Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized H NMR spectra

Proton NMR resonances of the endogenous metabolites creatine and phosphocreatine ((P)Cr), taurine (Tau), and carnosine (Cs, β-alanyl-l-histidine) were studied with regard to residual dipolar couplings and molecular mobility. We present an analysis of the direct ¹H–¹H interaction that provides information on motional reorientation of subgroups in these molecules in vivo. For this purpose, localized ¹H NMR experiments were performed on m. gastrocnemius of healthy volunteers using a 1.5-T clinical whole-body MR scanner. We evaluated the observable dipolar coupling strength SD₀ (S = order parameter) of the (P)Cr-methyl triplet and the Tau-methylene doublet by means of the apparent line splitting. These were compared to the dipolar coupling strength of the (P)Cr-methylene doublet. In contrast to the aliphatic protons of (P)Cr and Tau, the aromatic H2 (δ = 8 ppm) and H4 (δ = 7 ppm) protons of the imidazole ring of Cs exhibit second-order spectra at 1.5 T. This effect is the consequence of incomplete transition from Zeeman to Paschen-Back regime and allows a determination of SD₀ from H2 and H4 of Cs as an alternative to evaluating the multiplet splitting which can be measured directly in high-resolution ¹H NMR spectra. Experimental data showed striking differences in the mobility of the metabolites when the dipolar coupling constant D₀ (calculated with the internuclear distance known from molecular geometry in the case of complete absence of molecular dynamics and motion) is used for comparison. The aliphatic signals involve very small order parameters S ≈ (1.4 − 3) × 10⁻⁴ indicating rapid reorientation of the corresponding subgroups in these metabolites. In contrast, analysis of the Cs resonances yielded S ≈ (113 − 137) × 10⁻⁴. Thus, the immobilization of the Cs imidazole ring owing to an anisotropic cellular substructure in human m. gastrocnemius is much more effective than for (P)Cr and Tau subgroups. Furthermore, ¹H NMR experiments on aqueous model solutions of histidine and N-acetyl-l-aspartate (NAA) enabled the assignment of an additional signal component at δ = 8 ppm of Cs in vivo to the amide group at the peptide bond. The visibility of this proton could result from hydrogen bonding which would agree with the anticipated stronger motional restriction of Cs. Referring to the observation that all dipolar-coupled multiplets resolved in localized in vivo ¹H NMR spectra of human m. gastrocnemius collapse simultaneously when the fibre structure is tilted towards the magic angle (θ ≈ 55°), a common model for molecular confinement in muscle tissue is proposed on the basis of an interaction of the studied metabolites with myocellular membrane phospholipids.     

Ant colony optimization: Introduction and recent trends

Ant colony optimization is a technique for optimization that was introduced in the early 1990's. The inspiring source of ant colony optimization is the foraging behavior of real ant colonies. This behavior is exploited in artificial ant colonies for the search of approximate solutions to discrete optimization problems, to continuous optimization problems, and to important problems in telecommunications, such as routing and load balancing. First, we deal with the biological inspiration of ant colony optimization algorithms. We show how this biological inspiration can be transfered into an algorithm for discrete optimization. Then, we outline ant colony optimization in more general terms in the context of discrete optimization, and present some of the nowadays best-performing ant colony optimization variants. After summarizing some important theoretical results, we demonstrate how ant colony optimization can be applied to continuous optimization problems. Finally, we provide examples of an interesting recent research direction: The hybridization with more classical techniques from artificial intelligence and operations research.     

Cumulative "roof effect" in high-resolution in vivo 31P NMR spectra of human calf muscle and the Clebsch-Gordan coefficients of ATP at 1.5 T

NMR spectra of non-weakly coupled spin systems exhibit asymmetries in line intensities known as "roof effect" in 1D spectroscopy. Due to limited spectral resolution, this effect has not been paid much attention so far in in vivo spectroscopy. But when high-quality spectra are obtained, this effect should be taken into account to explain the quantum-mechanical fine structure of the system. Adenosine 5'-triphosphate (ATP) represents a 31P spin system with multiple line splittings which are caused by J-couplings of medium strength at 1.5 T. We analyzed the ATP roof effect in vivo, especially for the beta-ATP multiplet. The intensities of its outer resonances deviate by ca. 12.5% from a symmetrical triplet. As this asymmetry reflects the transition from Paschen-Back to Zeeman effect with total spin that is largely broken up, the Clebsch-Gordan coefficients of the system can be indicated in analogy to the hyperfine structure of hydrogen. Taking the roof effect into account, the chi2 of fitting in vivo ATP resonances is reduced by ca. 9% (p<0.005).     

Lattice electrons on a cylinder surface in the presence of rational magnetic flux and disorder

We consider a disordered two-dimensional system of independent lattice electrons in a perpendicular magnetic field with rigid confinement in one direction and generalized periodic boundary conditions (GPBC) in the other direction. The objects investigated numerically are the orbits in the plane spanned by the energy eigenvalues and the corresponding center of mass coordinate in the confined direction, parameterized by the phase characterizing the GPBC. The Kubo Hall conductivity is expressed in terms of the winding numbers of these orbits. For vanishing disorder the spectrum of the system consists of Harper bands with energy levels corresponding to the edge states within the band gaps. Disorder leads to broadening of the bands. For sufficiently large systems localized states occur in the band tails. We find that within the mobility gaps of bulk states the Diophantine equation determines the value of the Hall conductivity as known for systems with torus geometry (PBCs in both directions). Within the spectral bands of extended states the Hall conductivity fluctuates strongly. For sufficiently large systems the generic behavior of localization-delocalization transitions characteristic for the quantum Hall effect are recovered.     

Overcomplete Free Energy Functional for D = 1 Particle Systems with Next Neighbor Interactions

We deduce an overcomplete free energy functional for D=1 particle systems with next neighbor interactions, where the set of redundant variables are the local block densities _i of i interacting particles. The idea is to analyze the decomposition of a given pure system into blocks of i interacting particles by means of a mapping onto a hard rod mixture. This mapping uses the local activity of component i of the mixture to control the local association of i particles of the pure system. Thus it identifies the local particle density of component i of the mixture with the local block density _i of the given system. Consequently, our overcomplete free energy functional takes on the hard rod mixture form with the set of block densities _i representing the sequence of partition functions of the local aggregates of particle numbers i. The system of equations for the local particle density of the original system is closed via a subsidiary condition for the block densities in terms of . Analoguous to the uniform isothermal-isobaric technique, all our results are expressible in terms of effective pressures. We illustrate the theory with two standard examples, the adhesive interaction and the square-well potential. For the uniform case, our proof of such an overcomplete format is based on the exponential boundedness of the number of partitions of a positive integer (Hardy-Ramanujan formula) and on Varadhan's theorem on the asymptotics of a class of integrals.     

Towards the synthesis of MAX-phase functional coatings by pulsed laser deposition

Pulsed laser deposition with a Nd:YAG laser was used to grow thin films from a pre-synthesized Ti₃SiC₂ MAX-phase formulated ablation target on oxidized Si(1 0 0) and MgO(1 0 0) substrates. The depositions were carried out in a substrate temperature range from 300 to 900 K, and the pressure in the deposition chamber ranged from vacuum (10⁻⁵ Pa) to 0.05 Pa Argon background pressure. The properties of the films have been investigated by Rutherford backscattering spectrometry for film thickness and stoichiometric composition and X-ray diffraction for the crystallinity of the films. The silicon content of the films varied with the energy density of the laser beam. To suppress especially the silicon re-sputtering from the substrate, the energy of the incoming particles must be below a threshold of 20 eV. Therefore, the energy density of the laser beam must not be too high. At constant deposition energy density the film thickness depends strongly on the background pressure. The X-ray diffraction measurements show patterns that are typical of amorphous films, i.e. no Ti₃SiC₂ related reflections were found. Only a very weak TiC(2 0 0) reflection was seen, indicating the presence of a small amount of crystalline TiC.     

Pharmacological modulation of functional connectivity: the correlation structure underlying the phMRI response to d-amphetamine modified by selective dopamine D3 receptor antagonist SB277011A

Pharmacological MRI (phMRI) experiments utilise fMRI time series methods to map the central effect of pharmaceutical compounds. The typical univariate maps may, however, integrate the effects of several different neurotransmitter systems or underlying mechanisms. The results may thus be spatially and/or mechanistically nonspecific. Intersubject correlation analysis based on the phMRI response amplitude can more directly identify patterns of functional connectivity underlying the central effects of an acutely administered compound. In this article, we extend this approach to experiments where the effects of one compound in modulating the response to another are of interest. Specifically, we show a modulation of the correlation structure of a probe compound (d-amphetamine) by pretreatment with the selective dopamine D3 receptor antagonist SB277011A in the rat. The strongest modifications in the correlation patterns occurred in connection with the ventral tegmental area, the source of mesolimbic dopamine projections and a key substrate in the reward system.     

Dispersion measurements using time-of-flight remote detection MRI

Remote detection nuclear magnetic resonance and magnetic resonance imaging can be used to study fluid flow and dispersion in a porous medium from a purely Eulerian point of view (i.e., in a laboratory frame of reference). Information about fluid displacement is obtained on a macroscopic scale in a long-time regime, while local velocity distributions are averaged out. It is shown how these experiments can be described using the common flow propagator formalism and how experimental data can be analyzed to obtain effective porosity, flow velocity inside the porous medium, fluid dispersion and flow tracing of fluid.     

Experimental implementation of a low-frequency global sound equalization method based on free field propagation

An experimental implementation of a global sound equalization method in a rectangular room using active control is described in this paper. The main purpose of the work has been to provide experimental evidence that sound can be equalized in a continuous three-dimensional region, the listening zone, which occupies a considerable part of the complete volume of the room. The equalization method, based on the simulation of a progressive plane wave, was implemented in a room with inner dimensions of 2.70 m × 2.74 m × 2.40 m. With this method, the sound was reproduced by a matrix of 4 × 5 loudspeakers in one of the walls. After traveling through the room, the sound wave was absorbed on the opposite wall, which had a similar arrangement of loudspeakers, by means of active control. A set of 40 digital FIR filters was used to modify the original input signal before it was fed to the loudspeakers, one filter for each transducer. The optimal arrangement of the loudspeakers and the maximum frequency that can be equalized is analyzed theoretically in this paper. The presented experimental results show that sound equalization was possible from 10 Hz to approximately 425 Hz in the listening zone. A flat frequency response with deviations within ±5 decibels from the desired value was achieved. A higher demanding performance with deviations within ±1.5 decibels from a flat frequency response was attained in the interval between 20 Hz and 280 Hz. At the same time, the impulse response was quite well approximated to a delayed delta function in the listening zone. Examples of the spatial distribution of the sound field are also shown.