Recent reports have demonstrated that the correlation function of the fluorescence dichroism signal, measured as a probe of single molecule rotational dynamics, should not manifest a single exponential decay even for isotropic diffusion. This has called into question the attribution of observed nonexponential behavior in supercooled fluids and polymer systems to dynamical heterogeneity. We show here that, for the case of a high numerical aperture objective, the dichroism decay becomes indistinguishable from a single exponential. As a consequence, observed nonexponential decays can be associated with complex rotational dynamics. These effects are illustrated via simulated rotational trajectories for isotropic diffusion of a dipole.
Central nervous system (CNS)-infiltrating effector T cells play critical roles in the development and progression of multiple sclerosis (MS). However, current drugs for MS are very limited due to the difficulty of delivering drugs into the CNS. Here we identify a cell-permeable peptide, dNP2, which efficiently delivers proteins into mouse and human T cells, as well as various tissues. Moreover, it enters the brain tissue and resident cells through blood vessels by penetrating the tightly organized blood–brain barrier. The dNP2-conjugated cytoplasmic domain of cytotoxic T-lymphocyte antigen 4 (dNP2-ctCTLA-4) negatively regulates activated T cells and shows inhibitory effects on experimental autoimmune encephalomyelitis in both preventive and therapeutic mouse models, resulting in the reduction of demyelination and CNS-infiltrating T helper 1 and T helper 17 cells. Thus, this study demonstrates that dNP2 is a blood–brain barrier-permeable peptide and dNP2-ctCTLA-4 could be an effective agent for treating CNS inflammatory diseases such as MS.
There was no single shoulder outcome instrument that was superior to the others in terms of the measurement properties. Most of the tested shoulder outcome instruments did not reflect health-related quality of life well and poorly correlated with each other. This meant that the comparison of a given surgical result with different outcome instruments might be of little practical utility. Further prospective and serial studies should be conducted to develop better shoulder outcome instruments that have significant reliability, responsiveness, validity, and correlation with health-related quality of life. A careful combination of outcome instruments might be necessary to compensate the current evaluation systems.
Production of C 7 H 7 + in the unimolecular and photoinduced dissociations of ethylbenzene; methylcycloheptatriene; and o-, m-, and p-xylene ions has been investigated using mass-analyzed ion kinetic energy spectrometry. Both the benzylium and tropylium ions were produced near the reaction threshold, whereas only the benzylium ion was observed at higher internal energy achieved by photoabsorption. Experimental data suggest that interconversion between ethylbenzene and methylcycloheptatriene ions occurs more rapidly than their dissociations near the reaction threshold, whereas xylene ions undergo rate-determining isomerization to the methylcycloheptatriene structure, and dissociation occurs from the ethylbenzene/methylcycloheptatriene ion mixture. The processes occurring at higher internal energy are quite similar, except that the tropylium channel cannot compete against the benzylium channel because either the ethylbenzene ion-to-methylcycloheptatriene ion conversion or the dissociation of the methylcycloheptatriene ion to the tropylium ion is slower than the direct dissociation of the ethylbenzene ion. The above mechanistic picture is in disagreement with the prediction of a dynamic model reported previously. A series of investigations performed for the production of C 7 H 7 + from alkylbenzene ions shows an interesting trend of increasing benzylium production with the increase in the total number of carbon atoms in the alkyl substituents.
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