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The biochemical functions of the Cbfa1 core-binding factor were characterized in fetal mice with mutated Cbfa1 genes. The mutated mice died after birth due to a complete lack of bone formation that was induced by the disruption of the Cbfa1 gene. Histological analysis of the skeleton of the mice indicated the presence of low levels of osteopontin and osteolacin. Furthermore, maturational arrest occured during the early stage of osteoblast differentiation in the mutated mice embryos.

The purpose of this study was to determine the organ specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from a multi-institutional clinical trial (JCOG1015). Dose constraints used in the JCOG1015 were as follows; Spinal cord Dmax <50 Gy, Brain Dmax <70 Gy, Brainstem Dmax <54 Gy, Optic nerve Dmax <50 Gy, Eyeball Dmax <40 Gy, Lens Dmean <6 Gy, Parotid gland Dmean <26 Gy, pharyngeal constrictor muscle (PCM) Dmean <54 Gy, Larynx Dmean <54 Gy, Inner ear Dmean <45 Gy. Brain D1cc, brainstem D1cc, and thyroid Dmean were not stated but recorded. Patient data and dose-volume histograms (DVH) of organs-at-risk (OARs) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in the JCOG1015 trial. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. Estimated DVH cut-off values were brainstem D1cc:55.8 Gy for G1 myelitis, brain D1cc:72.1 Gy for ≥G1 central nerve necrosis, optic nerve Dmax:53.3 Gy for G2 vision impaired, eye-ball Dmax:36.6 Gy for G2 impaired, PCM Dmean:41.2 Gy for ≥G2 dysphagia, ipsilateral inner ear Dmean:44.0 Gy for ≥G2 hearing impaired, ipsilateral inner ear Dmean:51.5 Gy for ≥G2 middle ear inflammation, and thyroid Dmean: 45.6 Gy for G1 hypothyroidism. The 3- and 5-year cumulative incidence of late toxicity by dose metrics were shown in Table 1. The estimated cut-off values were similar to dose constraints criteria used in the JCOG1015 except for PCM. In patients who received higher dose than the dose constraints in brainstem and inner ear, incidence of myelitis and hearing impaired were notably high. The dose constraints criteria of the JCO1015 were appropriate for most OARs, although more strict dose constraints might be necessary for PCM. Dose constraints for inner ear and brainstem should be archived with higher priority. [ABSTRACT FROM AUTHOR]

We studied optical and electron transport properties of coupled InAs quantum dots (QDs) embedded in GaAs. Photoluminescence (PL) from the high dot density samples indicated asymmetry in the PL spectra when the ambient temperature is lower than about 50 K. Comparing this result with theoretical calculations, it is shown that this phenomenon is explained by the inter-dot electronic coupling effect. In the photo-conductance measurement, resonance peaks in the current–voltage characteristics were observed in the low-temperature region. The dependence of the resonance voltage on the magnetic field intensity was studied to extract the g-factor. It is also shown that the resonances are attributed to the current corresponding to the electron transport through QDs. According to these results, it is concluded that the inter-dot electronic coupling in the self-assembled InAs/GaAs QD systems occurs when the inter-dot spacing is as low as several nanometers and the ambient temperature is less than about 50 K. [Copyright &y& Elsevier]

Transient receptor potential (TRP) channels are cation channels with ubiquitous expression. Various TRP channels are functionally active at the ocular surface and are involved in tear secretion and multiple inflammatory processes. So far, the impact of TRP channels regarding the development of the lacrimal gland (LG) is unclear. While investigating TRP channels in the LG, the TRPM3 channel presented itself as a promising candidate to play a role in the development and functioning of the LG. Therefore, Trpm3 expression was analyzed in different embryonic and postembryonic LGs. Thus, gene expression of TRPM channels including Trpm2 , Trpm3 , Trpm4 and Trpm6 was analyzed by quantitative RT-PCR in murine LGs at different developmental stages. Localization of TRPM3 in LGs was examined by immunohistochemistry. Primary LG epithelial cells (LGEC) and mesenchymal cells (MC) from newborn mice were cultured (either separately or collectively) for three days, and Trpm3 expression was analyzed in LGEC and MC. As a result, gene expression of Trpm2 , Trpm4 and Trpm6 showed no significant difference in LGs in the different stages of development. However, Trpm3 gene expression was significantly higher in the embryonic stage than in the postnatal stage with the peak at E18. Postnatal, Trpm3 expression significantly decreased up to 28-fold until two years of age. Immunohistochemistry for TRPM3 revealed apical membranous expression in the excretory ducts, as well as in the acini of up to P7 old mice. Trpm3 expression in LGEC were significantly higher than that of MC. Our results indicate that Trpm3 expression in murine LG is age-dependent and peaks at age E18. Its expression is localized in the apical membrane of the glandular epithelium. However, its functional role still requires additional study in the LG. [ABSTRACT FROM AUTHOR]

Abstract: We report the fabrication of AlGaN/GaN high electron mobility transistor (HEMT) with high breakdown voltage by employing the metal-insulator-semiconductor (MIS) gate structure. SiO2, SiN, and TiO2 were used for the insulators. The gate leak current was significantly reduced by employing the MIS structure, and the breakdown voltage characteristics were improved. The breakdown voltage of the MIS–HEMTs increased non-linearly with the increase of gate-drain length L gd. The TiO2 insulator exhibited highest breakdown voltage of 2kV with the on-resistance of 15.6mΩcm2 for L gd =28μm. On the other hand, the breakdown voltage and on-resistance for SiN MIS–HEMT were found to be 1.7kV and 6.9mΩcm2, respectively. We demonstrated that AlGaN/GaN MIS–HEMTs are promising not only for high speed applications but also for high power switching applications. [Copyright &y& Elsevier]

The present study aimed to evaluate whether online adapted plan with artificial intelligence (AI) driven work flow could be used in clinical settings with variable changes of the targets and organs at risk (OARs) for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy at our institution between January and July 2020 were included for the analysis. All patients had been previously aligned daily with cone-beam computed tomography (CBCT) and treated by O-ring Linac. A simulated treatment was performed on the treatment emulator. Weekly fractions, once in every 4-5 fractions, were simulated in the treatment emulator for each patient using their previous on-treatment CBCTs. The dataset was divided into three groups according to the treatment period (1st-2nd week, 20 CBCTs), middle (3rd-4th week, 20 CBCTs), and late (5th-7th week, 30 CBCTs) period. In the present study, all of reference plan generation in treatment emulator were created on the initial plans of two-step method using 12 equidistant field IMRT. The prescribed dose was 70 Gy in 35 fractions and normalized to the dose of 68.6 Gy (98% dose) to 95% of the planning target volume (PTV). The adaptation process on treatment emulator includes auto-segmentation of daily anatomy, calculation of the dose in scheduled plans using the same monitor units and optimization and calculation of the dose in adapted plan. Dose-volume histogram (DVH) parameters between adapted and scheduled plans in terms of PTV (D 98% , D 95% , D 50% and D 2%), spinal cord (D max and D 1cc), brain stem (D max), ipsilateral and contralateral parotid glands (D median and D mean) were evaluated in each period. D 98% of PTV of adapted plan was significantly higher than that of scheduled plan in early and middle period (p = 0.02 and <0.01, respectively). D 95% of PTV of adapted plan was significantly higher than that of scheduled plan in all periods (p<0.01). D 2% of PTV of adapted plan was significantly lower than that of scheduled plan in all periods (p = 0.04, 0.04 and 0.02 in each period, respectively). There was not significant difference in D 50% of PTV between adapted and scheduled plan in all periods. In terms of OARs, D max of spinal cord of adapted plan was significantly lower than that of scheduled plan in all periods (p<0.01). Similarly, D 1cc of spinal cord of adapted plan was lower than that of scheduled plan. D mean of ipsilateral and contralateral parotid glands of adapted plan were lower than those of scheduled plan in the late period (p<0.01 and 0.03, respectively). The present study revealed that adapted plan with AI driven work flow could create dosimetrically better plans for pharyngeal cancer compared to scheduled plan. It was suggested that online adaptive radiotherapy could be necessary to maintain PTV coverage while reducing the dose to OARs in all periods for pharyngeal cancer. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The present study aimed to evaluate prognostic factors, particularly with respect to their role in establishing distinct prognostic subsets of human papillomavirus (HPV)-positive and -negative oropharyngeal cancer (OPC).Materials/methods: This study retrospectively evaluated 101 patients with OPC who underwent radiotherapy (RT) alone or chemoradiotherapy (CRT) at our institution between August 2008 and December 2018. Whole neck RT (44.0-50.0 Gy/22-25 fractions) was delivered by intensity-modulated RT (IMRT), followed by boost IMRT to high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Seventy patients (69.3%) received concurrent chemotherapy. Clinical factors which were potentially associated with prognosis were analyzed. Receiver-operating characteristic curve analysis was adopted to determine the most appropriate cut-off points of hematological biomarkers including the serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein/ albumin ratio (CRP/Alb).Results: The median follow-up period of the surviving patients was 68 (range; 8-164) months. The 5-year overall survival rate were 69.8%. Univariate analyses revealed that poor survival was associated with gender of male, smoking≥30 pack years, Eastern Cooperative Oncology Group performance status≥1, tumor-node-metastasis (TNM) stage of III-IV (8th edition), HPV-negative, LDH≥202, CRP/Alb≥0.15, LMR < 2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack years (P < 0.01), LDH ≥202 (P = 0.02). Patients were divided into two groups according to HPV status as HPV-positive and negative OPC and potential prognostic factors were assessed in univariate analyses. In HPV-positive OPC patients, poor survival was significantly associated with smoking ≥30 pack years (P = 0.03), LDH ≥202 (P = 0.04), and LMR < 2.90 (P < 0.01). In HPV-negative OPC patients, gender of male (P < 0.01), smoking ≥30 pack years (P < 0.01), LDH ≥202 (P < 0.01), and CRP/Alb ≥0.15 (P = 0.01) were significant predictors of poor survival.Conclusion: The present study revealed that high LDH levels predicted poor survival after definitive radiotherapy in both HPV-positive and HPV-negative OPC patients. High LDH levels were stronger poor prognostic factor than HPV status and TNM stage in this study. [ABSTRACT FROM AUTHOR]

Background: Corrected QT (QTc) interval prolongation can induce fatal arrhythmias such as torsade de pointes. Patients and methods: To assess the characteristics of QTc intervals and arrhythmias in women with early breast cancer who received FEC100 adjuvant chemotherapy, electrocardiograms (ECGs) were recorded before and after each chemotherapy. Associations between QTc interval prolongation and single nucleotide polymorphisms (SNPs) of potassium channel genes were also investigated. Results: A total of 131 ECG records were obtained in 34 patients who received 153 cycles of FEC100. QTc intervals could be measured in 127 records. There was a significant trend toward QTc interval prolongation after each treatment, persisting through four cycles of chemotherapy (P < 0.001). Median QTc interval prolongations were 13, 11, 18, and 14 ms in the first through fourth cycles of chemotherapy, respectively. QTc intervals differed significantly between cycles 1 and 4 before treatment as well as after treatment (P < 0.05). A single supraventricular premature contraction was noted in 3 (2.3%) of the 131 cycles in 2 (5.9%) of the 34 patients. There was no significant association between QTc interval prolongation and SNPs of potassium channel genes. Conclusion: This prospective study confirmed that FEC100 is associated with significant QTc interval prolongation in women with early breast cancer. [ABSTRACT FROM PUBLISHER]

An organic–inorganic compound was prepared by adding organic material to inorganic, semiconductor nanoparticles. Polyethylene glycol, tethered chains (PEG-TC) were added to the surface of CdS nanoparticles by a colloidal technique. The photoluminescence (PL) peak energy of the CdS nanoparticles gradually increased with the solvent density. Furthermore, by combining texas red streptavidin molecules with the PEG-TC on the surface of the CdS nanoparticles, the emission from texas red and change in the PL peak energy of CdS nanoparticle was observed. These results indicate that the recombination processes of the CdS nanoparticles can be controlled by the physical state of the PEG-TC chain. [Copyright &y& Elsevier]

We investigated the effects of argon and hydrogen plasmas on the structure and electrical properties of the surface of silicon wafers. Surface roughness and defect density were measured by atomic force microscopy and photothermal deflection spectroscopy, respectively. The electronic properties of the silicon surfaces were evaluated by forming a Schottky contact on the plasma-treated surfaces. A significant surface roughness was observed on hydrogen-plasma-treated surfaces whereas the roughness on argon-plasma-treated samples was much smaller. Whereas the surface defect density was larger after argon plasma than after hydrogen-plasma treatment. Submitting an argon-plasma-treated surface to a subsequent hydrogen plasma reduced the density of defects created by the first treatment. The ideality factors of the Schottky barrier diodes were qualitatively consistent with the surface defect density. The hydrogen plasma reacts with the silicon surface and introduces surface roughness by breaking Si–Si bonds. The hydrogen atoms bond to the surface defects and consequently reduce the defect density. In contrast, the argon plasma sputters the silicon surface uniformly and hence creates defects. [Copyright &y& Elsevier]

A surface anodization technique was applied to an amorphous silicon (a-Si) surface by means of an atomic force microscope (AFM). The oxide line height increased with increasing applied voltage. The height of these lines on the un-hydrogenated amorphous silicon (a-Si:H) film was greater than that on crystalline silicon (c-Si) due to the large defect density in the former. Although the height of the oxide lines did not depend on film thickness, their width increased with decreasing film thickness. The photoluminescence (PL) intensity of the nano-scale lattice pattern drawn on a-Si:H was measured by micro-scale PL equipment. The PL intensity from the area having narrow oxide lines was smaller than that from the non-oxidized area. This indicates that anodization affects not only the area observed by the AFM, but its effects also spread over a sub-micron region. [Copyright &y& Elsevier]

Silicon nitride films were synthesized by reactive pulsed laser ablation (PLA) of a Si target in N2 gas atmosphere. At different laser fluences and N2 gas pressures the infrared absorption peak attributed to Si–N bond was evaluated. The nitrogen concentration in the film increased with the increasing fluence. Nitrogen concentration depended also on N2 gas pressure; it increased as N2 pressure increase up to 10 Pa and then it decreased with further increasing N2 gas pressure. These results indicate that decomposition of N2 molecules and collisions of SiNx clusters with N2 molecules are essential to prepare silicon nitride films by PLA method. The PLA is a promising method to fabricate nitrogen rich silicon nitride films without using poisonous gases such as silane and ammonia. [Copyright &y& Elsevier]

A group of muscular dystrophies, dystroglycanopathy, is caused by abnormalities in post-translational modifications of dystroglycan (DG). To better understand the pathophysiological roles of DG modification and to establish effective treatment for dystroglycanopathy, we generated 2 distinct conditional knock-out (cKO) mice for fukutin, the first dystroglycanopathy gene identified for Fukuyama congenital muscular dystrophy. The first dystroglycanopathy model – myofiber-selective fukutin-cKO (MCK-fukutin-cKO) mice – showed mild muscular dystrophy. Forced exercise experiments in presymptomatic MCK-fukutin-cKO mice revealed that myofiber membrane fragility triggered disease manifestation. The second dystroglycanopathy model – muscle precursor cell (MPC)-selective cKO (Myf5-fukutin-cKO) mice – exhibited more severe phenotypes of muscular dystrophy. Using an isolated MPC culture system, we demonstrated that defects in the fukutin-dependent modification of DG lead to impairment of MPC proliferation, differentiation, and muscle regeneration. These results suggest that impaired MPC viability contributes to the pathology of dystroglycanopathy. Since our data suggested that frequent cycles of myofiber degeneration/regeneration accelerate substantial and/or functional loss of MPC, we expected that protection from disease-triggering myofiber degeneration provides therapeutic effects even in mouse models with MPC defects; therefore, we restored fukutin expression in myofibers. Adeno-associated virus (AAV)-mediated rescue of fukutin expression that was limited in myofibers successfully ameliorated the severe pathology even after disease progression. In addition, compared to other gene therapy studies, considerably low AAV titers were associated with therapeutic effects. Our findings indicated that fukutin-deficient dystroglycanopathy is a regeneration-defective disorder, and gene therapy is a feasible treatment for the wide range of dystroglycanopathy even after disease progression. [Copyright &y& Elsevier]