Neurofibrillary tangles and plaques are not accompanied by white matter pathology in aged triple transgenic-Alzheimer disease mice

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia in aging populations. Although senile plaques and neurofibrillary tangles are well-established hallmarks of AD, changes in cerebral white matter correlate with cognitive decline and may increase the risk of the development of dementia. We used the triple transgenic (3xTg)-AD mouse model of AD, previously used to show that white matter changes precede plaque formation, to test the hypothesis that MRI detectable changes occur in the corpus callosum, external capsule and the fornix. T₂-weighted and diffusion tensor magnetic resonance imaging and histological stains were employed to assess white matter in older (11–17 months) 3xTg-AD mice and controls. We found no statistically significant changes in white matter between 3xTg-AD mice and controls, despite well-developed neurofibrillary tangles and beta amyloid immunoreactive plaques. Myelin staining was normal in affected mice. These data suggest that the 3xTg-AD mouse model does not develop MRI detectable white matter changes at the ages we examined.     

Non-compact quantum groups associated with Abelian subgroups

LetG be a Lie group. For any Abelian subalgebra of the Lie algebra g ofG, and any , the difference of the left and right translates ofr gives a compatible Poisson bracket onG. We show how to construct the corresponding quantum group, in theC ^*-algebra setting. The main tool used is the general deformation quantization construction developed earlier by the author for actions of vector groups onC ^*-algebras.The research reported on here was supported in part by National Science Foundation grant DMS-9303386.     

Uncertainty-based experimental validation of nonlinear reduced order models

This paper presents the first results of a combined experimental–computational investigation focused on the validation of reduced order models of geometrically nonlinear structures in the presence of uncertainty. The validation approach considered here is based on the premise that the model is valid if the experimental results can be considered as random sample responses of the stochastic system of which the reduced order model is the mean. For the situation considered here, the power spectra of the experiments should lie within the 2nd and 98th percentiles of the response (forming the uncertainty band) of the stochastic model. Nominally clamped–clamped beams are considered to demonstrate the entire process. The construction of two mean reduced order models and their stochastic counterparts are first performed. Then, the validation effort is carried out by comparing experimentally obtained power spectra and their corresponding computational uncertainty bands. This process leads, for both reduced order models, to a very good representation of the important upper envelope (98th percentile) of the experimental data but a less good fit of the lower envelope (2nd percentile).     

On the interpretation of fluorescence anisotropy decays from probe molecules in lipid vesicle systems

Measurements of fluorescence depolarization decays are widely used to obtain information about the molecular order and rotational dynamics of fluorescent probe molecules in membrane systems. This information is obtained by least-squares fits of the experimental data to the predictions of physical models for motion. Here we present a critical review of the ways and means of the data analysis and address the question how and why totally different models such as Brownian rotational diffusion and wobble-in-cone provide such convincing fits to the fluorescence anistropy decay curves. We show that while these models are useful for investigating the general trends in the behavior of the probe molecules, they fail to describe the underlying motional processes. We propose to remedy this situation with a model in which the probe molecules undergo fast, though restricted local motions within a slowly rotating cage in the lipid bilayer structure. The cage may be envisaged as a free volume cavity between the lipid molecules, so that its position and orientation change with the internal conformational motions of the lipid chains. This approach may be considered to be a synthesis of the wobble-in-cone and Brownian rotational diffusion models. Importantly, this compound motion model appears to provide a consistent picture of fluorescent probe behavior in both oriented lipid bilayers and lipid vesicle systems.     

Effect of an entrained air bubble on the acoustics of an ink channel

Piezo-driven inkjet systems are very sensitive to air entrapment. The entrapped air bubbles grow by rectified diffusion in the ink channel and finally result in nozzle failure. Experimental results on the dynamics of fully grown air bubbles are presented. It is found that the bubble counteracts the pressure buildup necessary for the droplet formation. The channel acoustics and the air bubble dynamics are modeled. For good agreement with the experimental data it is crucial to include the confined geometry into the model: The air bubble acts back on the acoustic field in the channel and thus on its own dynamics. This two-way coupling limits further bubble growth and thus determines the saturation size of the bubble.     

Action Spectroscopy on Dense Samples of Photosynthetic Reaction Centers of Rhodobacter sphaeroides WT Based on Nanosecond Laser-Flash 13C Photo-CIDNP MAS NMR

Photochemically induced dynamic nuclear polarization magic-angle spinning nuclear magnetic resonance (photo-CIDNP MAS NMR) allows for the investigation of the electronic structure of the photochemical machinery of photosynthetic reaction centers (RCs) at atomic resolution. For such experiments, either continuous radiation from white xenon lamps or green laser pulses are applied to optically dense samples. In order to explore their optical properties, optically thick samples of isolated and quinone-removed RCs of the purple bacteria of Rhodobacter sphaeroides wild type are studied by nanosecond laser-flash ¹³C photo-CIDNP MAS NMR using excitation wavelengths between 720 and 940 nm. Action spectra of both the transient nuclear polarization as well as the nuclear hyperpolarization, remaining in the electronic ground state at the end of the photocycle, are obtained. It is shown that the signal intensity is limited by the amount of accessible RCs and that the different mechanisms of the photo-CIDNP production rely on the same photophysical origin, which is the photocycle induced by one single photon.     

Discovery of structurally diverse natural product antagonists of chemokine receptor CXCR3

The chemokines (CXCL9, CXCL10 and CXCL11) and associated CXCR3 receptor are expressed during the inflammatory process from multiple sclerosis, atherosclerosis or organ transplantation resulting in the recruitment of lymphocytes leading to tissue damage. It is hypothesized that blocking of the ligand/CXCR3 receptor interaction has potential to provide opportunity for development of agents that would block tissue rejection. In this paper, four classes of natural product inhibitors (IC₅₀ ranging 0.1–41 M) have been described that block the CXCR3 receptor interaction of IP-10 ligand. These include a cyclic thiopeptide (duramycin), polyketide glycosides (roselipins), steroidal glycosides (hypoglausin A and dioscin) and a novel alkyl pyridinium alkaloid that were isolated by bioassay-guided fractionation of the organic extracts derived from actinomycete, fungal, plant and marine sources and discovered using ¹²⁵ I IP-10/CXCR3 binding assay. Duramycin was the most potent with an IC₅₀ of 0.1 M. Roselipins 2A, 2B and 1A showed IC₅₀ values of 14.6, 23.5, and 41 M, respectively. Diosgenin glycosides dioscin, hypoglaucin A and kallstroemin D exhibited IC₅₀ values of 2.1, 0.47 and 3 M, respectively. A novel cyclic 3-alkyl pyridinium salt isolated from a sponge displayed a binding IC₅₀ of 0.67 M.     

The Michael Addition of Enamines to Propenamidines. A Convenient Synthesis of 2β-Amidinoethylcyclo-Alkanones by Amidinoethylation Reaction

A variety of propenamidines 3 have been reacted with enamines of cyclopentanone and cyclohexanone giving after hydrolysis of the Stork enamine 6, 2-β-amidinoethylcyclopentanones 8 and -hexanones 7. This reaction illustrates the electrophilic character of the C=C double bond due to the conjugated amidine function, thus providing with propenamidines 3 a new class of Michael acceptors for enamines.