaching a maximum at about 70% relative humidity. We conclude that EDMON measurements are strongly influenced by humidity and should therefore be corrected for sample humidity to obtain accurate estimates of exhaled propofol concentrations.
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Propofol , Humanos , Humedad , Pruebas Respiratorias/métodos , Naftiridinas , GasesRESUMEN
BACKGROUND: Analysis of exhaled air is a risk-free option for bedside diagnostics. Modern breath analysis can detect very low concentrations of volatile components. Current research focuses on drug monitoring and diagnosis of various diseases. OBJECTIVES: Presentation and discussion of current breath research relevant to intensive care medicine. MATERIALS AND METHODS: The literature in PubMed was searched using the following terms: "breath analysis", "volatile organic compounds", "critically ill" combined with "drug monitoring", "propofol", "heart failure", "pneumonia", "ARDS", "renal failure", "liver failure", "sepsis" or "hemorrhage". RESULTS: Intravenously administered propofol can now be measured reliably in exhaled air. Functional impairments of the heart, lungs, kidneys and liver show characteristic influences on the exhaled air, which could serve as a new diagnostic tool in the future. Animal experiments already show promising results to detect sepsis, hemorrhage and ventilator-induced lung injury. CONCLUSIONS: In the future, modern breath analysis could enable non-invasive drug monitoring and diagnostics of medical conditions relevant to intensive care medicine.
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Pruebas Respiratorias , Compuestos Orgánicos Volátiles , Pruebas Respiratorias/métodos , Espiración/fisiología , Humanos , Compuestos Orgánicos Volátiles/análisisRESUMEN
We present magneto-Raman spectroscopy measurements on suspended graphene to investigate the charge carrier density-dependent electron-electron interaction in the presence of Landau levels. Utilizing gate-tunable magnetophonon resonances, we extract the charge carrier density dependence of the Landau level transition energies and the associated effective Fermi velocity v_{F}. In contrast to the logarithmic divergence of v_{F} at zero magnetic field, we find a piecewise linear scaling of v_{F} as a function of the charge carrier density, due to a magnetic-field-induced suppression of the long-range Coulomb interaction. We quantitatively confirm our experimental findings by performing tight-binding calculations on the level of the Hartree-Fock approximation, which also allow us to estimate an excitonic binding energy of ≈6 meV contained in the experimentally extracted Landau level transitions energies.
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Scattering of fast neutral atoms with keV kinetic energies at alkali-halide surfaces under grazing angles displays intriguing diffraction patterns. The surprisingly strong persistence of quantum coherence despite the impulsive interaction with an environment at solid state density and elevated temperatures raises fundamental questions such as to the suppression of decoherence and of the quantum-to-classical crossover. We present an ab initio simulation of the quantum diffraction of fast helium beams at a LiF (100) surface in the 110 direction and compare with recent experimental diffraction data. From the quantitative reconstruction of diffraction images the vertical LiF-surface reconstruction, or buckling, can be determined.
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The full three-dimensional dispersion of the pi bands, Fermi velocities, and effective masses are measured with angle-resolved photoemission spectroscopy and compared to first-principles calculations. The band structure by density-functional theory underestimates the slope of the bands and the trigonal warping effect. Including electron-electron correlation on the level of the GW approximation, however, yields remarkable improvement in the vicinity of the Fermi level. This demonstrates the breakdown of the independent electron picture in semimetallic graphite and points toward a pronounced role of electron correlation for the interpretation of transport experiments and double-resonant Raman scattering for a wide range of carbon based materials.
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The phonon dispersion relations of bulk hexagonal boron nitride have been determined from inelastic x-ray scattering measurements and analyzed by ab initio calculations. Experimental data and calculations show an outstanding agreement and reconcile the controversies raised by recent experimental data obtained by electron-energy loss spectroscopy and second-order Raman scattering.
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We present Raman spectroscopy measurements on single- and few-layer graphene flakes. By using a scanning confocal approach, we collect spectral data with spatial resolution, which allows us to directly compare Raman images with scanning force micrographs. Single-layer graphene can be distinguished from double- and few-layer by the width of the D' line: the single peak for single-layer graphene splits into different peaks for the double-layer. These findings are explained using the double-resonant Raman model based on ab initio calculations of the electronic structure and of the phonon dispersion. We investigate the D line intensity and find no defects within the flake. A finite D line response originating from the edges can be attributed either to defects or to the breakdown of translational symmetry.
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Single-wall boron nitride nanotubes samples synthesized by laser vaporization of a hexagonal BN target under a nitrogen atmosphere are studied by UV and visible Raman spectroscopy. We show that resonant conditions are necessary for investigating phonon modes of BNNTs. Raman excitation in the UV (229 nm) provides preresonant conditions, allowing the identification of the A1 tangential mode at 1370 cm(-1). This is 5 cm(-1) higher than the E(2g) mode in bulk h-BN. Ab initio calculations show that the lower frequency of bulk h-BN with respect to large diameter nanotubes and the single sheet of h-BN is related to a softening of the sp2 bonds in the bulk due to interlayer interaction.
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Compuestos de Boro/análisis , Compuestos de Boro/química , Cristalización/métodos , Nanotubos/análisis , Nanotubos/química , Espectrometría Raman/métodos , Ensayo de Materiales , Conformación Molecular , Tamaño de la PartículaRESUMEN
A new form of potential sputtering has been found for impact of slow ( < or = 1500 eV) multiply charged Xe ions (charge states up to q = 25) on MgO(x). In contrast to alkali-halide or SiO2 surfaces this mechanism requires the simultaneous presence of electronic excitation of the target material and of a kinetically formed collision cascade within the target in order to initiate the sputtering process. This kinetically assisted potential sputtering mechanism has been identified to be present for other insulating surfaces as well.
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Current understanding of expression-site transcription in Trypanosoma brucei, has been refined by recent results of promoter manipulations at vsg expression sites (ES) and examination of the behavior of ES promoters in ectopic locations both within the ES and at other loci. In summary, ES promoter sequences inserted into non-transcribed rRNA spacers are generally inactive, or have low activity, in bloodstream and procyclic forms. Some mechanism apparently operates to ensure full activation of a single ES in bloodstream-form trypanosomes and the inactivity of all ES promoters in procyclic forms. As previously shown, a rRNA promoter can replace an ES promoter. In bloodstream forms, the replacement rRNA promoter was down-regulated in a 'silent' ES but it was active in procyclic forms. In addition to manipulations of endogenous promoters, we have recently shown that, when an ES promoter is replaced by a T7 promoter, the T7 promoter is unregulated but transcription is attenuated before the vsg, and another ES switches on to maintain cell viability. However, T7 transcription is repressed in the context of core ES-promoter sequences in both stages, particularly in procyclic forms. These observations strongly argue that sequences in the vicinity of the ES core promoter play a role in ES control by nucleating critical events in silencing as well as in activation. Deletions of sequences surrounding the ES core promoter, in situ, did not affect its activity or regulation. In bloodstream forms, rRNA or ES promoters inserted adjacent to silent telomeres or to a non-telomeric 'basic-copy' vsg were > 98% repressed. After transformation to procyclic forms, the sub-telomeric rRNA promoter regained about 10% of its maximal activity but the 'basic-copy' rRNA promoter was fully active. Similarly-positioned ES promoters remained silent in procyclic forms. These results suggest that telomere-proximal or vsg-proximal sequences might mediate suppression of transcription via position-effects that could be sufficient to suppress the expression of chromosome-internal vsgs or telomeric metacyclic vsgs, in bloodstream-form trypanosomes. Recent experiments with T7 promoters indicate that sequences within the ES core promoter might be responsible for silencing ES promoters in procyclic forms. Precedents for regulatory mechanisms that modulate transcription over large chromatin domains are reviewed and possible models for ES regulation are presented.
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Variación Antigénica , Regulación de la Expresión Génica , Transcripción Genética , Trypanosoma brucei brucei/genética , Glicoproteínas Variantes de Superficie de Trypanosoma/genética , Animales , Reordenamiento Génico , Regiones Promotoras Genéticas , Glicoproteínas Variantes de Superficie de Trypanosoma/inmunologíaRESUMEN
We previously described a system for exogenous control of gene expression in procyclic trypanosomes which depends upon the binding of a tetracycline-inducible repressor to operators situated at the transcriptional start site of the PARP promoter. The recombinant constructs are introduced into non-transcribed spacers of the ribosomal RNA repeat, in an orientation opposite to that of rRNA transcription. Using this system, gene expression could be regulated over four orders of magnitude, but it was not possible to express toxic gene products because selection of recombinant trypanosomes depended on the activity of the inducible promoter. We describe here the characteristics of vectors that include two promoters: a tetracycline-inducible one to drive expression of the toxic products, and a constitutive one to drive transcription of the selectable marker. Relatively high levels of non-induced (non-tetracycline-dependent) expression were seen in some trypanosome clones; this was not usually due to read-through of multiple tandemly-integrated plasmids or tet operator mutations. A variety of constructs differing in resistance marker, 3'-untranslated region (3'-UTR) and the nature of the constitutive promoter was tested. Vectors allowing the successful expression of toxic and other genes in both life cycle stages with regulation factors of up to 700 fold were obtained.
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Clonación Molecular/métodos , Regulación de la Expresión Génica , Vectores Genéticos , Proteínas Protozoarias , Toxinas Biológicas/biosíntesis , Trypanosoma brucei brucei/genética , Animales , ADN Ribosómico/genética , Genes Reporteros , Marcadores Genéticos , Luciferasas/biosíntesis , Luciferasas/genética , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Regiones Promotoras Genéticas , Toxinas Biológicas/genéticaRESUMEN
African trypanosomes are extracellular protozoan parasites that are transmitted from one mammalian host to the next by tsetse flies. Bloodstream forms express variant surface glycoprotein (VSG); the tsetse fly (procyclic) forms express instead the procyclic acidic repetitive protein (PARP). PARP mRNA is abundant in procyclic forms and almost undetectable in blood-stream forms. Post-transcriptional mechanisms are mainly responsible for PARP mRNA regulation but results of nuclear run-on experiments suggested that transcription might also be regulated. We measured the activity of genomically-integrated PARP, VSG and rRNA promoters in permanently-transformed blood-stream and procyclic form trypanosomes, using reporter gene constructs that showed no post-transcriptional regulation. When the constructs were integrated in the rRNA non-transcribed spacer, the ribosomal RNA and VSG promoters were not developmentally regulated, but integration at the PARP locus reduced rRNA promoter activity in bloodstream forms. PARP promoter activity was 5-fold down-regulated in bloodstream forms when integrated at either site. Regulation was probably at the level of transcriptional initiation, but elongation through plasmid vector sequences was also reduced.