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Bicyclic peptides exhibit improved metabolic stabilities and target specificities when compared to their linear or mono-cyclic counterparts; however, efficient and straightforward synthesis remains challenging due to their intricate architectures. Here, we present a highly selective and operationally simple one-pot chemoenzymatic tandem cyclization approach to synthesize bicyclic peptides with small to medium ring sizes. Penicillin-binding protein-type thioesterases (PBP-type TEs) efficiently cyclized azide/alkyne-containing peptides in a head-to-tail manner. Successive copper (I)-catalyzed azide-alkyne cycloaddition generated bicyclic peptides in one-pot, thus omitting the purification of monocyclic intermediates. This chemoenzymatic strategy enabled the facile synthesis of bicyclic peptides bearing hexa-, octa-, and undecapeptidyl head-to-tail cyclic scaffolds. Bicyclic peptides exhibit improved metabolic stabilities, membrane permeabilities, and target specificities over their linear and mono-cyclic counterparts, however, efficient bicyclization remains challenging. Here, the authors develop a one-pot tandem chemoenzymatic bicyclization by combination of penicillin-binding protein-type thioesterase-mediated head-to-tail macrolactamization and copper(I)-catalyzed azide–alkyne cycloaddition. [ABSTRACT FROM AUTHOR]

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78–28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42–571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA. [ABSTRACT FROM AUTHOR]

Objective: The present prospective study aimed to determine whether the addition of 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) to brain perfusion SPECT could improve the detection accuracy of misery perfusion on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). Methods: Oxygen extraction fraction (OEF) and brain perfusion were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine (IMP) SPECT, respectively, in 137 patients. IMZ SPECT was also performed. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories ipsilateral to the symptomatic cerebral hemisphere and in the contralateral posterior cerebral artery territory using a three-dimensional stereotaxic ROI template. The radioactive count of the MCA ROI to the contralateral posterior cerebral artery ROI was calculated on IMP SPECT (relative SPECT-IMP uptake) and IMZ SPECT (relative SPECT-IMZ uptake). The relative SPECT-IMZ uptake to the relative SPECT-IMP uptake was also calculated (relative SPECT-IMZ/IMP uptake). Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest PET-OEF value (one ROI per patient) was selected for analysis. Results: Significant correlations were observed between the PET-OEF and relative SPECT-IMP uptake (correlation coefficient, – 0.683) and relative SPECT-IMZ/IMP uptake (correlation coefficient, 0.875). The area under the receiver operating characteristic curve for detecting misery perfusion (PET-OEF > 51.3%) was significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake (difference between areas, 0.080; p = 0.0004). The sensitivity, specificity, and positive- and negative-predictive values for the relative SPECT-IMZ/IMP uptake for detecting misery perfusion were 100%, 92%, 81%, and 100%, respectively. The specificity and positive-predictive value were significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake. Conclusions: The addition of IMZ SPECT to brain perfusion SPECT improves the detection accuracy of misery perfusion on PET in adult patients with ischemic MMD. [ABSTRACT FROM AUTHOR]

Periventricular anastomosis in moyamoya disease (MMD) is an unusual angiographic finding that arises from perforating arteries such as the lenticulostriate artery (LSA), thalamic artery (THA), and anterior choroidal artery (AChA). This anastomosis is associated with increased hemorrhagic risk in MMD and can be corrected by direct revascularization surgery. The present supplementary analysis on a prospective cohort aimed to elucidate changes in periventricular anastomosis after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Twenty-two patients with misery perfusion in the symptomatic cerebral hemisphere who underwent indirect revascularization surgery alone also underwent six-vessel cerebral angiography via arterial catheterization before and at 6 months after surgery. Before surgery, two patients (9%) had positive periventricular anastomosis from the LSA and another (5%) from the AChA; all three of these periventricular anastomoses regressed after surgery, but these changes were not statistically significant (p = 0.0833). The degree of formation of collateral vessels from the LSA significantly decreased after surgery (p = 0.0143), but the degree of collateral vessels from the THA or AChA did not differ between pre- and postoperative conditions. Eight patients with postoperative regression of the collateral vessels from any perforating artery exhibited postoperative rich collateral flow from indirect revascularization. Periventricular anastomosis tended to regress after indirect revascularization surgery alone for adult patients with misery perfusion due to ischemic MMD. Collateral vessels formed from the LSA likely regressed after indirect revascularization surgery alone for such patients, but those vessels from the THA or AChA seldom changed. [ABSTRACT FROM AUTHOR]

The nucleation process of ZnTe thin films on sapphire substrates with a nanofaceted structure has been investigated. The nucleation process refers to three processes: low-temperature buffer layer deposition, buffer layer annealing, and migration enhanced epitaxy (MEE) layer formation. The r- and S-plane nanofaceted substrate on m-plane (1−100) sapphire was used to prepare ZnTe (110) layers. To obtain a high-quality ZnTe(110) thin film, selective nucleation on only the S-nanofacet surface was investigated. The initial growth processes were carefully studied. By optimizing the annealing time and significantly increasing the thickness of the MEE growth layers, the selectivity of ZnTe to the S-nanofacet surface was improved. Introduction of Zn-beam irradiation during annealing was effective to form a ZnTe thin film from the S-plane, and, as a result, a ZnTe(110) thin film with good crystallinity was successfully fabricated. In this paper, growth nuclei were characterized by field emission scanning electron microscopy (SEM), and the crystallinity of the thin film was evaluated by the X-ray diffraction (XRD) pole figure and the θ–2θ measurement. [ABSTRACT FROM AUTHOR]

Background: Adult patients with moyamoya disease (MMD) occasionally exhibit cerebral hyperperfusion after arterial bypass surgery, leading to persistent cognitive decline. The present supplementary analysis of a prospective 5-year cohort study aimed to determine whether cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD causes cerebral atrophy, and whether the development of cerebral atrophy is related to persistent cognitive decline. Methods: In total, 31 patients who underwent arterial bypass surgery also underwent fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and neuropsychological testing before surgery and at the end of a 5-year follow-up. The development of cerebral hyperperfusion and hyperperfusion syndrome after surgery was defined based on brain perfusion single-photon emission computed tomography (SPECT) findings and clinical symptoms. Univariate and multivariate logistic regression analyses of factors related to the development of cerebral atrophy on FLAIR MRI or cognitive decline on neuropsychological testing at the end of the 5-year follow-up were performed. Results: Eleven patients (35%) developed cerebral atrophy in the frontal lobe where the superficial temporal artery was anastomosed. Cerebral hyperperfusion on brain perfusion SPECT (odds ratio [OR], 50.6; p = 0.0008) or cerebral hyperperfusion syndrome (OR, 41.8; p = 0.0026) was independently associated with the development of cerebral atrophy, and cerebral atrophy development was significantly associated with cognitive decline (OR, 47.7; p = 0.0010). Conclusions: Cerebral hyperperfusion after arterial bypass surgery for adult patients with misery perfusion due to ischemic MMD can cause cerebral atrophy related to persistent cognitive decline. [ABSTRACT FROM AUTHOR]

Angiographic disease progression reportedly develops in adult moyamoya disease (MMD). However, more than half of patients analyzed underwent revascularization surgery. The present supplementary analysis of a 5-year prospective cohort with follow-up using magnetic resonance angiography (MRA) and cerebral blood flow (CBF) measurements was to elucidate the incidence and clinical features of angiographic disease progression in adult patients receiving medical management alone for ischemic MMD. Sixty-eight patients without misery perfusion in the symptomatic cerebral hemispheres underwent MRA and CBF measurement using brain perfusion single-photon emission computed tomography at inclusion and at the end of the 5-year follow-up. When neurological symptoms recurred or newly developed during the 5-year follow-up period, additional MRA and CBF measurements were also performed at that time. All four patients with further ischemic events during the 5-year follow-up period exhibited angiographic disease progression on MRA at such events. Of the remaining 64 patients without further events during the 5-year follow-up period, four exhibited angiographic disease progression on MRA at the end of the 5-year follow-up. CBF was significantly lower at the time of further ischemic events or at the end of the 5-year follow-up than at inclusion in eight patients with angiographic disease progression (p = 0.0117). The incidence of angiographic disease progression was 12% for 5 years in medically treated adult patients with ischemic MMD without cerebral misery perfusion. Patients with further ischemic events always exhibited angiographic disease progression. Cerebral perfusion was reduced in patients with angiographic disease progression even when further ischemic events did not occur. [ABSTRACT FROM AUTHOR]

The bivoltine strain of the domestic silkworm, Bombyx mori, has two generations per year. It shows a facultative diapause phenotype determined by environmental conditions, including photoperiod and temperature, and nutrient conditions during embryonic and larval development of the mother. However, it remains unclear how the environmental signals received during development are selectively utilized as cues to determine alternative diapause phenotypes. We performed a comparative analysis between the Kosetsu strain of B. mori and a Japanese population of the wild mulberry silkworm B. mandarina concerning the hierarchical molecular mechanisms in diapause induction. Our results showed that for the Kosetsu, temperature signals during the mother's embryonic development predominantly affected diapause determination through the thermosensitive transient receptor potential ankyrin 1 (TRPA1) and diapause hormone (DH) signaling pathways. However, embryonic diapause in B. mandarina was photoperiod-dependent, although the DH signaling pathway and thermal sensitivity of TRPA1 were conserved within both species. Based on these findings, we hypothesize that TRPA1-activated signals are strongly linked to the signaling pathway participating in diapause induction in Kosetsu to selectively utilize the temperature information as the cue because temperature-dependent induction was replaced by photoperiodic induction in the TRPA1 knockout mutant. [ABSTRACT FROM AUTHOR]

No matter the source of compounds, drug discovery campaigns focused directly on the target are entirely dependent on a consistent stream of reliable data that reports on how a putative ligand interacts with the protein of interest. The data will derive from many sources including enzyme assays and many types of biophysical binding assays such as TR-FRET, SPR, thermophoresis and many others. Each method has its strengths and weaknesses, but none is as information rich and broadly applicable as NMR. Here we provide a number of examples of the utility of NMR for enabling and providing ongoing support for the early pre-clinical phase of small molecule drug discovery efforts. The examples have been selected for their usefulness in a commercial setting, with full understanding of the need for speed, cost-effectiveness and ease of implementation. [ABSTRACT FROM AUTHOR]

Hardness distribution in the heterogeneous–nano (HN) structure developed in a heavily cold-rolled SUS316LN austenitic stainless steel was systematically investigated. The HN structure consisted of twin domains surrounded by shear bands, which were further embedded in the conventional low-angle lamellae. The twining planes of {111} in the twin domains were nearly parallel to the rolling direction (RD). The average twin spacing was 20–40 nm. The longitudinal direction of the lamellae was also nearly parallel to the RD, and the average interboundary spacing was about 100 nm. Rather shortened ultra-fine grains with an average size of 100 nm were well developed within the shear bands. Microstructural observations using the transmission Kikuchi diffraction technique revealed that both of the disorientation and the value of the kernel average misorientation in the twin domains were relatively low compared to those in the shear bands and lamellar grains, and the misorientation angle of twin boundaries within the twin domain still remained 60°. On the other hand, the misorientation angles among grains within the shear bands were considerably high. The intense strain localization within the shear bands during cold rolling would result in the instant formation of ultra-fine grains surrounded by high-angle boundaries. These results suggested that dislocation density within twin domains was lower than that of the shear bands and lamellar grains. Although the twin domains possess a smaller interboundary spacing than that in the shear bands and lamellar grains, nanoindentation tests revealed that hardnesses were almost identical among the component nanostructures. The nearly identical hardness among the component nanostructures would be ascribed to a lower amount of dislocation strengthening in the twin domains than that in the shear bands and lamellae. [ABSTRACT FROM AUTHOR]

The antidiabetic effects of a hot water extract of the stems of Salacia chinensis (SCE) were evaluated in vivo in ob/ob mice (genetically obese hyperglycemic mice). Administration of dietary feed containing 0.20 and 0.50% of SCE for 23 days to ob/ob mice significantly suppressed the elevation of both blood glucose and HbA1c levels, without significantly changing body weight and food intake. To characterize the antidiabetic effects of the thiosugar sulfonium constituent neokotalanol (1), which has potent α-glucosidase inhibitory activity, we performed a similar in vivo study. HbA1c levels were significantly suppressed in ob/ob mice after the administration of dietary feed containing 0.0003% of neokotalanol (1) for 20 days. These results indicate that SCE and neokotalanol (1) are potential leads for the development of novel antidiabetic agents. [ABSTRACT FROM AUTHOR]

AgGaTe2, AgAlTe2, CuGaTe2, and Ag(Ga,Al)Te2 layers were deposited by the close spaced sublimation method. The surface morphology and crystal quality of these Te-based chalcopyrite layers were systematically evaluated. Controlling the stoichiometry of these layers grown by the closed space sublimation was very difficult because Te preferentially detached from the source materials during the sublimation process and then Te vapor leaked out from the reactor. To solve this problem, the gap between the lid and reactor boat was minimized, and the vapor was encapsulated. As a result, the crystal quality of the AgGaTe2 and AgAlTe2 was improved. However, the controlling stoichiometry of CuGaTe2 remained difficult even after the Te vapor leakage was minimized. This behavior was attributed to the large vapor pressure difference between Cu and Te. The surface morphology of the grown AgGaTe2 and CuGaTe2 layers exhibited scattered grain structure, while that of AgAlTe2 possessed a continuous film structure. These different surface structures contributed to differing wettability between the chalcopyrite materials and substrates. It was found that AgAlTe2 exhibited a high wettability against a sapphire substrate, which promoted continuous film formation. [ABSTRACT FROM AUTHOR]

ZnTe thin films on sapphire substrate with nanofaceted structure have been studied. The nanofaceted structure of the m-plane (10-10) sapphire was obtained by heating the substrate at above 1100°C in air, and the r-plane (10-12) and S-plane (1-101) were confirmed. ZnTe layers were prepared on the nanofaceted m-plane sapphire substrates by molecular beam epitaxy (MBE). The effect of the nanofaceted structure on the orientation of the thin films was examined based on x-ray diffraction (XRD) pole figures. Transmission electron microscopy (TEM) was also employed to characterize the interface structures. The ZnTe layer on the nanofaceted m-plane sapphire substrate exhibited (331)-plane orientation, compared with (211)-plane without the nanofaceted structure. After thermal treatment, the m-plane surface vanished and (211) layer could not be formed because of the lack of surface lattice matching. On the other hand, (331)-plane thin film was formed on the nanofaceted m-plane sapphire substrate, since the (111) ZnTe domains were oriented on the S-facet. The orientation of the ZnTe epilayer depended on the atomic ordering on the surface and the influence of the S-plane. [ABSTRACT FROM AUTHOR]

Zinc telluride (ZnTe) epilayers were grown on S-plane ( $$10\bar{1}1$$ ) sapphire substrates by molecular beam epitaxy, and the epitaxial relationships between the two were compared with data previously obtained for layers grown on c-plane (0001), m-plane ( $$10\bar{1}0 $$ ) substrates, and r-plane ( $$1\bar{1}02 $$ ). The crystallographic relationship between the (111) plane of the ZnTe layer and (0001) plane of the substrate was studied using x-ray diffraction pole figure measurements. It was confirmed that two kinds of {111} oriented domains were formed on the S-plane substrate, and the dominant domain was (111)-oriented. Layers grown on S-plane substrate and on m-plane substrate exhibited the same epitaxial relationship, while the epitaxial relationship of the layer grown on the c-plane substrate exhibited a 60° rotation. These findings would be applicable to control the orientation of ZnTe epilayer surface for various device applications and for various physical property characterizations. [ABSTRACT FROM AUTHOR]

AgGaTe layers were successfully grown on Si substrates by the close-spaced sublimation method. The Si substrates were confirmed to be etched during AgGaTe layer growth when the layer was grown directly on the substrate. To eliminate melt-back etching, a buffer layer of AgTe was introduced. It was found that the AgTe buffer layer changed into the AgGaTe layer during the growth process, and a uniform AgGaTe layer with an abrupt interface was formed. Both the diffusion of Ga into AgTe and the growth of AgGaTe occurred simultaneously. It was confirmed that uniform AgGaTe layers could be formed without any traces of the AgTe layer or melt-back etching by tuning the growth parameters. A solar cell was also fabricated using the p-AgGaTe/n-Si heterojunction. This solar cell showed conversion efficiency of approximately 3%. [ABSTRACT FROM AUTHOR]

ZnTe/sapphire heterostructures were focused, and ZnTe thin films were prepared on highly mismatched sapphire substrates by molecular beam epitaxy. A sapphire substrate possessing an atomically-smooth step-terrace structure was used to improve the crystallinity and morphology of the produced ZnTe film. The growth mode of the ZnTe thin film on a sapphire substrate with an atomically-smooth step-terrace structure was found to shift to a two-dimensional growth mode, and a ZnTe thin film possessing a flat surface was obtained. The crystallographic properties of the ZnTe film suggested that the resulting layer consisted of a single (111)-oriented domain. The photoluminescence property was also improved, and the interface lattice alignment between the ZnTe and sapphire was also affected by the atomically-smooth step-terrace structure. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Interferon regulatory factor (IRF)4 plays a critical role in lymphoid development and the regulation of immune responses. Genetic deletion of IRF4 has been shown to suppress autoimmune disease in several mouse models, but its role in autoimmune diabetes in NOD mice remains unknown. Methods: To address the role of IRF4 in the pathogenesis of autoimmune diabetes in NOD mice, we generated IRF4-knockout NOD mice and investigated the impact of the genetic deletion of IRF4 on diabetes, insulitis and insulin autoantibody; the effector function of T cells in vivo and in vitro; and the proportion of dendritic cell subsets. Results: Heterozygous IRF4-deficient NOD mice maintained the number and phenotype of T cells at levels similar to NOD mice. However, diabetes and autoantibody production were completely suppressed in both heterozygous and homozygous IRF4-deficient NOD mice. The level of insulitis was strongly suppressed in both heterozygous and homozygous IRF4-deficient mice, with minimal insulitis observed in heterozygous mice. An adoptive transfer study revealed that IRF4 deficiency conferred disease resistance in a gene-dose-dependent manner in recipient NOD/severe combined immunodeficiency mice. Furthermore, the proportion of migratory dendritic cells in lymph nodes was reduced in heterozygous and homozygous IRF4-deficient NOD mice in an IRF4 dose-dependent manner. These results suggest that the levels of IRF4 in T cells and dendritic cells are important for the pathogenesis of diabetes in NOD mice. Conclusions/interpretation: Haploinsufficiency of IRF4 halted disease development in NOD mice. Our findings suggest that an IRF4-targeted strategy might be useful for modulating autoimmunity in type 1 diabetes. [ABSTRACT FROM AUTHOR]

AgGaTe, AgAlTe, and Ag(Ga,Al)Te layers were grown by the closed-space sublimation method on c-plane sapphire substrates. The crystallographic properties of the AgGaTe and AgAlTe layers were then analyzed by x-ray diffraction (XRD). Very strong 112 diffraction peaks were observed in the XRD spectra of both layers, and it was clear the (112) orientation was predominant in both layers. The orientation and domain structure of the AgAlTe layer were carefully analyzed by XRD pole-figure measurement, and the effect of substrate surface atomic arrangement on the crystallinity of the AgAlTe layer was investigated. On the basis of the pole-figure image, six types of {112} domain were confirmed in the layer, and [ $$ \bar{1} $$ 10] in one domain was regarded as aligned with the sapphire's a-axis when the layer was formed on the c-plane sapphire substrate surface. In addition to crystallographic characterization, the optical properties of the Ag(Ga,Al)Te layer were evaluated on the basis of transmittance measurements. The optical bandgap, derived from the transmittance spectrum, was approximately 2.0 eV. This value was between the bandgap values of AgGaTe and AgAlTe. These results showed that an alloy of AgGaTe and AgAlTe had been grown successfully. [ABSTRACT FROM AUTHOR]

AgGaTe and AgAlTe layers were grown on a-plane sapphire substrates by closed-space sublimation. These compounds replace Cd in CdTe with group I and III elements, and are, hence, expected to be ideal novel candidate materials for solar cells. The grown layers were confirmed to be stoichiometric AgGaTe and AgAlTe by x-ray diffraction (XRD). The AgAlTe layers had strong preference for the (112) orientation. The XRD spectrum of the AgGaTe layer was different from that of the AgAlTe layer, and strong peaks were observed for (103) and (110) diffraction. The variation in orientations of the grown layers was analyzed in detail by use of XRD pole figures, which revealed that the AgGaTe layers had an epitaxial relationship with the a-plane sapphire substrates. [ABSTRACT FROM AUTHOR]

ZnTe epilayers have been grown on 2°-tilted m-plane $$\left( {10\overline{1} 0} \right)$$ sapphire substrates by molecular beam epitaxy. Pole figure imaging was used to study the domain distribution within the layer, and the pole figures of 111, 220, 004, and 422 ZnTe and $$30\overline{3} 0$$ sapphire were measured. Computer simulation was used to analyze the symmetry of the diffraction patterns seen in the pole figure images. Stereographic projections were also compared with the pole figures of 422 and 211 ZnTe, confirming that single-domain (211)-oriented ZnTe epilayers had been grown on the 2°-tilted m-plane sapphire substrates. Although differences in crystal structure and lattice mismatch were severe in these heterostructures, precise control of the substrate surface's lattice arrangement would result in the formation of high-quality epitaxial layers. [ABSTRACT FROM AUTHOR]

It has generally been assumed that metals usually fail as a result of microvoid nucleation induced by particle fracture. Here, we concentrate on high-density micropores filled with hydrogen in aluminum, existence of which has been largely overlooked until quite recently. These micropores exhibit premature growth under external loading, thereby inducing ductile fracture, whereas the particle fracture mechanism operates only incidentally. Conclusive evidence of a micropore mechanism is provided by the observation of an instantaneous release of gas at failure. We can therefore conclude that the growth of micropores dominates ductile fracture. Since the material we used has a standard pore density, we can assume that an identical fracture mechanism operates in other aluminum alloys. This finding suggests that intense heat treatment, which is generally believed to enhance the mechanical properties through homogenization, may have entirely the opposite effect. This revelation will have a major impact on the engineering design of metals. [ABSTRACT FROM AUTHOR]

Purpose: In patients with unilateral internal carotid or middle cerebral artery (ICA or MCA) occlusive disease, the degree of crossed cerebellar hypoperfusion that is evident within a few months after the onset of stroke may reflect cerebral metabolic rate of oxygen in the affected cerebral hemisphere relative to that in the contralateral cerebral hemisphere. The aim of the present study was to determine whether the ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on positron emission tomography (PET) and single photon emission computed tomography (SPECT) correlates with oxygen extraction fraction (OEF) asymmetry in the cerebral hemisphere on PET in patients with chronic unilateral ICA or MCA occlusive disease and whether this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere in such patients. Methods: Brain blood flow and OEF were assessed using O-PET and N-isopropyl- p-[I]iodoamphetamine (I-IMP) SPECT, respectively. All images were anatomically standardized using SPM2. A region of interest (ROI) was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a three-dimensional stereotaxic ROI template, and affected-to-contralateral asymmetry in the MCA territory or contralateral-to-affected asymmetry in the cerebellar hemisphere was calculated. Sixty-three patients with reduced blood flow in the affected cerebral hemisphere on I-IMP SPECT were enrolled in this study. Results: A significant correlation was observed between MCA ROI asymmetry of PET OEF and the ratio of cerebellar hemisphere asymmetry of blood flow to MCA ROI asymmetry of blood flow on PET ( r = 0.381, p = 0.0019) or SPECT ( r = 0.459, p = 0.0001). The correlation coefficient was higher when reanalyzed in a subgroup of 43 patients undergoing a PET study within 3 months after the last ischemic event ( r = 0.541, p = 0.0001 for PET; r = 0.609, p < 0.0001 for SPECT). The blood flow ratio on brain perfusion SPECT in all patients provided 100 % sensitivity and 58 % specificity, with 43 % positive and 100 % negative predictive values for detecting abnormally elevated MCA ROI asymmetry of PET OEF. Conclusion: The ratio of blood flow asymmetry in the cerebellar hemisphere to blood flow asymmetry in the cerebral hemisphere on PET and SPECT correlates with PET OEF asymmetry in the cerebral hemisphere, and this blood flow ratio on SPECT detects misery perfusion in the affected cerebral hemisphere. [ABSTRACT FROM AUTHOR]

AgGaTe layers were deposited on Si substrates by the closed-space sublimation method. Multiple samples were deposited with various source temperatures and holding times, and constant temperature differential. Variation of the source temperature was used primarily to improve the stoichiometry of the film. Deposited films were evaluated by the θ-2 θ method of x-ray diffraction (XRD) and transmission electron microscopy. These results confirmed that the deposited films were stoichiometric (after optimizing the above parameters). From XRD, it was also clear that films deposited on Si (111) have strong preference for (112) orientation. [ABSTRACT FROM AUTHOR]

The influences of work hardening behavior of materials on ductile fracture, and especially on void growth and coalescence, have been investigated in model materials by in-situ X-ray computed tomography (XCT) coupled with tensile deformation. The model materials contain an artificial void array embedded in a metal matrix. By producing such materials with different metal matrices (pure copper, brass, Glidcop = copper strengthened by $$\text{ Al}_{2}\text{ O}_{3}$$ nanoparticles), the influences of the work hardening behaviors on void growth and coalescence/linkage process are analyzed. This set of experiments were performed at Japanese synchrotron radiation facility SPring-8 BL20XU beamline, whereby the X-ray tomography setup with one of the highest spatial resolution in the world is available. This beamline however provides less brilliant X-rays compared to the ESRF ID15 beamline where the our previous experiments were performed Hosokava et al. (Acta Mater, 60:2829-2839, ), (Acta Mater, 61:1021-1036, ). To compensate for the X-ray absorption problems, the specimens to be tested have to be much smaller, making the experiments more difficult. Nevertheless, the growth and linkage behaviors of the artificial voids were successfully visualized, and the plastic strain whereby the linkage takes place (referred to as the linkage strain, hereafter) were quantitatively captured. The models for void coalescence developed by Thomason and by Pardoen and Hutchinson both predict coalescence rather well for both brass and Glidcop, even though the linkage events were found to be dominated by the meso/macro shear localization process. [ABSTRACT FROM AUTHOR]

Intended aims of the paper are, firstly to conduct a realistic structural optimization of a nonconservative system, and secondly to give an experimental verification of the theoretically predicted stabilizing effect of shape optimization of cantilevered columns subjected to a rocket-based follower force. Flutter of a cantilevered column having a small solid rocket motor at its free end is considered in this paper. The shape optimization for maximum flutter load was conducted computationally with the design constraint that the width of the column should not be less than half of the initial width, in order to keep test-pieces elastic during compressive loading. The theory predicts that the flutter parameter of the shape optimized column with constant volume can be 1.2 times higher than that of the uniform column. Then the corresponding experiment was conducted. The mean thrust produced by the rocket motor was assumed constant during firing. As the applied load in the experiment was constant the free parameter for loading was the length of the columns. The mean thrust was 580 N and the burnout time was 3.2 s. Five test runs were conducted to find the experimental critical length of the uniform test columns. Following this, two runs were made with optimum columns having the same lengths as the corresponding uniform test columns. As the outcome, an experimental verification was given to structural optimization of cantilevered columns subjected to a rocket-based follower force. [ABSTRACT FROM AUTHOR]

Introduction: Several magnetic resonance (MR) imaging techniques are used to examine atherosclerotic plaque of carotid arteries; however, the best technique for visualizing intraplaque characteristics has yet to be determined. Here, we directly compared four kinds of T1-weighted (T1W) imaging techniques with pathological findings in patients with carotid stenosis. Methods: A total of 31 patients who were candidates for carotid endarterectomy were prospectively examined using a 1.5-T MRI scanner, which produced four kinds of T1W images, including non-gated spin echo (SE), cardiac-gated black-blood (BB) fast-SE (FSE), magnetization-prepared rapid acquisition with gradient echo (MPRAGE), and source image of three-dimensional time-of-flight MR angiography (SI-MRA). The signal intensity of the carotid plaque was manually measured, and the contrast ratio (CR) against the adjacent muscle was calculated. CRs from the four imaging techniques were compared to each other and correlated with histopathological specimens. Results: CRs of the carotid plaques mainly containing fibrous tissue, lipid/necrosis, and hemorrhage were significantly different with little overlaps (range: 0.92-1.15, 1.22-1.52, and 1.55-2.30, respectively) on non-gated SE. However, BB-FSE showed remarkable overlaps among the three groups (0.89-1.10, 1.07-1.23, and 1.01-1.42, respectively). MPRAGE could discriminate fibrous plaques from hemorrhagic plaques but not from lipid/necrosis-rich plaques: (0.77-1.07, 1.45-2.43, and 0.85-1.42, respectively). SI-MRA showed the same tendencies (1.01-1.39, 1.45-2.57, and 1.12-1.39, respectively). Conclusion: Among T1W MR imaging techniques, non-gated SE images can more accurately characterize intraplaque components in patients who underwent CEA when compared with cardiac-gated BB-FSE, MPRAGE, and SI-MRA images. [ABSTRACT FROM AUTHOR]

In this paper, we report techniques for mimicking and evaluating the human motion in real time by a therapeutic humanoid robot to improve the imitation skill of children with autism. For realizing the mimicking technique, we propose a method of selecting key frames using a Q-Learning approach to remove the significant noises. Then, in order to evaluate human motion in real time, we introduce a method of cluster-based framework of Mixture Gaussian and an Expectation-Maximization algorithm using parameters which are converted by Principal Component Analysis. Practical experiments have been performed to test the interaction of children with autism with the robot and evaluate the possibility of improving their imitation skills by training them to perform specific tasks through a robot. [ABSTRACT FROM AUTHOR]

Primary biliary cirrhosis (PBC) is frequently complicated with hepatocellular carcinoma (HCC), but complication with combined hepatocellular and cholangiocellular carcinoma (cHCC-CC) or cholangiocellular carcinoma (CCC) has not been reported. Here, we describe a case of PBC in which cHCC-CC occurred. The patient was a 70-year-old man who had developed jaundice at 62 years old. He was diagnosed with PBC based on a liver biopsy and blood tests. In August 2006, blood tests showed elevated alpha-fetoprotein, and a liver tumor in the right lobe and a metastatic lymphadenopathy in the back near to the head of the pancreas were detected by abdominal contrast-enhanced CT. A F-fluorodeoxyglucose-PET scan showed accumulation of the tracer in the tumor and in a lymph node at the back of the pancreas. The tumor and lymph node were removed, and the tumor was diagnosed pathologically as cHCC-CC based on the presence of features of HCC and CCC. This case is the first to show that a patient with PBC can develop cHCC-CC. This is of interest, since cHCC-CC may originate in hepatic stem cells or hepatic precursor cells. This case also suggests that cHCC-CC should be included as a differential diagnosis for a liver tumor complicated with PBC. [ABSTRACT FROM AUTHOR]

In the past, deformation/fracture (D/F) characteristics, defined as load-deformation relationships until the materials are fractured, have been analyzed and evaluated on the surface. The D/F characteristics are affected by more than 10,000 micro-scale internal structures like air bubbles (pores), dispersed particles and cracks in 1 mm3; therefore, it is required to analyze nano-scale D/F characteristics inside materials. In this paper, we propose an analysis method by obtaining displacement vectors of dispersed particles from nano-order 3D-CT images. A problem of matching over 10,000 dispersed particles between deformation is solved by a stratified matching. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine whether preoperative cerebrovascular reactivity (CVR) to acetazolamide measured by quantitative brain perfusion single-photon emission computed tomography (SPECT) predicts development of cerebral ischemic lesions on postoperative diffusion-weighted magnetic resonance imaging (DWI) that are caused by microemboli during carotid endarterectomy (CEA). One hundred and fifty patients with ipsilateral internal carotid artery stenosis (>70%) underwent CEA under transcranial Doppler monitoring of microembolic signals (MES) in the ipsilateral middle cerebral artery (MCA). Preoperative CVR to acetazolamide was measured using [123I] N-isopropyl- p-iodoamphetamine SPECT, and region of interest (ROI) analysis in the ipsilateral MCA territory was performed using a three-dimensional stereotaxic ROI template. DWI was performed within 3 days before and 24 h after surgery. Twenty-six patients (17.3%) developed new postoperative ischemic lesions on DWI. Logistic regression analysis demonstrated that, among the variables tested, a high number of MES during carotid dissection (95% CIs, 1.179 to 1.486; P < 0.0001) and preoperative reduced CVR to acetazolamide (95% CIs, 0.902 to 0.974; P = 0.0008), which were significantly associated with the development of new postoperative ischemic lesions on DWI. In 47 patients with MES during carotid dissection, the combination of number of MES during carotid dissection and CVR to acetazolamide identified development of new postoperative ischemic lesions on DWI with a positive predictive value of 100% or zero. Preoperative CVR to acetazolamide measured by quantitative brain perfusion SPECT predicts development of cerebral ischemic lesions on postoperative DWI that are caused by microemboli during CEA. [ABSTRACT FROM AUTHOR]

Cerebral hyperperfusion after carotid endarterectomy (CEA) results in cerebral hyperperfusion syndrome and cognitive impairment. The goal of the present study was to clarify the clinical significance of postoperative crossed cerebellar hypoperfusion (CCH) in patients with cerebral hyperperfusion after CEA by assessing brain perfusion with single-photon emission computed tomography (SPECT). Brain perfusion was quantitatively measured using SPECT and the [123I]N-isopropyl-p-iodoamphetamine-autoradiography method before and immediately after CEA and on the third postoperative day in 80 patients with ipsilateral internal carotid artery stenosis (≥70%). Postoperative CCH was determined by differences between asymmetry of perfusion in bilateral cerebellar hemispheres before and after CEA. Neuropsychological testing was also performed preoperatively and at the first postoperative month. Eleven patients developed cerebral hyperperfusion (cerebral blood flow increase of ≥100% compared with preoperative values) on SPECT imaging performed immediately after CEA. In seven of these patients, CCH was observed on the third postoperative day. All three patients with hyperperfusion syndrome exhibited cerebral hyperperfusion and CCH on the third postoperative day and developed postoperative cognitive impairment. Of the eight patients with asymptomatic hyperperfusion, four exhibited CCH despite resolution of cerebral hyperperfusion on the third postoperative day, and three of these patients experienced postoperative cognitive impairment. In contrast, four patients without postoperative CCH did not experience postoperative cognitive impairment. The presence of postoperative CCH with concomitant cerebral hyperperfusion reflects the development of hyperperfusion syndrome. Further, the presence of postoperative CCH in patients with cerebral hyperperfusion following CEA suggests development of postoperative cognitive impairment, even when asymptomatic. [ABSTRACT FROM AUTHOR]

We report a case of transient crossed cerebellar diaschisis secondary to cerebral hyperperfusion following carotid endarterectomy. The appearance of crossed cerebellar diaschisis under the presence of cerebral hyperperfusion may suggest the development of hyperperfusion syndrome. [ABSTRACT FROM AUTHOR]

A 58-year-old woman who had undergone resection of insulinoma 14 year earlier visited our clinic complaining of abdominal discomfort. Computerized tomographic scan showed multiple liver tumors, and a diagnosis of metastatic tumor of malignant islet cell tumor was confirmed histologically. No oversecretion of hormones or hypoglycemic episode was observed on readmission. Thus, the insulinoma seemed to have transformed to a clinically non-functioning tumor. The patient was treated with transcatheter arterial embolization, resulting in clinical improvement with marked reduction in tumor size. Features of interest in this case included; (1) transformation to non-functioning metastatic liver tumor 14 years after resection of insulinoma, (2) the usefulness of transcatheter arterial embolization for multiple metastatic tumor of malignant islet cell tumor. [ABSTRACT FROM AUTHOR]

X-ray diffraction reciprocal space maps and pole figures were used to analyse the cubic GaN epitaxial layers grown on (0 0 1) GaAs by r.f. plasma source MBE; the presence of hexagonal phase in cubic GaN layers was detected by high resolution x-ray analysis and the relationships among various crystal axes of cubic and hexagonal phase GaN were analysed with respect to V/III source-supply ratio. As for the growth conditions of the epitaxial layers, the V/III ratio was found to drastically affect the quality of the layers. High-temperature growth under near-stoichiometric conditions was necessary to obtain high quality epitaxial layers. It was found that inclusion of the hexagonal phase in the cubic GaN layers could be less than 0.4%, though previously reported typical c-GaN epitaxial layers included as much as 10–20% hexagonal phase GaN. On the basis of the measurements and analyses of reciprocal space maps and pole figures, it was revealed that the orientation of crystal axes of the hexagonal phase was unique in the present GaN epitaxial layers and they were different from those of previously reported c-GaN epitaxial layers. [ABSTRACT FROM AUTHOR]

A fluorescence enzyme immunoassay (FEIA) for the quantitative measurement of hepatitis C virus (HCV) core protein has recently been developed. In this study, we studied the clinical usefulness of this measurement in patients with acute hepatitis C. Eighteen patients with post-transfusion acute hepatitis C were enrolled in the study; 5 patients showed resolution of hepatitis with disappearance of HCV viremia, while the remaining 13 patients did not. A second generation HCV antibody, HCV RNA, and HCV core protein were measured in serial serum samples taken within 1 month of the onset of acute hepatitis and 3, 6, 12, 24, and 36 months after onset. Within the first month after disease onset, the positivity rates of HCV RNA (100%; P = 0.0014) and HCV core protein (89%; P = 0.0300) were both significantly higher than that of HCV antibody (56%). Six months after disease onset, the positivity rate of HCV antibody had increased, to 100%, and the positivity rates of HCV RNA and HCV core protein began to decrease. HCV core protein levels did not differ between patients with resolved and unresolved disease in the first month after disease onset. These findings indicate that FEIA, a simple assay, for the measurement of HCV core protein was useful for the early diagnosis of acute hepatitis C. [ABSTRACT FROM AUTHOR]

Two patients with acute hepatitis B with suggested sexual transmission of hepatitis G virus (HGV) are reported. A total of 18 patients with community acquired acute hepatitis B were analyzed in this study. Two of the 18 patients (patients 1 and 2) were positive for serum HGV RNA at the initial consultation. Both patients had had sexual contact with prostitutes several weeks before the onset of acute hepatitis, and hepatitis B virus (HBV) was suggested to be infected through the sexual contacts. These patients showed no other history of exposure to possible transmission routes for blood-borne hepatitis viruses. Patient 1 was diagnosed as with acute HGV infection because the antibody to HGV envelope-2 protein seroconverted to positive during the course of acute hepatitis. HGV RNA was negative in a serum sample collected from patient 2 before the onset of acute hepatitis, also suggesting acute HGV infection. These results indicate that in patients 1 and 2 HGV was infected along with HBV through sexual contact. The clinical manifestations of acute hepatitis in the two patients with HGV co-infection did not differ from those in the 16 patients with HBV infection alone. [ABSTRACT FROM AUTHOR]

We report a case of 23-yr-old man with glycogen storage disease (GSD) type Ia complicated by multiple hepatic adenomas. Analysis of the G-6-Pase gene using peripheral blood sample showed this patient to be homozygous for a G-to-T transversion at nucleotide 727 in exon 5. This mutation is prevalent among Japanese patients, suggesting that specific genotypes may correlate with different clinical courses or outcomes. [ABSTRACT FROM AUTHOR]

The effect of gas injection on an atmospheric thermal argon plasma flow in a water-cooled tube was investigated experimentally and numerically. The injection gas is argon, helium, or nitrogen. The static pressure with helium injection increases greatly because of its high thermal conductivity, while little increase occurs for nitrogen injection because of the dissociation. The increasing rate of the static pressure depends on the ratio of the momentum term to the viscosity term. The heat flux to the tube wall with gas injection changes less than that without injection. The numerical results showed variations similar to the experimental ones. [ABSTRACT FROM AUTHOR]

The momentum and energy transfer phenomena with large temperature difference were investigated experimentally and theoretically, using an argon atmospheric thermal plasma. The plasma was generated by an arc discharge, 4-6 kW, and flowed into a water-cooled copper tube for static pressure measurements and into a copper block with the same size hole (8 mm i.d.) for measuring heat fluxes using a transient method. The argon flow rate was 2.77-8.31×10 kg/s. The static pressure of the plasma flow shows a different variation from that of an ordinary flow and does not decrease monotonically. The axial distributions of the numerical calculations are in fair agreement with those of the experiments, and it is concluded that the contributions of recombination and of physical properties play important roles in the behavior of the confined thermal plasma flow. [ABSTRACT FROM AUTHOR]

We evaluated blood flow and oxygen metabolism in a patient with Lhermitte–Duclos disease using brain positron emission tomography. The lesion showed increased blood flow, reduced oxygen extraction fraction and normal metabolic rates of oxygen. These findings suggest that lesions of Lhermitte–Duclos disease may constitute hamartoma or hypertrophy rather than neoplasm. [ABSTRACT FROM AUTHOR]

Bone scintigraphy was performed in a 69-year-old male patient with adult T-cell leukemia suffering from right lower limb pain. Numerous sites of increased uptake were seen in the skull, left clavicle, bilateral humeri, bilateral radii and right femur and tibia. Bone radiographs showed multiple osteolytic lesions, most of which corresponded to the abnormal deposits on the bone scans with 740 MBq of99mTc-hydroxymethylene diphosphonate. This pattern is rarely reported, but bone involvement of adult T-cell leukemia is not uncommon. Bone involvement was remarkable on the appendicular skeleton when compared with common metastatic bone tumors. Bone scintigraphy may be useful in detecting bone involvement in adult T-cell leukemia. [ABSTRACT FROM AUTHOR]

The insect neuropeptide family FXPRLa, which carries the Phe-Xaa-Pro-Arg-Leu-NH2 sequence at the C-terminus, is involved in many physiological processes. Although ligand-receptor interactions in FXPRLa signaling have been examined using in vitro assays, the correlation between these interactions and in vivo physiological function is unclear. Diapause in the silkworm, Bombyx mori, is thought to be elicited by diapause hormone (DH, an FXPRLa) signaling, which consists of interactions between DH and DH receptor (DHR). Here, we performed transcription activator-like effector nuclease (TALEN)-based mutagenesis of the Bombyx DH-PBAN and DHR genes and isolated the null mutants of these genes in a bivoltine strain. All mutant silkworms were fully viable and showed no abnormalities in the developmental timing of ecdysis or metamorphosis. However, female adults oviposited non-diapause eggs despite diapause-inducing temperature and photoperiod conditions. Therefore, we conclude that DH signaling is essential for diapause induction and consists of highly sensitive and specific interactions between DH and DHR selected during ligand-receptor coevolution in Bombyx mori. [ABSTRACT FROM AUTHOR]

Studies the role of replication factor C (RFC) in the replication and repair of chromosomal DNA. Primary function of RFC; Subunits that comprise RFC; Solution structure of a protein-DNA complex that can be used to determine the biological role of the N-terminal half of RFC.