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Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being < 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile-Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8 ng/ml) than the rest (25.3 ± 11.3 ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein.

LiFePO 4 is a practically used cathode material for lithium-ion batteries due to a high theoretical capacity, high cycle capability and the high-rate performance. The metastable Li x FePO 4 (L x FP) phase with an intermediate composition appears in the non-equilibrium state at high-rate condition. However, the formation process of the metastable L x FP phase and its impact to the electrochemical property are still unclear. In order to elucidate these points, we directly observed the phase transition behavior by applying operando XRD during 10C charge-discharge. L x FP phase does not form in charge reaction but preferentially forms in discharge reaction. The phase transition from L x FP to Li-rich phase is less likely to proceed in the end of discharge reaction. The asymmetric phase transition between LiFePO 4 and FePO 4 results in decreasing the discharge capacity and increasing the irreversible capacity at high-rate conditions.

An epitaxial-film model electrode of LiCoO 2 (104) was fabricated on SrRuO 3 (100)/Nb:SrTiO 3 (100) using pulsed laser deposition. The 50 nm thick LiCoO 2 (104) film exhibited lithium (de-)intercalation activity with a first discharge capacity of 119 mAh g −1 between 3.0 and 4.4 V, followed by a gradual capacity fading with subsequent charge-discharge cycles. In contrast, a 3.2 nm thick Li 3 PO 4 -coated film exhibited a higher intercalation capacity of 148 mAh g −1 with superior cycle retention than the uncoated film. In situ surface X-ray diffraction measurements revealed a small lattice change at the coated surface during the (de-)intercalation processes compared to the uncoated surface. The surface modification of LiCoO 2 by the Li 3 PO 4 coating could lead to improvement of the structural stability at the surface region during lithium (de-)intercalation at high voltage.

Li-rich layered oxides have attracted attention as promising positive electrode materials for next-generation lithium-ion secondary batteries because of their high energy storage capacity. The participation of the oxygen anion has been hypothesized to contribute to these oxides' high capacity. In the present study, we used O K-edge and Mn L-edge X-ray absorption spectroscopy (XAS) to study the reversible redox reactions that occur in single-phase Li-rich layered manganese oxide, Li2MnO3. We semiquantitatively analyzed the oxygen and manganese reactions by dividing the charge/discharge voltage region into two parts. The O K-edge XAS indicated that the electrons at the oxygen site reversibly contributed to the charge compensation throughout the charge/discharge processes at operating voltages between 2.0 and 4.8 V vs. Li+/Li0. The Mn L-edge XAS spectra indicated that the Mn redox reaction occurred only in the lower-voltage region. Thus, at higher potentials, the electrons, mainly at the oxygen site, contributed to the charge compensation. Peaks whose energies were similar to peroxide appeared in and then disappeared from the O K-edge spectra obtained during the reversible redox cycles. These results indicate that the reorganization of the oxygen network in the crystal structure affects the redox components. By using two kinds of detection modes with different probing depths in XAS measurements, it was found that these redox reactions are bulk phenomena in the electrode.

The oxidation/reduction behaviours of lattice oxygen and transition metals in a Li-rich manganese-based layered oxide Li[Li0.25Ni0.20Mn0.55]O1.93 are investigated by using hard X-ray photoelectron spectroscopy (HAX-PES). By making use of its deeper probing depth rather than in-house XPS analyses, we clearly confirm the formation of O- ions as bulk oxygen species in the active material. They are formed on the 1st charging process as a charge compensation mechanism for delithiation and decrease on discharging. In particular, the cation-anion dual charge compensation involving Ni and O ions is suggested during the voltage slope region of the charging process. The Ni ions in the material are considered to increase the capacity delivered by a reversible anion redox reaction with the suppression of O2 gas release. On the other hand, we found structural deterioration in the cycled material. The O- species are still observed but are electrochemically inactive during the 5th charge-discharge cycle. Also, the oxidation state of Ni ions is divalent and inactive, although that of Mn ions changes reversibly. We believe that this is associated with the structural rearrangement occurring after the activation process during the 1st charging, leading to the formation of spinel- or rocksalt-like domains over the sub-surface region of the particles.

Temozolomide (TMZ) is one of the few effective anticancer agents against gliomas. However, acquisition of TMZ resistance or adaptation by gliomas is currently a crucial problem, especially increased invasiveness which is critical for the determination of clinical prognosis. This study investigated the molecular regulatory mechanisms of TMZ resistance in gliomas involved in invasiveness, particularly invadopodia formation, a molecular complex formed at the invasive front to cause extracellular matrix degradation during cellular local invasion. The TMZ-resistant clone of the U343 MG human glioma cell line (U343-R cells) was established. U343-R cells demonstrated higher invadopodia formation compared with U343 cells without TMZ resistance (U343-Con cells). Immunoblot analysis of DNA damage-related mitogen-activated protein kinase signals found increased phosphorylation of c-Jun terminal kinase (JNK) and higher activation of its downstream signaling in U343-R cells compared with U343-Con cells. Treatment of U343-R cells with specific inhibitors of JNK or siRNA targeting JNK suppressed up-regulation of invadopodia formation. In addition, paxillin, one of the known JNK effectors which is phosphorylated and affects cell migration, was phosphorylated at serine 178 in JNK activity-dependent manner. Expression of paxillin with mutation of the serine 178 phosphorylation site in U343-R cells blocked invadopodia formation. The present findings suggest that increased formation of invadopodia in U343-R cells is mediated by hyperactivation of JNK-paxillin signaling, and both JNK and paxillin might become targets of novel therapies against TMZ-resistant gliomas.

Introduction All-solid-state lithium-ion batteries (ASS-LIBs) are expected as next-generation LIBs because of high safety standard and power characteristics. However, ASS-LIBs still have several problems, such as short cycle life and high mass ratio of solid electrolytes. In order to solve these problems, it is necessary to clarify operation mechanisms of ASS-LIBs. In this study, we focused on electrochemical measurements, which have high versatility and high time resolution. Although three-electrode cells have been used in the electrochemical measurements of conventional LIBs to clarify the behavior of single electrodes, there have been few reports on three-electrode cells in ASS systems. [1] Moreover, electrochemical impedance spectroscopy (EIS) with three-electrode cells has never been reported in ASS-LIB systems. Thus, we synthesized chemically reduced Li4Ti5O12 (R-LTO) as an active material of the reference electrode and fabricated ASS three-electrode cells, and investigated electrochemical properties of LiCoO2 (LCO) composite electrode in Li-In|Li10GeP2S12(LGPS)|LCO cells by charge/discharge measurements and EIS measurements. Experimental methods R-LTO powder was synthesized by mixing of white Li4Ti5O12 powder with a tetrahydrofuran solution of lithium-naphthalenide. R-LTO reference electrode was fabricated by coating of the slurry composed of bluish black R-LTO powder, N-methyl-2-pyrrolidone and polyvinylidene fluoride on a nickel mesh current-collector. ASS three-electrode cell consisted of LCO composite electrode (LiNbO3-coated LCO:LGPS=7:3 wt%) as the working electrode, R-LTO reference electrode, LGPS as the solid electrolyte, and Li-In alloy as the counter electrode. Electrochemical measurements were carried out with a multichannel electrochemical system (VSP-300, Biologic). Results and Discussion Charge/discharge curves of the LCO electrodes and Li-In electrodes showed plateaus at around 2.35 V and –0.95 V vs. R-LTO, respectively. Assuming that the redox potential of Li7Ti5O12/ Li4Ti5O12 is 1.55 V vs. Li/Li+, we can calculate the plateau potentials of the LCO and Li-In electrodes to be 3.90 V and 0.60 V vs. Li/Li+, respectively. This clearly shows that the R-LTO reference electrodes successfully worked as an LTO redox couple. In the EIS measurements, the impedances of the LCO and the Li-In were successfully separated with the three-electrode cells since the impedance measured without the reference electrode agreed well with the combined impedance from those of the LCO and Li-In electrodes, which were separately measured with the reference electrode. We also investigated the temperature dependence and the state-of-charge (SOC) dependence of the LCO impedance. Figure 1 (a) shows the Nyquist plots obtained at 273, 288 and 298 K, and Figure 1 (b) gives the Arrhenius plots of two resistance values, R 2 and R 3, calculated with the equivalent circuit shown in the inset of Fig. 1 (a). The activation energy of R 3 was calculated to be 37 kJ mol–1, which is similar to that of the charge transfer resistance of LCO reported in ASS systems [2,3]. In addition, the SOC dependence of R 3 was similar to that of the charge transfer resistance observed for LCO electrode in a liquid electrolyte system [4]. From these results, R 3 can be assign to the charge transfer resistance. The activation energy of R 2 was 57 kJ mol–1, which is much higher than that of ionic conductivity of LGPS and also inconsistent with that of LCO electronic conductivity. Considering the SOC independence of R 2, we can assign R 2 to some interface or interphase resistance in the composite electrodes. The data with other electrode materials will be also reported in the presentation. References: [1] Y.J. Nam et al., J. Mater. Chem. A, 6, 14867 (2018). [2] Y. Iriyama et al., Solid State Ionics, 176, 31 (2005). [3] T. Ito et al., J. Power Sources, 360, 328 (2017). [4] N. Schweikert et al., Solid State Ionics, 226,15 (2012). Acknowledgment: This study was partially supported by SOLiD-EV of NEDO, Japan. Figure 1

Bifunctional electrocatalysts for both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER) are developed with perovskite-type oxide catalyst and antimony-doped tin oxide (ATO) as an oxidation-resistant conductive additive to increase the stability under an oxidizing atmosphere. In conventional carbon-supported catalysts, carbon plays an important role not only in increasing electric conductivity but also in catalyzing the first 2-electron reaction of the ORR. The ATO-mixed catalyst itself requires a perovskite-type oxide (ABO3) catalyst that is active in the first step of the ORR, such as La0.6Ca0.4MnO3 (LCMO), because of the poor ORR activity of ATO. On the other hand, OER performance strongly depends on the composition of the perovskite oxide and La0.6Ca0.4CoO3 (LCCO) shows high OER activity. Here, La0.6Ca0.4Co0.7Mn0.3O3 (LCCMO), in which Co and Mn are mixed at the B site of the perovskite-type oxide, mixed with ATO is proposed as a carbon-free bifunctional catalyst that shows activity for both the ORR and OER. The activity and durability of gas-diffusion air electrodes with the bifunctional catalysts are evaluated in zinc–air batteries, and the results suggest that the catalyst with ATO achieved similar charge-discharge performance and a longer lifetime compared to the conventional catalyst with carbon.

Background Chronic cerebrospinal fluid (CSF) over-drainage can induce compressive myelopathy without typical over-drainage manifestations. We present two cases of cervical myelopathy due to chronic CSF over-drainage that were successfully treated by gravitational add-on valve placement. Case description Patient 1 was a 38-year-old man who presented with pain and numbness in his left arm and hand, as well as weakness of the upper extremities. He had undergone cystoperitoneal shunting for a retro-cerebellar arachnoid cyst treatment. Patient 2 was an 83-year-old woman who presented with weakness and numbness of both upper and lower limbs. At the age of 72, ventriculoperitoneal shunting was performed for the treatment of hydrocephalus following subarachnoid hemorrhage. Magnetic resonance imaging (MRI) and three-dimensional computed tomography (3DCT) angiography revealed marked compression of the spinal cord and dural sac by enlarged epidural venous plexus in both patients. A gravitational valve was additionally inserted and patient’s symptoms improved. Post-operative MRI revealed decrease of the epidural venous plexus engorgement and resolution of the spinal cord compression. Conclusions Some rare pathophysiological relationships between intracranial hypotension and cervical myelopathy, can be difficult for diagnosis. Our findings indicate that proper diagnosis of such relationships after CSF shunt placement can provide relief of myelopathic symptoms.

Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category. Electronic supplementary material The online version of this article (10.1186/s40478-018-0630-1) contains supplementary material, which is available to authorized users.

Flow diverters (FDs) have been developed for intracranial aneurysms difficult to treat with conventional endovascular therapy and surgical clipping. We reviewed 94 patients with 100 large or giant unruptured internal carotid artery (ICA) aneurysms treated with Pipeline embolization device (PED) embolization from December 2012 to June 2017 at Juntendo University Hospital. The patients' mean age was 63.4 years (range, 19-88), and there were 90 women 89.4%. Aneurysm locations were: C4 (45), C3 (4), and C2 (51) in ICA segments. Mean aneurysm size and neck width were 16.9 ± 6.8 mm and 8.3 ± 4.4 mm, respectively, in 40 symptomatic and 60 asymptomatic aneurysms. Follow-up catheter angiographies of 85 patients with 90 aneurysms showed no filling in 62 aneurysms (68.9%), entry remnant in 16 (17.8%), subtotal filling in 11 (12.2), and total filling in 1 (1.1%) with a mean follow-up of 10.2 ± 5.6 months. In-stent stenosis occurred in 1 patient and parent artery occlusion in 2 during follow-up. Hemorrhagic complications occurred in 4 (4.3%): delayed aneurysm rupture (2) and intraparenchymal hemorrhage (2). Ischemic complications with neurological symptoms occurred in 2 (2.1%): very delayed device occlusion (1) and intraprocedural distal embolism (1). Eighteen patients (45%) showed improvement in pre-existing cranial nerve dysfunction because of the aneurysm's mass effect, 3 patients (7.5%) worsened. One patient died of systemic organ failure unassociated with the procedure. Morbidity and mortality rates were 4.3% and 1.1%, respectively. PED embolization for unruptured large and giant ICA aneurysms is safe and efficacious. Physicians should be observant of characteristic risks associated with FD therapy.

Background Experiencing a ventriculoperitoneal (VP) shunt complication is a major obstacle in the management of hydrocephalus. Degradation of a shunt catheter associated with surrounding tissue calcification could be 1 reason for a difference in facture rates. Furthermore, tissue reactions around cerebrospinal fluid shunts may be a sign of bacterial shunt infection, which is not uncommon. Case Description A 31-year-old man was living with a ventriculoperitoneal shunt since childhood. Consequently, his cerebrospinal fluid absorption was supposed to be modified by the shunt. Shunt malfunction later occurred concomitant with symptoms of headache and repeated vomiting. He had undergone shunt revision a year before presentation, but examination revealed that a new, extremely rare calcified lesion had formed in the aponeurosis of the abdomen, compressing the shunt tube. We removed it and replaced the shunt tube, thus relieving his symptoms. Conclusions We treated a rare case of shunt dysfunction caused by calcification of the aponeurosis coinciding with significant weight gain over the course of a year. To the best of our knowledge, this is the first report to describe a case of shunt malfunction caused by calcification of the aponeurosis.

The two pillars of descriptive and analytic epidemiological studies on intractable diseases are clarification of the number of patients showing symptoms and basic clinical features. This report introduces the importance of descriptive and analytic epidemiology of intractable diseases with regard to the significance, methodology, and points of attention through a nationwide survey of idiopathic normal pressure hydrocephalus (iNPH) that we experienced including specific survey methods, with introduction of reports from Japan and other countries.

Adipocytes are the prevalent stromal cell type in adult bone marrow (BM), and leukemia cells continuously adapt to deficiency of nutrients acquiring chemoresistant profiles in the BM microenvironment. We have previously shown that fatty acid metabolism is a key energy pathway for survival of acute myeloid leukemia (AML) cells in the adipocyte-abundant BM microenvironment. The novel fatty acid β-oxidation (FAO) inhibitor avocatin B, an odd-numbered carbon lipid derived from the avocado fruit, induced apoptosis and growth inhibition in mono-cultured AML cells. In AML cells co-cultured with BM adipocytes, FAO inhibition with avocatin B caused adaptive stimulation of free fatty acid (FFA) uptake through upregulation of FABP4 mRNA, enhanced glucose uptake and switch to glycolysis. These changes reflect the compensatory response to a shortage of FFA supply to the mitochondria, and facilitate the protection of AML cells from avocatin B–induced apoptosis in the presence of BM adipocytes. However, the combination treatment of avocatin B and conventional anti-AML therapeutic agent cytarabine (AraC) increased reactive oxygen species and demonstrated highly synergistic effects on AML cells under BM adipocyte co-culture condition. These findings highlight the potential for combination regimens of AraC and FAO inhibitors that target bone marrow-resident chemoresistant AML cells.

Background and Purpose: This study aimed to investigate the efficacy of cerebrospinal fluid shunt intervention for idiopathic normal pressure hydrocephalus (iNPH) using data from a nationwide epidemiological survey in Japan.Methods: We conducted a cross-sectional study using data from a nationwide epidemiological survey performed in Japan. Propensity score matching was used to select 874 patients from 1,423 patients aged ≥60 years, who were diagnosed with iNPH based on clinical guidelines following a hospital visit in 2012. Patients who experienced an improvement of at least 1 modified Rankin Scale (mRS) grade after the intervention were classified as “improved,” while the remaining patients were classified as “non-improved.” In the shunt intervention (n = 437) and non-shunt intervention (n = 437) groups, the differences in mRS grade improvement were analyzed using the Mann-Whitney U-test. Finally, we examined subjects in the shunt intervention group (n = 974) to compare the outcomes and complications of ventriculoperitoneal (VP) shunt (n = 417) with lumboperitoneal (LP) shunt (n = 540).Results: We examined subjects with iNPH to compare the non-shunt intervention group to the shunt intervention group following adjustment for age and mRS grade at baseline by propensity score matching (0.31–0.901). The mRS grade (mean [SD]) was found to improve with non-shunt intervention (2.46 [0.88]) and shunt intervention (1.93 [0.93]) (p < 0.001) in iNPH patients. The mRS outcome score and complications comparison between the VP and LP shunt groups did not show significant difference.Conclusions: In this study, analysis of the efficacy of shunts for possible iNPH conducted in Japan indicated a significant improvement in the mRS grade between baseline and outcome within 1 year, regardless of the surgical technique, and shunt intervention was found to be effective.

Background Fusion genes driving tumourigenesis have drawn the attention of researchers and oncologists. Despite the importance of such molecular alterations, there are no comprehensive reproducible methods for detecting fusion genes. Materials and methods Nineteen paediatric brain tumours of five types, namely pilocytic astrocytoma, oligodendroglioma, anaplastic astrocytoma, glioblastoma and, ganglioglioma, were examined to detect fusion genes using a pyrosequencing-based method following RNA isolation, cDNA synthesis and real-time polymerase chain reaction. Results Our method successfully detected KIAA1549-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) fusion in 14 out of 19 patients suffering from five types of paediatric brain tumours providing information on fusion breakpoints within 2 h. Conclusion A comprehensive method for detecting fusion genes in paediatric brain tumours was evaluated. This method identified KIAA1549-BRAF fusion variants quickly. Our results may help researchers interested in the role of fusion genes in tumourigenesis.

Aim Chronic subdural hematoma (CSDH) is a common neurosurgical clinical entity but the complication rates are not well established. Almost all CSDH patients undergo surgical intervention, but some patients are treated pharmacologically. In this study, we investigated the medical treatment of asymptomatic or mild symptomatic CSDH using only goreisan. Methods Eight patients with unilateral/bilateral CSDH without neurological disorder were given goreisan. Maximum vertical thickness of CSDH slice was measured on neuroradiological imaging. Treatment duration was defined as the period from when goreisan was first prescribed to the last visit, when either resolution of CSDH or neurosurgical intervention were indicated. Results Eight patients with 11 lesions (three patients had bilateral CSDH) were enrolled in this study and treated with only goreisan. The median treatment duration was 10 weeks. Two patients required surgery because of hematoma increase with neurological deterioration. Six of eight patients did not require surgery. Conclusions Medical treatment using goreisan for asymptomatic CSDH was effective. Some studies have demonstrated that aquaporin-4 (AQP4) plays an important role in CSDH. In recent studies, goreisan was found to inhibit AQP4 expressed on the outer membrane of CSDH. In the present patients, goreisan may have inhibited AQP4 on the outer membrane of CSDH, thereby decreasing membrane permeability. Therefore, we speculate that goreisan causes a decrease in CSDH hematoma volume. Furthermore, we speculate that goreisan may be associated with the inflammation process, thereby resolving CSDH.

Zinc-based secondary batteries are promising power sources with high energy density but their deterioration modes such as dendritic growth and shape changes need to be solved. These drastic morphology changes of the zinc electrode come from the nature of the discharged product that is easily dissolved in the alkaline electrolyte as zincate species. In this study, we attempt to preserve the zinc electrode morphology by employing the zinc oxidation-reduction processes in the vicinity of electrode, which is attained by controlling the electrolyte solvent property with mixing an organic solvent propylene carbonate (PC). The results show that the use of PC-water mixed solvent is effective in restricting the zincates dissolution into the electrolyte and preserving the zinc electrode morphology with no dendrite formation through 500 oxidation-reduction cycles is demonstrated in the electrolyte with high PC concentrations.

To examine the dynamical origin of high ionic conductivity of (Li2S)70(P2S5)30 glass ceramic obtained by annealing (Li2S)70(P2S5)30 glass, we applied 6/7Li and 31P solid-state NMR. NMR line shapes and spin–lattice relaxation times (T1) were measured as a function of temperature. The results showed that dynamics of the PS4 tetrahedra and P2S7 ditetrahedra units in (Li2S)70(P2S5)30 glass ceramic is not appreciable at temperatures below ca. 310 K, where the ionic conductivity is low. At higher temperatures, however, significant motion especially for the P2S7 ditetrahedra unit is apparent in both of 31P-T1 and 31P MAS line shapes. Further, we applied the 31P–31P dipolar correlation experiment to examine the 31P line width, which is reduced by motion at higher temperatures. It was shown that the line width of the P2S7 unit is attributable to the distribution of local structures of and around the P2S7 ditetrahedra unit. With these, we concluded that the significant motional fluctuation of the P2S7 ditetrahedra ...

The electrical properties of nickel-zirconia cermets as the anode material for solid oxide fuel cells (SOFCs) were studied for Sc2O3–Al2O3-stabilized ZrO2 (SASZ), together with conventional Y2O3-stabilized ZrO2 (YSZ). The reduction behavior of the cermets in terms of achieving better electrical conductivity was examined under constant temperature ramp rate (CTR) and constant temperature (CT) conditions. The reduction process and electrical conduction thus obtained were affected by the NiO particle size and porosity, and the zirconia composition of the starting NiO-zirconia composite material. All the NiO-zirconia anodes examined in this study exhibited high conductivity after reduction at a CT of 800 °C. The CTR condition resulted in lower electrical conductivity for the Ni-zirconia cermet. In particular, NiO-SASZ using coarse NiO powder exhibited only ionic conduction with a low electronic contribution, which was due to the absence of nickel–nickel percolation. Thermogravimetric analysis of the NiO reduction indicated that NiO-SASZ and NiO-YSZ had different reduction mechanism which might correspond to the interaction between NiO and zirconia and the long-term stability of these cermets. A kinetic analysis of the NiO reduction process revealed that fast and constant nucleation during the initial stage of reduction is important for the construction of nickel–nickel connections in the cermets.

The aim of this study was to quantitatively evaluate the function of the cranial diploic and spinal epidural veins as cerebrospinal fluid (CSF) drainage pathways by measuring lipocalin-type prostaglandin D synthase (PGDS) and cystatin C (CysC) dissolved in the blood of these veins. This was a prospective study involving 51 consecutive patients, 31 males and 20 females, who underwent 41 cranial and 10 spinal surgeries. Intraoperatively, peripheral venous blood and diploic venous blood, or peripheral venous blood and spinal epidural venous blood samples were simultaneously collected and immediately centrifuged. For all samples, dissolved albumin (for reference), PGDS and CysC were measured using an enzyme-linked immunosorbent assay. The diploic vein/peripheral vein ratios in five cranial locations and epidural vein/peripheral vein ratios were calculated and statistically evaluated for the three biomarkers. For PGDS, the diploic vein/peripheral vein ratio was significantly increased in the frontal (P = 0.011), temporal (P = 0.028), parietal (P = 0.046) and skull base (P = 0.039), while it did not reach statistical significance for CysC. For patients older than 45 years, the diploic vein/peripheral vein ratio for PGDS was significantly decreased in the frontal region (P = 0.028), and the epidural vein/peripheral vein ratio for CysC was significantly decreased (P = 0.014). These results show that the diploic veins constitute CSF drainage pathways with heterogeneous functional intensity at different cranial locations. Compared with the diploic veins, spinal epidural veins seem to drain less CSF. The cranial diploic and spinal epidural veins may jointly function as an alternative, age-related trans-dural CSF drainage system.

The traditional hypothesis of cerebrospinal fluid (CSF) hydrodynamics presumes that CSF is primarily produced in the choroid plexus (CP), then flows from the ventricles into the subarachnoid spaces, and mainly reabsorbed in the arachnoid granulations. This hypothesis is necessary to reconsider in view of recent research and clinical observations. This literature review presents numerous evidence for a new hypothesis of CSF hydrodynamics-(1) A significantly strong relationship exists between the CSF and interstitial fluid (IF), (2) CSF and IF are mainly produced and absorbed in the parenchymal capillaries of the brain and spinal cord. A considerable amount of CSF and IF are also absorbed by the lymphatic system, and (3) CSF movement is not unidirectional flow. It is only local mixing and diffusion.

Delithiation and lithiation behaviors of ordered spinel LiNi0.5Mn1.5O4 and disordered spinel LiNi0.4Mn1.6O4 were investigated by using in situ (in operando) 7Li NMR and ex situ 6Li MAS NMR spectroscopy. The in situ 7Li monitoring of the ordered spinel revealed a clear appearance and subsequent disappearance of a new signal from the well-defined phase Li0.5Ni0.5Mn1.5O4, suggesting the two-phase reaction processes among Li1.0Ni0.5Mn1.5O4, Li0.5Ni0.5Mn1.5O4, and Li0.0Ni0.5Mn1.5O4. Also, for the disordered spinel, Li0.5Ni0.4Mn1.6O4 was identified with a broad distribution in Li environment. High-resolution 6Li MAS NMR spectra were also acquired for the delithiated and lithiated samples to understand the detailed local structure around Li ions. We suggested that the nominal Li-free phase Li0.0Ni0.5Mn1.5O4 can accommodate a small amount of Li ions in its structure. The tetragonal phases Li2.0Ni0.5Mn1.5O4 and Li2.0Ni0.4Mn1.6O4, which occurred when the cell was discharged down to 2.0 V, were very different in the Li environment from each other. It is found that 6, 7Li NMR is highly sensitive not only to the Ni/Mn ordering in LiNi0.5Mn1.5O4 but also to the valence changes of Ni and Mn on charge-discharge process.

The cytotoxicity of the monofunctional alkylator, temozolomide (TMZ), is known to be mediated by mismatch repair (MMR) triggered by O6-alkylguanine. By contrast, the cytotoxicity of bifunctional alkylators, including carmustine (BCNU) and melphalan (MEL), depends on interstrand crosslinks formed through O6-alkylguanine, which is repaired by nucleotide excision repair and recombination. O6-alkylguanine is removed by O6-methylguanine-DNA methyltransferase (MGMT). The aim of the present study was to evaluate the cytotoxicity of TMZ, BCNU and MEL in two different leukemic cell lines (HL-60 and MOLT-4) in the context of DNA repair. The transcript levels of MGMT, ERCC1, hMLH1 and hMSH2 were determined using reverse transcription-quantitative polymerase chain reaction. In addition, the proliferation was measured using the trypan blue exclusion assay. Drug sensitivity was found to vary between the two cell lines. Treatment of the cells with TMZ, BCNU or MEL in combination with O6-benzylguanine, an MGMT inhibitor, was demonstrated to sensitize the two cell lines to these agents. However, the extent of sensitization was not found to be correlated with the expression levels of MGMT transcripts. Furthermore, the drug sensitivity was also not associated with the transcript levels of ERCC1, hMLH1 and hMSH2. Thus, leukemic cells were sensitized to alkylating agents by the inhibition of MGMT.

Zinc is a promising negative electrode material for aqueous battery systems whereas it shows insufficient rechargeability for use in secondary batteries. It has been reported that leaf-like dendrite deposits are often the origin of cell-failure, however, their nature and behavior on discharge (oxidation) - charge (reduction) cycling have been only poorly understood. Here we investigate the transformation of the leaf-like zinc dendrites using ex-situ scanning electron microscopy, X-ray computational tomography and in-situ X-ray diffraction. It is shown that the leaf-like zinc dendrites obtained under diffusion-limited conditions are nearly completely dissolved at a low oxidation current density of 1 mA cm−2 and cause re-evolution of the zinc dendrites. Oxidation at a high current density of 10 mA cm−2 leads to the formation of leaf-like zinc oxide residual products that result in particulate zinc deposits in the following reduction process, enabling good rechargeability. The reaction behavior of this oxide residue is detailed and discussed for the development of long-life zinc electrodes.

Li2FeSiO4 is a promising cathode material for lithium ion batteries because of its theoretically high capacity if two lithium ions can be extracted/inserted per formula unit; however, the extraction/insertion of two lithium ions from Li2FeSiO4 remains a challenge. Herein, we successfully synthesized carbon-coated Li2FeSiO4 nanoparticles which exhibit a capacity commensurate to a reversible two-lithium extraction/insertion at elevated temperature. This study investigates the mechanism underlying a two lithium ion extraction/insertion in Li2FeSiO4 using synchrotron X-ray absorption spectroscopy and X-ray diffraction. Our results reveal that the contribution of the Fe-3d band is dominant for the first lithium extraction process from Li2FeSiO4 to LiFeSiO4. During the second lithium extraction process from LiFeSiO4 to FeSiO4, however, ligand holes are formed in the O-2p band rather than further oxidation of Fe3+. Structural analyses further reveal a phase transformation between Li2FeSiO4 and LiFeSiO4, while a ...

Lifetimes of lithium-ion batteries are often affected by deterioration of positive electrodes. It is well-known that the deterioration of the positive electrodes can be reduced by using electrolyte additives; however, the mechanism underlying this cyclability improvement needs to be clarified. In this study, we investigate electronic structure at the electrode/electrolyte interface using in situ total-reflection fluorescence X-ray absorption spectroscopy to elucidate the mechanism underlying the cyclability improvement of a LiCoO2 electrode upon addition of vinylene carbonate (VC) to the electrolyte. The results indicate that the reduction of cobalt ions at the surface of the LiCoO2 electrode, which occurs upon soaking in the electrolyte in the absence of VC, is suppressed by the presence of the VC additive. The VC additive also suppresses irreversible change in the electronic structure of the cobalt ions at the LiCoO2 surface during successive charge/discharge processes. The effects of the VC additive ca...

A case of a patient with a ruptured true posterior communicating artery (PCoA) aneurysm is reported, who had been managed by early endovascular parent artery occlusion with coils. The small blister aneurysm was located at the proximal PCoA itself and directed superiorly. Postoperative course was uneventful. During 1-month follow-up, the patient recovered well and could care for herself. Aneurysms of the PCoA itself are very rare. As reported to date, surgical procedures would favor microsurgical clipping over endovascular coil embolization. Endovascular treatment may be a good alternative to surgical trapping for true PCoA blister aneurysm.

Liquid structures of Li/Mg/Cs-TFSA (TFSA: bis(trifluoromethylsulfonyl)amide, N(SO2CF3)2−) molten-salt systems have been investigated by Raman spectroscopy and high-energy X-ray diffraction. The Raman spectroscopic measurements indicate that the cis-conformer of the TFSA anion is more favorable than the trans-conformer in the molten salts containing Li+ and/or Mg2+, whereas the latter is dominant for a pure Cs[TFSA] molten salt. The present reverse Monte Carlo (RMC) structural modelling suggests that the coordination number of the anion around Mg, NMg-anion, decreased in Li0.1Mg0.1Cs0.8[TFSA]1.1 molten salt compared to that in Mg0.1Cs0.9[TFSA]1.1. The Mg-anion distance under the coexistence of Li+ is found to be about 10–15% longer than that without Li+ at around NMg-anion ∼ 1.5, which means the increase of free volume around Mg cations in the Li-contained molten salt. Thus, the electrodeposition of Mg in alkali-TFSA molten salts would be facilitated under the coexistence of Li cations.

Twenty years have passed since distraction osteogenesis was introduced into the field of craniomaxillofacial surgery, with distraction osteogenesis gradually consolidating its position for midface advancement in syndromic craniosynostosis. On the other hand, no consensus has been reached regarding its adaptation to calvarial bone. We reported that distraction osteogenesis was useful in posterior cranial vault expansion, and subsequently, similar reports have been successively observed worldwide. In posterior cranial vault distraction, intracranial capacity could be greatly expanded due to its simultaneous expansion with the scalp, with little risk of relapse because new bone is regenerated in the distraction gap. The possibility was suggested that the standard of first carrying out fronto-orbital advancement (FOA) for brachycephaly observed in syndromic craniosynostosis will greatly change posterior cranial vault distraction.

To improve the performance of rechargeable lithium-ion batteries, a microscopic understanding of the electrochemical reaction at the cathode is necessary. The spatial distribution of the electrode redox reaction for the LiFePO 4 cathode was analyzed by X-ray absorption fine structure (XAFS) imaging. Chemical state maps of the planar cathode electrode obtained by the in situ XAFS imaging revealed the inhomogeneity of the chemical state of Fe during the charge/discharge process. The chemical state maps for the reverse charge/discharge process demonstrated the reversibility of the inhomogeneous distribution. The in-plane radial progress of the reaction distribution strongly suggests that the inhomogeneous electrode reaction is caused by the difference in electrical conductivity; the charging and discharging reactions proceed through reaction channels with low electrical resistance in the cathode.

OBJECTIVEThe lateral recess is a unique structure communicating between the ventricle and cistern, which is exposed when treating lesions involving the fourth ventricle and the brainstem with surgical approaches such as the transcerebellomedullary fissure approach. In this study, the authors examined the microsurgical anatomy around the lateral recess, including the fiber tracts, and analyzed their findings with respect to surgical exposure of the lateral recess and entry into the lower pons.METHODSTen cadaveric heads were examined with microsurgical techniques, and 2 heads were examined with fiber dissection to clarify the anatomy between the lateral recess and adjacent structures. The lateral and medial routes directed to the lateral recess in the transcerebellomedullary fissure approach were demonstrated. A morphometric study was conducted in the 10 cadaveric heads (20 sides).RESULTSThe lateral recess was classified into medullary and cisternal segments. The medial and lateral routes in the transcerebellomedullary fissure approach provided access to approximately 140º–150º of the posteroinferior circumference of the lateral recess. The floccular peduncle ran rostral to the lateral recess, and this region was considered to be a potential safe entry zone to the lower pons. By appropriately selecting either route, medial-to-lateral or lateral-to-medial entry axis is possible, and combining both routes provided wide exposure of the lower pons around the lateral recess.CONCLUSIONSThe medial and lateral routes of the transcerebellomedullary fissure approach provided wide exposure of the lateral recess, and incision around the floccular peduncle is a potential new safe entry zone to the lower pons.

Medulloblastoma is a highly malignant brain tumor that predominately affects children and requires multimodal treatment, including chemotherapy with alkylating agents. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that plays an important role in tumor resistance to alkylating agents. Recent studies demonstrated that MGMT promoter methylation suppresses the expression of MGMT and is associated with favorable outcomes of malignant glioma patients. However, the MGMT methylation status and its prognostic impact on medulloblastoma have not been fully elucidated to date. The objective of the present study was to investigate the association between MGMT status and clinical outcomes of pediatric medulloblastoma patients. The records of 15 patients with medulloblastoma treated at our institution were reviewed, and the methylation status of 18 CpG sites in the MGMT promoter region was determined using bisulfite sequencing analysis. A larger number of methylated CpG sites was identified in 9 patients with complete remission (median, 5 sites; range, 2-9 sites) compared with that in 6 patients with relapse (median, 2 sites, range, 1-4 sites; P=0.041). These results suggest that a higher number of methylated CpG sites in the MGMT promoter region are associated with a favorable outcome of medulloblastoma.

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OBJECTIVEAneurysms of the middle cerebral artery (MCA) are still most often treated by clipping through standard craniotomy, but a longer hospital stay is one of the main drawbacks of this treatment. The authors developed a pterional keyhole clipping strategy for unruptured MCA aneurysms with the intention of minimizing hospital stay. In this paper, they report on their experience with this approach and analyze the long-term neurological and radiological outcomes.METHODSA total of 160 relatively small unruptured MCA aneurysms (mean 6.4 mm) were clipped through the pterional keyhole approach (19–30 mm, mean 24.6 mm) in 149 patients (aged 34–79 years, mean 62 years). Neurological and cognitive function were examined by several scales, including the modified Rankin Scale (mRS) and Mini–Mental State Examination (MMSE). Patients’ level of depression was assessed using the Beck Depression Inventory and Hamilton Depression Scale. The state of clipping was assessed at 1 year and then every few years after the operation.RESULTSThe mean duration of postoperative hospitalization was 2.3 ± 3.4 days; in 31.3% of the cases, the patients were discharged on the day after the operation (overnight hospital stay) and in 93.2% within 3 days. Of the patients younger than 60 years, 40.4% required only an overnight stay. Complete aneurysm neck clipping was confirmed in 157 cases (98.1%). None of the completely clipped aneurysms showed any recurrence during the mean follow-up period of 5.0 years. The mean length of clinical follow-up was 5.4 years. After 2 (1.3%) of the surgical procedures, the patients showed persistent neurological deficits, defined as mRS score 1, but the overall operative morbidity based on the International Study of Unruptured Intracranial Aneurysms (ISUIA) definition (mRS score ≥ 2 or MMSE score < 24) was 0% at the last examination. Depression scores were significantly improved after surgery, and in 85.6% of the cases the patients were satisfied with their cosmetic results.CONCLUSIONSPterional keyhole clipping is less invasive than clipping via standard craniotomy, minimizes hospital stay, and achieves durable treatment for relatively small unruptured MCA aneurysms.

A unique charge/discharge mechanism of amorphous TiS4 is reported. Amorphous transition metal polysulfide electrodes exhibit anomalous charge/discharge performance and should have a unique charge/discharge mechanism: neither the typical intercalation/deintercalation mechanism nor the conversion-type one, but a mixture of the two. Analyzing the mechanism of such electrodes has been a challenge because fewer tools are available to examine the “amorphous” structure. It is revealed that the electrode undergoes two distinct structural changes: (i) the deformation and formation of S–S disulfide bonds and (ii) changes in the coordination number of titanium. These structural changes proceed continuously and concertedly for Li insertion/extraction. The results of this study provide a novel and unique model of amorphous electrode materials with significantly larger capacities.

We previously reported increase in leucine-rich α2-glycoprotein (LRG) concentration in cerebrospinal fluid is associated with cognitive decline in humans. To investigate relationship between LRG expression in the brain and memory impairment, we analyzed transgenic mice overexpressing LRG in the brain (LRG-Tg) focusing on hippocampus. Immunostaining and Western blotting revealed age-related increase in LRG expression in hippocampal neurons in 8-, 24-, and 48-week-old controls and LRG-Tg. Y-maze and Morris water maze tests indicated retained spatial memory in 8- and 24-week-old LRG-Tg, while deteriorated in 48-week-old LRG-Tg compared with age-matched controls. Field excitatory postsynaptic potentials declined with age in LRG-Tg compared with controls at 8, 24, and 48 weeks. Paired-pulse ratio decreased with age in LRG-Tg, while increased in controls. As a result, long-term potentiation was retained in 8- and 24-week-old LRG-Tg, whereas diminished in 48-week-old LRG-Tg compared with age-matched controls. Electron microscopy observations revealed fewer synaptic vesicles and junctions in LRG-Tg compared with age-matched controls, which became significant with age. Hippocampal LRG overexpression contributes to synaptic dysfunction, which leads to memory impairment with advance of age.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown. PROCEDURE: We performed high-throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology. The expression of the identified gene was validated in 29 AT/RT samples by gene expression profiling, quantitative real-time polymerase chain reaction, and immunohisto- chemistry (IHC). Furthermore, we investigated the function of this gene by mutating it in rhabdoid tumor cells. RESULTS: TEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4’s co- activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma. IHC showed TEAD4 and YAP1 overexpression in all samples. Cell proliferation and migration were significantly reduced in TEAD4-mutated cells. CONCLUSIONS: We report the overexpression of TEAD4 in AT/RT, which is a key component of Hippo pathway. Recent reports revealed that dysregulation of the Hippo pathway is implicated in tumori- genesis and poor prognosis of several human cancers. Our results suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor.

The extracranial-intracranial (EC-IC) bypass using the maxillary artery (MA) has been successfully completed using a radial artery (RA) graft but the complicated anatomy and narrow exposure make it difficult. The purpose of this article is to define the microsurgical exposure of the MA through the middle fossa and describe the branches, diameter, and length of the MA available for the EC-IC bypass in the sphenopalatine fossa and anterior part of the infratemporal fossa. 5 cadaveric specimens were dissected bilaterally (10 MA dissections) to define the microsurgical anatomy of the MA through an intracranial approach. The exposable branches of the MA at the level of the infratemporal and sphenopalatine fossae were the anterior deep temporal, posterior superior alveolar, and infraorbital arteries. The origin of each branch could be exposed. The available section of the MA for use as a donor vessel is between the origin of the anterior deep temporal artery and the infraorbital artery. The mean exposable length of the MA was 19.4 mm. The mean outer diameter of the donor MA was 3.2 mm. Tension-free EC-IC bypass was possible using a RA graft between the MA and the middle cerebral artery, the MA and the supraclinoid internal carotid artery (ICA), or the MA and the petrous ICA. Exposure of the MA at the infratemporal and sphenopalatine fossae is complicated but provides length and diameter suitable as a donor artery for the EC-IC bypass. Clin. Anat. 31:724-733, 2018. © 2017 Wiley Periodicals, Inc.