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.

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.

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).

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.

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.

Application of profile fitting method to neutron time-of-flight protein single crystal diffraction data collected at the iBIX.

We developed and employed a profile fitting method for the peak integration of neutron time-of-flight diffraction data collected by the IBARAKI Biological Crystal Diffractometer (iBIX) at the Japan Proton Accelerator Research Complex (J-PARC) for protein ribonuclease A and α-thrombin single crystals. In order to determine proper fitting functions, four asymmetric functions were evaluated using strong intensity peaks. A Gaussian convolved with two back-to-back exponentials was selected as the most suitable fitting function, and a profile fitting algorithm for the integration method was developed. The intensity and structure refinement data statistics of the profile fitting method were compared to those of the summation integration method. It was clearly demonstrated that the profile fitting method provides more accurate integrated intensities and model structures than the summation integration method at higher resolution shells. The integration component with the profile fitting method has already been implemented in the iBIX data processing software STARGazer and its user manual has been prepared.

Radiological imaging features of glioblastoma with oligodendroglioma component: a comparison with conventional glioblastoma.

BACKGROUND: Glioblastoma with oligodendroglioma component (GBMO) is a subtype of conventional glioblastoma (cGBM), which is categorized as WHO grade IV. GBMO can be histopathologically distinguished from cGBM and the prognosis of GBMO is better than that of cGBM. However, no systematic review of GBMO imaging findings has been published to date. PURPOSE: To clarify the radiological imaging features of GBMO compared with those of cGBM. MATERIAL AND METHODS: The participants were 15 patients with GBMO and 32 patients with cGBM as a control group, all of whom were histopathologically diagnosed. A radiologist retrospectively reviewed the imaging findings of both computed tomography (CT) and magnetic resonance imaging (MRI) for density, signal intensity, contrast medium enhancement (CE), cortical swelling, and cortical swelling without CE. We statistically analyzed the imaging findings by Chi-squared test. RESULTS: Cortical swelling without CE in GBMO was significantly greater than that in cGBM (P = 0.004). Non-CE and heterogeneous solid enhancement were observed significantly more often in GBMO (P = 0.004). No other findings were significant. CONCLUSION: There was significant difference in the findings of the CE, which exhibited solid heterogeneous enhancement in GBMO. Cortical swelling without CE can be considered significantly characteristic of GBMO.

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.

MR Imaging of Uterine Epithelioid Trophoblastic Tumor: A Case Report.

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic neoplasm of chorionic-type intermediate trophoblasts, and it is most frequently located in the lower uterine segment and endocervix. Due to the epithelial-growth pattern with geographic necrosis exhibited by the neoplastic cells, ETT is commonly confused, both clinically and pathologically, with squamous cell carcinoma. Although there have been no previous reports of ETT focusing on computed tomography (CT) or magnetic resonance imaging (MRI) findings, we report a case of uterine ETT with special attention to the MRI findings referring to the pathological findings and MR images of previous reports. A 42-year-old Japanese woman (gravid 1, para 1) presented with uterus enlargement during screening, and complained of recent-onset lower abdominal pain. The MRI showed a solid tumor throughout the entire myometrium of the lower uterine segment, with the hemorrhagic cystic portion extending to the posterior subserosal space. Following hysterectomy, the final pathological diagnosis was ETT. An ETT is essentially a solid tumor composed of intermediate trophoblasts that exhibit an epithelial-like growth pattern and contain geographic necrosis with calcification. In our case, MRI revealed a non-specific-intensity solid tumor in the lower uterine segment with massive necrosis and hemorrhage extending to the subserosa. While it is difficult to distinguish between ETT and uterine carcinomas, recognition of certain tumor shapes and necrosis could enable more accurate diagnosis before treatment.

The Efficacy of Color-Mapped Diffusion-Weighted Images Combined With CT in the Diagnosis and Treatment of Cholesteatoma Using Transcanal Endoscopic Ear Surgery.

OBJECTIVE: To assess the efficacy of a color-mapped diffusion-weighted image combined with a computed tomography scan (CMDWI-CT) in preoperatively evaluating the anatomical location of cholesteatomas and determining whether a patient is indicated for transcanal endoscopic ear surgery (TEES) to reduce intraoperative switching to microscopic ear surgery (MES). STUDY DESIGN: Prospective case study. SETTING: A single university hospital. PATIENTS: Fifty-five patients scheduled for middle ear cholesteatoma surgery. INTERVENTION: The CMDWI-CT is produced in a multistep process. A color-mapped fusion image (CMFI) is created by performing MR cisternography on a 1-mm thin-slice nonecho planar diffusion-weighted imaging (non-EPI DWI) and then by performing color mapping on the resulting image to enhance cholesteatoma visualization. False positives are reduced by taking a T1-weighted image (T1WI), whereas false negatives are further reduced by preoperative endoscopic examination. As cholesteatomas are difficult to locate on a CMFI in the temporal bone region, we stripped out the MR cisternography data from the CMFI and then fused the CMFI to the initial computer tomography (CT) scan to create a CMDWI-CT. This CMDWI-CT better clarifies the cholesteatoma position within temporal bone. MAIN OUTCOME MEASURE(S): CMDWI-CT preoperative findings were compared with intraoperative findings. The positive predictive value and negative predictive value were also evaluated depending on the cholesteatoma location. RESULTS: CMDWI-CT facilitated accurate detection of the cholesteatoma anatomical location in the temporal bone region which was reflected in positive predictive and negative predictive values of over 90% for all areas of the middle ear. CONCLUSION: CMDWI-CT is a reliable diagnostic modality for evaluating the anatomical location of cholesteatomas that seem as high-signal regions on a CMFI and for determining whether TEES is indicated for treatment in such patients.

Detectability and anatomical correlation of middle ear cholesteatoma using fused thin slice non-echo planar imaging diffusion-weighted image and magnetic resonance cisternography (FTS-nEPID).

Cholesteatomas show high intensity in diffusion-weighted imaging (DWI). We performed fused thin slice non-echo planar imaging (EPI) DWI and magnetic resonance cisternography (FTS-nEPID) for cholesteatoma patients to increase the detectability of FTS-nEPID for cholesteatoma. The subjects are 77 consecutive patients who underwent FTS-nEPID as a preoperative study (mean age: 53.3±21.8, 47 men and 30 women). Otorhinolaryngologists performed the operations. We anatomically classified the middle ear into four portions. A radiologist evaluated the images for cholesteatoma and assessed the anatomical invasive range in four portions using only FTS-nEPID. We classified large cholesteatomas that invaded more than three portions and small ones that invaded less than two portions based on the results obtained from surgery, and calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). For all cholesteatomas with an existing diagnosis, the sensitivity, specificity, PPV, and NPV were 71%, 70%, 94%, and 27%, respectively. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 49%, 85%, 77%, and 64%, respectively. For large cholesteatomas with an existing diagnosis, the sensitivity was 86%. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 51%, 57%, 88%, and 18%, respectively. For small cholesteatomas with an existing diagnosis, the sensitivity, specificity, PPV, and NPV were 59%, 78%, 92%, and 30%, respectively. In anatomical evaluation, the sensitivity, specificity, PPV, and NPV were 40%, 85%, 60%, and 71%, respectively. FTS-nEPID may be useful for diagnosing cholesteatomas. Further research is needed for anatomical evaluation because there were many false-negative results.

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.

The efficacy of color mapped fusion images in the diagnosis and treatment of cholesteatoma using transcanal endoscopic ear surgery.

OBJECTIVE: To assess the efficacy of color mapped fusion images (CMFIs) in preoperatively evaluating the anatomic location of cholesteatomas and determining whether a patient is indicated for transcanal endoscopic ear surgery. STUDY DESIGN: Prospective case study. SETTING: A single university hospital. PATIENTS: Ninety-two patients scheduled for middle ear cholesteatoma surgery. INTERVENTION: Imaging analysis was first performed using echo planar diffusion-weighted imaging (EPI) for the first patient group with mixed results. Imaging analysis was then performed using 1-mm thin-slice non-EPI combined with magnetic resonance cisternography in a second group. The resulting image was then processed using color mapping to create a CMFI that enhanced cholesteatoma visualization. A second non-EPI was also performed on the third group, incorporating a T1-weighted image (T1WI) to reduce false-positives. MAIN OUTCOME MEASURE(S): Preoperative findings from EPI, non-EPI/CMFIs, and non-EPI/T1WI-enhanced CMFIs were compared with intraoperative findings. The positive predictive value and negative predictive value were also evaluated for each group. RESULTS: Both the positive predictive value and negative predictive value obtained from the CMFIs were high in all areas of the middle ear, and CMFI facilitated accurate detection of the anatomic location of cholesteatomas of 3 mm or larger. The incidence of false-positives was further reduced in the final 18 patients by performing T1WI to distinguish between cholesteatomas and cholesterin granulomas. CONCLUSION: CMFI combined with T1WI is a reliable diagnostic modality for evaluating the anatomic location of cholesteatomas 3 mm or larger and determining whether transcanal endoscopic ear surgery is indicated for treatment in such cases.

Clinical significance of mammillary body enhancement in Wernicke encephalopathy: report of 2 cases and review of the literature.

In 2 cases of Wernicke encephalopathy in which the initial symptom was double vision, the only abnormal finding on magnetic resonance (MR) imaging was abnormal enhancement of the mammillary bodies. The mammillary bodies are the region most vulnerable to abnormal enhancement. Because MR imaging with contrast enhancement can detect such abnormal enhancement at an early stage, it should be performed more often in patients with oculomotor disorders to avoid underdiagnosis of Wernicke encephalopathy.

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.

Delineation of malignant glioma by turbo spin echo multislice motion-sensitized driven-equilibrium (TSE-MSDE) with gadolinium-based contrast media: a case report.

T1-weighted images by turbo spin echo multislice motion-sensitized driven-equilibrium with gadolinium-based contrast media clearly delineated the brainstem invasion of a malignant glioma in an 80-year-old woman compared with other magnetic resonance imaging sequences.