Balanced steady-state free precession with parallel imaging gives distortion-free fMRI with high temporal resolution

Research on the functions of the human brain requires that functional magnetic resonance imaging (MRI) moves towards producing images with less distortion and higher temporal and spatial resolution. This study compares passband balanced steady-state free precession (bSSFP) acquisitions with and without parallel imaging (PI) to investigate whether combining PI with this pulse sequence is a viable option for functional MRI. Such a novel combination has the potential to offer the distortion-free advantages of bSSFP with the reduced acquisition time of PI. Scans were done on a Philips 3T Intera, using the installed bSSFP pulse sequence, both with and without the sensitivity encoding (SENSE) PI option. The task was a visual flashing checkerboard, and the viewing window covered the visual cortex. Sensitivity comparisons with and without PI were done using the same manually drawn region of interest for each time course of the subject, and comparing the z-score summary statistics: number of voxels with z>2.3, the mean of those voxels, their 90th percentile and their maximum value. We show that PI greatly improves the temporal resolution in bSSFP, reducing the volume acquisition time by more than half in this study to 0.67 s with 3-mm isotropic voxels. At the same time, a statistically significant increase was found for the maximum z-score using bSSFP with PI as compared to without it (P=.02). This improvement can be understood in terms of physiological noise, as demonstrated by noise measurements. This produces observed increases in the overall temporal signal to noise of the functional time series, giving greater sensitivity to functional activations with PI. This study demonstrates for the first time the possibility of combining PI with bSSFP to achieve distortion-free functional images without loss of sensitivity and with high temporal resolution.     

Application of accelerator mass spectrometry to macromolecules: preclinical pharmacokinetic studies on a polybisphosphonate

Data on the use of accelerator mass spectrometry (AMS) in conjunction with in vivo studies of macromolecular drugs are scarce. The present study shows the versatility of this technique when investigating the pharmacokinetics (PK) of a macromolecular drug candidate, a polybisphosphonate conjugate (ODX). The aforementioned is a polymer (molecular weight ~30 kDa) constituting a carbohydrate backbone with covalently linked ligands (aldendronate and aminoguanidine) and is intended for treatment of osteoporosis and the therapy of bone metastasis from prostate cancer. The conjugate is prepared through partial oxidation of the carbohydrate and sequential coupling of the ligands by reductive amination. ¹⁴ C was incorporated in the conjugate by means of coupling a commercially available ¹⁴ C‐lysine in the conjugation sequence. Fifteen rats were injected intravenously with ¹⁴ C‐labelled ODX (150 µg, 14 Bq/rat) and blood samples were collected at 1, 2, 4, 6, and 24 h post‐injection (3 rats/time point). Liver, spleen and kidney samples were collected at 4 and 24 h post‐injection. Blood from each time point (triplicate) were collected for AMS measurement determining the isotopic ratio (¹⁴ C/¹² C) and consequently the drug concentration in blood. ODX showed a transient presence in blood circulation; 93% of the total dose was cleared from the circulation within 1 h. The half‐life after 1 h was estimated to be about 3 h; 0.7% of the administered ¹⁴ C dose of ODX remained in circulation after 24 h. The major ¹⁴ C accumulation was in the liver, the spleen and the kidneys indicating the probable route of metabolism and excretion. This study demonstrates the versatility of AMS for pharmacological in vivo studies of macromolecules. Labelling with ¹⁴ C is relatively simple, inexpensive and the method requires minimal radioactivity, eliminating the need for radioprotection precautions in contrast to methods using scintillation counting. Copyright © 2011 John Wiley & Sons, Ltd.     

Control of olefin geometry in macrocyclic ring-closing metathesis using a removable silyl group

Introducing a silyl group at one of the internal olefin positions in diolefinic substrates results in E-selective olefin formation in macrocyclic ring-forming metathesis. The application of this method to a range of macrocyclic (E)-alkenylsiloxanes is described. Protodesilylation of alkenylsiloxane products yields novel Z-configured macrocycles.     

Edge resonance in an elastic semi-infinite cylinder

We study the three-dimensional elasticity operator in a semi-infinite circular cylinder subject to free boundary conditions, in the case of zero Poisson ratio. We prove, adapting the method from [15], i.e., by first finding an invariant subspace for the elasticity operator such that the essential spectrum has a strictly positive lower bound and then finding a test function in this space for which the variational quotient takes a value below the bottom of the essential spectrum, that there is an eigenvalue embedded in the continuous spectrum. Physically, an eigenvalue corresponds to a "trapped mode", that is, a harmonic oscillation localized near the edge. This effect, known in mechanics as the "edge resonance" has been extensively studied numerically and experimentally. Our paper extends the mathematical justification of such phenomena provided by [15] to a three-dimensional setting     

RANS predictions of turbulent diffusion flames: comparison of a reactor and a flamelet combustion model to the well stirred approach

The flame stabilisation process in turbulent non-premixed flames is not fully understood and several models have been developed to describe the turbulence–chemistry interaction. This work compares the performance of the multiple Representative Interactive Flamelet (mRIF) model, the Volume Reactor Fraction Model (VRFM), and the Well-Stirred reactor (WS) model in describing such flames. The predicted ignition delay and flame lift-off length of n-heptane sprays are compared to experimental results published within the Engine Combustion Network (ECN). All of the models predict the trend of ignition delay reasonably well. At a low gas pressure (42 bar) the ignition delay is overpredicted compared to the experimental data, but the difference between the models is not significant. However, the predicted lift-off lengths differ. At high pressure (87 bar) the difference between the models is small. All models slightly underpredict the lift-off length compared to the experimental data. At low gas pressure (42 bar) the mRIF model gives the best results. The VRFM and WS models predict excessively short lift-off lengths, but the VRFM model gives better results than the WS model. The flame structures of the models are also compared. The WS model and the VRFM model yield a well defined flame stabilisation point whereas the mRIF model does not. The flame of the mRIF model is more diffuse and the model is not able to predict flame propagation. All models were able to predict the experimental trends in lift-off and ignition delay, but certain differences between them are demonstrated.     

Nanoimprinted distributed feedback lasers comprising TiO2 thin films: Design guidelines for high performance sensing

Design guidelines for optimizing the sensing performance of nanoimprinted second order distributed feedback dye lasers are presented. The guidelines are verified by experiments and simulations. The lasers, fabricated by UV‐nanoimprint lithography into Pyrromethene doped Ormocomp thin films on glass, have their sensor sensitivity enhanced by a factor of up to five via the evaporation of a titanium dioxide (TiO₂) waveguiding layer. The influence of the TiO₂ layer thickness on the device sensitivity is analyzed with a simple model that accurately predicts experimentally measured wavelength shifts induced by varied superstrate refractive indices. The superstrate refractive index is additionally shown to determine which of the possible waveguiding modes dominates for lasing, indicating a method to flexibly select the polarization of the laser. The detection limit of the sensor system is further discussed, finding an optimum at 7.5· 10⁻⁶ RIU. Wavelength changes caused by dye bleaching must be taken into account for long‐term measurements.     

A theoretical study of the solvent shift to the transition in formaldehyde with an effective discrete quantum chemical solvent model including non-electrostatic perturbation

An effective solvent model with an explicit solvent representation is described. The modelled perturbation of the solute due to the discrete solvent molecules includes polarization and a non-electrostatic interaction. The latter depends on the overlap between the solute wave function and the solvent orbitals and approximately accounts for the restraint the Pauli principle puts on the space which the solute wave function is allowed to occupy, and consequently also models the exchange repulsion between solute and solvent. The wave function of the solute is a linear combination with variational coefficients of orthogonal states obtained with the complete active space state interaction (CASSI) method. With this model, the solvent shift to the n→ π* transition in hydrated formaldehyde is studied and the analysis of the results investigates the different contributions to the total shift; the non-electrostatic interaction is found to be of significance and capable of coupling with the electrostatic interaction in qualitatively different ways for the ground and first excited state. Solvent density distributions for hydrated formaldehyde are also reported.     

A reformulation framework for global optimization

In this paper, we present a global optimization method for solving nonconvex mixed integer nonlinear programming (MINLP) problems. A convex overestimation of the feasible region is obtained by replacing the nonconvex constraint functions with convex underestimators. For signomial functions single-variable power and exponential transformations are used to obtain the convex underestimators. For more general nonconvex functions two versions of the so-called αBB-underestimator, valid for twice-differentiable functions, are integrated in the actual reformulation framework. However, in contrast to what is done in branch-and-bound type algorithms, no direct branching is performed in the actual algorithm. Instead a piecewise convex reformulation is used to convexify the entire problem in an extended variable-space, and the reformulated problem is then solved by a convex MINLP solver. As the piecewise linear approximations are made finer, the solution to the convexified and overestimated problem will form a converging sequence towards a global optimal solution. The result is an easily-implementable algorithm for solving a very general class of optimization problems.