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841.

Background

A recent human clinical trial of an Alzheimer's disease (AD) vaccine using amyloid beta (Aβ) 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine.

Results

All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue.

Conclusion

Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.  相似文献   
842.
We previously launched a high-resolution photoacoustic (PA) imaging scanner based on a unique lensless design for in vivo skin imaging. The design, imaging algorithm and characteristics of the system are described in this paper. Neither an optical lens nor an acoustic lens is used in the system. In the imaging head, four sensor elements are arranged quadrilaterally, and by checking the phase differences for PA waves detected with these four sensors, a set of PA signals only originating from a chromophore located on the sensor center axis is extracted for constructing an image. A phantom study using a carbon fiber showed a depth-independent horizontal resolution of 84.0 ± 3.5 µm, and the scan direction-dependent variation of PA signals was about ± 20%. We then performed imaging of vasculature phantoms: patterns of red ink lines with widths of 100 or 200 μm formed in an acrylic block co-polymer. The patterns were visualized with high contrast, showing the capability for imaging arterioles and venues in the skin. Vasculatures in rat burn models and healthy human skin were also clearly visualized in vivo.  相似文献   
843.
Thermal reactions of alkali salts of 4-(1-bromoethyl)benzoic acid in bulk were investigated. These reactions were found to produce unexpectedly the graft copolymer, poly(4-vinylbenzoate)-graft-oligo(oxycarbonyl-1,4-phenylenethylidene) ( 1 ). The relative reactivity of the oligocondensation as well as the vinyl polymerization of the salts decreased in the following order: K > Na > Li. The reaction polymerization rate proceeded rapidly during the initial 15 min, and then slowed down.  相似文献   
844.
A C4h symmetrically substituted phthalocyanine, 1,8,15,22-tertrakis(2,4-dimethylpent-3-oxy)phthalocyanine (H2TdMPPc), was used to synthesize Tb3+-phthalocyanine double-decker complexes ([Tb(TdMPPc)2]s). Because H2TdMPPc has C4h symmetry, S,S, R,R, and meso isomers of [Tb(TdMPPc)2] were obtained depending on the difference in the direction of the coordination plane of two C4h-type phthalocyanines with respect to a central Tb3+ ion. We investigated the physical properties of these [Tb(TdMPPc)2] isomers, including their single-ion magnetic properties, and found that the spin-reversal energy barrier (Ueff) of the meso isomer was apparently higher than that of the enantiomers. Detailed crystal structural analyses indicated that the meso isomer has a more symmetrical structure than do the enantiomers, thereby suggesting that the higher Ueff of the meso isomer originated from the more highly symmetrical structure.  相似文献   
845.
846.
A novel methodology (electrostatic self‐assembly and covalent fixation) has been proposed for designing unusual polymer topologies such as star polymers, polymacromonomers, dumbbell‐shaped polymers as well as model network polymers. Thus new telechelic polymers having moderately strained cyclic onium salt group as single or both end groups were prepared and subjected to an ion‐exchange reaction to introduce multifunctional carboxylate anions as a counter‐anion. The electrostatically self‐assembled products were then subjected, either directly or after subsequent manipulation, to heat treatment to convert the ionic interaction into the covalent linkage by the ring‐opening reaction to produce a variety of topologically unique polymer architectures in high yields.  相似文献   
847.
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