Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M−1cm−1 in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives.
Summary:In humans there is a substantial decline in NREM electroencephalographic (EEG) slow-wave activity with advancing age. The present findings show that similar age-related EEG changes occur in the cat. Slow-wave (0.5-4.0 Hz) EEG activity during NREM sleep was compared in six young adult (2-4 years) and six aged (10-12 years) cats of either sex. Computer measures of slow-wave incidence and amplitude disclosed significant age-and gender-related differences. Although old male and female animals were of comparable age, only males showed significant EEG alterations. These consisted of an attenuation of slow-wave amplitude over posterolateral cortex and reductions in both the incidence and amplitude of slow-wave activity over sensorimotor cortex. Key Words: Aging-Among the electroencephalographic (EEG) changes commonly associated with advancing age in humans is a marked decline in the incidence and amplitude of slow-wave (0.5-3.0 Hz) activity during NREM sleep. This decline, as documented by both visual (1-6) and computer-assisted (5,7-9) EEG scoring techniques, is a consistent feature of the aging process. It begins in adolescence and continues across the lifespan, often resulting by the eighth decade in the complete loss of 0.5-3.0 Hz wave forms (4).Although it is well established that EEG slow-wave activity is attenuated in old age, the contributions of intracerebral and extracerebral factors to this process have not been well delineated. Intracerebral factors, including the loss of neuropil and dendritic ramifications, undoubtedly playa key role. However, because EEG potentials are conventionally recorded from scalp leads, extracerebral factors such as changes in brain volume, thickening of the meninges, and alterations in skull and scalp conductivity-all of which distance and insulate electrodes from the cortical surface-are also probably implicated. Unfortunately, usual methodological constraints make it difficult to assess the respective contributions of these factors to EEG changes in human subjects. However, this opportunity is afforded in animal studies where recording electrodes can be placed directly on the cortical surface.The principal aim of the present investigation was to assess the extent to which EEG spectral characteristics change as a function of age in the laboratory cat. In an earlier study
Good dispersion of compounded ingredients in a rubber formulation is important for mechanical performance. After mixing, certain materials can remain undispersed within the rubber matrix, which could lead to critical flaws, influencing performance according to the Griffith failure criteria. High resolution X-ray computed tomography (XCT) offers a unique opportunity to measure phase domain size and distributions. Fillers such as carbon black or silica can be differentiated from sulfur or zinc oxide, providing an opportunity to determine dispersion characteristics of the various phases. The XCT technique has become an important characterization tool for three-dimensional and higher dimension material science due to the availability of polychromatic micro-focus x-ray sources and efficient high spatial resolution detectors with superior scintillators. High resolution XCT provides very rich data quantifying mixing efficiency of particulates in a matrix, such as insoluble sulfur or silica particles in rubber. Imaging with X-rays provides attenuation, phase, or scattering contrast and will prove to be a critical method for evaluating the field of rubber crosslinking, considering realistic environments in situ. This paper highlights methodology development and validation and provides insight on the dispersion of polymeric (insoluble) sulfur in rubber formulations. Dispersion assessment is compared using three techniques: high resolution XCT, population survival analysis in tensile testing, and optical microscopy.
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