Dual nuclear magnetic resonance for probing intrinsic bone structure and a potential gut–bone axis in ovariectomized rats

Currently, the existence of a gut–bone axis receives massive attention, and while sound premises and indirect proofs exist for the gut–bone axis concept, few studies have provided actual data linking the gut and bone physically. This study aimed to exploit the versatile nature of nuclear magnetic resonance (NMR) to link NMR relaxometry data on bone mineralization with NMR spectroscopic profiling of gut metabolites. For this purpose, sample material was obtained from a 6-week intervention study with ovariectomized (OVX) rats (n = 49) fed with seven different diets varying in calcium content (0.2–6.0 mg/kg) and prebiotic fiber content (0–5.0% w/w). This design ensured a span in (i) calcium available for bone mineralization and (ii) metabolic activity in the gut. After termination of the intervention, longitudinal (T₁), transverse (T₂) relaxation, and mechanical bone strength were measured on the excised femur bones. A PLS model with high predictability (Q² = 0.86, R² = 0.997) was demonstrated between T₂ decay curves and femur mechanical strength. Correlations were established between bone T₂ populations and gut short-chain fatty acids. In conclusion, the present dual NMR approach showed strong correlation between T₂ relaxation and mechanical strength of the bone, and when metabolic activity in the gut was modulated by inulin, the potential existence of a gut–bone axis was demonstrated.     

On numerical density approximations of solutions of SDEs with unbounded coefficients

We study a numerical method to compute probability density functions of solutions of stochastic differential equations. The method is sometimes called the numerical path integration method and has been shown to be fast and accurate in application oriented fields. In this paper we provide a rigorous analysis of the method that covers systems of equations with unbounded coefficients. Working in a natural space for densities, L ¹, we obtain stability, consistency, and new convergence results for the method, new well-posedness and semigroup generation results for the related Fokker-Planck-Kolmogorov equation, and a new and rigorous connection to the corresponding probability density functions for both the approximate and the exact problems. To prove the results we combine semigroup and PDE arguments in a new way that should be of independent interest.     

Ornstein–Uhlenbeck processes in Hilbert space with non-Gaussian stochastic volatility

We propose a non-Gaussian operator-valued extension of the Barndorff-Nielsen and Shephard stochastic volatility dynamics, defined as the square-root of an operator-valued Ornstein–Uhlenbeck process with Lévy noise and bounded drift. We derive conditions for the positive definiteness of the Ornstein–Uhlenbeck process, where in particular we must restrict to operator-valued Lévy processes with “non-decreasing paths”. It turns out that the volatility model allows for an explicit calculation of its characteristic function, showing an affine structure. We introduce another Hilbert space-valued Ornstein–Uhlenbeck process with Wiener noise perturbed by this class of stochastic volatility dynamics. Under a strong commutativity condition between the covariance operator of the Wiener process and the stochastic volatility, we can derive an analytical expression for the characteristic functional of the Ornstein–Uhlenbeck process perturbed by stochastic volatility if the noises are independent. The case of operator-valued compound Poisson processes as driving noise in the volatility is discussed as a particular example of interest. We apply our results to futures prices in commodity markets, where we discuss our proposed stochastic volatility model in light of ambit fields.     

Artifacts in dynamical simulations of coarse-grained model lipid bilayers

With special focus on dissipative particle dynamics simulations of anisotropic and complex soft matter, such as lipid bilayers in water, we have investigated the occurrence of artifacts in the results obtained from dynamical simulations of coarse-grained particle-based models. The particles are modeled by beads that interact via soft repulsive conservative forces (as defined in dissipative particle dynamics simulations), harmonic bond potentials, as well as bending potentials imparting stiffness to the lipid tails. Two different update schemes are investigated: dissipative particle dynamics with a velocity-Verlet-like integration scheme [G. Besold, I. Vattulainen, M. Karttunen, and J. M. Polson, Phys. Rev. E 63, R7611 (2000)] and Lowe-Andersen thermostatting [C. P. Lowe, Europhys. Lett. 47, 145 (1999)] with the standard velocity-Verlet integration algorithm. By varying the integration time step, we examine various physical quantities, in particular pressure profiles and kinetic bead temperatures, for their sensitivity to artifacts caused by the specific combination of integration technique and the thermostat. We then propose a simple fingerprint method that allows monitoring the presence of simulation artifacts.     

Thiophene chemistry—X Preparation, tautomeric structure and hydrogen bonding studies of thioisomaltol (2-acetyl-3-hydroxythiophene) and some related 3-hydroxythiophenes

Different acetyl- and carbethoxysubstituted 3-t-butoxythiophenes have been prepared via organometallic reagents. Dealkylation of these t-butyl ethers in the presence of a catalytic amount of p-toluenesulphonic acid at 150° gives the corresponding 3-hydroxythiophenes in almost quantitative yields. Spectroscopic investigations by NMR and IR show that carbonyl (acetyl or carbalkoxy)-substituted 3-hydroxythiophenes exist exclusively in the hydroxyaromatic form in polar and non-polar media and in the pure (solid or liquid) state. The only exception is 5-carbethoxy-2,3-dihydroxythiophene which is shown to exist in one of is two possible unsaturated γ-thiolactone forms. the NMR and IR-spectra show the presence of hydrogen bonding and when intramolecular hydrogen bonding is sterically possible its strength, as measured by the chemical shft of the enolic proton (NMR) and shifts to lower wave numbers for both the hydroxyl and carbonyl frequencies (IR), is discussed along with observations for compounds with similar structures. Long-range spin coupling between the aromatic C-5 proton and the OH proton is observed in one case.     

Acquisition and quantification of ion images with a camera-based detection system and classical quantification algorithms

The quantitative analytical characteristics of a camera-based detection system for secondary ion microscopy are studied in detail. Through multiple exposures, ion images with large dynamic ranges are obtained. The quantification of these images by the sensitivity factor method and the matrix ion species ratio method is described and evaluated by the analysis of steel and aluminum standard reference materials.     

Temperature-promoted large-volume solute enrichment in column-switching miniaturized liquid chromatography: determination of an antioxidant

A two-valve sub-ambient temperature-promoted reversed-phase packed-capillary liquid-chromatography column-switching system has been tailored for sensitive determination of hydrophobic compounds. Such compounds are not easily dissolved in solvent mixtures of non-eluting properties that traditionally are used for solute enrichment in reversed-phase liquid chromatography. Enrichment-column solute focusing of large sample volumes was promoted by use of sub-ambient temperatures only, allowing the use of sample solvents that were stronger or equal to the mobile phase solvent strength. Subsequent column switching and enrichment-column temperature increment provided efficient low-dispersion back-flushed enrichment-column solute desorption onto the analytical column, where the solute was subjected to temperature-programmed gradient action. The antioxidant, Irganox 1076 (octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) extracted from low density polyethylene with 100% acetonitrile served as a hydrophobic model compound. The mobile phase consisted of acetonitrile containing 10 mM triethylamine and formic acid, and the 0.25 mm id enrichment-column and analytical column in lengths of 27 and 250 mm, respectively, were packed with 3.5 microm Kromasil C18 particles. Sample volumes of up to 500 microL were successfully focused on the enrichment column at 5 degrees C using loading flow rates of up to 40 microL min(-1) prior to temperature programming to 90 degrees C. The concentration limit of detection of Irganox 1076 was 6 ng mL(-1) when using an injection volume of 500 microL. The within-assay precision was in the range 3.5-6.8% (n = 6) while the between-day precision was 7.5% (n = 3) relative standard deviation. The method was linear within the investigated mass range 3-100 ng (R2 = 0.9993).     

Determination of the enantiomer fraction of PBB 149 by gas chromatography/electron capture negative ionization tandem mass spectrometry in the selected reaction monitoring mode

Enantioselective determination of the atropisomers of 2,2',3,4',5',6-hexabromobiphenyl (PBB 149) in a purified sample from a bird egg was attempted in this work. By application of the classic method for PBB determination, i.e. gas chromatography coupled to electron capture negative ionization mass spectrometry (GC/ECNI-MS) using the bromide ions, the enantiomers interfered with another brominated compound. Subsequent measurements clarified that this interference did not occur in the mass chromatogram of the molecular ion of PBB 149. Therefore, a GC/ECNI tandem mass spectrometry (MS/MS) method was developed, based on the fragmentation of [M]-. A suitable precursor-product ion transition was found for m/z 627.5 --> 80 +/- 1.5, representing the most abundant ion trace of the molecular ion and the bromide ions. Optimization of the ion source temperature, the methane gas pressure, and the collision voltages resulted in a robust method that could solve the problem. Subsequent injections of a technical PBB product (Firemaster BP-6) resulted in the anticipated racemic proportion (enantiomer fraction (EF) = 0.50 +/- 0.02 (n = 8)). By contrast, the EF in the purified extract of a bird egg was found to be 0.42 +/- 0.02 (n = 10), indicative of a significant enantioenrichment of the second eluting atropisomer. Additional measurements were performed on a non-chiral column. These measurements allowed for the detection of 16 hexabromobiphenyls (hexa-BBs) in Firemaster BP-6. These comparisons verified that PBB 149 enantiomers did not interfere with an isomer that could falsify the enantiomer fraction in the sample. The novel method using GC/ECNI-MS/MS in the selected reaction monitoring (SRM) mode was eight times more sensitive than application of conventional GC/ECNI-MS selected ion monitoring (SIM) analysis of the molecular ion.     

Temperature‐Programmed Packed Capillary Liquid Chromatography Coupled to Fourier‐Transform Infrared Spectroscopy

Temperature‐programmed packed capillary liquid chromatography has been coupled off‐line to Fourier‐transform infrared spectroscopy, utilizing a commercially available interface with a pneumatic nebulizer rebuilt to handle low flow rates at elevated temperatures. The modified interface showed excellent performance with regard to non‐aqueous reversed phase separations of polymer additives, resulting in constructed Gram‐Schmidt chromatograms comparable to chromatograms obtained using UV detection. The spray of the in‐house constructed nebulizer was not influenced by temperature changes of the column effluent, and hence temperature‐programmed gradient separations could be used successfully. The relative standard deviation of peak height was 4.4% (n = 5) and the mass limit of detection was determined to be about 40 ng, using a polymer antioxidant as model compound. The present instrumental coupling has been used for characterization of the antioxidant Irgafos P‐EPQ.