Synthesis and characterization of bent fluorine-containing donor-π-acceptor molecules as intense luminophores with large Stokes shifts.

Herein, we prepared novel bent fluorine-containing donor-π-acceptor (D-π-A) molecules from commercially available octafluorocyclopentene using a facile two-step procedure, revealing that the above molecules absorb UV-light and exhibit yellow photoluminescence (PL) with high PL efficiencies (ΦPL) in solution. The corresponding Stokes shifts exceeded 10 000 cm-1, and the maximum PL wavelength (λPL) strongly depended on solvent polarity or intermolecular interactions in the solid state. On the basis of a Lippert-Mataga plot, PL was confidently assigned to radiative relaxation from an intramolecular charge-transfer excited state. Moreover, the synthesized luminophores showed intense PL even in the crystalline state and exhibited alkoxy chain length-dependent PL behavior (e.g., high ΦPL, λPL = 486-540 nm).

Syntheses and Structures of d10 Coinage Metal Complexes of Electron-Accepting Phosphine Ligands Featuring a 3,3,4,4,5,5-Hexafluorocyclopentene Framework.

Cu(I), Ag(I), and Au(I) complexes of monophosphine or bisphosphine ligands based on the 3,3,4,4,5,5-hexafluorocyclopentene skeleton were synthesized and structurally characterized by X-ray crystallographic analysis. The electron-withdrawing nature of these polyfluorinated phosphines was experimentally revealed via UV/vis absorption studies and crystal structure analysis. Successful catalytic application of the Au(I) complex for alkyne hydration reactions was investigated.

Correlation between hypoxic area in primary brain tumors and WHO grade: differentiation from malignancy using 18F-fluoromisonidazole positron emission tomography.

Background 18F-fluoromisonidazole positron emission tomography (FMISO-PET) has been used for identification of hypoxic areas in tumors, and since hypoxia causes hypoxia-inducible factor-1 and enhancement of tumor growth, identifying the hypoxic area in the tumor tissue is important. Purpose To evaluate the usefulness of FMISO-PET in the grading of primary brain tumors. Material and Methods FMISO-PET was performed preoperatively on 41 consecutive patients with pathologically confirmed brain tumor. A neuroradiologist retrospectively measured both maximum standardized uptake value (SUVmax) and mean SUV (SUVmean) in the tumor and normal cerebellar parenchyma. Maximum tumor/normal control ratio (T/Nmax) and mean tumor/normal control ratio (T/Nmean) were calculated and analyzed. Results There was a positive correlation between World Health Organization (WHO) grade and both T/Nmax and T/Nmean (r = 0.731 and 0.713, respectively). When all cases were divided into benign (WHO grade II) and malignant groups (III and IV), there were significant differences between the two groups in both T/Nmax and T/Nmean ( P < 0.001). If the cutoff value was defined as T/Nmax = 1.25 and T/Nmean = 1.23, T/Nmax had a sensitivity of 90.0% and a specificity of 90.9% while T/Nmean had a sensitivity of 93.3% and a specificity of 90.9% in differentiating the benign group from the malignant group. Conclusion Both T/Nmax and T/Nmean in FMISO-PET have a positive correlation with primary brain tumor grading, making FMISO-PET useful in diagnosing the malignancy of primary brain tumors.

Insights into the Proton Transfer Mechanism of a Bilin Reductase PcyA Following Neutron Crystallography.

Phycocyanobilin, a light-harvesting and photoreceptor pigment in higher plants, algae, and cyanobacteria, is synthesized from biliverdin IXα (BV) by phycocyanobilin:ferredoxin oxidoreductase (PcyA) via two steps of two-proton-coupled two-electron reduction. We determined the neutron structure of PcyA from cyanobacteria complexed with BV, revealing the exact location of the hydrogen atoms involved in catalysis. Notably, approximately half of the BV bound to PcyA was BVH(+), a state in which all four pyrrole nitrogen atoms were protonated. The protonation states of BV complemented the protonation of adjacent Asp105. The "axial" water molecule that interacts with the neutral pyrrole nitrogen of the A-ring was identified. His88 Nδ was protonated to form a hydrogen bond with the lactam O atom of the BV A-ring. His88 and His74 were linked by hydrogen bonds via H3O(+). These results imply that Asp105, His88, and the axial water molecule contribute to proton transfer during PcyA catalysis.

Computed Tomographic Findings of Enterohemorrhagic Escherichia coli O157 Infection: An Analysis of a 7-Case Regional Outbreak.

PURPOSE: We experienced an outbreak of enterohemorrhagic Escherichia coli (EHEC) colitis. The purpose of this study was to reveal the computed tomographic (CT) findings on EHEC colitis. METHODS: The subjects were 7 patients with EHEC colitis, which was caused by eating a contaminated Japanese rice cake. Contrast CT was performed on all patients. Two radiologists evaluated the CT findings (the thickness of colon wall, the range of thickened colon, and the existence of dirty fat signs around the colon, ascites, and swelling of lymph nodes), in accordance with our PACS system. RESULTS: Wall swelling of the proximal colon from cecum to ascending colon was noted in all patients. Small intestine lesions were not noted in any cases. CONCLUSIONS: We should consider EHEC infection as part of a differential diagnosis when the findings of severe right colitis are seen without enteritis.

Evaluation of performance for IBARAKI biological crystal diffractometer iBIX with new detectors.

The IBARAKI biological crystal diffractometer, iBIX, is a high-performance time-of-flight neutron single-crystal diffractometer for elucidating mainly the hydrogen, protonation and hydration structures of biological macromolecules in various life processes. Since the end of 2008, iBIX has been available to users' experiments supported by Ibaraki University. Since August 2012, an upgrade of the 14 existing detectors has begun and 16 new detectors have been installed for iBIX. The total measurement efficiency of the present diffractometer has been improved by one order of magnitude from the previous one with the increasing of accelerator power. In December 2012, commissioning of the new detectors was successful, and collection of the diffraction dataset of ribonucrease A as a standard protein was attempted in order to estimate the performance of the upgraded iBIX in comparison with previous results. The resolution of diffraction data, equivalence among intensities of symmetry-related reflections and reliability of the refined structure have been improved dramatically. iBIX is expected to be one of the highest-performance neutron single-crystal diffractometers for biological macromolecules in the world.

Hydrogen-bond network and pH sensitivity in human transthyretin.

Transthyretin (TTR) is a tetrameric protein. TTR misfolding and aggregation are associated with human amyloid diseases. Dissociation of the TTR tetramer is believed to be the rate-limiting step in the amyloid fibril formation cascade. Low pH is known to promote dissociation into monomer and the formation of amyloid fibrils. In order to reveal the molecular mechanisms underlying pH sensitivity and structural stabilities of TTR, neutron diffraction studies were conducted using the IBARAKI Biological Crystal Diffractometer with the time-of-flight method. Crystals for the neutron diffraction experiments were grown up to 2.5 mm(3) for four months. The neutron crystal structure solved at 2.0 Å revealed the protonation states of His88 and the detailed hydrogen-bond network depending on the protonation states of His88. This hydrogen-bond network is involved in monomer-monomer and dimer-dimer interactions, suggesting that the double protonation of His88 by acidification breaks the hydrogen-bond network and causes the destabilization of the TTR tetramer. Structural comparison with the X-ray crystal structure at acidic pH identified the three amino acid residues responsible for the pH sensitivity of TTR. Our neutron model provides insights into the molecular stability related to amyloidosis.

Hybridization of Wide-Angle X-ray and Neutron Diffraction Techniques in the Crystal Structure Analyses of Synthetic Polymers.

The development in the crystal structure analysis of synthetic polymers using the hybridized combination of wide-angle X-ray and neutron diffraction (WAXD and WAND, respectively) techniques has been reviewed with many case studies performed by the authors. At first, the technical development was reviewed, in which the usage of high-energy synchrotron X-ray source was emphasized for increasing the total number of the observable diffraction peaks, and several examples were introduced. Secondly, the usage of the WAND method was introduced, in which the successful extraction of hydrogen atomic positions was described. The third example is to show the importance for the hybrid combination of these two diffraction methods. The quantitative WAXD data analysis gave the crystal structures of at-poly(vinyl alcohol) (at-PVA) and at-PVA-iodine complex. However, the thus-proposed structure models were found not to reproduce the observed WAND data very much. The reason came from the remarkable difference in the atomic scattering powers of the constituting atomic species between WAXD and WAND phenomena. The introduction of statistical disorder solved this serious problem, which reproduced both of the observed WAXD and WAND data consistently. The more systematic combination of WAXD and WAND methods, or the so-called X-N method, was applied also to the quantitative evaluation of the bonded electron density distribution along the skeletal chains, where the results about polydiacetylene single crystals were presented as the first successful study. Finally, the application of WAND technique in the trace of structural changes induced under the application of external stress or temperature was described. The future perspective is described for the development of structural science of synthetic polymers on the basis of the combined WAXD/WAND techniques.

Hydrogen-bond network and pH sensitivity in transthyretin: Neutron crystal structure of human transthyretin.

Transthyretin (TTR) is a tetrameric protein associated with human amyloidosis. In vitro, the formation of amyloid fibrils by TTR is known to be promoted by low pH. Here we show the neutron structure of TTR, focusing on the hydrogen bonds, protonation states and pH sensitivities. A large crystal was prepared at pD 7.4 for neutron protein crystallography. Neutron diffraction studies were conducted using the IBARAKI Biological Crystal Diffractometer with the time-of-flight method. The neutron structure solved at 2.0Å resolution revealed the protonation states of His88 and the detailed hydrogen-bond network depending on the protonation states of His88. This hydrogen-bond network is composed of Thr75, Trp79, His88, Ser112, Pro113, Thr118-B and four water molecules, and is involved in both monomer-monomer and dimer-dimer interactions, suggesting that the double protonation of His88 by acidification breaks the hydrogen-bond network and causes the destabilization of the TTR tetramer. In addition, the comparison with X-ray structure at pH 4.0 indicated that the protonation occurred to Asp74, His88 and Glu89 at pH 4.0. Our neutron model provides insights into the molecular stability of TTR related to the hydrogen-bond network, the pH sensitivity and the CH···O weak hydrogen bond.

Focal deformity of the cranial nerves observed on multislice motion-sensitized driven equilibrium (MSDE) in patients with neurovascular compression.

OBJECTIVE: Our purpose is to demonstrate the deformity of the cranial nerves by arterial compression using a novel technique, multislice motion-sensitized driven equilibrium (MSDE). METHODS: Subjects were 10 patients with neurovascular compression (5 patients with trigeminal neuralgia and 5 patients with hemifacial spasm). We observed the existence and extent of deformity of nerves by MSDE. Afterward, we compared operative findings with preoperative imaging findings and evaluated the validity of the latter. RESULTS: All compressing, blood vessels could be correctly identified through preoperative evaluation. Of all patients, 7 showed deformity of the cranial nerves, which was consistent with operative findings except in one case. In postoperative evaluation, patients' neurological symptoms improved and the deformity disappeared. Three patients did not show deformity on preoperative MSDE images. In these patients, neural compression was also not observed during the operation. CONCLUSIONS: The deformity of cranial nerves in patients with neurovascular compression was clearly shown using MSDE.

Neutron structure analysis using the IBARAKI biological crystal diffractometer (iBIX) at J-PARC.

The IBARAKI Biological Crystal Diffractometer (iBIX), a new diffractometer for protein crystallography at the next-generation neutron source at J-PARC (Japan Proton Accelerator Research Complex), has been constructed and has been operational since December 2008. Preliminary structure analyses of organic crystals showed that iBIX has high performance even at 120 kW operation and the first full data set is being collected from a protein crystal.

[Beginning of use of a new biological neutron diffractometer (iBIX) in J-PARC].

Ibaraki Prefectural Government together with Ibaraki University and Japan Atomic Energy Agency (JAEA) has almost finished constructing a time-of-flight (TOF) neutron diffractometer for biological macromolecules for industrial use at J-PARC, IBARAKI Biological Crystal Diffractometer (iBIX). Since 2009, Ibaraki University has been asked to operate this machine in order for users to do experiments by Ibaraki Prefecture. The diffractometer is designed to cover sample crystals which have their cell edges up to around 150 A. It is expected to measure more than 100 samples per year if they have 2 mm(3) in crystal volume, and to measure even around 0.1 mm(3) in crystal volume of biological samples. The efficiency of iBIX is also expected about 100 times larger than those of the present high performance diffractometers at JRR-3 in JAEA when 1MW power realizes in J-PARC. Since December 2008, iBIX has been open to users and several proteins and organic compounds were tested under 20 kW proton power of J-PARC. It was found that one of their proteins was diffracted up to 1.4 A in d-spacing, which was nearly comparable resolution to that of BIX-3 in JRR-3 when used the same crystal as at iBIX for reasonable exposure time. In May 2009, 14 detector units were set up. By the end of fiscal year 2009, the basic part of data reduction software will be finished and an equipment blowing low temperature gas to the sample will be installed with the cooperation of JAEA.

Current status and near future plan of neutron protein crystallography at J-PARC.

The IBARAKI Biological Crystal Diffractometer (iBIX) has been available for use at MLF (Material and Life Science Facility) in J-PARC (Japan Proton Accelerator Research Complex) since 2008. The development in state-of-the-art detector systems could enable iBIX to become one of the highest-performance neutron single-crystal diffractometers in the world. Here, together with other various developments, such as data reduction software, crystal growth, and new techniques in measurement coupled analysis, we provided new hydrogen and water structural data of several proteins and macromolecules. Although the proton power at MLF has not yet reached its planned maximum (1MW), a more powerful neutron source will be soon needed for neutron protein crystallography. A future idea is also proposed and discussed in this article.

MR imaging of fetal omphalocele: a case report.

We report a case of a fetal omphalocele in which the internal structure of the hernia sac was imaged in detail by magnetic resonance (MR) imaging. The hernia sac consisted of amnion, Wharton jelly, and externally, peritoneum. The umbilical vascular channels (2 arteries, one vein) were surrounded by Wharton jelly. Use of MR imaging facilitates a more accurate evaluation of fetal omphalocele with regard to hernial sac, intestinal structure, and differential diagnosis.

Status of the neutron time-of-flight single-crystal diffraction data-processing software STARGazer.

The STARGazer data-processing software is used for neutron time-of-flight (TOF) single-crystal diffraction data collected using the IBARAKI Biological Crystal Diffractometer (iBIX) at the Japan Proton Accelerator Research Complex (J-PARC). This software creates hkl intensity data from three-dimensional (x, y, TOF) diffraction data. STARGazer is composed of a data-processing component and a data-visualization component. The former is used to calculate the hkl intensity data. The latter displays the three-dimensional diffraction data with searched or predicted peak positions and is used to determine and confirm integration regions. STARGazer has been developed to make it easier to use and to obtain more accurate intensity data. For example, a profile-fitting method for peak integration was developed and the data statistics were improved. STARGazer and its manual, containing installation and data-processing components, have been prepared and provided to iBIX users. This article describes the status of the STARGazer data-processing software and its data-processing algorithms.

Differential subcellular targeting and activity-dependent subcellular localization of diacylglycerol kinase isozymes in transfected cells.

Diacylglycerol kinase (DGK) plays a pivotal role in cellular signal transduction through regulating levels of the second messenger diacylglycerol (DG). Previous studies have revealed that DGK is composed of a family of isozymes that show remarkable heterogeneity in terms of molecular structure, functional domains, tissue and cellular gene expression. Recently, it has been shown that DG is produced in various subcellular compartments including the plasma membrane, internal membranes, cytoskeleton, and nucleus. However, it remains unclear how DG is regulated at distinct subcellular sites. To address this point, we have used an epitope-tag expression system in cultured cells and investigated the subcellular localization of DGK isozymes under the same experimental conditions. We show here that DGK isozymes are targeted differentially to unique subcellular sites in transfected COS7 cells, including the cytoplasm, actin stress fibers, Golgi complex, endoplasmic reticulum, and nucleus. It is also shown that among the isozymes overexpression of DGKbeta causes fragmentation of actin stress fibers while a kinase-dead mutant of DGKbeta abolishes its colocalization with actin stress fibers. These data strongly suggest that each isozyme may be responsible for the metabolism of DG that is produced upon stimulation at a different and specific subcellular site and that DGKbeta activity might have effects on the reorganization of actin stress fibers in transfected COS7 cells.

Results of a questionnaire survey for symptom of late complications caused by radiotherapy in breast conserving therapy.

PURPOSE: The present study aimed to determine the prevalence of subjective symptoms of late complications mainly caused by radiotherapy in breast-conserving therapy (BCT), and to identify patients and treatment factors that may predict such complications. MATERIALS AND METHODS: A cross-sectional survey was conducted on 247 patients who had had early breast cancer and who were free of recurrence after BCT. Self-administered questionnaires were mailed to the 247 patients. Patient and treatment factors were analyzed. RESULTS: Responses were received from 193 of the 247 patients. Common perceptions of late complications included shrinking in size (85%), pain (73%), firmness (65%), thickening of the arm (34%), and changes in skin color (19%). However, high-grade toxicity (above Grade 2) was perceived in only 0.52-7.8% of patients. In multivariate models, shrinking in size was associated with age (P=0.020), pain was associated with additional boost irradiation (P=0.015), and firmness was associated with time after surgery (P=0.004). CONCLUSIONS: Late complications as perceived by the patient herself after BCT are common, but tend to be of minimal severity. Most predictive factors are inevitably associated with late complications. However, the boost irradiation may not be indicated for every patient from a QOL perspective.

Comparisons of the time-activity curves of the cardiac blood pool and liver uptake by 99mTc-GSA dynamic SPECT and measured 99mTc-GSA blood concentrations.

OBJECTIVES: The aim of this study was to determine the time-activity curve in the cardiac and hepatic region by 99mTc-GSA dynamic SPECT which is clinically used in liver scintigraphy and evaluate the temporal changes in the consistency and errors at the absolute scale using the regression equation of changes in the blood concentration of 99mTc-GSA. METHODS: In 11 patients who underwent 99mTc-GSA dynamic SPECT over the 30 min period after IV injection, the percentages of activity in the collected blood and in the blood pool estimated by dynamic SPECT were determined as the plasma clearance by blood collection and as the blood clearance by cardiac pooling. Extrahepatic uptake, expressesd as 100--(% uptake in the liver by dynamic SPECT (%)) was calculated as the blood clearance by the liver. The regression equation (Y = Y0 + Ae(-alphat)) was determined from the changes in the counts, expressed as a percent. Percent errors and the differences in the Y-intercept (Y0), coefficient (A) and slope (alpha) on the regression curve were compared. RESULTS: Blood pool clearance gradually exceeded the measured plasma clearance. The clearance by the liver started from a very low initial value and gradually became equal to that of plasma clearance over the first 15 minutes and exceeded it over the second 15 minutes. The Y-intercept was significantly higher in the blood pool clearance than that in the measured plasma clearance (p < 0.001), and the coefficient was significantly lower in the former than the latter (p < 0.001). The coefficient and slope were significantly lower in the hepatic clearance than the plasma clearance (p < 0.001, p < 0.005). CONCLUSION: The time-activity curve of the blood pool showed a tendency towards overestimation in the second half of the examination, probably due to scatter effect from the liver. The time-activity curve of liver uptake showed a tendency towards overestimation in the first half of the examination, probably due to the high concentration in the hepatic blood pool, and underestimation in the second half.

MR findings of cerebral white matter in Cockayne syndrome.

The characteristic magnetic resonance (MR) findings of Cockayne syndrome have been reported; however, the corresponding characteristics on diffusion-weighted and fluid-attenuated inversion recovery (FLAIR) imaging are yet to be documented. In this adult case with Cockayne syndrome, we identified small patchy subcortical lesions visualized as areas of high intensity on diffusion-weighted images and low intensity on FLAIR images. It is possible that these findings reflect active demyelinating lesions.

Diagnosis of Intracranial Artery Dissection.

Cerebral arterial dissection is defined as a hematoma in the wall of a cervical or an intracranial artery. Cerebral arterial dissection causes arterial stenosis, occlusion, and aneurysm, resulting in acute infarction and hemorrhage. Image analysis by such methods as conventional angiography, computed tomography, magnetic resonance imaging, and so on plays an important role in diagnosing cerebral arterial dissection. In this study, we explore the methods and findings involved in the diagnosis of cerebral arterial dissection.