Vinylallenes—VII: Nouvelle synthese de la dimethyl-3,11 nonacosanone-2, phermone sexuelle de la blatte germanique

A new synthesis of the titled pheromone is given ; it uses as the key step the Oxy-Cope reaction of a 4-ethynyl hexa-1,5-diene 3-ol.     

Kinetic analysis of an extended single-path sequence of first-order reactions. The reaction of mesitonitrile in sulfuric acid

The system of a sequence of five first-order reactions, A → B → C → D → E → F, has been analyzed kinetically. An actual example is proposed in the reaction of mesitonitrile in 89.8% (w/w) sulfuric acid at 98.3°C. The analysis provides estimates of concentration ratios as functions of time, and the progress of the buildup and decay of the intermediate species can be monitored. The kinetics have been measured for the hydration of mesitonitrile, the hydrolysis of mesitamide, and the sulfonation of mesitylenesulfonic acid in 89.8% sulfuric acid. The calculated values of the concentration ratios of mesitylenedisulfonic acid as a function of time were satisfactorily close to those found in experiment.     

Functional MRI and multivariate autoregressive models

Connectivity refers to the relationships that exist between different regions of the brain. In the context of functional magnetic resonance imaging (fMRI), it implies a quantifiable relationship between hemodynamic signals from different regions. One aspect of this relationship is the existence of small timing differences in the signals in different regions. Delays of 100 ms or less may be measured with fMRI, and these may reflect important aspects of the manner in which brain circuits respond as well as the overall functional organization of the brain. The multivariate autoregressive time series model has features to recommend it for measuring these delays and is straightforward to apply to hemodynamic data. In this review, we describe the current usage of the multivariate autoregressive model for fMRI, discuss the issues that arise when it is applied to hemodynamic time series and consider several extensions. Connectivity measures like Granger causality that are based on the autoregressive model do not always reflect true neuronal connectivity; however, we conclude that careful experimental design could make this methodology quite useful in extending the information obtainable using fMRI.     

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax

The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C₁₈ column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at −70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose.     

Racemic and (+)-ethyl 2-acetamido-2-carboxy-5-oxohexanoate

Racemic ethyl 2-acetamido-2-carboxy-5-oxohexanoate has been isolated by single hydrolysis of the corresponding diethyl ester and resolved essentially quantitatively by diastereomeric salt formation with (–)-quinine. The (+)-isomer was retrieved from the less-soluble quininium salt. Racemate crystals, (plusmn;)-1, are monoclinic, space group P2₁/c, a = 7.609(4)Å, b = 16.731(7)Å, c = 10.746(5) Å, = 99.83(4)° enantiomeric crystals, (+)-1, are monoclinic, space group P2₁, a = 5.857(2)Å, b = 15.282(4)Å, c = 7.618(2)Å, = 95.62(2)°. Molecular packing is similar in the two structures; the enantiomer has a 0.7% higher volume per molecule and the lower fusion temperatures by 3°C. In both structures, carboxylic acids donate hydrogen bonds to the amide carbonyls of adjacent molecules without reciprocation. Amides form three-centered hydrogen bonds to carboxy oxygen of an intramolecular carboxylic acid group and to oxygen of a ketone carbonyl in an adjacent molecule.     

A nonrigid registration algorithm for longitudinal breast MR images and the analysis of breast tumor response

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can estimate parameters relating to blood flow and tissue volume fractions and therefore may be used to characterize the response of breast tumors to treatment. To assess treatment response, values of these DCE-MRI parameters are observed at different time points during the course of treatment. We propose a method whereby DCE-MRI data sets obtained in separate imaging sessions can be co-registered to a common image space, thereby retaining spatial information so that serial DCE-MRI parameter maps can be compared on a voxel-by-voxel basis. In performing inter-session breast registration, one must account for patient repositioning and breast deformation, as well as changes in tumor shape and volume relative to other imaging sessions. One challenge is to optimally register the normal tissues while simultaneously preventing tumor distortion. We accomplish this by extending the adaptive bases algorithm through adding a tumor-volume preserving constraint in the cost function. We also propose a novel method to generate the simulated breast magnetic resonance (MR) images, which can be used to evaluate the proposed registration algorithm quantitatively. The proposed nonrigid registration algorithm is applied to both simulated and real longitudinal 3D high resolution MR images and the obtained transformations are then applied to lower resolution physiological parameter maps obtained via DCE-MRI. The registration results demonstrate the proposed algorithm can successfully register breast MR images acquired at different time points and allow for analysis of the registered parameter maps.     

The neural correlates of calculation ability in children: an fMRI study

Most studies investigating mental numerical processing involve adult participants and little is known about the functioning of these systems in children. The current study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of numeracy and the influence of age on these correlates with a group of adults and a group of third graders who had average to above average mathematical ability. Participants performed simple and complex versions of exact and approximate calculation tasks while in the magnet. Like adults, children activated a network of brain regions in the frontal and parietal lobes during the calculation tasks, and they recruited additional brain regions for the more complex versions of the tasks. However, direct comparisons between adults and children revealed significant differences in level of activation across all tasks. In particular, patterns of activation in the parietal lobe were significantly different as a function of age. Findings support previous claims that the parietal lobe becomes more specialized for arithmetic tasks with age.     

Nonlinear blood oxygen level-dependent responses for transient activations and deactivations in V1 - insights into the hemodynamic response function with the balloon model

We report studies of the nonlinear nature of blood oxygen level-dependent (BOLD) responses to short transient deactivations in human visual cortex. Both functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS) have been used to compare and contrast the hemodynamic response functions (HRFs) associated with transient activation and deactivation in primary visual cortex. We show that signal decreases for short duration deactivations are smaller than corresponding signal increases in activation studies. Moreover, the standard balloon model of BOLD effects may be modified to account for the observed nonlinear nature of deactivations by appropriate changes to simple hemodynamic parameters without recourse to new assumptions about the nature of the coupling between activity and oxygen use.     

Multiplicative intrinsic component optimization (MICO) for MRI bias field estimation and tissue segmentation

This paper proposes a new energy minimization method called multiplicative intrinsic component optimization (MICO) for joint bias field estimation and segmentation of magnetic resonance (MR) images. The proposed method takes full advantage of the decomposition of MR images into two multiplicative components, namely, the true image that characterizes a physical property of the tissues and the bias field that accounts for the intensity inhomogeneity, and their respective spatial properties. Bias field estimation and tissue segmentation are simultaneously achieved by an energy minimization process aimed to optimize the estimates of the two multiplicative components of an MR image. The bias field is iteratively optimized by using efficient matrix computations, which are verified to be numerically stable by matrix analysis. More importantly, the energy in our formulation is convex in each of its variables, which leads to the robustness of the proposed energy minimization algorithm. The MICO formulation can be naturally extended to 3D/4D tissue segmentation with spatial/sptatiotemporal regularization. Quantitative evaluations and comparisons with some popular softwares have demonstrated superior performance of MICO in terms of robustness and accuracy.