Noninvasive detection of amyloid-β (Aβ) deposits in the brain would be beneficial for an early and presymptomatic diagnosis of Alzheimer's disease (AD). We developed THK-265 as a candidate near-infrared fluorescence (NIRF) probe for the in vivo detection of amyloid deposits in the brain. The maximal emission wavelength of THK-265 was greater than 650nm and it showed high quantum yield and molar absorption coefficients. A fluorescence binding assay showed its high binding affinity to Aβ fibrils (Kd = 97 nM). THK-265 clearly stained amyloid plaques in AD neocortical brain sections and showed a moderate log p value (1.8). After intravenous administration of THK-265 in amyloid-β protein precursor (AβPP) transgenic mice, amyloid deposits in the brain were clearly labeled with THK-265. Furthermore, in vivo NIRF imaging demonstrated significantly higher fluorescence intensity in the brains of AβPP transgenic mice than in those of wild-type mice. As THK-265 showed profound hyperchromic effect upon binding to Aβ fibrils, good discrimination between AβPP transgenic and wild-type mice was demonstrated even early after THK-265 administration. Furthermore, the fluorescence intensity of THK-265 correlated with amyloid plaque burden in the brains of AβPP transgenic mice. These findings strongly support the usefulness of THK-265 as an NIRF imaging probe for the noninvasive measurement of brain amyloid load.

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We investigate the Hopf algebra structure in string worldsheet theory and give a unified formulation of the quantization of string and the space-time symmetry. We reformulate the path integral quantization of string as a Drinfeld twist at the worldsheet level. The coboundary relation shows that the Drinfeld twist defines a module algebra which is equivalent to operators with normal ordering. Upon applying the twist, the space-time diffeomorphism is deformed into a twisted Hopf algebra, while the Poincar\'e symmetry is unchanged. This suggests a characterization of the symmetry: unbroken symmetries are twist invariant Hopf subalgebras, while broken symmetries are realized as twisted ones. We provide arguments that relate this twisted Hopf algebra to symmetries in path integral quantization.Comment: 35 pages, no figure, v2: references and comments added, typos corrected, v3: requires PTP style, title changed, final version published in PT

To clarify the physiologic roles of granulocyte colony-stimulating factor (G-CSF) in infectious states in vivo, we examined the serum levels of G-CSF in patients with infection. Serum samples from 24 patients in the acute stage of infection (14 men and 10 women, age 65 to 101, without hematologic disorders), as well as samples from 32 age- matched normal elderly volunteers were investigated. Sixteen of the initial 24 patients were reexamined after the recovery phase. G-CSF levels were examined by quantitative enzyme immunoassay. The G-CSF level in normal elderly controls, 25.3 +/- 19.7 pg/mL, was not different from that reported in other findings. There was no statistically significant relationship between their G-CSF level and peripheral white blood cell count or neutrophilic granulocyte count. The G-CSF level in the acute stage of infection was 731.8 +/- 895.0 pg/mL, with a range of 30 to 3,199 pg/mL. There was no significant difference in G-CSF levels between patients with respiratory tract infection and those with urinary tract infection. In all 16 cases examined, the serum G-CSF level in the acute stage of infection was significantly higher than that after recovery phase, the latter being the same as the level in normal elderly controls. G-CSF must therefore play a significant role in human infectious states in vivo.

In a previous paper, we investigated the Hopf algebra structure in string theory and gave a unified formulation of the quantization of the string and the spacetime symmetry. In this paper, this formulation is applied to the case with a nonzero B-field background, and the twist of the Poincaré symmetry is studied. The Drinfeld twist accompanied by the B-field background gives an alternative quantization scheme, which requires a new normal ordering. In order to obtain a physical interpretation of this twisted Hopf algebra structure, we propose a method to decompose the twist into two successive twists and we give two different possibilities of decomposition. The first is a natural decomposition from the viewpoint of the twist quantization, leading to a new type of twisted Poincaré symmetry. The second decomposition reveals the relation of our formulation to the twisted Poincaré symmetry on the Moyal type noncommutative space.