Epithelioid glioblastoma is a rare aggressive variant of glioblastoma (GBM) characterized by a dismal prognosis of about 6 months and frequent leptomeningeal dissemination. A recent study has revealed that 50% of epithelioid GBMs harbor three genetic alterations – BRAF V600E mutation, TERT promoter mutations, and homozygous deletions of CDKN2A/2B . Emerging evidence support the effectiveness of targeted therapies for brain tumors with BRAF V600E mutation. Here we describe a dramatic radiographical response to combined therapy with BRAF and MEK inhibitors in a patient with epithelioid GBM harboring BRAF V600E mutation, characterized by thick spinal dissemination. From relapsed tumor procured at autopsy, we established a cell line retaining the BRAF V600E mutation, TERT promoter mutation and CDKN2A/2B loss. Intracranial implantation of these cells into mice resulted in tumors closely resembling the original, characterized by epithelioid tumor cells and dissemination, and invasion into the perivascular spaces. We then confirmed the efficacy of treatment with BRAF and MEK inhibitor both in vitro and in vivo. Epithelioid GBM with BRAF V600E mutation can be considered a good treatment indication for precision medicine, and this patient-derived cell line should be useful for prediction of the tumor response and clarification of its biological characteristics. Electronic supplementary material The online version of this article (10.1186/s40478-019-0774-7) contains supplementary material, which is available to authorized users.

Idiopathic basal ganglia calcification (IBGC), or Fahr's disease, is a neurological disorder characterized by widespread calcification in the brain. Recently, several causative genes have been identified, but the histopathologic features of the brain lesions and expression of the gene products remain unclear. Here, we report the clinical and autopsy features of a 62-year-old Japanese man with familial IBGC, in whom an SLC20A2 mutation was identified. The patient developed mild cognitive impairment and parkinsonism. A brain CT scan demonstrated abnormal calcification in the bilateral basal ganglia, thalami and cerebellum. An MRI study at this point revealed glioblastoma, and the patient died 6 months later. At autopsy, symmetric calcification in the basal ganglia, thalami, cerebellar white matter and deeper layers of the cerebral cortex was evident. The calcification was observed in the tunica media of small arteries, arterioles and capillaries, but not in veins. Immunohistochemistry using an antibody against type III sodium-dependent phosphate transporter 2 (PiT-2), the SLC20A2 product, demonstrated that astrocytic processes were labeled in several regions in control brains, whereas in the patient, reactivity in astrocytes was apparently weak. Immunoblotting demonstrated a marked decrease of PiT-2 in the patient. There are few autopsy reports of IBGC patients with confirmation of the genetic background. The autopsy features seem informative for better understanding the histogenesis of IBGC lesions.

We present the evidence of the low defect density at Ge/GeO 2 interfaces in terms of firstprinciples total energy calculations. The energy advantages of the atom emission from the Ge/GeO 2 interface to release the stress due to the lattice mismatch are compared with those from the Si/SiO 2 interface. The energy advantages of the Ge/GeO 2 are found to be smaller than those of the Si/SiO 2 because of the high flexibility of the bonding networks in GeO 2 . Thus, the suppression of the Ge-atom emission during the oxidation process leads to the improved electrical properties of the Ge/GeO 2 interfaces.

Perception of nasal stuffiness, together with rhinomanometric and acoustic rhinometric assessments were evaluated before and after nasal and/or sinus surgery in 50 Japanese adult patients. Nasal resistance on both expiration and inspiration correlated well with the patients' perceptions (P<0.05). Nasal volumes (0-4 cm and 0-7 cm) obtained from acoustic rhinometry measurements also correlated well with perception (P<0.05). No significant relationships were found between rhinomanometric and acoustic rhinometric results. Perceptional nasal obstruction, rhinomanometric and acoustic rhinometric results (except for the sectional areas at the I-notch) improved significantly after the operations. Rhinomanometry and acoustic rhinometry are valuable methods for assessing nasal stuffiness, but we must take account of the differences between the two methods.

The effect of SiO2 layers during the thermal oxidation of a 4H-SiC(0001) substrate is examined by performing the first-principles total-energy calculations. Although it is expected that a CO molecule is the most preferable product during the oxidation, CO2 molecules are mainly emitted from the SiC surface at the initial stage of the oxidation. As the oxidation proceeds, CO2 emission becomes less favorable and CO molecules are emitted from the interface. We conclude that the interface stress due to the lattice constant mismatch between 4H-SiC(0001) and SiO2 is responsible for the removal of C during the oxidation, resulting in the characteristic electronic property of the interface fabricated by the thermal oxidation.

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Density functional theory calculations are carried out to investigate the atomic and electronic structures of the 4H -SiC(0001)/SiO 2 interface. We find two characteristic interface atomic structures in scanning transmission electron microscopy images: One is an interface in which the density of atoms at the first interfacial SiC bilayer is greater than that in the SiC substrate, while the other is an interface where the density of atoms at the first interfacial SiC bilayer is lower. Density functional theory calculations reveal that the difference in the scanning transmission electron microscopy images is a reflection of the atomic structures of these two interfaces. In addition, it has been reported that the floating states, which appear at the conduction band edge of a 4H -SiC(0001)/SiO 2 interface, affect the electronic structure of the interface and cause marked scattering of the electrons flowing along the interface [S. Iwase, C. J. Kirkham, and T. Ono, Phys. Rev. B 95, 041302(R) (2017)]. Interestingly, we find that the floating states do not appear at the conduction band edge of one of the two interfaces. These results provide physical insights into understanding and controlling the electronic structure and carrier mobility of electronic devices using wide-band-gap semiconductors.

The detailed analysis of the structural variations of three GeO 2 and SiO 2 polymorphs 7 (α-quartz, α-cristobalite, and rutile) under compression and expansion pressure is re-8 ported. First-principles total-energy calculations reveal that the rutile structure is the 9 most stable phase among the phases of GeO 2 , while SiO 2 preferentially forms quartz.